COVID-19 vaccine

From Wikipedia the free encyclopedia

How COVID-19 vaccines work. The video shows the process of vaccination, from injection with RNA or viral vector vaccines, to uptake and translation, and on to immune system stimulation and effect.
Map of countries by approval status
  Approved for general use, mass vaccination underway
  EUA (or equivalent) granted, mass vaccination underway
  EUA granted, limited vaccination
  Approved for general use, mass vaccination planned
  EUA granted, mass vaccination planned
  EUA pending
  No data available

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 during early 2020.[1] The initial focus of SARS-CoV-2 vaccines was on preventing symptomatic, often severe illness.[2] On 10 January 2020, the SARS-CoV-2 genetic sequence data was shared through GISAID, and by 19 March, the global pharmaceutical industry announced a major commitment to address COVID-19.[3] In 2020, the first COVID-19 vaccines were developed and made available to the public through emergency use authorization.[4] Initially, most COVID-19 vaccines were two dose vaccines, with the sole exception being the single-dose Janssen COVID-19 vaccine.[4] However, immunity from the vaccines has been found to wane over time, requiring people to get booster doses of the vaccine to maintain immunity against COVID-19.[4]

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.[4][5][6] According to a June 2022 study published in The Lancet, COVID-19 vaccines prevented an additional 14.4 to 19.8 million deaths in 185 countries and territories from December 8, 2020, to December 8, 2021.[7][8] 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.[9]

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.[10][11] COVID-19 vaccines are not associated with a higher risk of adverse effects during pregnancy or while breastfeeding.[12][13][14] Temporary changes to the menstrual cycle in young women have been reported, although these changes are "small compared with natural variation and quickly reverse".[15] Serious adverse events associated COVID-19 vaccines, such as allergic reactions, are generally rare but of high interest to the public.[4][16] Because COVID-19 vaccines are relatively new, new claims about possible side effects are still being made, and sometimes reports conflict.[17]

As of 26 May 2022, 11.81 billion doses of COVID-19 vaccines have been administered worldwide based on official reports from national public health agencies.[18] By December 2020, more than 10 billion vaccine doses had been preordered by countries,[19] with about half of the doses purchased by high-income countries comprising 14% of the world's population.[20] 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.[21][22]

Background

A US airman receiving a COVID-19 vaccine, December 2020

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.[23] 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.[24] 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[25] and MERS[26] 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.[27][28][29] There is no cure or protective vaccine proven to be safe and effective against SARS in humans.[30][31] There is also no proven vaccine against MERS.[32] 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.[30][33] As of March 2020, there was one (DNA-based) MERS vaccine which completed Phase I clinical trials in humans,[34] and three others in progress, all being viral-vectored vaccines: two adenoviral-vectored (ChAdOx1-MERS, BVRS-GamVac) and one MVA-vectored (MVA-MERS-S).[35]

Vaccines that use an inactive or weakened virus that has been grown in eggs typically take more than a decade to develop.[36][37] 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.[36] Viral vector vaccines were also developed for the COVID-19 pandemic after the technology was previously cleared for Ebola.[36]

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.[38] A study is investigating the long-lasting protection against SARS-CoV-2 provided by the mRNA vaccines.[39][40]

Formulation

As of September 2020, eleven of the vaccine candidates in clinical development use adjuvants to enhance immunogenicity.[41] 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.[42] 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.[42][43] 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.[43] 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.[43] The alum adjuvant initiates diverse molecular and cellular mechanisms to enhance immunogenicity, including release of proinflammatory cytokines.[42][43]

Sequencing

In November 2021, the full nucleotide sequences of the AstraZeneca and Pfizer/BioNTech vaccines were released by the UK Medicines and Healthcare products Regulatory Agency, in response to a freedom of information request.[44][45]

Clinical research

COVID-19 vaccine clinical research uses clinical research to establish the characteristics of COVID-19 vaccines. These characteristics include efficacy, effectiveness and safety. Thirty vaccines are authorized for use by national governments, including eight approved for emergency or full use by at least one WHO-recognised stringent regulatory authority; while five are in Phase IV. 204 vaccines are undergoing clinical trials that have yet to be authorized.[46] Nine clinical trials consider heterologous vaccination courses.

Thirty-three vaccines are authorized by at least one national regulatory authority for public use:[47][48]

As of July 2021, 330 vaccine candidates were in various stages of development, with 102 in clinical research, including 30 in Phase I trials, 30 in Phase I–II trials, 25 in Phase III trials, and 8 in Phase IV development.[47]

Post-vaccination complications

Post-vaccination embolic and thrombotic events, termed vaccine-induced immune thrombotic thrombocytopenia (VITT),[49][50][51][52][53] vaccine-induced prothrombotic immune thrombocytopenia (VIPIT),[54] thrombosis with thrombocytopenia syndrome (TTS),[55][52][53] vaccine-induced immune thrombocytopenia and thrombosis (VITT),[53] or vaccine-associated thrombotic thrombocytopenia (VATT),[53] are rare types of blood clotting syndromes that were initially observed in a number of people who had previously received the Oxford–AstraZeneca COVID‑19 vaccine (AZD1222)[a] during the COVID‑19 pandemic.[54][60] It was subsequently also described in the Janssen COVID‑19 vaccine (Johnson & Johnson) leading to suspension of its use until its safety had been reassessed.[61] On May 5, 2022 the FDA posted a bulletin limiting the use of the Janssen Vaccine to very specific cases due to further reassesment of the risks of TTS, although the FDA also stated in the same bulletin that the benefits of the vaccine outweigh the risks.[62]

