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  • Published: 10 February 2022

The rapid progress in COVID vaccine development and implementation

  • Alan D. T. Barrett   ORCID: orcid.org/0000-0003-3740-7448 1 ,
  • Richard W. Titball   ORCID: orcid.org/0000-0002-0162-2077 2 ,
  • Paul A. MacAry   ORCID: orcid.org/0000-0002-1139-8996 3 ,
  • Richard E. Rupp 1 , 4 ,
  • Veronika von Messling   ORCID: orcid.org/0000-0002-3972-8723 5 ,
  • David H. Walker 1 , 6 &
  • Nicolas V. J. Fanget   ORCID: orcid.org/0000-0001-8478-2342 7  

npj Vaccines volume  7 , Article number:  20 ( 2022 ) Cite this article

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January 2022 is the second anniversary of the identification of Coronavirus disease 2019 (COVID-19) 1 caused by severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2). Scientifically, during the COVID pandemic, we have come a very long way in a very short period of time and demonstrated the power of twenty-first century science and technology when a pandemic situation catalyzed the adoption of novel vaccine technologies at record speed. Rapid sequencing of the virus genome allowed initial development to start in January 2020 2 and we had our first authorized vaccines by December 2020 3 .

NPJ Vaccines has published over 65 papers on SARS-CoV-2 that cover the entire breadth of vaccinology from basic science to attitudes of the public to COVID vaccines. With this in mind, the editors of NPJ Vaccines have selected 17 articles that exemplify the rapid progress made with COVID vaccine development in the last 2 years.

Our first COVID paper described the outbreak of SARS-CoV-2 pneumonia in China with the first confirmed cases on December 29, 2019, and the urgent need for vaccines 4 . The scientific and medical community quickly realized that a vaccine would be essential for controlling the disease. Work started on developing inactivated, live attenuated, nucleic acid, subunit and vectored vaccines, and the various potential technologies and their advantages and drawbacks were summarized briefly in a Comment 4 . As laboratories around the world shifted to studying the virus, its biology and interactions with the immune system were also clarified.

SARS-CoV-2 is typical of many RNA viruses being enveloped with a major surface glycoprotein (in this case the Spike (S) protein) that is involved in binding to the cell receptor of the virus, angiotensin-converting enzyme 2 (ACE2), and is the major target for neutralizing antibodies. In particular, the receptor binding domain (RBD) of the S-protein is the target of the most potent neutralizing antibodies 5 . Importantly, immunization can achieve higher levels of antibody to the S-protein than natural exposure to the virus 6 . However, like many RNA viruses SARS-CoV-2 has a low-fidelity replication complex that allows the viral genome to mutate rapidly as it adapts to new conditions. Many SARS-CoV-2 laboratory isolates have been made in monkey kidney Vero cells. A very important study by Funnell et al. (2021) 7 showed that Vero cell culture passaging of isolates must be undertaken carefully, as this can lead to the generation of virus variants with critical changes in the region of the S-protein furin cleavage site, affecting the use of such viruses in in vitro neutralization tests and in vivo challenge studies. Similarly, there are a number of different neutralization assays used to measure neutralizing antibodies and there is a need to standardize such assays using the World Health Organization standard that measures neutralization titers in International Units 8 . Mutations in the S-protein have proved to be particularly important for vaccine development, as they can result in changes in the interaction of the protein with both ACE2 and antibodies. The first major mutation identified in the S-protein was the D614G substitution, which became the dominant variant by June 2020. A range of studies reported in NPJ Vaccines have shown that antibodies to the Wuhan spike protein are able to neutralize a range of variants, including the Omicron variant, albeit with reduced potency towards some variants 9 , which is mostly due to mutations in the RBD of variants 5 . The reduced neutralizing activity of antibodies towards variants can, to some extent, be addressed using a third immunizing dose 10 .

Although vaccines depend on the native S-protein for inducing potent neutralizing antibody responses alongside T-cell responses, the presentation of the S-protein to the immune system differs substantially between the different vaccine platform technologies 11 . It is clear that differences in the presentation of the S-protein to the immune system can have a profound effect on the nature of the immune response 11 . This is elegantly illustrated in a study on the immune responses to a human adenovirus 26-vectored vaccine encoding modified forms of the S-protein 12 . A wide range of other approaches have been proposed, including using the anti-tuberculosis vaccine Bacille Calmette-Guérin (BCG), which has inherent immunostimulatory properties 13 . This might provide ways of re-programming the innate response to achieve single-dose protective immunity and could be of great value in both high- and low-income countries.

One of the intriguing features of the immune response induced by many coronavirus infections is the lack of a long-lived protective immune response, in particular the waning antibody responses. Bachmann et al. (2021) 14 suggest this is due, in part, to the topography of SARS-CoV-2 virus, where S-protein is perpendicular to the surface of virions and embedded in a fluid membrane, such that neutralizing epitopes are loosely “floating.” Another feature of the S-protein is the N-linked glycosylation sites, which can mask epitopes. In the case of SARS-CoV-2, it was found that glycans masked epitopes on the S2 subunit domain of the S-protein, but not the S1 subunit domain, which includes the RBD 15 . These findings highlight the importance of understanding the basic biology of the virus to enable the development of effective vaccines.

Meanwhile vaccine development continued apace, and by February 2021 Kyriakidis et al. (2021) 16 described 64 candidate vaccines, developed using different technologies (mRNA, replication-defective viral vector, virus-like particle, inactivated virus and protein subunit), as they entered phase III clinical trials. By May 2021 McDonald et al. (2021) 17 were able to compile a systematic review and meta-analysis that compared reactogenicity, immunogenicity, and efficacy of 18 candidate vaccines based on studies in non-human primates and humans. Not surprisingly, the different vaccines varied in their abilities to induce antibodies (including neutralizing antibodies), T-cell responses, and their reactogenicity and efficacy.

Following the authorization or licensing of a vaccine, implementation becomes the critical issue, especially with respect to vaccine hesitancy. Kreps et al. (2021) 18 investigated attitudes of the general public towards COVID-19 vaccination and identified that the public were confused in their understanding of the differences between “Emergency Use Authorization” and conventional “licensure.” The findings of studies such as this one have implications regarding public health strategies for implementation of many vaccines, not only COVID, to increase levels of vaccination in the general public. Another concern of the public is around the safety and efficacy of vaccines in special populations. For example, Low et al. (2021) 19 undertook an important study that demonstrated codominant IgG and IgA expression with minimal vaccine mRNA in milk of lactating women, who received the Pfizer-BioNTech BNT162b2 and no adverse events in infants who breastfed from these vaccinees.

Finally, the COVID pandemic has identified the need for pandemic preparedness in the future for other pathogens and Monrad et al. (2021) 20 discuss the important issues of how we could finance such activities moving forward.

We hope that you will find these papers interesting and informative, they are representative of the work we have published in NPJ Vaccines . We encourage you to look at these other equally interesting reports, which collectively provide an incomparable breadth of information and a resource for everyone interested in this field.

Li, Q. et al. Early transmission dynamics in Wuhan, China, of novel coronavirus–infected pneumonia. New Engl. J. Med. 382 , 1199–1207 (2020).

Article   CAS   Google Scholar  

Wu, F. et al. A new coronavirus associated with human respiratory disease in China. Nature 579 , 265–269 (2020).

Medicines and Healthcare products Regulatory Agency. Regulatory approval of Pfizer/BioNTech vaccine for COVID-19. https://www.gov.uk/government/publications/regulatory-approval-of-pfizer-biontech-vaccine-for-covid-19 (Medicines and Healthcare products Regulatory Agency, 2020).

Shang, W., Yang, Y., Rao, Y. & Rao, X. The outbreak of SARS-CoV-2 pneumonia calls for viral vaccines. NPJ Vaccines 5 , 18 (2020).

Kleanthous, H. et al. Scientific rationale for developing potent RBD-based vaccines targeting COVID-19. NPJ Vaccines 6 , 128 (2021).

Assis, R. et al. Distinct SARS-CoV-2 antibody reactivity patterns elicited by natural infection and mRNA vaccination. NPJ Vaccines 6 , 132 (2021).

Funnell, S. G. P. et al. A cautionary perspective regarding the isolation and serial propagation of SARS-CoV-2 in Vero cells. NPJ Vaccines 6 , 83 (2021).

Chmielewska, A. M., Czarnota, A., Bieńkowska-Szewczyk, K. & Grzyb, K. Immune response against SARS-CoV-2 variants: the role of neutralization assays. NPJ Vaccines 6 , 142 (2021).

Zou, J. et al. The effect of SARS-CoV-2 D614G mutation on BNT162b2 vaccine-elicited neutralization. NPJ Vaccines 6 , 44 (2021).

Brinkkemper, M. et al. A third SARS-CoV-2 spike vaccination improves neutralization of variants-of-concern. NPJ Vaccines 6 , 146 (2021).

Heinz, F. X. & Stiasny, K. Distinguishing features of current COVID-19 vaccines: knowns and unknowns of antigen presentation and modes of action. NPJ Vaccines 6 , 104 (2021).

Bos, R. et al. Ad26 vector-based COVID-19 vaccine encoding a prefusion-stabilized SARS-CoV-2 Spike immunogen induces potent humoral and cellular immune responses. NPJ Vaccines 5 , 91 (2020).

Counoupas, C. et al. A single dose, BCG-adjuvanted COVID-19 vaccine provides sterilising immunity against SARS-CoV-2 infection. NPJ Vaccines 6 , 143 (2021).

Bachmann, M. F., Mohsen, M. O., Zha, L., Vogel, M. & Speiser, D. E. SARS-CoV-2 structural features may explain limited neutralizing-antibody responses. NPJ Vaccines 6 , 2 (2021).

Wintjens, R., Bifani, A. M. & Bifani, P. Impact of glycan cloud on the B-cell epitope prediction of SARS-CoV-2 Spike protein. NPJ Vaccines 5 , 81 (2020).

Kyriakidis, N. C., López-Cortés, A., González, E. V., Grimaldos, A. B. & Prado, E. O. SARS-CoV-2 vaccines strategies: a comprehensive review of phase 3 candidates. NPJ Vaccines 6 , 28 (2021).

McDonald, I., Murray, S. M., Reynolds, C. J., Altmann, D. M. & Boyton, R. J. Comparative systematic review and meta-analysis of reactogenicity, immunogenicity and efficacy of vaccines against SARS-CoV-2. NPJ Vaccines 6 , 74 (2021).

Kreps, S., Dasgupta, N., Brownstein, J. S., Hswen, Y. & Kriner, D. L. Public attitudes toward COVID-19 vaccination: The role of vaccine attributes, incentives, and misinformation. NPJ Vaccines 6 , 73 (2021).

Low, J. M. et al. Codominant IgG and IgA expression with minimal vaccine mRNA in milk of BNT162b2 vaccinees. NPJ Vaccines 6 , 105 (2021).

Monrad, J. T., Sandbrink, J. B. & Cherian, N. G. Promoting versatile vaccine development for emerging pandemics. NPJ Vaccines 6 , 26 (2021).

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Richard W. Titball

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A.D.T.B. wrote the draft of the editorial. R.W.T. and N.V.J.F. commented on and edited the editorial. All authors commented on the editorial, and participated in the selection of articles highlighted in the Collection.

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A.D.T.B., R.W.T., P.A.M., R.E.R., V.v.M., and D.H.W. are editors of NPJ Vaccines .

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Barrett, A.D.T., Titball, R.W., MacAry, P.A. et al. The rapid progress in COVID vaccine development and implementation. npj Vaccines 7 , 20 (2022). https://doi.org/10.1038/s41541-022-00442-8

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Research Article

Knowledge, acceptance and perception on COVID-19 vaccine among Malaysians: A web-based survey

Contributed equally to this work with: Nurul Azmawati Mohamed, Mohd Dzulkhairi Mohd Rani, Muslimah Ithnin, Che Ilina Che Isahak

Roles Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Validation, Visualization, Writing – original draft, Writing – review & editing

Affiliation Faculty of Medicine and Health Sciences, Universiti Sains Islam Malaysia, Nilai, Negeri Sembilan, Malaysia

Roles Conceptualization, Data curation, Investigation, Methodology, Project administration, Writing – original draft, Writing – review & editing

* E-mail: [email protected]

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Roles Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Software, Validation, Visualization, Writing – review & editing

Roles Data curation, Formal analysis, Methodology, Writing – original draft

Roles Conceptualization, Funding acquisition, Supervision, Validation

  • Nurul Azmawati Mohamed, 
  • Hana Maizuliana Solehan, 
  • Mohd Dzulkhairi Mohd Rani, 
  • Muslimah Ithnin, 
  • Che Ilina Che Isahak

PLOS

  • Published: August 13, 2021
  • https://doi.org/10.1371/journal.pone.0256110
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Table 1

Coronavirus disease 2019 or COVID-19 is caused by a newly discovered coronavirus, SARS-CoV-2. The Malaysian government has planned to procure COVID-19 vaccine through multiple agencies and companies in order to vaccinate at least 70% of the population. This study aimed to determine the knowledge, acceptance and perception of Malaysian adults regarding the COVID-19 vaccine.

Methodology

An online survey was conducted for two weeks in December 2020. A bilingual, semi-structured questionnaire was set up using Google Forms and the generated link was shared on social media (i.e., Facebook and WhatsApp). The questionnaire consisted of questions on knowledge, acceptance and perception of COVID-19 vaccine. The association between demographic factors with scores on knowledge about COVID-19 vaccine were analysed using the Mann-Whitney test for two categorical variables, and the Kruskal-Wallis test used for more than two categorical variables.

A total of 1406 respondents participated, with the mean age of 37.07 years (SD = 16.05) years, and among them 926 (65.9%) were female. Sixty two percent of respondents had poor knowledge about COVID-19 vaccine (mean knowledge score 4.65; SD = 2.32) and 64.5% were willing to get a COVID-19 vaccine. High knowledge scores associated with higher education background, higher-income category and living with who is at higher risk of getting severe COVID-19. They were more likely to be willing to get vaccinated if they were in a lower age group, have higher education levels and were female.

Even though knowledge about vaccine COVID-19 is inadequate, the majority of the respondents were willing to get vaccinated. This finding can help the Ministry of Health plan for future efforts to increase vaccine uptake that may eventually lead to herd immunity against COVID-19.

Citation: Mohamed NA, Solehan HM, Mohd Rani MD, Ithnin M, Che Isahak CI (2021) Knowledge, acceptance and perception on COVID-19 vaccine among Malaysians: A web-based survey. PLoS ONE 16(8): e0256110. https://doi.org/10.1371/journal.pone.0256110

Editor: Eman Sobh, Al-Azhar University, EGYPT

Received: February 16, 2021; Accepted: August 1, 2021; Published: August 13, 2021

Copyright: © 2021 Mohamed et al. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: The Supporting Information File is available at 10.6084/m9.figshare.14932605 .

Funding: The authors received no specific funding for this work.

Competing interests: The authors have declared that no competing interests exist.

