- - Major COVID-19 vaccines are considered safe and tolerant, although surveillance for long-term safety outcomes is needed.
- - Previously infected individuals can still be at risk of being reinfected with SARS-CoV-2, and it could be beneficial for these individuals to receive vaccination against COVID-19.
- - The risk of infection in people who have not received COVID-19 vaccines or been partially vaccinated is higher than that of fully vaccinated people.
- - There is little evidence regarding the long-term protection of COVID-19 vaccination, and therefore no clear answers can be given regarding whether booster shots should be given.
- Premature lifting or relaxation of non-pharmaceutical interventions (NPIs) when sufficient immunity in the population has yet to be established may result in substantial increase in COVID-19 new cases, hospitalizations, and mortalities.
Vaccination, which stimulates protective immune responses against acute and chronic infectious diseases, has been proved as one of the greatest achievements in public health. Vaccination saves lives.
In the United States, with the help of vaccination, the incidences of a number of infectious diseases, including smallpox, measles, polio, rubella, pertussis, mumps, and diphtheria, have been successfully reduced by more than 90% with some of them being completely eradicated (i.e., smallpox) or nearly eradicated (percent decrease > 99%, such as polio and measles) (Orenstein et al., 2017).
Vaccines against SARS-CoV-2 have been developed, deployed, and administered at a record speed with the aim to put the COVID-19 pandemic under control. To date, over 5 billion doses of COVID-19 vaccines have been administered around the globe (Johns Hopkins Coronavirus Resource Center). In the meantime, mass vaccination campaigns also raised doubts, questions as well as hesitations.
In previous OE Originals, we mainly focused on addressing vaccine hesitancy by discussing the efficacy, effectiveness, scheduling of vaccinations against COVID-19 in general and SARS-CoV-2 variants of concern (VOCs) in particular (e.g., Alpha, Beta, Gamma, and Delta SARS-CoV-2).
In this present OE Original, we examine evidence and further discuss COVID-19 vaccination questions that are frequently asked, such as the safety of COVID-19 vaccines, receiving vaccination when previously infected, reinfection with SARS-CoV-2 in fully vaccinated individuals, long-term protection that COVID-19 vaccines can provide, and the role of non-pharmaceutical interventions (NPIs).
Past Relevant OE Originals*
* Evidence regarding COVID-19 emerges rapidly. Above OE Originals and Insights can only reflect the best available evidence at the time of publication.
#1. Are COVID-19 vaccines, especially mRNA vaccines, safe? Short Answer: YES
A survey published in The Lancet identified that concern about the safety of COVID-19 vaccines due to rush development (36%, 139/388) and concern about potential side effects after receiving COVID-19 vaccines (10%, 38/388) were top two reasons why people would not receive COVID-19 vaccines (Dodd et al., 2021). Such safety concerns even existed in those who would get vaccinated (11%, 311/2859) (Dodd et al., 2021). Moreover, the use of the mRNA vaccine platform to develop vaccines against COVID-19 is also causing safety concerns for some. The mRNA vaccine platform is relatively new, compared to vaccine platforms such as inactivated virus, live-attenuated virus, or antigenic proteins. Before the COVID-19 pandemic, there were no mRNA vaccines approved by governing bodies such as the United States Food and Drug Administration (FDA).
In terms of safety concerns over the expedited vaccine development process, Lefebvre et al. (2021) argued that acceleration in vaccine development did not necessarily mean the compromise of vaccine safety. There are a number of reasons why the process was expedited for COVID-19 vaccine development and deployment (Lefebvre et al., 2021). First, there was an unprecedented scientific and financial deployment with the aim to accelerate the development and production of COVID-19 vaccines. Moreover, we already had knowledge about coronavirus immunity which was mainly from previous studies on 2003 SARS-CoV (Severe Acute Respiratory Syndrome-associated coronavirus) and 2012 MERS-CoV (Middle East Respiratory Syndrome-associated coronavirus) Third, the COVID-19 pathogen was rapidly characterized and found to be relatively stable for vaccine development. Fourth, nucleic acid and viral vector vaccine platforms have been extensively investigated and widely utilized in viruses such as Zika virus, SARS-CoV, and MERS-CoV. Finally, without sacrificing scientific rigor, clinical trials on COVID-19 vaccines were conducted at a record speed.
In terms of the safety concerns over mRNA vaccines, evidence suggests they are safe. The mRNA vaccine platform is relatively new but it is not a brand-new vaccine platform developed to fight specifically against COVID-19 (Anand et al., 2021). As a matter of fact, mRNA vaccines have been investigated in humans for oncologic therapies for about a decade (ClinicalTrials.gov Identifier: NCT01684241). For infectious diseases such as H10N8 and H7N9 influenza viruses, clinical trials have also been conducted in humans (Feldman et al., 2019). Safety data from Feldman et al. (2019) found no vaccine-related serious adverse events.