In April 2021, AstraZeneca and the European Medicines Agency (EMA) updated their information for healthcare professionals about AZD1222, saying it is "considered plausible" that there is a causal relationship between the vaccination and the occurrence of thrombosis in combination with thrombocytopenia and that, "although such adverse reactions are very rare, they exceeded what would be expected in the general population".[60][63][64][65]

Vaccine types

Conceptual diagram showing three vaccine types for forming SARS‑CoV‑2 proteins to prompt an immune response: (1) RNA vaccine, (2) subunit vaccine, (3) viral vector vaccine
Vaccine platforms being employed for SARS-CoV-2. Whole virus vaccines include both attenuated and inactivated forms of the virus. Protein and peptide subunit vaccines are usually combined with an adjuvant in order to enhance immunogenicity. The main emphasis in SARS-CoV-2 vaccine development has been on using the whole spike protein in its trimeric form, or components of it, such as the RBD region. Multiple non-replicating viral vector vaccines have been developed, particularly focused on adenovirus, while there has been less emphasis on the replicating viral vector constructs.[66]

At least nine different technology platforms are under research and development to create an effective vaccine against COVID-19.[41][67] Most of the platforms of vaccine candidates in clinical trials are focused on the coronavirus spike protein (S protein) and its variants as the primary antigen of COVID-19 infection,[41] since the S protein triggers strong B-cell and T-cell immune responses.[68][69] However, other coronavirus proteins are also being investigated for vaccine development, like the nucleocapsid, because they also induce a robust T-cell response and their genes are more conserved and recombine less frequently (compared to Spike).[69][70][71] Future generations of COVID-19 vaccines that may target more and conserved genomic regions will also act as an insurance against the manifestation of catastrophic scenarios concerning the future evolutionary path of SARS-CoV-2, or any similar Coronavirus epidemic/pandemic.[72]

Platforms developed in 2020 involved nucleic acid technologies (nucleoside-modified messenger RNA and DNA), non-replicating viral vectors, peptides, recombinant proteins, live attenuated viruses, and inactivated viruses.[23][41][73][74]

Many vaccine technologies being developed for COVID-19 are not like vaccines already in use to prevent influenza, but rather are using "next-generation" strategies for precise targeting of COVID-19 infection mechanisms.[41][73][74] Several of the synthetic vaccines use a 2P mutation to lock the spike protein into its prefusion configuration, stimulating an adaptive immune response to the virus before it attaches to a human cell.[75] Vaccine platforms in development may improve flexibility for antigen manipulation, and effectiveness for targeting mechanisms of COVID-19 infection in susceptible population subgroups, such as healthcare workers, the elderly, children, pregnant women, and people with weakened immune systems.[41][73]

mRNA vaccines

Diagram of the operation of an RNA vaccine. Messenger RNA contained in the vaccine enters cells and is translated into foreign proteins, which trigger an immune response.

Several COVID-19 vaccines, including the Pfizer–BioNTech and Moderna vaccines, have been developed to use RNA to stimulate an immune response. When introduced into human tissue, the vaccine contains either self-replicating RNA or messenger RNA (mRNA), which both cause cells to express the SARS-CoV-2 spike protein. This teaches the body how to identify and destroy the corresponding pathogen. RNA vaccines often, but not always, use nucleoside-modified messenger RNA. The delivery of mRNA is achieved by a coformulation of the molecule into lipid nanoparticles which protect the RNA strands and help their absorption into the cells.[76][77][78][79]

RNA vaccines were the first COVID-19 vaccines to be authorized in the United Kingdom, the United States and the European Union.[80][81] Authorized vaccines of this type are the Pfizer–BioNTech[82][83][84] and Moderna vaccines.[85][86] The CVnCoV RNA vaccine from CureVac failed in clinical trials.[87]

Severe allergic reactions are rare. In December 2020, 1,893,360 first doses of Pfizer–BioNTech COVID-19 vaccine administration resulted in 175 cases of severe allergic reaction, of which 21 were anaphylaxis.[88] For 4,041,396 Moderna COVID-19 vaccine dose administrations in December 2020 and January 2021, only ten cases of anaphylaxis were reported.[88] Lipid nanoparticles (LNPs) were most likely responsible for the allergic reactions.[88]

Adenovirus vector vaccines

These vaccines are examples of non-replicating viral vector vaccines, using an adenovirus shell containing DNA that encodes a SARS‑CoV‑2 protein.[89][90] The viral vector-based vaccines against COVID-19 are non-replicating, meaning that they do not make new virus particles, but rather produce only the antigen which elicits a systemic immune response.[89]