Introduction

Coronavirus disease 2019 or COVID-19 is caused by a newly discovered coronavirus, SARS- CoV-2. This new infection was believed to have emerged from Wuhan City, Hubei Province, China in December 2019. On March 11 2020, the World Health Organization (WHO) declared COVID-19 as a pandemic [ 1 ]. Until early June 2021, this emergent disease has infected more than 170 million people around the world and caused more than 3 million deaths [ 1 ]. The rate of infection had not seem to slow down in the majority of the affected countries, and varying degrees of lockdowns have been issued in the effort to contain the spread of the virus. In Malaysia, a resurgence of infections began in late September 2020 with a rapid increase in the number of infections, at more than 4000 cases daily since mid-January 2021 [ 2 ]. As of June 15 2021, Malaysia has reported 3968 COVID-19 deaths or a 0.6 percent fatality rate out of 662,457 cases [ 2 ].

Currently, there are more than 100 candidates of COVID-19 vaccines under development [ 3 ]. About 11 months after the emergence of the disease, the Food and Drug Administration (FDA) has approved the use of Pfizer/BioNTech and Moderna COVID-19 vaccines in a mass immunization programme [ 4 ]. Phase three clinical trials for Pfizer/BioNTech vaccines enrolled 43,661 participants, while Moderna vaccines involving 30,000 participants [ 5 , 6 ]. The clinical trial results showed that these vaccines can protect recipients from a COVID-19 infection by forming antibodies and providing immunity against a COVID-19 virus [ 4 ]. There are also other companies in the race for vaccine development and in the final stages of trials. It is expected that many vaccines will be ready for distribution by early or mid-2021 [ 7 ]. The United Kingdom was among the first countries that have started mass immunization COVID-19 vaccine [ 8 ]. Apart from Moderna and Pfizer that use mRNA as the active substance, other vaccines use various other types of antigen such as viral vector, attenuated virus and inactivated virus [ 9 ]. The use of mRNA is a new technology for vaccine development, where the vaccine contains messenger RNA instructs cells to produce a protein that acts as an antigen.

As safe and effective vaccines are being made available, the next challenge will be dealing with vaccine hesitancy. Vaccine hesitancy, identified as one of the ten most important current health threats, is defined as the reluctance or refusal to vaccinate despite the availability of vaccines [ 10 ]. Wong et al. (2011) conducted a population-based study in Hong Kong on the acceptance of the COVID-19 vaccine using the health belief model (HBM) and found that perceived severity, perceived vaccine benefits, cues to action, self-reported health outcomes, and trust were all positive indicators of acceptance. Perceived vulnerability to infection had no significant association with acceptance, whereas perceived access barriers and harm were negative predictors [ 11 ]. In addition, another community-based study found that people’s desire to get vaccinated against COVID-19 has fallen dramatically during the pandemic, with over half of the population were hesitant or unwilling to get vaccinated [ 12 ].

Misinformation and unsubstantiated rumours regarding COVID-19 vaccines have been around and repeatedly shared on social media platforms even before the release of an effective vaccine [ 13 ]. The use of mRNA genetic material in several vaccines have been sensationalized by some, with the false claims that the vaccine can alter human DNA [ 14 ] Additionally, the rapid development of COVID-19 vaccines has reportedly raised concerns regarding the safety and long term effects, even among the medical staffs [ 15 ]. Findings from studies among healthcare workers (HCWs) are alarming, as a small percentage of HCWs do not intend to get the COVID-19 vaccine [ 16 , 17 ].

The Malaysian government has procured COVID-19 vaccine through a government-to- government deal with the Republic of China, direct purchase from pharmaceutical companies and the COVID-19 Global Vaccine Access (Covax) Facility. With these arrangements, Malaysia is expected to receive its first batch of COVID-19 vaccines to immunise 6.4 million people as early as end of February 2021 [ 18 ]. We embarked on this study to determine the knowledge, acceptance and perception of the COVID-19 vaccine among the Malaysian adult population. The findings from this study will provide data and crucial information for the government to find strategies to increase public understanding and the uptake of COVID-19 vaccine.

This cross-sectional, online population-based survey was conducted from 1 st to 15 th December 2020. The study sample size was estimated using the Raosoft sample size calculator. A minimum of 385 participants were required at a margin of error of 5%, a 95% confidence interval (CI), and a population size of 32.6 million at a 50% response distribution. A bilingual, semi-structured questionnaire was adopted and adapted from Reiter et al. (2020) [ 19 ], and then set up via Google Forms. The access link was then shared via online platforms including Facebook and WhatsApp, initiated by all project members. The sharing was escalated by our family members, friends, colleagues, and acquaintances. The inclusion criteria for respondents’ eligibility include those more than 18 years old, and an understanding of the Malay or English language. The respondents were requested to take part in the survey by completing the questionnaire without any time restrictions. Reliability measurement was tested earlier on 50 respondents for both the English and Malay version of the questionnaire. Cronbach alpha values for knowledge, perceived susceptibility, perceived barriers and perceived benefits were 0.718, 0.714, 0.714 and 0.834, respectively for the English version. Whereas the Cronbach alpha values for the Malay version were 0.665, 0.688, 0.787 and 0.889, respectively.

The questionnaire consists of four sections: Section A on demographic and COVID-19 status, Section B on the knowledge on COVID-19 vaccine, Section C on the acceptance of COVID- 19 vaccine and Section D on perception based on the Health Belief Model (HBM). For section B (knowledge), participants were given three options: Yes, No and Do not know. One mark was given for any correct answer and 0 mark for any wrong answer and do not know answers. The maximum knowledge score was 10, and those who obtained marks above the median of the total score (6 and above) will be categorized as having good knowledge. Section C consists of questions on the willingness to take the vaccine and the reason, cost of the vaccine and factors influencing the decision. For Section D, five options were given: strongly agree, agree, neutral, disagree and strongly disagree, for perceived susceptibility and barriers. The questionnaire used in this study is not published under a CC-BY license, and other researchers may cite the related article when referencing the questionnaire.

Ethical consideration

This research was approved by the Ethics Committee of Universiti Sains Islam Malaysia with the code project of USIM/JKEP/2021-126. The subjects consented to participate in this survey by volunteering to complete and submit the questionnaire.

Study variables

Dependent variables..

COVID-19 knowledge score.

Acceptance to COVID-19 vaccine.

Independent variables.

Age, gender, educational status, income category, presence of any chronic diseases, history of been infected with COVID-19, history of family members or friends been infected with COVID-19, living with someone who is at higher risks of getting severe COVID-19 including living with elderly or family members with comorbidity or having long-term medical follow up or chronic medication.

Data analysis

All data were entered into the Microsoft Excel spreadsheet and then loaded and coded into the SPSS version 23 software for final analysis. Simple descriptive analyses, including frequencies, percentages, mean, and standard deviation (SD) were computed for demographic characteristics, the knowledge scores regarding COVID-19 vaccine, and the perceived susceptibility, barriers and benefits to the COVID-19 vaccine. Histogram with normality curve and Kolmogorov–Smirnov test was used to check for the normal distribution of data in this study. Since the data were not normally distributed, the non-parametric tests were used for inferential analysis. The association between demographic factors with scores on knowledge regarding COVID-19 vaccine was analysed using the Mann-Whitney test for two categorical variables, and the Kruskal-Wallis test used for more than two categorical variables. A Chi-square test was carried out to determine the significant level of association and the relationship between the categorical independent variables of demographic factors and outcome variables of acceptance to the COVID-19 vaccine. Statistical significance was defined at p <0.05.

Demographic data

A total of 1406 respondents participated in this online survey. The mean age was 37.07 years (SD = 16.05; range = 18–81) and 926 (65.9%) of the respondents were female. The detailed characteristics of the respondents are shown in Table 1 .

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https://doi.org/10.1371/journal.pone.0256110.t001

Knowledge regarding COVID-19 vaccine

A total of 872 (62.0%) of the respondents had poor knowledge about COVID-19 vaccine ( Fig 1 ). The statement “COVID-19 vaccines will be given via injection”, had the most percentage of correct answers (82.1%). The statement with the lowest percentage of correct answers was “Everyone including children can receive COVID-19 vaccination” and “COVID-19 vaccine can also protect us from influenza,” in which only 14.7% and 18.5% of respondents gave the correct answer. Table 2 shows the knowledge questions and scores for each statement.

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https://doi.org/10.1371/journal.pone.0256110.g001

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https://doi.org/10.1371/journal.pone.0256110.t002

Table 3 shows the association between demographic factors and knowledge scores. Higher education level, higher income and living with high-risk individuals were significantly associated with higher knowledge score.

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https://doi.org/10.1371/journal.pone.0256110.t003

Acceptance towards COVID-19 vaccine

Almost two thirds of the respondents (64.5%) indicated willingness to get vaccinated ( Fig 2 ). The majority agreed that the government should provide free vaccination to high-risk groups. More than 70% of the respondents would pay a maximum of RM 100 for the vaccine and only a small proportion (4.6%) reported not being able to afford the vaccine at any price. The effectiveness of the vaccine and suggestions from the Ministry of Health were the factors that most strongly influenced the decision to get the vaccination. Table 4 shows the details of the questions and their scores.

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https://doi.org/10.1371/journal.pone.0256110.g002

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https://doi.org/10.1371/journal.pone.0256110.t004

Table 5 shows the association of demographic factors and the acceptance to COVID-19 vaccines. Lower age group, higher education level, female, and not having chronic diseases were significantly associated with acceptance to COVID-19 vaccine.

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https://doi.org/10.1371/journal.pone.0256110.t005

Perceived susceptibilities, barriers, benefits, and cues to action towards COVID-19 vaccine

About 55.9% perceived that they were able to spread the virus to other people and 30% of the respondents perceived that they were susceptible to get severe COVID-19 infection About 75% did not agree that COVID-19 vaccine could cause infection. More than half were worried about the vaccine’s adverse effects and almost one third of them agreed that scary information about COVID-19 vaccine was rampant on social media. The majority believed that the vaccine could protect themselves and other people who are not vaccinated. Almost half were neutral in terms of vaccine cost and safety. Table 6 provides details of the perception scores. All components in HBM have a significant association with acceptance towards COVID-19, as shown in Table 7 .

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https://doi.org/10.1371/journal.pone.0256110.t006

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https://doi.org/10.1371/journal.pone.0256110.t007

Discussions

Since the announcement of the effectiveness of the two rapidly developed vaccines by Pfizer and Moderna, news and articles about vaccines have been circulating in the mass media and social media. This study found that electronic media and social media, including the Malaysian Ministry of Health (MOH) website were the most sought platforms for information regarding the COVID-19 vaccine. Only a small proportion of respondents received the information via newspapers, journal articles and medical-related websites. Previous studies have shown that the use of mass media can yield a positive impact on health-risk behaviours in the community [ 21 ]. However, with the recent advancement of informative technologies, social media is rapidly evolving and gaining more popularity than traditional mass media. Even the traditional mass media is adapting and evolving to fit into the social media platforms. Validated health information shared in social media delivers rapid and successful dissemination of knowledge [ 22 ]. On the other hand, excess information can lead to media fatigue, misinformation and the spread of fake news [ 23 ]. Health literacy is also an important aspect to determine the effectiveness of understanding and appraising the information [ 24 ].

To date, there is no published article about the level of knowledge of the COVID-19 vaccine among the Malaysian population. Previously, a study was done among Malaysian parents revealed that poor knowledge has interfered with their decision on HPV vaccination among their children [ 25 ]. Inadequate knowledge regarding vaccination can be due to low education background, poor socioeconomic status or obtaining information from their peer layman [ 26 , 27 ]. This study found that more than half of the respondents had poor knowledge of the COVID-19 vaccine. Higher education level, higher income and living with high-risk individuals were significantly associated with higher knowledge score.

Malaysian populations were found to have good knowledge, attitude and perception regarding COVID-19 prevention [ 28 ]. This is possibly the main reason for the higher acceptance of COVID-19 vaccine among the respondents, despite having low knowledge on the vaccine. Our acceptance rate is almost similar to Saudi Arabia (64.7%) [ 29 ] and the United Kingdom (64%) [ 30 ], better than Turkey (49.7%) [ 31 ], but lower than China (91.3%) [ 32 ] and Indonesia (93.3%) [ 33 ]. Lower age group, higher education level, female, and not having chronic diseases were significantly associated with acceptance to COVID-19 vaccine. In Saudi Arabia, willingness to accept the COVID-19 vaccine was relatively high among older age groups, married, education level postgraduate degree or higher, non-Saudi, and those employed in the government sector [ 29 ]. Although the acceptance rate is similar to Saudi Arabia, one distinct difference is that while in Malaysia, the younger age groups showed greater acceptance, in Saudi it is the older age groups.

The success of any vaccination programme to achieve herd immunity depends on the vaccine acceptance and uptake rate. The herd immunity threshold depends on the basic reproduction number (R0). With the R0 of 2–3, no population immunity and that all individuals are equally susceptible and equally infectious, the herd immunity threshold for SARS-CoV-2 would be expected to range between 50% and 67% in the absence of any interventions [ 34 ]. In this study, only one-third of the respondents were not willing to get vaccinated. This finding is in line with other studies done in other parts of the world. A study done in France in March 2020 showed that 26% of respondents refused vaccination, more prevalent among low-income people, young women and people older than 75 years old [ 30 ]. Another study done in the USA among the general population found that only 21% of respondents were not willing to be vaccinated [ 19 ]. Reasons for vaccine refusal including but not limited to safety, effectiveness, costs and side effects.

In order to achieve herd immunity, the vaccine hesitancy issue should be addressed. The Ministry of Health Malaysia has scaled up the vaccine promotional programmes, particularly through social media and mass media. More dialogues and forums involving experts from the ministry and universities have frequently been aired in the television and Facebook Live. In the beginning of the mass vaccination programme, the media also highlighted the vaccination process of the top leaders to increase the public confidence. Misinformation about the negative effects of vaccine from irresponsible parties had been monitored closely by the government. In addition, an emergency law to tackle fake news related to COVID-19 was introduced in March 2021 with hefty fines and jail terms of up to six years [ 35 ].

Worryingly, we found that those with existing chronic diseases have significantly lower acceptance rates than those who were healthy. Patients with cardiovascular disease, hypertension, diabetes, congestive heart failure, chronic kidney disease and cancer have been shown to have a greater risk of mortality compared to patients with COVID-19 without these comorbidities [ 36 ]. Early vaccination for this population is critical to ensure their health and safety. Therefore, they will be given high priority for the COVID-19 vaccine. More information should be conveyed to this population about the risk of severe COVID-19 and the benefit of vaccination.

While the majority agreed that the government should provide free vaccination to the high-risk groups, more than 70% of the respondents would pay a maximum of RM 100 for the vaccine and only a small proportion (4.6%) cannot afford the vaccine. This is consistent with a previous Malaysian study in April 2020 when the COVID-19 vaccine was still in its early development [ 37 ]. However, the cost is not an issue since the Malaysian Government has decided to give free vaccination to Malaysian citizen. The effectiveness of the vaccine and recommendation from the MOH were the highest factors that influence the decision to get the vaccination. This agrees with a study in Indonesia where 93.3% of respondents would like to be vaccinated if the vaccine is 95% effective and the acceptance decreased to 60.7% for a vaccine with 50% effectiveness [ 33 ].

A previous study done in Malaysia showed an increase in the perception of susceptibility to infection as the COVID-19 pandemic progressed [ 38 ]. Effective preventative behaviours such as personal hygiene and physical distancing to control SAR- CoV-2 transmission largely depend on the perceived susceptibility to infection [ 39 , 40 ]. Perception of disease susceptibility also correlates with better health-seeking behaviour [ 41 , 42 ].

