COVID-19 vaccine
A COVID‑19 vaccine is a vaccine intended to provide acquired immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID‑19).
Prior to the COVID‑19 pandemic, an established body of knowledge existed about the structure and function of coronaviruses causing diseases like severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). This knowledge accelerated the development of various vaccine platforms in early 2020.[1] The initial focus of SARS-CoV-2 vaccines was on preventing symptomatic, often severe, illness.[2] In 2020, the first COVID‑19 vaccines were developed and made available to the public through emergency authorizations[3] and conditional approvals.[4][5] Initially, most COVID‑19 vaccines were two-dose vaccines, with the exception of a single-dose Janssen COVID‑19 vaccine[3] and vaccines with three-dose schedules, Razi Cov Pars[6] and Soberana.[7] However, immunity from the vaccines has been found to wane over time, requiring people to get booster doses of the vaccine to maintain protection against COVID‑19.[3]
The COVID‑19 vaccines are widely credited for their role in reducing the spread of COVID‑19 and reducing the severity and death caused by COVID‑19.[3][8] According to a June 2022 study, COVID‑19 vaccines prevented an additional 14.4 to 19.8 million deaths in 185 countries and territories from 8 December 2020 to 8 December 2021.[9][10] Many countries implemented phased distribution plans that prioritized those at highest risk of complications, such as the elderly, and those at high risk of exposure and transmission, such as healthcare workers.[11][12]
Common side effects of COVID‑19 vaccines include soreness, redness, rash, inflammation at the injection site, fatigue, headache, myalgia (muscle pain), and arthralgia (joint pain), which resolve without medical treatment within a few days.[13][14] COVID‑19 vaccination is safe for people who are pregnant or are breastfeeding.[15]
As of 1 May 2024, 13.58 billion doses of COVID‑19 vaccines have been administered worldwide, based on official reports from national public health agencies.[16] By December 2020, more than 10 billion vaccine doses had been preordered by countries,[17] with about half of the doses purchased by high-income countries comprising 14% of the world's population.[18]
Despite the extremely rapid development of effective mRNA and viral vector vaccines, worldwide vaccine equity has not been achieved. The development and use of whole inactivated virus (WIV) and protein-based vaccines have also been recommended, especially for use in developing countries.[19][20]
The 2023 Nobel Prize in Physiology or Medicine was awarded to Katalin Karikó and Drew Weissman for the development of effective mRNA vaccines against COVID-19.[21][22][23]
COVID‑19 vaccine doses administered by continent as of October 11, 2021. For vaccines that require multiple doses, each individual dose is counted. As the same person may receive more than one dose, the number of doses can be higher than the number of people in the population.
Map showing share of population fully vaccinated against COVID-19 relative to a country's total population[note 1]
![Map showing share of population fully vaccinated against COVID-19 relative to a country's total population[note 1]](http://upload.wikimedia.org/wikipedia/commons/thumb/b/b4/World_map_of_share_of_people_who_received_all_doses_prescribed_by_the_initial_COVID-19_vaccination_protocol.png/510px-World_map_of_share_of_people_who_received_all_doses_prescribed_by_the_initial_COVID-19_vaccination_protocol.png)
Prior to COVID‑19, a vaccine for an infectious disease had never been produced in less than several years – and no vaccine existed for preventing a coronavirus infection in humans.[24] However, vaccines have been produced against several animal diseases caused by coronaviruses, including (as of 2003) infectious bronchitis virus in birds, canine coronavirus, and feline coronavirus.[25] Previous projects to develop vaccines for viruses in the family Coronaviridae that affect humans have been aimed at severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). Vaccines against SARS[26] and MERS[27] have been tested in non-human animals.