Authorized vaccines of this type are the Oxford–AstraZeneca COVID-19 vaccine,[91][92][93] the Sputnik V COVID-19 vaccine,[94] Convidecia, and the Janssen COVID-19 vaccine.[95][96]

Convidecia and the Janssen COVID-19 vaccine are both one-shot vaccines which offer less complicated logistics and can be stored under ordinary refrigeration for several months.[97][98]

Sputnik V uses Ad26 for its first dose, which is the same as Janssen's only dose, and Ad5 for the second dose, which is the same as Convidecia's only dose.[99]

On 11 August 2021, the developers of Sputnik V proposed, in view of the Delta case surge, that Pfizer test the Ad26 component (termed its 'Light' version)[100] as a booster shot:

Delta cases surge in US & Israel shows mRNA vaccines need a heterogeneous booster to strengthen & prolong immune response. #SputnikV pioneered mix&match approach, combo trials & showed 83.1% efficacy vs Delta. Today RDIF offers Pfizer to start trial with Sputnik Light as booster.[101]

Inactivated virus vaccines

Inactivated vaccines consist of virus particles that are grown in culture and then killed using a method such as heat or formaldehyde to lose disease producing capacity, while still stimulating an immune response.[102]

Authorized vaccines of this type are the Chinese CoronaVac[103][104][105] and the Sinopharm BIBP[106] and WIBP vaccines; the Indian Covaxin; later this year the Russian CoviVac;[107] the Kazakhstani vaccine QazVac;[108] and the Iranian COVIran Barekat.[109] Vaccines in clinical trials include the Valneva COVID-19 vaccine.[110][unreliable source?][111]

Subunit vaccines

Subunit vaccines present one or more antigens without introducing whole pathogen particles. The antigens involved are often protein subunits, but can be any molecule that is a fragment of the pathogen.[112]

The authorized vaccines of this type are the peptide vaccine EpiVacCorona,[113] ZF2001,[67] MVC-COV1901,[114] and Corbevax.[115][116] Vaccines with pending authorizations or include the Novavax COVID-19 vaccine,[117] Soberana 02 (a conjugate vaccine), and the Sanofi–GSK vaccine.

The V451 vaccine was previously in clinical trials, which were terminated because it was found that the vaccine may potentially cause incorrect results for subsequent HIV testing.[118][119][unreliable source?]

Other types

Additional types of vaccines that are in clinical trials include virus-like particle vaccines, multiple DNA plasmid vaccines,[120][121][122][123][124][125] at least two lentivirus vector vaccines,[126][127] a conjugate vaccine, and a vesicular stomatitis virus displaying the SARS‑CoV‑2 spike protein.[128]

Scientists investigated whether existing vaccines for unrelated conditions could prime the immune system and lessen the severity of COVID-19 infection.[129] There is experimental evidence that the BCG vaccine for tuberculosis has non-specific effects on the immune system, but no evidence that this vaccine is effective against COVID-19.[130]

Vaccine types by delivery methods

Currently, all coronavirus vaccines available, regardless of the different types of technology they are based on, are administrated by injection. However, various other types of vaccine delivery methods have been studied for future coronavirus vaccines.[131]

Intranasal

Intranasal vaccines target mucosal immunity in the nasal mucosa which is a portal for viral entrance to the body.[132][133] These vaccines are designed to stimulate nasal immune factors, such as IgA.[132] In addition to inhibiting the virus, nasal vaccines provide ease of administration because no needles (and the accompanying needle phobia) are involved.[133][134] Nasal vaccines have been approved for influenza,[133][134] but not for COVID-19.

Planning and development

Since January 2020, vaccine development has been expedited via unprecedented collaboration in the multinational pharmaceutical industry and between governments.[41]

Multiple steps along the entire development path are evaluated, including:[23][135]

  • the level of acceptable toxicity of the vaccine (its safety),
  • targeting vulnerable populations,
  • the need for vaccine efficacy breakthroughs,
  • the duration of vaccination protection,
  • special delivery systems (such as oral or nasal, rather than by injection),
  • dose regimen,
  • stability and storage characteristics,
  • emergency use authorization before formal licensing,
  • optimal manufacturing for scaling to billions of doses, and
  • dissemination of the licensed vaccine.

Challenges

There have been several unique challenges with COVID-19 vaccine development.

The urgency to create a vaccine for COVID-19 led to compressed schedules that shortened the standard vaccine development timeline, in some cases combining clinical trial steps over months, a process typically conducted sequentially over several years.[136] Public health programs have been described as in "[a] race to vaccinate individuals" with the early wave vaccines.[137]

Timelines for conducting clinical research – normally a sequential process requiring years – are being compressed into safety, efficacy, and dosing trials running simultaneously over months, potentially compromising safety assurance.[136][138] As an example, Chinese vaccine developers and the government Chinese Center for Disease Control and Prevention began their efforts in January 2020,[139] and by March were pursuing numerous candidates on short timelines, with the goal to showcase Chinese technology strengths over those of the United States, and to reassure the Chinese people about the quality of vaccines produced in China.[136][140]