More than half of our respondents perceived that they could cause the spread of the virus. People with a higher perceived risk of COVID-19 infection are also more likely to support the vaccine [ 33 ]. The low percentage of perceived severity is likely due to the large number of younger respondents with no medical illness. Our respondents had perceived barriers to accepting the COVID-19 vaccine due to its adverse effects, vaccine availability and scary information about vaccines in social media. The majority perceived that vaccination could protect them and others from COVID-19 infection. This is consistent with other findings from other countries [ 43 – 45 ]. Moreover, the respondents believed that the vaccine is beneficial due to recommendations by the MOH and the fact that they can lead a normal life after vaccination. Conversely, more studies have to be done to assess the ability of vaccines to prevent disease transmissibility. According to the CDC, people should continue wearing masks, wash hands frequently and practise physical distancing after getting the COVID-19 vaccine until herd immunity is achieved [ 46 ]. Perceived susceptibility, benefit and cues to action are associated with higher acceptance toward COVID-19 vaccine, and our finding is in concordance with other HBM studies [ 11 , 47 , 48 ].

To the best of our knowledge, this is the first study on the knowledge, acceptability and perception of COVID-19 vaccine in Malaysia. One limitation of this study was the use of convenience sampling via social media platforms. The distribution of the respondents might not reflect the actual population since most respondents were internet-savvy young adults. We suggest a larger study that includes respondents from diverse backgrounds, ethnicity, economic status and locations. Multiple public platform sharing is needed to increase the respondent’s rate. Various data collection methods such as telephone interviews and face-to-face interviews should also be employed.

While waiting for vaccines to arrive, continuous education should be conducted to increase understanding and to clear up any misunderstandings or misinformation about the vaccine. Ideally, health education should be comprehensive and multilingual yet layman friendly. The important messages should reach out to all citizens from all walks of life, including those in the rural areas and technology illiterates. In addition to web-based and application-based educational tools, printed materials and face-to-face public talks may benefit certain groups of the population. Public talks involving religious groups can be conducted in the houses of worship by the experts.

Conclusions

This study provides early insight into the Malaysian population’s knowledge, acceptability and perception regarding COVID-19 vaccines. Knowledge about vaccines was relatively poor, particularly among low education levels, low income and not living with high-risk groups. The acceptability rate was significantly low among males, those with chronic diseases and those with low income. Education level of bachelor’s degree and higher was associated with better acceptance towards COVID-19 vaccine. This finding can help the Ministry of Health to plan for future efforts to increase vaccine uptake that may eventually lead to herd immunity against SARS-CoV-2. The efforts should focus on those with insufficient knowledge and low acceptance, particularly those with chronic diseases and less financially fortunate people.

Acknowledgments

We like to thank the Faculty of Medicine and Health Sciences and Universiti Sains Islam Malaysia for assisting us in publishing this paper.

  • View Article
  • Google Scholar
  • 2. Ministry of Health Malaysia. COVID-19 Latest Update. [Internet]. 2020 [cited 2021 June 15]. Available from: http://covid-19.moh.gov.my/
  • PubMed/NCBI
  • 6. Pfizer Inc. Pfizer and Biontech Conclude Phase 3 Study Of Covid-19 Vaccine Candidate, Meeting All Primary Efficacy Endpoints. 2020. [cited 2020 Dec 12] Available from https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-conclude-phase-3-study-covid-19-vaccine
  • 14. Reuters. False claim: A COVID-19 vaccine will genetically modify humans [Internet]. 2020. [cited 2020 Dec 13]. Available from: https://www.reuters.com/article/uk-factcheck-covid-19-vaccine-modify-idUSKBN22U2BZ
  • 20. Department of Statistic Malaysia. Household Income & Basic Amenities Survey Report 2019 [Internet]. 2020. Available from: https://www.dosm.gov.my/v1/index.php?r=column/cthemeByCat&cat=120&bul_id=TU00TmRhQ1N5TUxHVWN0T2VjbXJYZz09&menu_id=amVoWU54UTl0a21NWmdhMjFMMWcyZz09
  • 35. Malaysia Imposes Emergency Law to Clamp Down on COVID-19 Fake News. [Internet]. Times The Straits. [cited 2021 May 28]. Available from: https://www.straitstimes.com/asia/se-asia/malaysia-imposes-emergency-law-to-clamp-down-on-covid-19-fake-news .
  • 46. Frequently Asked Questions about COVID-19 Vaccination [Internet]. Centers for Disease Control and Prevention. 2020 [cited 2020 Dec 24]. Available from: https://www.cdc.gov/coronavirus/2019-ncov/vaccines/faq.html

COVID-19 mRNA Vaccines: Lessons Learned from the Registrational Trials and Global Vaccination Campaign

Affiliations.

  • 1 Biology and Nutritional Epidemiology, Independent Research, Copper Hill, USA.
  • 2 Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, USA.
  • 3 Biostatistics and Epidemiology, Independent Research, Research Triangle Park, USA.
  • 4 Immunology and Public Health Research, Independent Research, Ottawa, CAN.
  • 5 Epidemiology and Biostatistics, Independent Research, Basel, CHE.
  • 6 Data Science, Independent Research, Los Angeles, USA.
  • 7 Cardiology, Epidemiology, and Public Health, McCullough Foundation, Dallas, USA.
  • 8 Cardiology, Epidemiology, and Public Health, Truth for Health Foundation, Tucson, USA.
  • PMID: 38274635
  • PMCID: PMC10810638
  • DOI: 10.7759/cureus.52876

Our understanding of COVID-19 vaccinations and their impact on health and mortality has evolved substantially since the first vaccine rollouts. Published reports from the original randomized phase 3 trials concluded that the COVID-19 mRNA vaccines could greatly reduce COVID-19 symptoms. In the interim, problems with the methods, execution, and reporting of these pivotal trials have emerged. Re-analysis of the Pfizer trial data identified statistically significant increases in serious adverse events (SAEs) in the vaccine group. Numerous SAEs were identified following the Emergency Use Authorization (EUA), including death, cancer, cardiac events, and various autoimmune, hematological, reproductive, and neurological disorders. Furthermore, these products never underwent adequate safety and toxicological testing in accordance with previously established scientific standards. Among the other major topics addressed in this narrative review are the published analyses of serious harms to humans, quality control issues and process-related impurities, mechanisms underlying adverse events (AEs), the immunologic basis for vaccine inefficacy, and concerning mortality trends based on the registrational trial data. The risk-benefit imbalance substantiated by the evidence to date contraindicates further booster injections and suggests that, at a minimum, the mRNA injections should be removed from the childhood immunization program until proper safety and toxicological studies are conducted. Federal agency approval of the COVID-19 mRNA vaccines on a blanket-coverage population-wide basis had no support from an honest assessment of all relevant registrational data and commensurate consideration of risks versus benefits. Given the extensive, well-documented SAEs and unacceptably high harm-to-reward ratio, we urge governments to endorse a global moratorium on the modified mRNA products until all relevant questions pertaining to causality, residual DNA, and aberrant protein production are answered.

Keywords: autoimmune; cardiovascular; covid-19 mrna vaccines; gene therapy products; immunity; mortality; registrational trials; risk-benefit assessment; sars-cov-2 (severe acute respiratory syndrome coronavirus -2); serious adverse events.

Copyright © 2024, Mead et al.

Publication types

ORIGINAL RESEARCH article

Vaccine side effects following covid-19 vaccination among the residents of the uae—an observational study.

\nSubhashini Ganesan,*&#x;

  • 1 G42 Healthcare, Abu Dhabi, United Arab Emirates
  • 2 Insights Research Organization and Solutions, Abu Dhabi, United Arab Emirates
  • 3 Sheikh Khalifa Medical City, SEHA, Abu Dhabi, United Arab Emirates
  • 4 College of Medicine and Health Sciences, Khalifa University, Abu Dhabi, United Arab Emirates
  • 5 Ambulatory Healthcare Services, SEHA, Abu Dhabi, United Arab Emirates
  • 6 College of Medicine and Health Sciences, UAE University, Abu Dhabi, United Arab Emirates

COVID-19 vaccines have proven to be very safe in the clinical trials, however, there is less evidence comparing the safety of these vaccines in real-world settings. Therefore, we aim to investigate the nature and severity of the adverse effects reported and the differences based on the type of vaccine received. A survey was conducted among 1,878 adult (≥18 years) COVID-19 vaccine recipients through online survey platforms and telephonic interviews during March to September 2021. The factors potentially associated with the reported side effects like age, gender, ethnicity, comorbidities, and previous COVID-19 infection were analyzed based on the type of vaccine received. Differences in adverse events and the severity were compared between inactivated and mRNA vaccine recipients. The major adverse effects reported by the COVID-19 vaccine recipients were pain at the site of injection, fatigue and drowsiness, and headache followed by joint/muscle pain. The adverse effects were more common among recipients of mRNA Pfizer-BioNTech vaccine than among recipients of inactive Sinopharm vaccine with the odds ratio of 1.39 (95% CI 1.14–1.68). The average number of adverse effects reported between individuals who had received Sinopharm and Pfizer-BioNTech vaccines was 1.61 ± 2.08 and 2.20 ± 2.58, respectively, and the difference was statistically significant ( p <0.001). Severe adverse effects after COVID-19 vaccinations were rare and 95% of the adverse effects reported after either an inactivated or mRNA vaccine were mild requiring no or home-based treatment. The study found that individuals less than 55 years of age, female gender, with history of one or more comorbid conditions, who had received mRNA Pfizer- BioNTech vaccine, and with history of COVID-19 infections are at higher odds of developing an adverse effect post COVID-19 vaccination compared to the others.

Introduction

In the world's fight against the COVID-19 pandemic, vaccines emerged as the greatest savior for humankind and many vaccine candidates were developed and entered clinical trials in early 2020. Many of these vaccines obtained emergency approval and governments around the world started vaccination campaigns against COVID-19 ( 1 , 2 ).

The United Arab Emirates (UAE) government had successfully completed the vaccination trial for the BBIBP-CorV or Sinopharm vaccine which was approved for general public in December 2020 ( 3 ). Since then, vigorous vaccination of the population was undertaken and the UAE tops the world in the vaccine distribution rate per 100 people ( 4 )and has effectively vaccinated more than 90% of the population so far ( 5 ). Apart from Sinopharm, the UAE government has also approved mRNA Pfizer-BioNTech, adenovirus-based AstraZeneca, and Sputnik V and other vaccines and made them accessible for all people in the UAE.

The worldwide vaccination coverage for COVID-19 vaccination is still low and as of 24 November 2021, only 42% of the world population have received initial two doses of COVID-19 vaccination ( 6 ). Data published from the vaccine trials have demonstrated that the adverse effects of the COVID-19 vaccine most commonly include fever, fatigue, muscle pain, joint pain, and headache and serious adverse events were rarely reported ( 7 – 10 ). In the Sinopharm inactivated vaccine trial, the most common adverse reaction observed was injection site pain followed by fever and all the adverse reactions reported were mild and self-limiting and did not require any treatment ( 7 ). The Pfizer-BioNTech mRNA vaccine trial has reported that the most common adverse effect was mild to moderate fatigue and headache ( 8 ). Similarly, AstraZeneca and Sputnik vaccine trials have also reported only mild/moderate side effects ( 9 , 10 ).

Global safety studies on vaccine reactogenicity have shown that the mRNA COVID-19 vaccine recipients have reported injection site or local reactions more frequently than systemic reactions and serious adverse events were rare ( 11 , 12 ). Younger population and females have reported more side effects than the others ( 13 ). Despite published safety data on COVID-19 vaccines, people around the globe have expressed their concerns and hesitancy in vaccination, and studies have shown that the intention to get vaccinated is associated with positive vaccination beliefs ( 14 ). Surveys have shown that people worry about the potential adverse effects of the COVID-19 vaccine which they believe would be worse than the disease itself ( 15 , 16 ). Even among healthcare professionals, vaccine acceptance has been found to be sub-optimal with doubts about vaccine safety, the quality control, and potential adverse effects given its rapid development ( 17 , 18 ).

A survey done in the UAE on vaccine perception for COVID-19 vaccine showed that safety of the vaccine with no major side effects emerged as the greatest motivating factor to get vaccinated ( 19 ). As vaccine-related fears on safety and side effects play a role in determining the decision regarding vaccination, studies are conducted to monitor the safety of COVID-19 vaccines globally ( 20 ). All these reports establish that the major concern for people to get vaccinated is the side effects or adverse events following COVID-19 vaccination.

Therefore, this survey would give an insight into the actual adverse effects experienced by the recipients of the COVID-19 vaccine and will help us understand the nature of the adverse effects of these different vaccines. This insight would also help instill confidence in people on getting vaccinated against COVID-19.

Study Design and Study Setting

A cross-sectional study based on an online survey and telephonic interviews was conducted between 14 March 2021 and 4 September 2021 among the residents of the UAE. The survey was designed to identify the side effects reported after receiving a COVID-19 vaccination and no personal identification details were collected. An electronic consent was obtained during the online survey and only participants who agreed entered the survey. Participants in telephonic interviews also consented orally before they were presented with the survey. The study was approved by the Medical Research Department, DOH, Abu Dhabi, UAE (approval number: DOH/CVDC/2021/329).

Study Participants

Participants from all nationalities, gender, and age 18 years and above, who had received at least one dose of the COVID-19 vaccination, who were able to give consent and were currently residing in the UAE were included in the survey. The survey form was designed using Google Forms and the participants were approached through social media platforms. A total of 744 participants consented and completed the survey online. Apart from this, telephonic interviews were conducted and the participants were selected randomly from the vaccine database of those who had received the COVID-19 vaccination during the period of the study available at the Ambulatory Healthcare Services, SEHA. This is Abu Dhabi's largest health services provider, which operates all public hospitals and clinics in the emirate of Abu Dhabi. It provides vaccination against COVID-19, manages vaccine-related complications, and operates all COVID-19 dedicated hospitals in Abu Dhabi. Stratified random sampling was used to ensure good representation and samples were stratified based on age group and type of vaccine received. The selected participants were contacted, and among those who were willing to participate, the survey was completed through a telephone interview. A total of 1,796 vaccine recipients were selected from the database based on the stratification criteria and were approached. The response rate was 63.1% with 1,134 completing the interview. Of the others who did not participate, 4.7% refused to participate, 20% did not answer the phone calls, and the rest were identified as having wrong numbers or having language barriers. The interviews were done by family medicine residents who were trained for this purpose. Therefore, a total of 1,878 participants completed the survey, of which 1,134 participants were interviewed through a telephonic survey and 744 participants completed the online survey form.

The Survey Tool

The questionnaire was designed to capture the reactogenicity to the COVID-19 vaccine and the factors that were related to the development of the vaccine's side effects. Based on the literature review of the side effects reported post-COVID-19 vaccination ( 8 – 14 ), the adverse effects were listed in our survey and avenues to add additional side effects were provided. The factors that were studied in the literature and found to be associated with the development of the side effects were captured by designing specific questions on age, gender, nationality, educational status, monthly income, comorbid conditions, previous history of COVID-19 infection, type of COVID-19 vaccine received, and the number of doses received to elicit the responses ( 11 – 13 , 21 ).