Vaccines are usually expected to cause temporary post-vaccination side effects (e.g., injection-site pain, redness, swelling, induration at the injection site, fever, myalgia, headache) as a result of activation of immune responses, which is known as vaccine reactogenicity (Hervé et al., 2019). As for the side effects after receiving COVID-19 vaccines including mRNA vaccines, evidence from systematic reviews may shed some light. Overall, COVID-19 vaccines are considered safe and tolerant (Pormohammad et al., 2021; Yuan et al., 2020). Life-threatening or extreme adverse events, such as pulmonary emboli, deep vein thrombosis, and anaphylaxis were very rare for both mRNA vaccines (e.g., the Pfizer-BioNTech vaccine, Moderna vaccine) and adenovirus-vectored vaccines (e.g., the AstraZeneca vaccine), whereas mild and temporary adverse events, such as site pain, swelling, redness, fever, headache, fatigue, induration, vomiting, myalgia, chills, pruritus, diarrhea, and arthralgia, were relatively common (Pormohammad et al., 2021; Yuan et al., 2020). To be noticed, the evidence regarding safety came from randomized controlled trials (RCTs) which only allow a limited observation period. COVID-19 vaccines surveillance for long-term safety outcomes is still necessary.
#2. If someone has previously had COVID-19 or been asymptomatically infected by SARS-CoV-2, does he/she need to get vaccinated? Short Answer: YES
Data suggests that previously infected individuals can still be at risk of being reinfected with COVID-19, and thereby receiving vaccination against COVID-19 could be beneficial.
A study of a Danish cohort, which was published in The Lancet and involved around 4 million people, investigated the risk of reinfection, which was represented by patients becoming positive for SARS-CoV-2 by polymerase chain reaction (PCR) tests for the second time (Hansen et al., 2021). This Danish dataset was of great value because it was based on a universally accessible testing program for both symptomatic and non-symptomatic Danish residents, which might elicit more marginal levels of protective immunity by detecting a far higher proportion of asymptomatic COVID-19 cases.
Overall, Hansen et al. (2021) concluded that it might be necessary to implement protective measures such as vaccination for those who had previously had COVID-19, especially for those aged 65 years and older. Specifically, Hansen et al. (2021) found that natural infection with SARS-CoV-2 provided some extent of protection against reinfection, which was estimated to be about 80.5% [95% confidence interval (CI): 75.4% to 84.5%]. Such protection decreased in people aged 65 years and older (47.1%; 95% CI: 24.7% to 62.8%) (Hansen et al., 2021).
Getting vaccinated could offer benefits to individuals previously infected with COVID-19. Manisty et al. (2021) detected the immune response against the SARS-CoV-2 S1 spike protein 19 to 29 days after the participants received the first dose of the Pfizer-BioNTech COVID-19 vaccine. Interestingly, the study found that among those who had a previous SARS-CoV-2 infection, vaccination with one dose markedly increased the immune response against the SARS-CoV-2 S1 spike protein more than 140-fold from peak pre-vaccine levels (Manisty et al., 2021).
#3. If fully vaccinated individuals can still get the infection, does one still need to get vaccinated? Short Answer: Yes
Reinfections with SARS-CoV-2 occurring in fully vaccinated individuals is called breakthrough infections. The United States Centers for Disease Control and Prevention (CDC) defines a breakthrough infection as “the detection of SARS-CoV-2 RNA or antigen in a respiratory specimen collected from a person >=14 days after they have completed all recommended doses of a United States Food and Drug Administration (FDA)-authorized COVID-19 vaccine.” Public Health Ontario gives a similar definition and defines a SARS-CoV-2 breakthrough infection as “a case with a symptom onset date 14 or more days following the final dose of vaccine” (Ontario Agency for Health Protection and Promotion, 2021).
Breakthrough infections do happen but it does not mean full vaccination is meaningless. The risk of infection in people who have not received COVID-19 vaccines [odds ratio (OR): 2.34; 95% CI: 1.58 to 3.47] or been partially vaccinated (OR: 1.56; 95% ci: 0.81 to 3.01) is higher than that of fully vaccinated people (Cavanaugh et al., 2021).
Evidence also suggests that most infections occur in unvaccinated people rather than those who have been fully vaccinated or partially vaccinated. Public Health Ontario reported breakthrough cases among over 9.75 million fully vaccinated Ontario residents between December 14, 2020 and August 21, 2021. The report showed that COVID-19 cases in unvaccinated people accounted for 94.8% of all cases, while only 0.9% and 4.3% of COVID-19 cases happened in fully vaccinated and partially vaccinated individuals, respectively (Ontario Agency for Health Protection and Promotion, 2021). Unvaccinated individuals were about 8.0 times more likely to get infected with SARS-CoV-2, compared to fully vaccinated individuals (Ontario Agency for Health Protection and Promotion, 2021).