The rapid development and urgency of producing a vaccine for the COVID-19 pandemic was expected to increase the risks and failure rate of delivering a safe, effective vaccine.[73][74][141] Additionally, research at universities is obstructed by physical distancing and closing of laboratories.[142][143]

Vaccines must progress through several phases of clinical trials to test for safety, immunogenicity, effectiveness, dose levels and adverse effects of the candidate vaccine.[144][145] Vaccine developers have to invest resources internationally to find enough participants for Phase II–III clinical trials when the virus has proved to be a "moving target" of changing transmission rates across and within countries, forcing companies to compete for trial participants.[146] Clinical trial organizers also may encounter people unwilling to be vaccinated due to vaccine hesitancy[147] or disbelief in the science of the vaccine technology and its ability to prevent infection.[148] As new vaccines are developed during the COVID-19 pandemic, licensure of COVID-19 vaccine candidates requires submission of a full dossier of information on development and manufacturing quality.[149][150][151]

Organizations

Internationally, the Access to COVID-19 Tools Accelerator is a G20 and World Health Organization (WHO) initiative announced in April 2020.[152][153] It is a cross-discipline support structure to enable partners to share resources and knowledge. It comprises four pillars, each managed by two to three collaborating partners: Vaccines (also called "COVAX"), Diagnostics, Therapeutics, and Health Systems Connector.[154] The WHO's April 2020 "R&D Blueprint (for the) novel Coronavirus" documented a "large, international, multi-site, individually randomized controlled clinical trial" to allow "the concurrent evaluation of the benefits and risks of each promising candidate vaccine within 3–6 months of it being made available for the trial." The WHO vaccine coalition will prioritize which vaccines should go into Phase II and III clinical trials, and determine harmonized Phase III protocols for all vaccines achieving the pivotal trial stage.[155]

National governments have also been involved in vaccine development. Canada announced funding of 96 projects for development and production of vaccines at Canadian companies and universities with plans to establish a "vaccine bank" that could be used if another coronavirus outbreak occurs,[156] and to support clinical trials and develop manufacturing and supply chains for vaccines.[157]

China provided low-rate loans to one vaccine developer through its central bank, and "quickly made land available for the company" to build production plants.[138] Three Chinese vaccine companies and research institutes are supported by the government for financing research, conducting clinical trials, and manufacturing.[158]

The United Kingdom government formed a COVID-19 vaccine task force in April 2020 to stimulate local efforts for accelerated development of a vaccine through collaborations of industry, universities, and government agencies. The UK's Vaccine Taskforce contributed to every phase of development from research to manufacturing.[159]

In the United States, the Biomedical Advanced Research and Development Authority (BARDA), a federal agency funding disease-fighting technology, announced investments to support American COVID-19 vaccine development, and manufacture of the most promising candidates.[138][160] In May 2020, the government announced funding for a fast-track program called Operation Warp Speed.[161][162] By March 2021, BARDA had funded an estimated $19.3 billion in COVID-19 vaccine development.[163]

Large pharmaceutical companies with experience in making vaccines at scale, including Johnson & Johnson, AstraZeneca, and GlaxoSmithKline (GSK), formed alliances with biotechnology companies, governments, and universities to accelerate progression toward effective vaccines.[138][136]

History

COVID‑19 vaccine research samples in a NIAID lab freezer (30 January 2020)

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the virus that causes COVID-19, was isolated in late 2019.[164] Its genetic sequence was published on 11 January 2020, triggering the urgent international response to prepare for an outbreak and hasten development of a preventive COVID-19 vaccine.[165][166][167] Since 2020, vaccine development has been expedited via unprecedented collaboration in the multinational pharmaceutical industry and between governments.[168] By June 2020, tens of billions of dollars were invested by corporations, governments, international health organizations, and university research groups to develop dozens of vaccine candidates and prepare for global vaccination programs to immunize against COVID‑19 infection.[166][169][170][171] According to the Coalition for Epidemic Preparedness Innovations (CEPI), the geographic distribution of COVID‑19 vaccine development shows North American entities to have about 40% of the activity, compared to 30% in Asia and Australia, 26% in Europe, and a few projects in South America and Africa.[165][168]

In February 2020, the World Health Organization (WHO) said it did not expect a vaccine against SARS‑CoV‑2 to become available in less than 18 months.[172] Virologist Paul Offit commented that, in hindsight, the development of a safe and effective vaccine within 11 months was a remarkable feat.[173] The rapidly growing infection rate of COVID‑19 worldwide during 2020 stimulated international alliances and government efforts to urgently organize resources to make multiple vaccines on shortened timelines,[174] with four vaccine candidates entering human evaluation in March (see COVID-19 vaccine § Trial and authorization status).[165][175]

On 24 June 2020, China approved the CanSino vaccine for limited use in the military, and two inactivated virus vaccines for emergency use in high-risk occupations.[176] On 11 August 2020, Russia announced the approval of its Sputnik V vaccine for emergency use, though one month later only small amounts of the vaccine had been distributed for use outside of the phase 3 trial.[177]