The questionnaire was prepared both in English and Arabic languages. The Arabic translation was done by language experts and back-translated by two native speakers to understand any discrepancies and then corrected and approved by the language experts.

The construct validity of the questionnaire was established by four experts with epidemiology, public health, and family medicine background and experience in vaccine trials and vaccination programs. The questionnaire was pilot tested among 5 participants to understand the feasibility and was refined based on feedback.

The survey had a screening question on vaccination which screened all participants who were not vaccinated. Only the participants who had received at least one dose of the COVID-19 vaccine were presented further for the survey.

The first part of the survey included questions on demographic variables like age, sex, education, and nationality. The second part of the survey included questions on comorbid conditions like diabetes, hypertension, chronic lung diseases, cardiovascular, cancer, autoimmune diseases, and other chronic diseases. This section also included a question on the previous history of allergies and associated immunodeficiency or taking medication like high-dose corticosteroids, immunosuppressants, or cancer medicines to rule out any immunocompromised state. The third section included questions on the previous infection with COVID-19 and the severity of the infection. The fourth section of the survey was on vaccination, the type of vaccination taken against COVID-19, the number of doses taken, and the adverse effects experienced after vaccination for COVID-19. The final section of the survey was only for people who had experienced any adverse effects. This section included more questions to understand the nature of adverse effects. Questions on doses of vaccination after which they developed adverse effects and the severity of the adverse effects were included. Participants were asked to grade the severity of side effects by using a Likerts scale of 1–10, where 1 denotes “mild symptoms” and 10 denotes “extremely severe symptoms”. To assess severity more objectively, we also asked the participants whether the side effects required any treatment, if so, was it home-based treatment, consultation with a health professional, or hospital-based treatment.

The age of the participants was stratified into three groups <35 years, 35–54 years, and 55 years and above, which was based on previous literature and the age stratification widely employed in the studies reviewed on systematic review and metanalysis of the impact of age difference on COVID-19 vaccine safety ( 12 , 22 ). The adverse effects were classified into local and systemic side effects for analysis. The local side effects included injection site reactions like pain at the site of vaccination, redness, swelling/lymph node enlargement, and itch. The systemic side effects included fever, headache, muscle, and joint pain, flu-like symptoms, etc.

Sample Size

The study was conducted only among residents of the UAE, which has a population of approximately 10 million people, and at the time of the study, 4 million doses were administered, that is approximately 40% of the total population had received at least one dose of their vaccination against COVID-19 ( 23 ). Hence, with 40 % vaccination coverage with power 80% and relative precision of 10%, the sample size was calculated to be 1,200 which accommodated a non-response rate of 50%.

Statistical Analysis

The adverse effects experienced post-COVID-19 vaccination are expressed in percentage (%) and a chi-square test was used to test the significance of the difference between the demographics and other variables of interest (comorbid conditions, previous history of COVID-19 infection, etc.) against adverse effects. The difference in adverse effects based on the type of vaccine and doses was also compared using the chi-square test and the odds ratio was calculated. p value < 0.05 was considered statistically significant. All statistical analyses were done using SPSS software version 28.0.

Of the 1,878 participants who completed our survey, 940 (50 %) belonged to the 35–55-year age group, 1,151 (61.3%) were females, 526 (28%) had associated comorbid conditions, and 332(17.7%) had a history of a previous infection with COVID-19. The demographical details of all the participants are described in Supplementary Table S1 .

A total of 941 (50.1%) people received inactivated Sinopharm vaccine, 890 (47.4%) received mRNA Pfizer-BioNTech vaccine, and 11 (0.6%) received Adenovirus vector AstraZeneca vaccine; 36 (1.9%) were not aware of the details of the vaccine received. Among the study participants, 1,795 (95.6%) had received two or more doses of COVID-19 vaccination and 83 (4.4%) had received one dose of vaccination.

Adverse Reactions Following COVID-19 Vaccination

A total of 1,217 (64.8%) study participants reported one or more side effects following COVID-19 vaccination. The major adverse effects reported by the COVID-19 vaccine recipients were pain at the site of injection (47%), fatigue and drowsiness (28.2%), and joint/muscle pain (23.1%) followed by headache (17.7%) and fever (14.4%) ( Supplementary Table S2 ). The percentage of side effects reported based on the type of vaccine is shown in Figure 1 . Since most of the study participants either received an inactivated Sinopharm or mRNA Pfizer-BioNTech vaccine and only a negligible percentage of the people had received other vaccines further analyses were done on these two vaccine groups only.

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Figure 1 . Adverse effects reported post-COVID-19 vaccination.

Adverse Effects Following Inactivated Sinopharm Vaccine and the Factors Associated

A total of 574 (61%) of the Sinopharm vaccine recipients reported adverse effects following vaccination. The analysis of various factors related to reactogenicity among the participants who received the Sinopharm vaccine found that younger age group (<55 years), female gender, individuals with higher educational status (graduate/postgraduate), and people with associated comorbidities reported a statistically significant higher percentage of adverse effects than the others ( Table 1 ).

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Table 1 . Association of factors with the adverse effects after receiving the inactive Sinopharm vaccine.

Adverse Effects Following Pfizer-BioNTech (MRNA) Vaccine and the Factors Associated

A total of 610 (68.5%) reported adverse effects following the Pfizer-BioNTech vaccination. The association of demographic variables, comorbid conditions, and previous history of COVID-19 infection with the adverse effects following the Pfizer-BioNTech vaccine showed that age of <35 years, higher educational status, higher income, individuals with comorbidities, and individuals who had a history of previous infection with COVID-19 reported a statistically significant higher percentage of adverse effects than the others ( Table 2 ).

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Table 2 . Association of the risk factors with adverse effects after receiving the mRNA Pfizer vaccine.

Comparison of Adverse Effects Between Sinopharm and Pfizer-BioNTech Vaccine Recipients

The adverse effects were more common among recipients of the mRNA Pfizer-BioNTech vaccine than among recipients of the inactive Sinopharm vaccine with the odds ratio of 1.39 (95% CI 1.14–1.68); 4 out of 10 participants reported no side effects after receiving the Sinopharm vaccine compared to the Pfizer-BioNTech vaccine recipients among which 3 out of 10 reported no side effects ( Supplementary Table S3 ).

Vaccine Dose and Adverse Effects

Among the recipients of inactivated Sinopharm vaccine 214 (22.7%), 208 (22.1%) and 128 (13.6%) reported adverse effects after the first, second, and both doses, respectively. Similarly, among the recipients of mRNA Pfizer-BioNTech vaccine, 103 (11.6%), 268 (30.1%), and 232 (26.1%) reported adverse effects after the first, second, and both doses, respectively ( Supplementary Table S3 ).

The first-dose Sinopharm vaccine recipients are 2.9 times more likely to develop adverse effects compared to the first-dose recipients of the Pfizer-BioNTech vaccine ( p < 0.001), however, after the second dose, recipients of the Pfizer-BioNTech vaccine were 1.4 times more likely to develop an adverse effect than the second-dose Sinopharm vaccine recipients ( p : 0.007) ( Supplementary Table S3 ).

Local and Systemic Side Effects

The Sinopharm vaccine recipients reported 393 (41.8%) and 417(44.3%) local and systemic symptoms, respectively. Among the Pfizer vaccine recipients, 478(53.7%) reported local symptoms and 432 (48.5%) reported systemic symptoms after vaccination.

While no statistically significant difference was observed with the local adverse effects reported after the first and second dose of the Sinopharm and Pfizer vaccine recipients, respectively, a statistically significant higher percentage of systemic adverse effects was reported after the first dose in the Sinopharm vaccine recipients (78.5%) compared to the first-dose Pfizer vaccine recipients (64.1%) (odds ratio 2.04 p -value-0.007). However, after the second dose of the Pfizer vaccine, recipients reported more systemic side effects (86.6%), which was statistically significant compared to the systemic side effects reported after the second dose of the Sinopharm vaccine (72.1%) (odds ratio 1.12, p -value <0.001) ( Supplementary Table S3 ).

Age and Vaccine Adverse Effects

Based on age group, among people <35 years of age, there was no significant difference in the occurrence of the side effects based on the type of vaccine but among people in the 35–54 age group and in the age group ≥55 years, those who received the Pfizer-BioNTech vaccine were 1.44 (95% CI 1.18,1.75) and 1.83 (95% CI 1.38, 2.43) times more at risk of having an adverse effect than those who received the Sinopharm vaccine ( Supplementary Table S4 ). Similar results were seen when the average number of side effects reported were considered among the different age groups based on the vaccine received.

Number of Sides Effects Reported

Considering the number of side effects reported, 54.5 and 6.5% of the inactive vaccine recipients reported 1–5 side effects and 6–14 side effects, respectively, compared to the mRNA vaccine recipients of which 55.9 and 12.7% reported 1–5 side effects and 6–14 side effects, respectively. The average number of adverse effects reported between individuals who had received the Sinopharm and Pfizer-BioNTech vaccine was 1.61 ± 2.08 and 2.20 ± 2.58, respectively, and the difference was statistically significant ( p < 0.001).

Statistically significant difference was observed among people in the 35–54-years age group and ≥ 55-years age group. Based on the number of side effects reported in the 35–54-years age group and 55-years age group, those who received the Pfizer-BioNTech vaccine on an average reported 3.49± 2.70 and 2.93 ± 2.34 adverse effects, respectively, compared to 2.42 ± 1.76 and 2.18 ±1.55, among those who received the Sinopharm vaccine. No statistically significant difference was observed in the <35 years of age cohort ( Figure 2 ).

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Figure 2 . Adverse effects reported based on the age group and severity. The blue line represents the median of the number of adverse events reported across all age groups.

Severity of Side Effects

A total of 1,137 (62.2%) graded the severity of the symptoms, of which 924 (81%) graded it with a score below 5; 1,154 (63.0%) answered the question on the treatment for side effects, of which only 59 (5.0%) required consultation or hospital visit, 1,095 (95.0%) did not require any treatment or only home-based treatments. No severe adverse events were reported ( Figure 2 and Supplementary Figure S1 ).

The observed proportion of adverse effects that required either a doctor's advice or a hospital-based treatment was slightly higher in the age group ≥55 years but no statistical significance was observed between the two vaccine recipients among the different age groups ( Supplementary Table S5 ).

Vaccine reactogenicity represents various local and systemic manifestations because of the inflammatory response to vaccination. The reactogenicity depends on various factors like the host characteristics (age, gender, etc.), type of vaccine, composition, route of administration, and many others ( 24 ). Therefore, it is likely that most individuals would exhibit vaccine reaction post-COVID-19 vaccination. The survey shows that around 65% of the study participants experienced some adverse reaction due to the COVID-19 vaccination. None of the study participants reported severe allergic reactions to the COVID-19 vaccines. The most common adverse effects experienced among both the inactivated and the mRNA vaccine recipients were pain at the site of vaccination followed by fever, fatigue, and headache among the mRNA Pfizer-BioNTech recipients and fatigue and headache among the inactivated Sinopharm vaccine recipients, respectively. The rarest adverse effect reported among the Sinopharm vaccine recipients was enlarged swollen lymph nodes and change or loss of taste; while among the mRNA Pfizer-BioNTech vaccine recipients, temporary one-sided facial weakness was reported by one participant followed by enlarged swollen lymph nodes. Similar rare adverse effects were also reported in a study from Saudi Arabia on the Pfizer-BioNTech vaccine recipients ( 25 ). The nature of the adverse effects reported were similar to the adverse events mentioned in the safety and efficacy study of the Sinopharm and Pfizer-BioNTech vaccines but the percentage observed in this study was higher than reported in the trials ( 7 , 8 ). However, other reports on real-world data have reported a similar percentage of adverse effects observed among both inactivated and mRNA vaccine recipients ( 26 – 28 ).

Among the participants who received the Sinopharm vaccine, younger age group (<55 years), female gender, individuals with higher educational status, higher income, and people with comorbidities had reported a statistically significant higher percentage of adverse effects which was again supported by evidence from other studies on the inactivated vaccine ( 21 , 29 ). Among the Pfizer-BioNTech vaccine recipients, statistically significant associations with the vaccine's adverse effects were observed among participants in the age group of 35 years and above with higher educational status, higher income, individuals with comorbidities, and among individuals who had a history of a previous infection with COVID-19. Studies have demonstrated similar findings where higher vaccine reactogenicity was observed among individuals previously infected with the COVID-19 infection ( 26 , 30 , 31 ).

The mRNA vaccine when first developed was considered safer than inactivated vaccines as it is noninfectious and there is no potential risk of infection ( 32 ). However, in our study, the mRNA Pfizer-BioNTech vaccine showed a statistically significant higher percentage of adverse effects compared to the inactivated Sinopharm vaccine but 53.7% reported the adverse effects among the mRNA Pfizer-BioNTech vaccine recipients were local adverse effects. The mRNA Pfizer-BioNTech vaccine recipients also reported a greater number of side effects compared to inactive Sinopharm vaccine recipients. A study that has compared the Sinopharm and Pfizer-BioNTech vaccines has reported more moderate to severe adverse effects after the Pfizer-BioNTech vaccination ( 33 ) and another has reported a similar higher percentage of local adverse effects with the Pfizer-BioNTech vaccination than systemic adverse effects ( 26 ).

While the percentage of side effects reported did not vary with the number of doses among the inactive Sinopharm vaccine recipients, it was observed that among the mRNA vaccine recipients, the number of adverse effects reported after the second dose was 2.6 times higher than after the first dose of the vaccine. Furthermore, local side effects were reported after the first dose and more systemic side effects were reported after the second dose, which was in agreement with the findings reported in a survey conducted in the United Kingdom ( 26 ).

This study showed that among the inactive Sinopharm vaccine recipients, individuals in the younger age group reported significantly higher side effects than the older age groups. Among the mRNA vaccine recipients, individuals in the 35–54-year age group reported more adverse effects than the older individuals but the difference was not statistically significant and the younger individuals (<35 years) reported statistically significantly lesser side effects than the older individuals. On the contrary, another study published on the mRNA vaccine showed that younger age was associated with greater odds of adverse effects. This might be due to the difference in the age group among which the study was conducted as most of the study participants of this study were between 38 and 66 years ( 34 ). Now that COVID-19 vaccination for children is recommended, a similar survey is needed to understand the response of the younger age group, especially that in this study we found that among the Sinopharm vaccine recipients, the younger age group of <35 years reported more side effects than among those in the age group of ≥35 years.

In our survey, only 5% of the adverse effects required consultation with a doctor or treatment at the hospital and more than 80% of the participants reported a severity score of <5 supporting the fact that most adverse effects following vaccination were mild in nature and self-limiting.

The strength of this study is the comparison of the adverse effects between inactive and mRNA COVID-19 vaccines, the availability of both inactive Sinopharm and mRNA Pfizer-BioNTech vaccines in the UAE allowed cross-vaccine comparison in the same population. To the best of our knowledge, this is the first study to do a detailed comparison of these two different types of vaccines with a relatively large sample size. Another strength of this study is that the information bias was controlled to a large extent by cross-verification. Among all the participants who were contacted through a telephone interview, the survey details on the side effects and medical advice or treatment of the same were verified using the electronic medical records (EMR). The highly electronically integrated healthcare system in Abu Dhabi ensures easy accessibility for researchers to report more accurate and comprehensive data. Our study also has some limitations as the survey was on voluntary basis individuals who are more concerned about their health or have better health-seeking behaviors are most likely to participate in these surveys creating a participant bias. The results of the study are based on survey-based results, so with any other cross-sectional study, the results do not allow for causality interpretation.