In addition, disease severity is also lesser in fully vaccinated individuals than those who are not. COVID-19-related hospitalization and mortality in unvaccinated people accounted for approximately 92.4% and 92.1% of all cases reported between December 14, 2020 and August 21, 2021, respectively (Ontario Agency for Health Protection and Promotion, 2021). However, hospitalization and mortality in fully vaccinated individuals only accounted for about 0.9% and 1.3%, respectively (The rest were made up with cases in partially vaccinated individuals) (Ontario Agency for Health Protection and Promotion, 2021). Unvaccinated individuals aged 60 years or older were about 22.8 times more likely to be hospitalized due to COVID-19, compared to fully vaccinated individuals within the same age range (Ontario Agency for Health Protection and Promotion, 2021).
#4. What do we know about the long-term protection that COVID-19 vaccines can provide? Do we need a booster shot? Short Answer: Likely Yes
The COVID-19 vaccines began to roll out in December 2020, only about 10 months ago. As a result, there lacks empirical evidence regarding the long-term protection of COVID-19 vaccination, and therefore no clear answers can be given regarding the booster shots.
Some studies might shed light on this issue, indicating that a booster might be needed. Mathematical modeling published in MedRxiv estimated that 1 year after symptom onset, the anti-Spike IgG, anti-receptor binding domain (RBD) IgG, and anti-nucleocapsid IgG waned to 36%, 31%, and 7% of the titers 2 weeks after symptom onset, respectively (Pelleau et al., 2021).
A review which was conducted by Hamady et al. (2021) compared antibody responses to different human coronaviruses (e.g., SARS-CoV, MERS-CoV) in order to understand the long-term immunity in SARS-CoV-2. The authors found that antibodies to most coronaviruses wane and the titers became undetectable within 2 years of infection (Hamady et al., 2021). The authors further estimated that natural antibody-mediated protection for SARS-CoV-2 would probably last for 1 to 2 years (Hamady et al., 2021). Booster doses might be necessary if COVID-19 vaccine-induced antibodies followed a similar course.
#5. If one gets fully vaccinated, does he/she still need to implement non-pharmaceutical interventions (NPIs) such as wearing masks? Short Answer: Yes
For fully vaccinated individuals, CDC recommends that people who are immunocompromised should continue to wear masks even if they have received full doses of COVID-19 vaccines. Moreover, fully vaccinated individuals in an area of high transmission of the Delta variant may also wear masks indoors in public to prevent the spread of COVID-19.
Without NPIs, vaccination alone may not be sufficient to contain the pandemic, especially when sufficient immunity in the population has yet to be established. Currently, the percentages of fully vaccinated individuals range from as high as about 60% to 70% in countries like Canada, United Kingdom, and United Arab Emirates to as low as 20% to 30% in countries such as Brazil, Mexico, and Russia (Our World in Data). In some countries, the coverage is even lower to less than 10% (Our World in Data).
Several modelling studies emphasize the critical role of NPIs during the period when COVID-19 vaccines are being distributed and administered. For example, Patel’s et al. (2021) model suggested that premature relaxation of NPIs against COVID-19 when vaccination coverage is low may result in substantial increases in new cases, hospitalizations, and deaths. Specifically, in the scenario in which the vaccine efficacy is 50% and vaccination coverage is 25%, lifting NPIs would result in over 1.4 million more SARS-CoV-2 infections than keeping NPI would (Patel’s et al., 2021). In the scenario in which the vaccine efficacy is 90% and vaccination coverage is 75%, incidence of SARS-CoV-2 infections would become similar between removing NPIs (527,409 cases) and keeping NPIs (450,575 cases) (Patel’s et al., 2021). Moreover, under the circumstances in which NPIs are lifted, high vaccination rate seems to be a more important contributing factor to reducing the incidence of new COVID-19 cases: 75% vaccination coverage and 50% vaccine efficacy (13% absolute risk reduction) would lead to greater risk reduction than 25% vaccination coverage and 90% vaccine efficacy (8%) would (Patel’s et al., 2021).
Moore’s et al. (2021) also highlighted the risks of mortality due to COVID-19 associated with early or rapid relaxation of NPIs. If NPIs are lifted starting January 2022, the vaccine efficacy is 60%, as well as 95% individuals in care homes or over 80 years of age, 85% of those aged 50 to 79 years, and 75% of those aged 18 to 49 years are fully vaccinated, Moore’s et al. (2021) model predicted that about 96,700 deaths due to COVID-19 would occur before January 2024. When the vaccine efficacy remains the same but the vaccine uptake increases (90%, 80% 70% in three population groups), the incidence of deaths would drop to about 63,000 (Moore’s et al., 2021).
Current evidence suggests that COVID-19 vaccines are safe and tolerant and can be beneficial to those who have previously been infected with SARS-CoV-2. Moreover, breakthrough infections (reinfection in fully vaccinated individuals) do occur but the risk of reinfection after being fully vaccinated is lower than that in people who have not received COVID-19 vaccines or been partially vaccinated, and disease severity is also lesser. Third, there is insufficient evidence regarding the long-term protection of COVID-19 vaccines. Finally, premature removal or relaxation of non-pharmaceutical interventions when sufficient immunity in the population has yet to be established may result in substantial increase in COVID-19 new cases, hospitalizations, and mortalities.
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