The Pfizer–BioNTech partnership submitted an Emergency Use Authorization (EUA) request to the U.S. Food and Drug Administration (FDA) for the mRNA vaccine BNT162b2 (active ingredient tozinameran) on 20 November 2020.[178][179] On 2 December 2020, the United Kingdom's Medicines and Healthcare products Regulatory Agency (MHRA) gave temporary regulatory approval for the Pfizer–BioNTech vaccine,[180][181] becoming the first country to approve the vaccine and the first country in the Western world to approve the use of any COVID‑19 vaccine.[182][183][184] As of 21 December 2020, many countries and the European Union[185] had authorized or approved the Pfizer–BioNTech COVID‑19 vaccine. Bahrain and the United Arab Emirates granted emergency marketing authorization for the Sinopharm BIBP vaccine.[186][187] On 11 December 2020, the FDA granted an EUA for the Pfizer–BioNTech COVID‑19 vaccine.[188] A week later, they granted an EUA for mRNA-1273 (active ingredient elasomeran), the Moderna vaccine.[189][190][191][192]

On 31 March 2021, the Russian government announced that they had registered the first COVID‑19 vaccine for animals.[193] Named Carnivac-Cov, it is an inactivated vaccine for carnivorous animals, including pets, aimed at preventing mutations that occur during the interspecies transmission of SARS-CoV-2.[194]

Despite the extremely rapid development of effective mRNA and viral vector vaccines, worldwide vaccine equity has not been achieved. The ongoing development and use of whole inactivated virus (WIV) and protein-based vaccines has been recommended, especially for use in developing countries, to dampen further waves of the pandemic.[195][196]

Effectiveness

As of August 2021, studies reported that the COVID-19 vaccines available in the United States are "highly protective against severe illness, hospitalization, and death due to COVID-19".[197] In comparison with fully vaccinated people, the CDC reported that unvaccinated people were 10 times more likely to be hospitalized and 11 times more likely to die.[198][199]

Dr. Jeff Duchin, the Health Officer of King County, Washington found that unvaccinated people were six times more likely to test positive, 37 times more likely to be hospitalized, and 67 times more likely to die, compared to those who had been vaccinated.[200]

CDC reported that vaccine effectiveness fell from 91% against Alpha to 66% against Delta.[201] One expert stated that "those who are infected following vaccination are still not getting sick and not dying like was happening before vaccination."[202] By late August 2021 the Delta variant accounted for 99 percent of U.S. cases and was found to double the risk of severe illness and hospitalization for those not yet vaccinated.[203]

A September 2021 study published in The Lancet found that having two doses of a COVID-19 vaccine halved the odds of long COVID.[204]

In November 2021, a study by the ECDC estimated that 470,000 lives over the age of 60 had been saved since the start of vaccination roll-out in the European region.[205]

On 10 December 2021, the UK Health Security Agency reported that early data indicated a 20- to 40-fold reduction in neutralizing activity for Omicron by sera from Pfizer 2-dose vaccinees relative to earlier strains. After a booster dose (usually with an mRNA vaccine),[206] vaccine effectiveness against symptomatic disease was at 70%–75%, and the effectiveness against severe disease was expected to be higher.[207]

According to early December 2021 CDC data, "unvaccinated adults were about 97 times more likely to die from COVID-19 than fully vaccinated people who had received boosters".[208]

A meta analysis looking into COVID-19 vaccine differences in immunosuppressed individuals found that people with a weakened immune system, are less able to produce neutralizing antibodies. For example, organ transplant recipients needing three vaccines to achieve seroconversion.[209] A study on the serologic response to mRNA vaccines among patients with lymphoma, leukemia and myeloma found that one-quarter of patients did not produce measurable antibodies, varying by cancer type.[210]

An April 2022 study published in JAMA Network Open found that natural immunity offered similar protection from mild and severe cases of COVID-19 as the vaccines.[211]

Waning effectiveness

In English care homes, elderly residents' protection against severe illness, hospitalization and death was high immediately after vaccination, but protection declined significantly in the months following vaccination. Protection among care home staff, who were younger, declined much more slowly. Regular boosters are recommended for older people and boosters every six months for care home residents appear reasonable.[212]

Effectiveness against transmission

Fully vaccinated individuals with breakthrough infections have peak viral load similar to unvaccinated cases and can efficiently transmit infection in household settings.[213]

Adverse events

For most people, the side effects, also called adverse effects, from COVID-19 vaccines are mild and can be managed at home.

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 introduction of a foreign substance into the body.[214] 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.[10][11] Also 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.[215] These side effects are less common or weaker in inactivated vaccines.[215]

COVID-19 vaccines are not associated with a higher risk of adverse effects during pregnancy or while breastfeeding.[12][13][14] Temporary changes to the menstrual cycle in young women have been reported, although these changes are "small compared with natural variation and quickly reverse".[15] 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, and they have about twice the usual risk of a clinically significant delay (about 10% of these women, compared to about 4% of unvaccinated women).[15] Cycle lengths return to normal after two menstrual cycles post-vaccination.[15] Women who received doses in separate cycles had approximately the same natural variation in cycle lengths as unvaccinated women.[15] Other temporary menstrual effects have been reported, such as heavier than normal menstrual bleeding after vaccination.[15]