In conclusion, the adverse effects of both the inactivated and mRNA vaccines developed mostly within 24 h of vaccination and about 95% were mild requiring no or home-based treatment. The adverse effects are more likely to be systemic side effects and younger individuals, females, and people with comorbidities are more likely to report adverse effects following inactivated Sinopharm vaccine. Among the mRNA Pfizer-BioNTech vaccine recipients, the adverse effects are more likely to be local after the first dose and systemic after the second dose and observed more among people with associated comorbid conditions and with a previous history of COVID-19 infection.

Thus, most adverse effects reported are mild and this public knowledge on the nature of side effects and the factors associated with greater odds of side effects would instill confidence and overcome vaccine hesitancy among people and enhance vaccine coverage which is the need of the hour.

Data Availability Statement

The data supporting the conclusion of this article is available with the corresponding author, which shall be provided on approval upon request.

Ethics Statement

The studies involving human participants were reviewed and approved by Institutional Review Board, Department of Health, Abu Dhabi, UAE. The patients/participants provided their informed consent to participate in this study.

Author Contributions

SG, LK, and WZ: conception, design of work, and acquisition. MM, NM, MS, AS, HE, RM, NS, KS, and AF: design of work and acquisition. FC, SG, LK, and WZ: analysis. NK, KW, FC, SG, LK, WZ, and FA: interpretation of data. NK, KW, SG, LK, WZ, and FA: drafting and substantively revising the manuscript. All authors read and approved the final manuscript.

Conflict of Interest

SG, FC, KW, FA, and WZ were employed by G42 Healthcare. SG and WZ was employed by Insights Research Organization and Solutions. MM, NM, MS, AS, HE, RM, NS, KS, and AF were employed by Ambulatory Healthcare Services, SEHA.

The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher's Note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Acknowledgments

We thank Mr. Santosh Elavalli and Mr. Rohaan Pereira for their support in conducting this study.

Supplementary Material

The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fpubh.2022.876336/full#supplementary-material

1. Krammer F. SARS-CoV-2 vaccines in development. Nature. (2020) 586:516–27. doi: 10.1038/s41586-020-2798-3

PubMed Abstract | CrossRef Full Text | Google Scholar

2. Andreadakis Z, Kumar A, Román RG, Tollefsen S, Saville M, Mayhew S. The COVID-19 vaccine development landscape. Nat Rev Drug Discov. (2020) 19:305–6. doi: 10.1038/d41573-020-00073-5

3. Khaleej Times. UAE Vaccine for Coronavirus: Sinopharm's Jab Approved . Available at: https://www.khaleejtimes.com/coronavirus-pandemic/uae-vaccine-for-coronavirus-sinopharms-jab-approved (December 9, 2020).

Google Scholar

4. Khaleej Times. UAE Covid Vaccination Rate Increases: Tops World in One Category . Available at: https://www.khaleejtimes.com/coronavirus-pandemic/uae-covid-vaccination-rate-increases-tops-world-in-one-category

5. National Emergency Crisis Disasters Management Authority (NCEMA). UAE Coronavirus (COVID-19) Updates . Available at: https://covid19.ncema.gov.ae/en (accessed on November 24, 2021).

6. Our World in Data. Coronavirus (COVID-19) Vaccinations . Available online at: https://ourworldindata.org/covid-vaccinations#what-share-of-the-population-has-received-at-least-one-dose-of-the-covid-19-vaccine (accessed November 24, 2021).

7. Xia S, Duan K, Zhang Y, Zhao D, Zhang H, Xie Z, et al. Effect of an inactivated vaccine against SARS-CoV-2 on safety and immunogenicity outcomes: interim analysis of 2 randomized clinical trials. JAMA. (2020) 324:951–60. doi: 10.1001/jama.2020.15543

8. Mulligan MJ, Lyke KE, Kitchin N, et al. Phase I/II study of COVID-19 RNA vaccine BNT162b1 in adults. Nature. (2020) 586:589–93. doi: 10.1038/s41586-020-2639-4

9. Folegatti PM, Ewer KJ, Aley PK, et al. Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial. Lancet . (2020) 396:467–78. doi: 10.1016/S0140-6736(20)31604-4

10. Logunov DY, Dolzhikova IV, Zubkova OV, Tukhvatullin AI, Shcheblyakov DV, et al. Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from Russia. Lancet. (2020) 396:887–97. doi: 10.1016/S0140-6736(20)31866-3

11. Chapin-Bardales J, Gee J, Myers T. Reactogenicity following receipt of mRNA-based COVID-19 vaccines. JAMA. (2021) 325:2201–2. doi: 10.1001/jama.2021.5374

12. Mahallawi WH, Mumena WA. Reactogenicity and Immunogenicity of the Pfizer and AstraZeneca COVID-19 Vaccines. Front Immunol . (2021) 12:794642. doi: 10.3389/fimmu.2021.794642

13. Saita M, Yan Y, Ito K, Sasano H, Seyama K, Naito T. Reactogenicity following two doses of the BNT162b2 mRNA COVID-19 vaccine: real-world evidence from healthcare workers in Japan. J Infect Chemother. (2022) 28:116–9. doi: 10.1016/j.jiac.2021.09.009

14. Warren GW, Lofstedt R. COVID-19 vaccine rollout risk communication strategies in Europe: a rapid response. J Risk Res . (2021) 0:1–11. doi: 10.1080/13669877.2020.1870533

CrossRef Full Text | Google Scholar

15. Neumann-Böhme S, Varghese NE, Sabat I, Barros PP, Brouwer W, van Exel J, et al. Once we have it, will we use it? A European survey on willingness to be vaccinated against COVID-19. Eur J Health Econ. (2020) 21:977–82. doi: 10.1007/s10198-020-01208-6

16. Pogue K, Jensen JL, Stancil CK, Ferguson DG, Hughes SJ, Mello EJ, et al. Influences on attitudes regarding potential COVID-19 vaccination in the United States. Vaccines. (2020) 8:582. doi: 10.3390/vaccines8040582

17. Dror AA, Eisenbach N, Taiber S, Morozov NG, Mizrachi M, Zigron A, et al. Vaccine hesitancy: the next challenge in the fight against COVID-19. Eur J Epidemiol. (2020) 35:775–9. doi: 10.1007/s10654-020-00671-y

18. Riad A, Abdulqader H, Morgado M, Domnori S, Koščík M, Mendes JJ, et al. IADS-SCORE. Global prevalence and drivers of dental students' COVID-19 vaccine hesitancy. Vaccines. (2021) 9:566. doi: 10.3390/vaccines9060566

19. Ahamed F, Ganesan S, James A, Zaher WA. Understanding perception and acceptance of Sinopharm vaccine and vaccination against COVID−19 in the UAE. BMC public health . (2021) 21:1–11. doi: 10.1186/s12889-021-11620-z

20. Riad A, Schünemann H, Attia S, Peričić TP, Žuljević MF, Jürisson M, et al. COVID-19 Vaccines Safety Tracking (CoVaST): protocol of a multi-center prospective cohort study for active surveillance of COVID-19 vaccines' side effects. Int J Environ Res Public Health. (2021) 18:7859. doi: 10.3390/ijerph18157859

21. Riad A, Sagiroglu D, Üstün B, Pokorná A, Klugarová J, Attia S, et al. Prevalence and risk factors of CoronaVac side effects: an independent cross-sectional study among healthcare workers in Turkey. J Clin Med. (2021) 10:2629. doi: 10.3390/jcm10122629

22. Wang J, Tong Y, Li D, Li J, Li Y. The impact of age difference on the efficacy and safety of COVID-19 vaccines: a systematic review and meta-analysis. Front Immunol . (2021) 12:758294. doi: 10.3389/fimmu.2021.758294

23. Khaleej Times. UAE Covid Vaccination Doses Cross 4 million . Available at: https://www.khaleejtimes.com/coronavirus-pandemic/uae-covid-vaccination-doses-cross-4-million (February 5, 2021).

24. Hervé C, Laupèze B, Del Giudice G, Didierlaurent AM, Da Silva FT. The how's and what's of vaccine reactogenicity. NPJ Vaccines. (2019) 4:1–1. doi: 10.1038/s41541-019-0132-6

25. El-Shitany NA, Harakeh S, Badr-Eldin SM, Bagher AM, Eid B, Almukadi H, et al. Minor to moderate side effects of Pfizer-BioNTech COVID-19 vaccine among Saudi residents: a retrospective cross-sectional study. Int J Gen Med. (2021) 14:1389. doi: 10.2147/IJGM.S310497

26. Menni C, Klaser K, May A, Polidori L, Capdevila J, Louca P, et al. Vaccine side-effects and SARS-CoV-2 infection after vaccination in users of the COVID Symptom Study app in the UK: a prospective observational study. Lancet Infect Dis. (2021). doi: 10.1016/S1473-3099(21)00224-3

27. Saeed BQ, Al-Shahrabi R, Alhaj SS, Alkokhardi ZM, Adrees AO. Side effects and perceptions following Sinopharm COVID-19 vaccination. Int J Infect Dis. (2021) 111:219–26. doi: 10.1016/j.ijid.2021.08.013

28. Zhang MX, Zhang TT, Shi GF, Cheng FM, Zheng YM, Tung TH, et al. Safety of an inactivated SARS-CoV-2 vaccine among healthcare workers in China. Exp Rev Vaccines. (2021) 14:1–8. doi: 10.1080/14760584.2021.1925112

29. Jayadevan R, Shenoy RS, Anithadevi TS. Survey of symptoms following COVID-19 vaccination in India. medRxiv. (2021). doi: 10.1101/2021.02.08.21251366

30. Saadat S, Rikhtegaran-Tehrani Z, Logue J, Newman M, Frieman MB, Harris AD, et al. Single dose vaccination in healthcare workers previously infected with SARS-CoV-2. medRxiv . (2021) published online Feb 1. (preprint). doi: 10.1101/2021.01.30.21250843

31. Krammer F, Srivastava K, Simon V. Robust spike antibody responses and increased reactogenicity in seropositive individuals after a single dose of SARS-CoV-2 mRNA vaccine. medRxiv . (2021) published online Feb 1. (preprint). doi: 10.1101/2021.01.29.21250653

32. Pardi N, Hogan MJ, Porter FW, Weissman D. mRNA vaccines—a new era in vaccinology. Nat Rev Drug Discov. (2018) 17:261–79. doi: 10.1038/nrd.2017.243

33. Hatmal MM, Al-Hatamleh MA, Olaimat AN, Hatmal M, Alhaj-Qasem DM, Olaimat TM, et al. Effects and perceptions following COVID-19 vaccination in Jordan: a randomized, cross-sectional study implementing machine learning for predicting severity of side effects. Vaccines. (2021) 9:556. doi: 10.3390/vaccines9060556

34. Beatty AL, Peyser ND, Butcher XE, Cocohoba JM, Lin F, Olgin JE, et al. Analysis of COVID-19 Vaccine Type and Adverse Effects Following Vaccination. JAMA Network Open. (2021) 4:e2140364. doi: 10.1001/jamanetworkopen.2021.40364

Keywords: SARS-CoV-2, COVID-19, adverse (side) effects, Pfizer-BioNTech vaccine, Sinopharm vaccine

Citation: Ganesan S, Al Ketbi LMB, Al Kaabi N, Al Mansoori M, Al Maskari NN, Al Shamsi MS, Alderei AS, El Eissaee HN, Al Ketbi RM, Al Shamsi NS, Saleh KM, Al Blooshi AF, Cantarutti FM, Warren K, Ahamed F and Zaher W (2022) Vaccine Side Effects Following COVID-19 Vaccination Among the Residents of the UAE—An Observational Study. Front. Public Health 10:876336. doi: 10.3389/fpubh.2022.876336

Received: 15 February 2022; Accepted: 31 March 2022; Published: 06 May 2022.

Reviewed by:

Copyright © 2022 Ganesan, Al Ketbi, Al Kaabi, Al Mansoori, Al Maskari, Al Shamsi, Alderei, El Eissaee, Al Ketbi, Al Shamsi, Saleh, Al Blooshi, Cantarutti, Warren, Ahamed and Zaher. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Subhashini Ganesan, Subhashini.g@g42.ai

† These authors have contributed equally to this work and share first authorship

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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COVID‐19 vaccine research and development: ethical issues

1 Department of Microbiology, Faculty of Medicine Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta Indonesia

2 Medical and Health Research Ethics Committee, Faculty of Medicine Public Health and Nursing, Universitas Gadjah Mada / Dr. Sardjito General Hospital, Yogyakarta Indonesia

The achievements of vaccine research and development bring a hope to our societies that we may cope with the COVID‐19 pandemic. There are two aspects that should be maintained in balance: the immediate necessity for speed of vaccine research and the inherent need for protection of research subjects, which is the foremost concern of research ethics. This narrative review highlights ethical issues in COVID‐19 vaccine research and development that every stakeholder needs to be aware of and to consider.

Introduction

COVID‐19 is a deadly disease which continues to affect many countries in the world. The incidence is higher in the Americas (14 117 714 cases and 486 843 deaths) and Europe (4 515 514 cases and 222 624 deaths) than in South East Asia (4 786 594 cases and 84 541 deaths), Africa (1 088 093 cases and 23 101 deaths) and the Western Pacific (520 012 cases and 11 306 deaths) [ 1 ].

Vaccines are the most important public health measure to protect people from COVID‐19 worldwide, since SARS‐CoV‐2 is highly contagious and infects populations widely and globally [ 2 ]. Traditionally, vaccine development takes years, even decades: from about 40 years for polio to 5 years for Ebola,most vaccines took 15 years on average [ 3 , 4 ]. The trial process for vaccines consists of several steps which need to be conducted systematically and in a measurable stride. The length of this process is correlated with the nature of the vaccine itself, which is to protect healthy people from being infected by pathogens. Adverse events and deleterious effects will not be tolerated, vaccines are not the same as drugs that are consumed by the sick. The risk–benefit analysis for prescription drugs and vaccine administration is different.

The invention of a successful and widely available COVID‐19 vaccine will be a great leap forward for humankind, but there are several challenges to overcome: (1) a lack of understanding of the pathogenesis and the predictive role of vaccines in the clinical pathway of persons being infected by SARS‐CoV‐2 [ 5 , 6 , 7 ], (2) a huge disagreement among experts about how to determine the most immunogenic epitopes and antigens of SARS‐CoV‐2 [ 8 , 9 ], (3) the finding that antibody‐dependent enhancement (ADE) may contribute to the exaggeration of SARS‐CoV‐2 disease [ 10 , 11 ], (4) the lack of established animal models for COVID‐19 vaccine challenge testing, which raises the speculation of using controlled human infection (CHI) as a potential approach [ 3 ], and finally, (5) speculation that the duration of protection by immune response in natural infection is not long enough [ 12 ].

The race for COVID‐19 vaccine invention and development against the spread and catastrophic effects of the disease is real. WHO released a draft list of COVID‐19 candidate vaccines on 3 September 2020. At least 34 vaccine candidates are in clinical evaluation to date [ 13 ]. Several new technologies are used as COVID‐19 vaccine development platforms. Conventional techniques for the development of vaccines such as inactivated, inactivated with adjuvant and live attenuated are still being used. However, reversed vaccinology approaches are also being emplyed, such as a recombinant subunit vaccine, and a more advanced approach using vector delivery systems, along with RNA‐ and DNA‐based vaccines (Table  1 ) [ 4 , 9 , 13 ].