According to studies published in 2005 and 2006, the identification and development of novel vaccines and medicines to treat SARS was a priority for governments and public health agencies around the world at that time.[28][29][30] There is no cure or protective vaccine proven to be safe and effective against SARS in humans.[31][32] There is also no proven vaccine against MERS.[33] When MERS became prevalent, it was believed that existing SARS research might provide a useful template for developing vaccines and therapeutics against a MERS-CoV infection.[31][34] As of March 2020, there was one (DNA-based) MERS vaccine that completed Phase I clinical trials in humans,[35] and three others in progress, all being viral-vectored vaccines: two adenoviral-vectored (ChAdOx1-MERS, BVRS-GamVac) and one MVA-vectored (MVA-MERS-S).[36]
Vaccines that use an inactive or weakened virus that has been grown in eggs typically take more than a decade to develop.[37][38] In contrast, mRNA is a molecule that can be made quickly, and research on mRNA to fight diseases was begun decades before the COVID‑19 pandemic by scientists such as Drew Weissman and Katalin Karikó, who tested on mice. Moderna began human testing of an mRNA vaccine in 2015.[37] Viral vector vaccines were also developed for the COVID‑19 pandemic after the technology was previously cleared for Ebola.[37]
As multiple COVID‑19 vaccines have been authorized or licensed for use, real-world vaccine effectiveness (RWE) is being assessed using case control and observational studies.[39][40] A study is investigating the long-lasting protection against SARS-CoV-2 provided by the mRNA vaccines.[41][42]
Formulation
As of September 2020, eleven of the vaccine candidates in clinical development use adjuvants to enhance immunogenicity.[44] An immunological adjuvant is a substance formulated with a vaccine to elevate the immune response to an antigen, such as the COVID‑19 virus or influenza virus.[134] Specifically, an adjuvant may be used in formulating a COVID‑19 vaccine candidate to boost its immunogenicity and efficacy to reduce or prevent COVID‑19 infection in vaccinated individuals.[134][135] Adjuvants used in COVID‑19 vaccine formulation may be particularly effective for technologies using the inactivated COVID‑19 virus and recombinant protein-based or vector-based vaccines.[135] Aluminum salts, known as "alum", were the first adjuvant used for licensed vaccines and are the adjuvant of choice in some 80% of adjuvanted vaccines.[135] The alum adjuvant initiates diverse molecular and cellular mechanisms to enhance immunogenicity, including the release of proinflammatory cytokines.[134][135]
In June 2024, the US Food and Drug Administration (FDA) advised the manufacturers of the licensed and authorized COVID-19 vaccines that the COVID-19 vaccines (2024-2025 Formula) for use in the United States beginning in fall 2024 should be monovalent JN.1 vaccines.[136]
For most people, the side effects, also called adverse effects, from COVID‑19 vaccines are mild and can be managed at home. The adverse effects of the COVID‑19 vaccination are similar to those of other vaccines, and severe adverse effects are rare.[262][263] Adverse effects from the vaccine are higher than placebo, but placebo arms of vaccine trials still reported adverse effects that can be attributed to the nocebo effect.[264]
All vaccines that are administered via intramuscular injection, including COVID‑19 vaccines, have side effects related to the mild trauma associated with the procedure and the introduction of a foreign substance into the body.[265] These include soreness, redness, rash, and inflammation at the injection site. Other common side effects include fatigue, headache, myalgia (muscle pain), and arthralgia (joint pain), all of which generally resolve without medical treatment within a few days.[13][14] Like any other vaccine, some people are allergic to one or more ingredients in COVID‑19 vaccines. Typical side effects are stronger and more common in younger people and in subsequent doses, and up to 20% of people report a disruptive level of side effects after the second dose of an mRNA vaccine.[266] These side effects are less common or weaker in inactivated vaccines.[266] COVID‑19 vaccination-related enlargement of lymph nodes happens in 11.6% of those who received one dose of the vaccine and in 16% of those who received two doses.[267]
Experiments in mice show that intramuscular injections of lipid excipient nanoparticles (an inactive substance that serves as the vehicle or medium) cause particles to enter the blood plasma and many organs, with higher concentrations found in the liver and lower concentrations in the spleen, adrenal glands, and ovaries. The highest concentration of nanoparticles was found at the injection site itself.[268]
COVID‑19 vaccination is safe for breastfeeding people.[15] Temporary changes to the menstrual cycle in young women have been reported. However, these changes are "small compared with natural variation and quickly reverse."[269] In one study, women who received both doses of a two-dose vaccine during the same menstrual cycle (an atypical situation) may see their next period begin a couple of days late. They have about twice the usual risk of a clinically significant delay (about 10% of these women, compared to about 4% of unvaccinated women).[269] Cycle lengths return to normal after two menstrual cycles post-vaccination.[269] Women who received doses in separate cycles had approximately the same natural variation in cycle lengths as unvaccinated women.[269] Other temporary menstrual effects have been reported, such as heavier than normal menstrual bleeding after vaccination.[269]
Serious adverse events associated COVID‑19 vaccines are generally rare but of high interest to the public.[270] The official databases of reported adverse events include
Increased public awareness of these reporting systems and the extra reporting requirements under US FDA Emergency Use Authorization rules have increased reported adverse events.[272] Serious side effects are an ongoing area of study, and resources have been allocated to try and better understand them.[273][274][275] Research currently indicates that the rate and type of side effects are lower-risk than infection. For example, although vaccination may trigger some side effects, the effects experienced from an infection could be worse. Neurological side effects from getting COVID‑19 are hundreds of times more likely than from vaccination.[276]
Documented rare serious effects include:
There are rare reports of subjective hearing changes, including tinnitus, after vaccination.[278][283][284][285]