Serious adverse events associated COVID-19 vaccines are generally rare but of high interest to the public.[16] The official databases of reported adverse events include the World Health Organization's VigiBase, the United States Vaccine Adverse Events Reporting System (VAERS) and the United Kingdom's Yellow Card Scheme. Increased public awareness of these reporting systems and the extra reporting requirements under US FDA Emergency Use Authorization rules have resulted in an increased volume of reported adverse events.[216]

Rare serious effects include:

Because COVID-19 vaccines are relatively new, new claims about possible side effects are still being made, and sometimes reports conflict.[17] For example, there are rare reports of subjective hearing changes, including tinnitus, after vaccination,[218] but these claims have not yet been substantiated in subsequent research.[17]

The rate and type of side effects is also compared to the alternatives. For example, although vaccination may trigger some side effects, the alternative of natural infection is much worse. Neurological side effects from getting COVID-19 are hundreds of times more likely than from vaccination.[219]

Mix and match

According to studies, the combination of two different COVID-19 vaccines, also called cross vaccination or mix-and-match method, provides protection equivalent to that of mRNA vaccines – including protection against the Delta variant. Individuals who receive the combination of two different vaccines produce strong immune responses, with side effects no worse than those caused by standard regimens.[220]

Duration of immunity

Available data show that fully vaccinated individuals and those previously infected with SARS-CoV-2 have a low risk of subsequent infection for at least 6 months.[221][222][223] Data are currently insufficient to determine an antibody titer threshold that indicates when an individual is protected from infection. Multiple studies show that antibody titers are associated with protection at the population level, but individual protection titers remain unknown. For some populations, such as the elderly and the immunocompromised, protection levels may be reduced after both vaccination and infection. Finally, current data suggest that the level of protection may not be the same for all variants of the virus.[221]

As new data continue to emerge,[224] recommendations will need to be updated periodically. It is important to note that at this time, there is no authorized or approved test that providers or the public can use to reliably determine if a person is protected from infection.[221]

Society and culture

Distribution

Note about table to the right: Number and percentage of people who have received at least one dose of a COVID-19 vaccine (unless noted otherwise). May include vaccination of non-citizens, which can push totals beyond 100% of the local population. Table is updated daily by a bot.[note 2]