Candidate COVID‐19 Vaccines in Clinical Trial Phases*

The attempts to accelerate vaccine development are associated with efforts to streamline the process. Unfortunately, streamlining may have consequences for the traditional ethics of vaccine research and development, especially the long‐held principles of beneficence and non‐maleficence. This short narrative review summarises the ethical issues that may emerge from the current directions in COVID‐19 vaccine research and development during the pandemic.

Vaccine candidates must fulfil several requirements: safety, efficacy and quality. Because of the current escalation of the global COVID‐19 pandemic, some aspects may change. The speed of vaccine development may push public health ministers, heads of states and the pharmaceutical industry to change their strategy for bulk budget investment for vaccine research. They must decide to prepare mass production events based on the limited data of promising vaccine candidates [ 14 ]. The need to protect billions of earth’s inhabitants pushes governments and societies of the world to a ‘great expectation’ for the new vaccine. The overriding expectation, although with diverse interests, may influence the objective judgement typically required of candidate vaccine safety. Protecting human lives should be the priority.

mRNA‐ [ 15 ] and DNA‐based vaccine technologies [ 9 , 16 ] are being implemented in humans, especially as vaccine candidates. Several concerns about mRNA vaccine safety have been identified besides its promising potential advantages. The most important risks include the possibility that mRNA vaccines may generate strong type I interferon responses that could lead to inflammation and autoimmune conditions [ 17 ]. The safety concerns of DNA‐based vaccines involve the possibility that the targeting of DNA into the chromosomal DNA of the acceptor will trigger mutagenic effects in the functional gene located in the insertion loci [ 18 ]. At present, there are no mRNA‐ and DNA‐based vaccines against any disease authorised to be marketed.

The strategy of DNA vaccines is similar to gene therapy in that a delivery system, such as plasmid, delivers targeted DNA into cells, where it is translated into proteins that induce the acceptors’ immune response to generate targeted T‐cell and antibody responses [ 19 ]. We have experience in using DNA for several gene therapies mostly related to inherited diseases or familial predispositions. Mainstream gene therapy scientists have stated that gene therapy is only suitable for terminally ill patients because the risks are very high [ 20 ]. Vaccine administration is completely different from interventions with gene therapy since the vaccine is for healthy human subjects, and the risk–benefit consideration would be completely different too. Both terminally ill and healthy persons have the same risk for the introduction of foreign DNA into their body, but terminally ill persons may benefit through having a chance to recover from their deadly disease, whereas healthy individuals may not have any benefit because they have never encountered the particular pathogen.

When we perform the risk assessment of new technology, it is based on a theoretical framework without direct evidence concerning to what extent the probability of the risk may occur. Theoretically, DNA vaccine may be able to induce autoimmune diseases and can be inserted into any part of the chromosomes [ 21 ]. Scientists know how the mechanism works and are able to predict the risk if it might happen. But nobody knows for certain how great the probability is of producing mutagenic and deleterious effects in one part of a gene sequence when inserted into another. For example, when a test subject named Jessie Gelsinger was injected with adeno‐associated viruses (AAVs), nobody expected the deadly risk that ultimately occurred in this research subject [ 22 ]. Accordingly, the risk–benefit assessment in the use of new technology should be done carefully. It is true that sometimes we have to deal with a risk possibility that is not immediately present but theoretically possible, and vice versa. Mitigation to the deleterious effect could be started prior to the clinical trial. However, there is always the possible existence of risks that have not been identified yet and will only show in the later phases of clinical trials.

In the current pandemic, all societies expect a breakthrough in medical and health technology. In a situation where understanding of the new disease is poor and no satisfactory medical technology is available for prevention and treatment yet, it is natural to think that ‘doing something is better than nothing’. This is going to make safety judgement among stakeholders more prone to deterioration.

Controlled human infection (CHI)

One of the crucial steps of vaccine development is the challenge test, which is used to measure the potential protection of the candidate. The challenge test is usually part of the pre‐clinical study in an animal model. However, in the case of COVID‐19 and some other diseases, an animal model is not available, although there are candidates that need to be verified [ 3 , 23 , 24 , 25 ]. It seems the pathogen does not produce a similar clinical course in common animal models, which excludes safety and efficacy data from animal models alone. There was a proposal of human challenge testing to replace the pre‐clinical challenge test in animal models, with the use of controlled human infection (CHI). It will solve the problem of the animal models’ unreliability and gain time for the developers especially in phase III [ 3 , 26 ].

To some extent, it is possible to perform these challenge tests with human volunteers. It sounds like an unsafe experimentation, but the choices are extremely limited. The next question is how can we do this experiment with the current ethical review process? The WHO has issued a guideline for CHI [ 27 ]. The guideline is broad and needs local ethics committee approval for its implementation. Considerations of the pros and cons of CHI are widely discussed in COVID‐19 vaccine development. Previously, CHI was used to develop vaccines against malaria [ 28 ], typhoid [ 29 ] and cholera [ 30 ], which are diseases with established treatment [ 31 ]. Subjects who suffered from deleterious effects after experimentation could be rescued by the established treatment. Application of CHI in COVID‐19 is a very different story because there is no standard treatment for this new and highly contagious disease. Nevertheless, there have been thousands of volunteers from 162 countries who declared their willingness to be participants in this CHI [ 32 ]. The need for a vaccine is prevalent in people’s minds and equally necessary from the public health point of view. Without any precedents, it is going to be difficult to judge the risks benefits in this matter [ 33 ].

Controlled human infection could be done in a situation where there is an attenuated virus strain available, for example, using an artificial mutant virus. This approach is to prevent fatal outcomes in trial subjects. But the challenge test results from attenuated virus may not be generalisable – the attenuated strain may not be similar enough to the naturally circulating virus. In addition, producing the attenuated virus may require another step that will take almost as much time to perform as the regular phase III in typical controlled clinical trials. This additional step in an already complicated process will render futile the main purpose to gain more time to develop an effective vaccine [ 34 ].

Location and population

Development sites of COVID‐19 vaccines are involving research subjects from many countries, for example USA, Russia, Argentina, Brazil, Germany, India, Saudi Arabia, Pakistan and others [ 35 ]. The need of multi‐centred research is obvious in the vaccine development. The safety, tolerability, and efficacy of the vaccines should be obtained from different geographic areas, ethnicities, prevalence and varieties of the virus circulating in the areas [ 36 ]. The attempt to fulfil this requirement may result in the involvement of countries with limited resources and whose underdeveloped infrastructure would make the people involved become even more vulnerable as research subjects from the ethical and humane point of view. The possible exploitation of vulnerable people from less developed countries should be reviewed thoroughly. The vaccine trial should give them equitable advantages in trade, such as capacity building, transfer of technology and access to the vaccine during the current pandemic of COVID‐19.

Another concern is the availability of an adequate health facility and system to ensure that trial subjects and their families and/or communities have access to treatment and proper care in case of serious adverse events related to the trial outcomes. This must be assessed before any clinical trials begin. Providing the most comprehensive health services to the trial population will be an added value for population involvement in the trial. The best practice of vaccine clinical trials should have direct benefits for the community, such as improvement and availability of basic health facilities [ 37 ]

Vaccine acceptors are sometimes segmented into target groups, which is related to the host distribution of the target disease, for example by gender, age and specific population in the endemic area. A vaccine clinical trial is usually started in adult subjects and continued to more vulnerable subjects such as infants, young children, the elderly and women. Clinical vaccine trials will recruit vulnerable subjects. Protection measures to safeguard the vulnerable and marginalised populations should be carefully scrutinised during review. Ethical considerations must be adjusted to the individual situation to protect these vulnerable subjects from exploitation and later abandonment [ 38 ].

However, in an emergency pandemic situation, the definition of vulnerability needs to be openly discussed, and emergency calls for exceptions. The exclusion of vulnerable groups may diminish trial validity because of selection bias, so they should not be excluded without reasonable scientific and ethical justification [ 39 ].

Post‐trial access

After clinical vaccine trials, the subjects should have access to the developed vaccine. This is part of their direct advantage for their involvement in the research. While it is mentioned in the international ethical guidelines, not all researchers know and are aware of this important obligation [ 40 ]. The current COVID‐19 vaccine development involves multi‐country and intercontinental research recruiting subjects from different countries and regions. The post‐trial access to COVID‐19 vaccines should be expanded beyond the community where the trial is performed to include the country and region.

Post‐trial access is a matter which must be addressed from the very beginning of research design. Community engagement should be considered prior to the trial and involve all stakeholders: sponsors, industries, developers, investigators, subjects of the trial, communities and the government where the trial is performed.

In summary, the current COVID‐19 vaccine research and development involves people from many countries, which raises ethical issues that must be addressed by all stakeholders. Even in the emergency of a pandemic, the urgency of providing an effective COVID‐19 vaccine for humankind must be balanced with the exigency of research ethics that must be maintained. In any event, the safety and well‐being of research subjects must be protected, especially that of vulnerable subjects.

Sustainable Development Goals (SDGs): SDG 3 (good health and well‐being)

  • Introduction
  • Conclusions
  • Article Information

eTable 1. Characteristics of Preventive Medicine Trial Cohort Participants and Reported COVID-19 Cases to Date

eTable 2. Adjusted Odds of COVID-19 by Level of Physical Activity Before the COVID-19 Pandemic, Restricting Follow-Up Through December 2020

eTable 3. Adjusted Odds of COVID-19 Hospitalization by Level of Physical Activity Before the COVID-19 Pandemic, Restricting Follow-Up Through December 2020

eTable 4. Adjusted Odds of COVID-19 by Level of Physical Activity Before the COVID-19 Pandemic, With Additional Adjustment for SARS-CoV-2 Vaccination Status

eTable 5. Adjusted Odds of COVID-19 Hospitalization by Level of Physical Activity Before the COVID-19 Pandemic, With Additional Adjustment for SARS-CoV-2 Vaccination Status

eTable 6. Adjusted Odds of COVID-19 by Level of Physical Activity Before the COVID-19 Pandemic, Combining Consistently Inactive and Insufficiently Active Participants in 1 Group vs Sufficiently Active

eTable 7. Adjusted Odds of COVID-19 Hospitalization by Level of Physical Activity Before the COVID-19 Pandemic, Combining Consistently Inactive and Insufficiently Active Participants in 1 Group vs Sufficiently Active

eFigure. Data Collection and Completeness of COVID-19 Outcomes

Data Sharing Statement

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Muñoz-Vergara D , Wayne PM , Kim E, et al. Prepandemic Physical Activity and Risk of COVID-19 Diagnosis and Hospitalization in Older Adults. JAMA Netw Open. 2024;7(2):e2355808. doi:10.1001/jamanetworkopen.2023.55808

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Prepandemic Physical Activity and Risk of COVID-19 Diagnosis and Hospitalization in Older Adults

  • 1 Osher Center for Integrative Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
  • 2 Division of Preventive Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
  • 3 Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts

Question   Are higher prepandemic physical activity (PA) levels associated with lower risk of developing or being hospitalized for COVID-19?

Findings   In this cohort study of 61 557 women and men aged 45 years or older who reported 5890 incident cases of COVID-19 and 626 hospitalizations, those who achieved at least 7.5 metabolic equivalent hours per week of PA before the pandemic had significantly reduced odds of COVID-19 diagnosis and hospitalization compared with the inactive group.

Meaning   Higher prepandemic PA levels were associated with lower odds of developing and being hospitalized for COVID-19.

Importance   Higher prepandemic physical activity (PA) levels have been associated with lower risk and severity of COVID-19.

Objective   To investigate the association between self-reported prepandemic PA levels and the risk and severity of COVID-19 in older US adults.

Design, Setting, and Participants   This cohort study combined cohorts from 3 ongoing prospective randomized clinical trials of US adults aged 45 years or older who provided prepandemic self-reports of baseline leisure-time PA and risk factors for COVID-19 outcomes using the most recent questionnaire completed as of December 31, 2019, as the baseline PA assessment. In multiple surveys from May 2020 through May 2022, participants indicated whether they had at least 1 positive COVID-19 test result or were diagnosed with or hospitalized for COVID-19.

Exposure   Prepandemic PA, categorized into 3 groups by metabolic equivalent hours per week: inactive (0-3.5), insufficiently active (>3.5 to <7.5), and sufficiently active (≥7.5).

Main Outcome and Measures   Primary outcomes were risk of COVID-19 and hospitalization for COVID-19. Multivariable logistic regression was used to estimate odd ratios (ORs) and 95% CIs for the association of COVID-19 diagnosis and/or hospitalization with each of the 2 upper PA categories vs the lowest PA category.

Results   The pooled cohort included 61 557 participants (mean [SD] age, 75.7 [6.4] years; 70.7% female), 20.2% of whom were inactive; 11.4%, insufficiently active; and 68.5%, sufficiently active. A total of 5890 confirmed incident cases of COVID-19 were reported through May 2022, including 626 hospitalizations. After controlling for demographics, body mass index, lifestyle factors, comorbidities, and medications used, compared with inactive individuals, those insufficiently active had no significant reduction in infection (OR, 0.96; 95% CI, 0.86-1.06) or hospitalization (OR, 0.98; 95% CI, 0.76-1.28), whereas those sufficiently active had a significant reduction in infection (OR, 0.90; 95% CI, 0.84-0.97) and hospitalization (OR, 0.73; 95% CI, 0.60-0.90). In subgroup analyses, the association between PA and SARS-CoV-2 infection differed by sex, with only sufficiently active women having decreased odds (OR, 0.87; 95% CI, 0.79-0.95; P  = .04 for interaction).

Conclusions and Relevance   In this cohort study of adults aged 45 years or older, those who adhered to PA guidelines before the pandemic had lower odds of developing or being hospitalized for COVID-19. Thus, higher prepandemic PA levels may be associated with reduced odds of SARS-CoV-2 infection and hospitalization for COVID-19.

Research supports physical activity (PA) for health and reductions in major morbidity and mortality. 1 , 2 Adherence to US guidelines of at least 150 min/wk of moderate to vigorous PA may help prevent or mitigate effects of cardiovascular disease (CVD), cancer, type 2 diabetes, and other chronic conditions. 3 - 6 Some health benefits of PA are attributable to the delay of age-related immunosenescence, reduced low-grade systemic inflammation, and boosted immunity. 7 - 10 However, significant gaps exist in the evidence that PA protects against infectious diseases.

The COVID-19 pandemic provides a unique opportunity to address the association of PA with infection. 8 , 11 - 14 A recent study found that meeting PA guidelines before COVID-19 diagnosis was associated with fewer severe outcomes, including hospitalization, admission to intensive care, and death. 15 Other studies have assessed potential for PA and other healthy lifestyle factors, such as healthy body weight, limited alcohol intake, or high-quality diet, to synergically boost the immune system to prevent or ameliorate the severity of COVID-19. 16 - 18 However, the generalizability of these findings to older adults is limited in studies published to date.

This study pooled data from 3 large, ongoing prospective trial cohorts of older adults who self-reported PA levels before the COVID-19 pandemic and were prospectively followed up for SARS-CoV-2 infection and hospitalization through 2021. We hypothesized that higher levels of prepandemic PA would be associated with reduced risk of SARS-CoV-2 infection and COVID-19 hospitalization.

This prospective cohort study combined participants from 3 large-scale randomized clinical trials (RCTs) directed by our research group: the Cocoa Supplement and Multivitamin Outcomes Study (COSMOS), a double-blind, placebo-controlled, factorial RCT of a cocoa extract and multivitamin supplement in the prevention of CVD and cancer among 21 442 women aged 65 years or older and men aged 60 or older 19 , 20 ; the Vitamin D and Omega-3 Trial (VITAL), a double-blind, placebo-controlled, factorial RCT of fatty acid supplements in the prevention of CVD and cancer among 25 871 women aged 55 or older and men aged 50 or older 21 ; and the Women’s Health Study (WHS), a double-blind, placebo-controlled, factorial RCT of low-dose aspirin and vitamin E in the primary prevention of CVD and cancer among 39 876 US female health professionals aged 45 or older. 22 - 24 The institutional review board at Mass General Brigham approved all study-related activities. Written informed consent was obtained from participants in all 3 trials. We followed the Strengthening the Reporting of Observational Studies in Epidemiology ( STROBE ) reporting guideline. 25

In May, June, and August 2020, we sent 3 separate online REDCap surveys asking about COVID-19 symptoms, testing, diagnoses, treatments, severity of illness, and risk factors to COSMOS, VITAL, and WHS participants who provided email addresses and were willing to be contacted by email to complete surveys online (eFigure in Supplement 1 ). Those who responded to at least 1 survey or study follow-up questionnaire and had PA measurements were included. In addition, we repeated questions on COVID-19 testing, diagnoses, and hospitalization from the previous year on regular annual follow-up questionnaires for each cohort in 2021 and 2022.

To assess prepandemic self-reported PA (as validated in previous studies 3 , 19 , 22 ) and other relevant risk factors, we leveraged long-term prospective questionnaire data in COSMOS, VITAL, and WHS and used the most recent annual questionnaire on or before December 31, 2019 (median year of completion, 2017; range, 2003-2019), as the baseline for the PA assessment. We asked 2 questions about typical PA habits over the past year: (1) “During the past year, what was your approximate average time (in minutes) per week spent at each of the following recreational activities (eg, walking, jogging, running, aerobic exercise, etc)?” and (2) “On average, how many flights of stairs (1 flight is typically 10 steps) do you climb daily?” Participant responses were converted into total reported PA as metabolic equivalent [MET] hours per week by assigning MET values to different activities and estimating total energy expenditure based on reported duration and frequency of those activities for a given week. 3 - 6 Based on US and World Health Organization (WHO) PA guidelines, 4 , 6 we created 3 PA categories, in MET-h/wk, for our analyses: inactive (0-3.5), insufficiently active (>3.5 to <7.5), and sufficiently active (≥7.5). Our determination for being at least sufficiently active was based on the lower bounds for recommended moderate to vigorous PA (≥3 METs for 150 minutes per week), resulting in 450 MET-min/wk, or 7.5 MET-h/wk. 6

Other self-reported covariates included those collected at the most recent annual questionnaire closest to December 31, 2019, before the start of the COVID-19 pandemic. Demographic variables included sex; age; and race and ethnicity (African American or Black; Asian or Native American; Hispanic or Latinx; non-Hispanic White; and other [ie, different from the 4 other categories], unknown, or not reported), ascertained by self-report and included to explore racial and ethnic differences in subgroup analyses. We also examined educational attainment (no high school, high school, some college, college graduate, and postcollege) and income (<$30 000, $30 000 to <$50 000, $50 000 to <$100 000, and ≥$100 000). 19 , 21 , 22 Lifestyle factors included smoking status (never, past, and current) and alcohol consumption (rarely or never, monthly, weekly, and daily). Body mass index (BMI, calculated as weight in kilograms divided by height in meters squared) was based on self-reported height and weight. We also considered several comorbidities and medications used at the end of 2019. Comorbidities were adjudicated by a committee of physicians and investigators according to standardized procedures (cancer, myocardial infarction, and stroke) 26 or based on self-reports of medications and/or diagnoses (history of diabetes, hypertension, or statin use). Current medications used included nonsteroidal anti-inflammatory drugs and aspirin.

Based on 3 REDCap surveys in 2020 and annual follow-up questionnaires, we classified participants as having had COVID-19 if they reported a test positive for SARS-CoV-2 or its antibodies, were told by a health care professional that they were probably or definitely diagnosed with COVID-19, or reported being hospitalized for COVID-19 on any of the questionnaires. Participants also provided the month and year of a positive test result, diagnosis, and/or hospitalization for COVID-19. We used the date of questionnaire return for missing dates. We separately defined severity of COVID-19 based on whether individuals reported COVID-19 hospitalization. We used information on all reported diagnoses, test results, and hospitalizations for COVID-19 through May 10, 2022.

Our primary outcomes were risk of SARS-CoV-2 infection and hospitalization due to COVID-19. We compared demographics, lifestyle factors, comorbidities, and medications among the 3 PA groups using analysis of variance tests for continuous variables and χ 2 tests for categorical variables. Multivariable logistic regression models estimated the odd ratios (ORs) and 95% CIs for the association of each of the 2 upper PA categories (vs the lowest PA category) with SARS-CoV-2 infection and hospitalization for COVID-19 (model 1 adjusted for demographic characteristics, model 2 added lifestyle factors, and model 3 added comorbidities and medications). We also considered a priori subgroup analyses by sex, BMI, race and ethnicity, and income 27 and post hoc analyses by history of CVD and cancer. We evaluated these potential multiplicative modifications of associations using the Wald test for homogeneity. Two-sided P  < .05 was considered significant.

We conducted 3 sensitivity analyses to evaluate the stability and reliability of our results. First, we restricted analyses through December 31, 2020, before SARS-CoV-2 vaccines became widely available in the US. Second, we conducted analyses adding SARS-CoV-2 vaccination status, initially collected on annual questionnaires to all participants starting January 2021. Third, we combined the consistently inactive and insufficiently active groups vs the sufficiently active group. Analyses were performed using SAS, version 9.4 (SAS Institute Inc).

A total of 69 604 adults aged 45 years or older were invited to participate, of whom 61 557 (88.4%) responded and comprised the cohort for our analyses. eTable 1 in Supplement 1 provides the number of individuals who reported positive test results and/or hospitalizations per study, along with other demographic characteristics. As of December 31, 2019, the cohort had a mean (SD) age of 75.7 (6.4) years; 70.7% were female, and 29.3% were male ( Table 1 ). For PA, 20.2% of participants reported being inactive; 11.4%, insufficiently active; and 68.5%, sufficiently active. A total of 7.5% of participants were African American or Black; 2.1%, Asian or Native American; 2.3%, Hispanic or Latinx; 87.2%, non-Hispanic White; and 0.9%, other, unknown, or unreported race and ethnicity. Also, 24.1% of the cohort reported a BMI of 30 or greater. Participants with higher educational and income levels and those who never smoked were more likely to report sufficient PA. During follow-up, there were 5890 incident cases of COVID-19 and 626 of hospitalization due to COVID-19 (eFigure in Supplement 1 ).

In all models, sufficiently active participants had significantly lower odds of SARS-CoV-2 infection (eg, model 3: OR, 0.90; 95% CI, 0.84-0.97; P  = .01) compared with those who were inactive ( Table 2 ). In the insufficiently active group, PA was not associated with odds of SARS-CoV-2 infection compared with the inactive group in any model (eg, model 3: OR, 0.96; 95% CI, 0.86-1.06; P  = .89). Participants who were sufficiently active had consistently lower odds of hospitalization due to COVID-19 (eg, model 3: OR, 0.73; 95% CI, 0.60-0.90; P  = .001) compared with those who were inactive ( Table 3 ). In the insufficiently active group, there was no association of PA with odds of COVID-19 hospitalization (eg, model 3: OR, 0.98; 95% CI, 0.76-1.28; P  = .25).

In subgroup analyses, the association between PA and COVID-19 differed by sex. Women who were sufficiently active had decreased odds of SARS-CoV-2 infection compared with inactive women (OR, 0.87; 95% CI, 0.79-0.95; P  = .04 for interaction) ( Table 4 ). There was no association in men. No evidence of association modification was observed for BMI, race and ethnicity, income, and CVD or cancer. In sensitivity analyses restricting results to follow-up through December 2020 (before widespread vaccination programs), the number of cases was reduced by 53.5% (2739 cases). There was no association between sufficient PA and SARS-CoV-2 infection in any model (eg, model 3: OR, 0.98; 95% CI, 0.88-1.09; P  = .58). The lack of an association persisted for the insufficiently active group (eg, model 3: OR, 1.01; 95% CI, 0.88-1.17; P  = .72). However, the odds of COVID-19 hospitalization through December 2020 were significantly lower for the sufficiently active than for the inactive group (eg, model 3: OR, 0.64; 95% CI, 0.49-0.83; P  = .003) (eTables 2 and 3 in Supplement 1 ).

We also conducted a sensitivity analysis adjusting for potential confounding by SARS-CoV-2 vaccination status in model 3. The ORs for infection and hospitalization did not substantially change for the sufficiently active group (eg, infection: OR, 0.89; 95% CI, 0.82-0.96; P  = .007; hospitalization: OR, 0.74; 95% CI, 0.60-0.92; P  = .005) (eTables 4 and 5 in Supplement 1 ). SARS-CoV-2 vaccination was associated with substantially decreased odds of infection (OR, 0.55; 95% CI, 0.50-0.61; P  < .001) and hospitalization (OR, 0.37; 95% CI, 0.30-0.47; P  < .001) for all PA levels assessed before the COVID-19 pandemic. Our third sensitivity analysis combined the consistently inactive and insufficiently active groups to assess whether sufficient PA was still associated with lower odds of SARS-CoV-2 infection and COVID-19 hospitalization in model 3. The decreased ORs for infection and hospitalization did not substantially change for the sufficiently active group (eg, infection: OR, 0.92; 95% CI, 0.86-0.98, P  = .01; hospitalization: OR, 0.74; 95% CI, 0.62-0.89; P  = .001) (eTables 6 and 7 in Supplement 1 ).

In this cohort study, sufficiently active participants had significantly reduced odds of SARS-CoV-2 infection and of hospitalization due to COVID-19 compared with those who were inactive. This difference was not observed between the insufficiently active and inactive groups. Results were robust across models adjusting for multiple covariates. These findings parallel a previously reported association between high PA levels and reduced odds of infection and mortality due to viral and bacterial pneumonia. 28 Other studies have reported potential inverse associations between PA levels and risk and/or severity of COVID-19; their results included a wider age range in adult populations. 15 - 18 , 29 Our findings extend the understanding of the association between PA and vulnerability to infections, specifically with highly infectious respiratory viruses, among older adults. 10

We found reduced odds of infection across all 3 models when comparing the sufficiently active vs inactive groups. There was no apparent benefit of PA in the insufficiently active group. This suggests that the association between PA and COVID-19 may depend on the amount, intensity, and/or type of PA. 11 , 15 Cho et al 30 found equivalent ORs for COVID-19 among individuals engaging in both moderate (10 MET-h/wk) and vigorous (17.5 MET-h/wk) PA. Ahmadi et al 31 reported inverse associations between PA and COVID-19 for both insufficiently (<10 MET-h/wk) and sufficiently (≥10 MET-h/wk) active individuals. Rowlands et al 32 also described higher odds of nonsevere COVID-19 when adjusting for PA intensity (accelerometer-assessed) and self-reported PA levels (moderate to vigorous PA [MVPA]: 7.5-15 MET-h/wk). Lee et al 33 reported a consistent inverse association of PA with risk of COVID-19 among individuals practicing both aerobic and muscle strengthening exercises but not either alone and among those fulfilling the recommended range of 8.3 to 17 MET-h/wk. Regardless of differences in study designs, population characteristics, and PA or risk of SARS-CoV-2 infection and severity assessments, these studies are consistent with our findings regarding the inverse association between PA levels and risk of SARS-CoV-2 infection and COVID-19 severity. Also, our findings parallel the conclusions from 2 systematic reviews and meta-analyses characterizing the association between PA and risk of infection with other community-acquired respiratory infectious viruses, such as influenza and current variants of SARS-CoV-2. 10 , 13

For the association between PA and hospitalization due to COVID-19, our results align with those reported by English and Scottish health surveys, which also found an inverse association between MVPA (≥150-minute/wk) and COVID-19 mortality among 97 844 participants who, on average, were 56 years of age. 34 A study of comparatively younger adults also found an association between PA and hospitalization due to COVID-19 among those consistently meeting PA guidelines, even after multivariable adjustment. 15 A study characterizing associations between accelerometer-assessed PA and severe COVID-19 cases (ie, hospitalization or death) found lower odds of severe cases when adjusting for intensity and MVPA (7.5-15 MET-h/wk). 32 Other studies reported similar patterns. 18 , 30 , 33 , 35 Therefore, PA may prevent more severe cases of COVID-19 among those at greater risk of major morbidity and mortality, potentially explaining the lower odds of COVID-19 hospitalization among those meeting PA guidelines. 31

Our subgroup analyses suggest that the inverse association between PA and COVID-19 outcomes may be greater among women, potentially due to differences in respiratory system physiology. 36 As other studies indicated that older age, male sex, ethnicity status, low socioeconomic status, and having multiple morbidities were associated with higher risk of COVID-19 and more severe cases, 31 - 33 , 37 - 40 future studies should clarify whether the role of PA extends to both short- and long-term COVID-19–related outcomes in these groups.

When we restricted our follow-up through December 2020 to examine risk of infection before the introduction of COVID-19 vaccines, the inverse associations of prepandemic PA with COVID-19 were absent, possibly suggesting residual confounding; for example, behavioral and psychosocial factors may have modified the association between PA and risk of SARS-CoV-2 infection. 41 When we added vaccination status to model 3, the inverse association between meeting PA guidelines and COVID-19 was sustained. A previous study reported similar findings in a younger population. 16 Moreover, in agreement with previous studies, 29 , 42 , 43 the association of the COVID-19 vaccine with reduced risk of infection and hospitalization were evident regardless of PA status. Likewise, when we compared the combined inactive and insufficiently active groups with the sufficiently active group, the inverse associations remained. Previous studies also indicated the relevance of PA parameters in meeting PA guidelines (eg, ≥7.5 MET-h/wk). 4 , 32

Increased PA may protect against COVID-19 and other infectious diseases through various mechanisms. It enhances immune surveillance mechanisms by increasing the activity of natural killer cells and neutrophils and the number of circulating monocytes and lymphocytes and by modulating inflammatory processes through different mediators, such as cytokines, myokines, immunoglobulins (Igs), cortisol, and oxylipins. 7 - 9 , 31 , 33 Moreover, the increment of blood flow during PA biomechanically augments the lamina shear stress over endothelial cells, which triggers the production and bioavailability of nitric oxide, counteracting the oxidative and proinflammatory effect of SARS-CoV-2 infection. 44 , 45 Physical activity also improves neurocognitive functioning and well-being, slows neurodegeneration, and optimizes stress response. 46 In the myofascial system, the immunological and neurological pathways interplay by promoting muscle-derived anti-inflammatory interleukin 6 (ie, myokine production), long-term reduction of proinflammatory mediators, and release of endocannabinoids. 46 - 48 Physical activity increases levels of salivary IgA, an antibody known to protect against respiratory viruses. 10 , 49 , 50 Still, the exact mechanisms by which PA and more specific components of PA (eg, frequency, duration, intensity, and type) affect these physiological pathways warrant further investigation. 8 , 11 , 12 , 14

This study has strengths. The prospective design allowed us to define PA using validated questionnaires before the COVID-19 pandemic for the subsequent risk of COVID-19 and hospitalization due to COVID-19 as collected during the pandemic via multiple longitudinal surveys. Furthermore, we adjusted for a range of demographic, lifestyle, and clinical factors defined just before the COVID-19 pandemic.