Updated June 29, 2022.
COVID-19 vaccine distribution by country[225]
Location Vaccinated[b] Percent[c]
World[d][e] 5,270,851,525 66.93%
China China[f] 1,294,045,000 89.60%
India India 1,016,119,457 72.92%
European Union European Union[g] 337,575,706 75.49%
United States United States[h] 259,426,758 78.14%
Brazil Brazil 216,368,592 101.11%
Indonesia Indonesia 201,000,560 72.73%
Pakistan Pakistan 136,961,847 60.82%
Bangladesh Bangladesh 129,343,045 77.78%
Japan Japan 103,755,699 82.31%
Mexico Mexico 88,336,802 67.81%
Vietnam Vietnam 86,238,110 87.85%
Russia Russia 81,771,142 56.04%
Philippines Philippines 75,286,371 67.80%
Germany Germany 64,697,198 77.11%
Iran Iran 64,545,209 75.91%
Turkey Turkey 57,857,831 68.03%
Thailand Thailand 56,696,337 81.05%
France France 54,452,352 80.76%
United Kingdom United Kingdom 53,568,338 78.54%
Italy Italy[i] 50,801,764 84.15%
Egypt Egypt 49,617,353 47.59%
South Korea South Korea 45,067,332 87.84%
Colombia Colombia 42,418,509 82.74%
Spain Spain 41,254,310 88.25%
Argentina Argentina 41,153,979 90.24%
Myanmar Myanmar 33,004,742 60.22%
Canada Canada 32,773,313 86.09%
Peru Peru 29,494,496 88.41%
Ethiopia Ethiopia 29,380,780 24.93%
Nigeria Nigeria 28,340,766 13.41%
Malaysia Malaysia 28,037,371 85.54%
Saudi Arabia Saudi Arabia 26,713,922 75.59%
Morocco Morocco 24,946,369 66.80%
Nepal Nepal 22,995,709 77.49%
Poland Poland 22,734,350 60.15%
Australia Australia 22,348,768 86.66%
Mozambique Mozambique 22,184,668 68.98%
Venezuela Venezuela 22,157,232 77.19%
South Africa South Africa 22,015,067 36.67%
Taiwan Taiwan 21,172,341 88.75%
Uzbekistan Uzbekistan 19,611,361 57.79%
Chile Chile 17,999,320 93.69%
Sri Lanka Sri Lanka 17,073,712 79.42%
Uganda Uganda 16,032,667 34.02%
Ukraine Ukraine 15,729,617 36.19%
Ecuador Ecuador 15,182,320 84.87%
Cambodia Cambodia 15,068,135 88.92%
Netherlands Netherlands 12,804,977 74.56%
Angola Angola 12,700,926 37.43%
Kenya Kenya 12,641,679 22.99%
Iraq Iraq 10,833,447 26.31%
Cuba Cuba 10,678,561 94.35%
Ghana Ghana 10,352,002 32.62%
United Arab Emirates United Arab Emirates 9,991,089 100.00%
Portugal Portugal 9,722,534 95.62%
Kazakhstan Kazakhstan 9,522,541 50.13%
Belgium Belgium 9,247,662 79.50%
Rwanda Rwanda 9,076,533 68.37%
Guatemala Guatemala 8,294,525 45.45%
Algeria Algeria 8,210,605 18.40%
Romania Romania 8,175,103 42.74%
Ivory Coast Ivory Coast 8,026,397 29.67%
Greece Greece 7,918,960 76.36%
Sweden Sweden 7,838,695 77.15%
Tanzania Tanzania 7,588,592 12.34%
Dominican Republic Dominican Republic 7,235,324 66.05%
Tunisia Tunisia 7,234,385 60.61%
Bolivia Bolivia 7,229,825 61.10%
Czech Republic Czech Republic 6,965,223 64.95%
Austria Austria 6,830,332 75.53%
Hong Kong Hong Kong 6,740,395 89.24%
Israel Israel 6,712,156 72.24%
Belarus Belarus 6,425,755 68.05%
Hungary Hungary 6,411,384 66.55%
Zimbabwe Zimbabwe 6,314,124 41.84%
Honduras Honduras 6,293,459 62.54%
Switzerland Switzerland 6,087,852 69.85%
Sudan Sudan 5,929,766 13.20%
Nicaragua Nicaragua 5,917,353 88.29%
Laos Laos 5,817,695 78.84%
Afghanistan Afghanistan 5,629,522 14.13%
Azerbaijan Azerbaijan 5,353,536 52.37%
Guinea Guinea 5,338,820 39.55%
Tajikistan Tajikistan 5,189,877 53.23%
Singapore Singapore 5,019,556 92.04%
Denmark Denmark 4,830,996 83.10%
Jordan Jordan 4,800,016 46.74%
El Salvador El Salvador 4,610,987 70.74%
Finland Finland 4,516,731 81.41%
Costa Rica Costa Rica 4,437,629 86.35%
Norway Norway 4,341,527 79.43%
New Zealand New Zealand 4,292,598 83.74%
Republic of Ireland Republic of Ireland 4,090,229 82.09%
Paraguay Paraguay 3,944,590 54.64%
Benin Benin 3,638,324 29.22%
Panama Panama 3,482,802 79.49%
Kuwait Kuwait 3,432,854 79.31%
Serbia Serbia 3,354,075 48.81%
Oman Oman 3,266,729 62.54%
Zambia Zambia 3,240,892 17.13%
Uruguay Uruguay 2,996,924 85.99%
Democratic Republic of the Congo Democratic Republic of the Congo 2,979,005 3.22%
Slovakia Slovakia 2,822,347 51.79%
Lebanon Lebanon 2,698,736 39.87%
Syria Syria 2,694,839 14.75%
Qatar Qatar 2,646,349 90.30%
Somalia Somalia 2,591,679 15.84%
Burkina Faso Burkina Faso 2,449,746 11.40%
Sierra Leone Sierra Leone 2,383,636 29.28%
Croatia Croatia 2,315,402 56.73%
Senegal Senegal 2,300,648 13.38%
Mongolia Mongolia 2,272,965 68.27%
Libya Libya 2,269,135 32.61%
Chad Chad 2,218,493 13.12%
Niger Niger 2,198,758 8.75%
Togo Togo 2,092,750 24.68%
Bulgaria Bulgaria 2,091,676 30.33%
Malawi Malawi 2,047,317 10.42%
State of Palestine Palestine 2,007,851 38.44%
Lithuania Lithuania 1,952,343 72.58%
Mauritania Mauritania 1,925,871 40.33%
Mali Mali 1,781,525 8.54%
Liberia Liberia 1,751,520 33.81%
Botswana Botswana 1,696,430 70.77%
Georgia (country) Georgia 1,631,237 40.99%
Kyrgyzstan Kyrgyzstan 1,570,937 23.70%
Cameroon Cameroon 1,559,801 5.73%