Several limitations should be considered. First, the comparatively higher prevalence of sufficiently active participants in the combined cohort may reflect inherent volunteer bias for initially healthier individuals originally recruited and randomized into long-term clinical trials with continued follow-up. 19 , 22 , 51 Second, because PA levels were self-reported, information inaccuracies (eg, random misclassification) could have penalized the insufficiently active group. 2 Third, we likely underestimated COVID-19 cases due to missed asymptomatic cases without available serologic data and to underreporting typically seen in prospective studies. Longer follow-up for COVID-19 outcomes would have increased case counts, but the wider-spread integration of vaccines would have made it more difficult to isolate the role of PA. Furthermore, we did not account for changes in PA before and during the pandemic. Fourth, our definition of COVID-19 severity relied on hospitalization alone; however, some individuals with moderate or severe cases may not have been hospitalized. Fifth, we could not rule out the possibility of unmeasured confounders associated with high PA, including wearing masks, social distancing, and other protective behaviors, 52 - 54 despite extensive control for known confounders. 55 Sixth, although some participants were enrolled in more than 1 of the included studies, our main findings for risk of COVID-19 and hospitalization were unchanged in sensitivity analyses limited to those in 1 study only. Seventh, the cohort corresponded to a subset of participants from 3 parent RCTs and was largely a non-Hispanic White population (ie, sampling bias) recruited for specific purposes (eg, the WHS recruited only females); the generalizability of our findings to groups with different genders, ages, races and ethnicities, and comorbidities (ie, healthy volunteer bias) warrants further study. 56

In this cohort study of adults aged 45 years or older, meeting PA guidelines was associated with significantly lower odds of developing and being hospitalized for COVID-19. Future studies including quantitative control of PA parameters, broader racial and ethnic diversity, and information from other potential confounders (eg, sleep quality, dietary patterns, access to health care, and preventive behaviors) are warranted.

Accepted for Publication: December 19, 2023.

Published: February 13, 2024. doi:10.1001/jamanetworkopen.2023.55808

Open Access: This is an open access article distributed under the terms of the CC-BY License . © 2024 Muñoz-Vergara D et al. JAMA Network Open .

Corresponding Author: Dennis Muñoz-Vergara, DVM, MPH, Division of Preventive Medicine, Brigham and Women’s Hospital, 900 Commonwealth Ave East, Boston, MA 02215 ( [email protected] ).

Author Contributions: Drs Kim and Sesso had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Muñoz-Vergara and Wayne contributed equally to this work.

Concept and design: Wayne, Manson, Sesso.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Muñoz-Vergara, Wayne, Sesso.

Critical review of the manuscript for important intellectual content: All authors.

Statistical analysis: Muñoz-Vergara, Kim.

Obtained funding: Wayne, Lee, Sesso.

Administrative, technical, or material support: Muñoz-Vergara, Lee, Manson, Sesso.

Supervision: Wayne, Manson, Sesso.

Conflict of Interest Disclosures: Dr Lee reported receiving grants from the National Institutes of Health (NIH) during the conduct of the study. Dr Buring reported receiving grants from the NIH during the conduct of the study. Dr Manson reported receiving grants from the NIH during the conduct of the study and from Mars Edge outside the submitted work. Dr Sesso reported receiving grants from the NIH during the conduct of the study and from Mars Edge outside the submitted work. No other disclosures were reported.

Funding/Support: Brigham and Women’s Hospital provided internal investigator-initiated funding support for COVID-19 surveys and follow-up (Dr Sesso). The Women’s Health Study (WHS) is supported by grants CA047988, UM1 CA182913, HL043851, HL080467, and HL099355 from the NIH. The Vitamin D and Omega-3 Trial (VITAL) is supported by grants U01 CA138962, R01 CA138962, and R01 AT011729 from the NIH. Pharmavite LLC (vitamin D 3 ) and Pronova BioPharma/BASF (omega-3 fatty acids) donated the study agents, matching placebos, and packaging. Quest Diagnostics performed the serum 25-hydroxyvitamin D and plasma phospholipid omega-3 measurements at no additional cost. The Cocoa Supplement and Multivitamin Outcomes Study (COSMOS) is supported by an investigator-initiated grant from Mars Edge, a segment of Mars, Incorporated, dedicated to nutrition research and products, which included infrastructure support and the donation of study pills and packaging. Pfizer Consumer Healthcare (now part of GSK Consumer Healthcare) provided support through the partial provision of study pills and packaging. COSMOS is also supported in part by grants AG050657, AG071611, EY025623, and HL157665 from the NIH and contracts 75N92021D00001, 75N92021D00002, 75N92021D00003, 75N92021D00004, and 75N92021D00005 from the NIH through the Women’s Health Initiative. This study was supported by grant K24AT009282 from the National Center for Complementary and Integrated Health, NIH (Dr Wayne).

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Data Sharing Statement: See Supplement 2 .

Additional Contributions: We thank the COSMOS, VITAL, and WHS study participants and research staff for their tremendous dedication and commitment.

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COMMENTS

  1. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

    There were 8 cases of Covid-19 with onset at least 7 days after the second dose among participants assigned to receive BNT162b2 and 162 cases among those assigned to placebo; BNT162b2 was 95%...

  2. Comprehensive literature review on COVID-19 vaccines and role of SARS

    Since the outbreak of the COVID-19 pandemic, there has been a rapid expansion in vaccine research focusing on exploiting the novel discoveries on the pathophysiology, genomics, and molecular biology of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

  3. COVID-19 Vaccine: A comprehensive status report

    2. Vaccination strategies. Many efforts have been directed towards the development of the vaccines against COVID-19, to avert the pandemic and most of the developing vaccine candidates have been using the S-protein of SARS-CoV-2 (Dhama et al., 2020).As of July 2, 2020, the worldwide SARS-CoV-2 vaccine landscape includes 158 vaccine candidates, out of which 135 are in the preclinical or the ...

  4. PDF Background paper on Covid-19 disease and vaccines

    1 This document is no longer authoritative and will not be updated. Related information can be obtained at https://www.who.int/groups/strategic-advisory-group-of-experts-on-immunization/ DRAFT Prepared by the SAGE Working Group on COVID-19 Vaccines 22 December 2020 2 Contents

  5. Safety & effectiveness of COVID-19 vaccines: A narrative review

    Sputnik V (Gam-COVID-Vac), which is a dual vector-based vaccine that combines type 26 and rAd5 recombinant adenovirus (rAd), exhibited 91.6 per cent efficacy against COVID-19 17.

  6. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine

    The mRNA-1273 vaccine is a lipid nanoparticle-encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome...

  7. Covid-19 Vaccines

    Table 1. Protective Efficacy of Coronavirus Disease 2019 (Covid-19) Vaccines against the Ancestral Viral Strain in the United States and against the Omicron Variant in South Africa. Figure 2....

  8. Influence of a COVID-19 vaccineâ s effectiveness and safety ...

    Using a May 2020 survey, Malik et al. (3) found 67% reported they would accept a COVID-19 vaccine (similar to our 38% very likely + 29% some-what likely 67%), but likely acceptance varied by demographic group, with males, older adults, Asians, and college graduates more prone to accept (3).

  9. Evaluating COVID-19 vaccines in the real world

    The effectiveness of the mRNA vaccines in preventing COVID-19 disease progression in 2021 set new expectations about the role of prevention interventions for the disease. Efficacy observed in the trials was more than 90%.1,2 The efficacy of other vaccines evaluated in large randomised trials, such as the Oxford-AstraZeneca (70%) and Sputnik V (91%) vaccines, have been criticised for elements ...

  10. Oxford-AstraZeneca COVID-19 vaccine efficacy

    Oxford-AstraZeneca COVID-19 vaccine efficacy 2020 has been a difficult year for all, but has seen 58 vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) be developed and in clinical trials, with some vaccines reportedly having more than 90% efficacy against COVID-19 in clinical trials.

  11. Efficacy and safety of COVID-19 vaccines

    Authors' conclusions: Compared to placebo, most vaccines reduce, or likely reduce, the proportion of participants with confirmed symptomatic COVID-19, and for some, there is high-certainty evidence that they reduce severe or critical disease. There is probably little or no difference between most vaccines and placebo for serious adverse events.

  12. PDF February 2022

    The development of effective COVID-19 vaccines, treatments and public health interventions alone has provided humanity with some hope for the future. This updated report once again brings a spotlight to the immense and tireless global research effort to control COVID-19. The global coordination and support for the world's leading scientists and

  13. COVID vaccines and safety: what the research says

    16 February 2021 COVID vaccines and safety: what the research says It is clear that coronavirus vaccines are safe and effective, but as more are rolled out, researchers are learning about...

  14. COVID-19 vaccine waning and effectiveness and side-effects of boosters

    The effectiveness against infection of COVID-19 vaccines waned considerably 5-8 months after primary vaccination, although it remained high, particularly among people younger than 55 years. Vaccine boosters were effective in restoring protection against infection and had a good safety profile in the community.

  15. PDF Next Generation COVID-19 Vaccines

    Scalability: The feasibility to rapidly manufacture next-generation platforms on a large scale is currently unclear. Vaccine effectiveness: Data on vaccine efficacy and real-world effectiveness against emerging variants is sparse and mostly from high-income nations. SARS-CoV-2 genome: A key bottleneck is the rapidly evolving mutational change in the SARS-

  16. The rapid progress in COVID vaccine development and implementation

    NPJ Vaccines has published over 65 papers on SARS-CoV-2 that cover the entire breadth of vaccinology from basic science to attitudes of the public to COVID vaccines. With this in mind, the...

  17. Neonatal Outcomes After COVID-19 Vaccination in Pregnancy

    Several of the neonatal outcomes were selected because they touched areas of interest in previous reports of possible adverse events associated with mRNA COVID-19 vaccines administered to children or adults. 3,4,19 Suspected adverse events in adults and children—ie, events that have been observed following vaccination, but which were not ...

  18. Knowledge, acceptance and perception on COVID-19 vaccine among ...

    Background Coronavirus disease 2019 or COVID-19 is caused by a newly discovered coronavirus, SARS-CoV-2. The Malaysian government has planned to procure COVID-19 vaccine through multiple agencies and companies in order to vaccinate at least 70% of the population. This study aimed to determine the knowledge, acceptance and perception of Malaysian adults regarding the COVID-19 vaccine ...

  19. Efficacy and Safety of COVID-19 Vaccines: A Systematic Review and Meta

    The adenovirus-vectored and mRNA-based vaccines for COVID-19 showed the highest efficacy after first and second doses, respectively. The mRNA-based vaccines had higher side effects. Remarkably few experienced extreme adverse effects and all stimulated robust immune responses.

  20. COVID-19 mRNA Vaccines: Lessons Learned from the ...

    Our understanding of COVID-19 vaccinations and their impact on health and mortality has evolved substantially since the first vaccine rollouts. Published reports from the original randomized phase 3 trials concluded that the COVID-19 mRNA vaccines could greatly reduce COVID-19 symptoms. In the inter …

  21. Vaccines

    More than 13.5 billion COVID-19 vaccine doses were delivered between 2021 and 2023 through a mix of delivery platforms, with mass vaccination campaigns being the main approach. In 2022, with the continued circulation of SARS-CoV2 and the need for periodic boosters being most likely, countries were required to plan for more sustainable approaches to provide COVID-19 vaccinations. In this ...

  22. Safety and Efficacy of NVX-CoV2373 Covid-19 Vaccine

    Vaccine efficacy was 86.3% (95% CI, 71.3 to 93.5) against the B.1.1.7 variant and 96.4% (95% CI, 73.8 to 99.4) against non-B.1.1.7 strains. Too few non-White participants were enrolled in the ...

  23. Frontiers

    A survey done in the UAE on vaccine perception for COVID-19 vaccine showed that safety of the vaccine with no major side effects emerged as the greatest motivating factor to get vaccinated . As vaccine-related fears on safety and side effects play a role in determining the decision regarding vaccination, studies are conducted to monitor the ...

  24. The impact of ABO blood types on humoral immunity responses and

    This study evaluated the possible effects of blood types on coronavirus disease (COVID-19) vaccine immunogenicity and antibody (Ab) persistency. Five different vaccinated groups against COVID-19 were investigated at Pasteur Institute of Iran from April 2021 to December 2022.

  25. Long-term effectiveness of COVID-19 vaccines against infections

    Our analyses indicate that vaccine effectiveness generally decreases over time against SARS-CoV-2 infections, hospitalisations, and mortality. The baseline vaccine effectiveness levels for the omicron variant were notably lower than for other variants. Therefore, other preventive measures (eg, face-mask wearing and physical distancing) might be necessary to manage the pandemic in the long term.

  26. PDF The Impact of Covid-19 on Student Experiences and Expectations

    The Impact of COVID-19 on Student Experiences and Expectations: Evidence from a Survey Esteban M. Aucejo, Jacob F. French, Maria Paola Ugalde Araya, and Basit Zafar NBER Working Paper No. 27392 June 2020 JEL No. I2,I23,I24 ABSTRACT In order to understand the impact of the COVID-19 pandemic on higher education, we surveyed approximately 1,500 stu...

  27. COVID‐19 vaccine research and development: ethical issues

    The invention of a successful and widely available COVID‐19 vaccine will be a great leap forward for humankind, but there are several challenges to overcome: (1) a lack of understanding of the pathogenesis and the predictive role of vaccines in the clinical pathway of persons being infected by SARS‐CoV‐2 [ 5, 6, 7 ], (2) a huge disagreement amon...

  28. A Systematic Review of the COVID Vaccine's Impact on the ...

    Aims & Objectives The objective of this study was to conduct a systematic review of research pertaining to the COVID-19 vaccine and its association with neurological complications.

  29. Prepandemic Physical Activity and Risk of COVID-19 Diagnosis and

    Key Points. Question Are higher prepandemic physical activity (PA) levels associated with lower risk of developing or being hospitalized for COVID-19?. Findings In this cohort study of 61 557 women and men aged 45 years or older who reported 5890 incident cases of COVID-19 and 626 hospitalizations, those who achieved at least 7.5 metabolic equivalent hours per week of PA before the pandemic ...

  30. PDF TESTIMONY OF DR. PETER MARKS, M.D., Ph.D. DIRECTOR CENTER FOR BIOLOGICS

    safety monitoring of all COVID-19 vaccines using state-of-the-art methods. CBER monitors the safety of approved and authorized COVID-19 vaccines through both passive . and active safety surveillance systems in coordination and collaboration with other federal . agencies such as the CDC, and other academic and large non-government healthcare data