Latvia Latvia 1,345,920 72.09%
Albania Albania 1,325,464 46.14%
Madagascar Madagascar 1,290,584 4.54%
Slovenia Slovenia 1,265,743 60.89%
Bahrain Bahrain 1,238,289 70.83%
South Sudan South Sudan 1,164,135 10.23%
Armenia Armenia 1,128,072 38.01%
Central African Republic Central African Republic 1,124,848 22.86%
Moldova Moldova 1,081,073 26.87%
Mauritius Mauritius 977,183 76.74%
Bosnia and Herzegovina Bosnia and Herzegovina 943,394 28.91%
Lesotho Lesotho 933,825 43.25%
Kosovo Kosovo 903,615 50.70%
Estonia Estonia 863,093 65.13%
North Macedonia North Macedonia 853,737 40.99%
East Timor Timor-Leste 822,666 61.22%
Jamaica Jamaica 812,502 27.33%
Trinidad and Tobago Trinidad and Tobago 751,177 53.53%
Fiji Fiji 706,496 78.25%
Yemen Yemen 697,956 2.29%
Republic of the Congo Republic of the Congo 693,902 12.27%
Bhutan Bhutan 692,909 88.85%
Cyprus Cyprus 668,264 74.58%
Macau Macau 613,429 93.17%
Guinea-Bissau Guinea-Bissau 529,604 26.28%
Namibia Namibia 496,475 19.19%
Luxembourg Luxembourg 481,281 75.81%
Guyana Guyana 478,010 60.48%
Malta Malta 476,837 92.39%
The Gambia Gambia 449,464 18.07%
Brunei Brunei 444,293 100.63%
Maldives Maldives 398,751 73.35%
Eswatini Eswatini 387,468 33.05%
Cape Verde Cabo Verde 355,377 63.25%
Comoros Comoros 341,302 38.42%
Papua New Guinea Papua New Guinea 337,243 3.70%
Iceland Iceland 309,770 84.00%
Gabon Gabon 308,745 13.55%
Montenegro Montenegro 291,500 46.41%
Northern Cyprus Northern Cyprus 284,357 74.39%
Solomon Islands Solomon Islands 283,298 40.24%
Suriname Suriname 267,820 45.26%
Equatorial Guinea Equatorial Guinea 267,610 18.46%
Belize Belize 247,975 61.24%
Haiti Haiti 241,385 2.09%
Samoa Samoa 229,291 114.56%
Djibouti Djibouti 188,889 18.85%
New Caledonia New Caledonia 188,411 65.37%
French Polynesia French Polynesia 188,352 66.67%
Vanuatu Vanuatu 172,232 54.77%
The Bahamas Bahamas 166,471 41.94%
Barbados Barbados 162,576 56.51%
São Tomé and Príncipe Sao Tome and Principe 123,088 55.11%
Curaçao Curaçao 108,278 65.70%
Tonga Tonga 108,263 101.41%
Aruba Aruba 89,179 83.19%
Seychelles Seychelles 84,943 85.88%
Jersey Jersey 83,554 82.67%
Kiribati Kiribati 80,566 66.37%
Isle of Man Isle of Man 69,560 81.44%
Antigua and Barbuda Antigua and Barbuda 64,091 64.92%
Cayman Islands Cayman Islands 61,307 92.19%
Saint Lucia Saint Lucia 59,560 32.30%
Andorra Andorra 57,880 74.82%
Guernsey Guernsey 54,146 85.42%
Bermuda Bermuda 48,554 78.20%
Grenada Grenada 43,743 38.71%
Gibraltar Gibraltar 42,074 124.88%
Faroe Islands Faroe Islands 41,715 85.04%
Greenland Greenland 41,243 72.52%
Saint Vincent and the Grenadines Saint Vincent and the Grenadines 36,742 33.02%
Dominica Dominica 32,865 45.54%
Turkmenistan Turkmenistan 32,240 0.53%
Turks and Caicos Islands Turks and Caicos Islands 31,989 81.55%
Saint Kitts and Nevis Saint Kitts and Nevis 31,162 58.20%
Sint Maarten Sint Maarten 28,357 65.31%
Liechtenstein Liechtenstein 26,744 69.91%
Monaco Monaco 26,672 67.49%
San Marino San Marino 26,357 77.50%
British Virgin Islands British Virgin Islands 19,389 63.73%
Caribbean Netherlands Caribbean Netherlands 19,109 72.26%
Cook Islands Cook Islands 15,033 85.55%
Burundi Burundi 14,929 0.12%
Anguilla Anguilla 10,813 71.49%
Nauru Nauru 9,464 87.04%
Wallis and Futuna Wallis and Futuna 6,483 58.44%
Tuvalu Tuvalu 6,368 53.40%
Saint Helena, Ascension and Tristan da Cunha Saint Helena, Ascension and Tristan da Cunha 4,361 71.83%
Falkland Islands Falkland Islands 2,632 75.57%
Montserrat Montserrat 2,044 41.04%
Niue Niue 1,650 102.23%
Tokelau Tokelau 968 70.76%
Pitcairn Islands Pitcairn Islands 47 100.00%
North Korea North Korea 0 0.00%
  1. ^ The Oxford–AstraZeneca COVID‑19 vaccine is codenamed AZD1222,[56] and later supplied under brand names, including Vaxzevria[57] and Covishield.[58][59]
  2. ^ Number of people who have received at least one dose of a COVID-19 vaccine (unless noted otherwise).
  3. ^ Percentage of population that has received at least one dose of a COVID-19 vaccine. May include vaccination of non-citizens, which can push totals beyond 100% of the local population.
  4. ^ Countries which do not report data for a column are not included in that column's world total.
  5. ^ Vaccination Note: Countries which do not report the number of people who have received at least one dose are not included in the world total.
  6. ^ Does not include special administrative regions (Hong Kong and Macau) or Taiwan.
  7. ^ Data on member states of the European Union are individually listed, but are also summed here for convenience. They are not double-counted in world totals.
  8. ^ Vaccination Note: Includes Freely Associated States
  9. ^ Vaccination Note: Includes Vatican City

As of 18 June 2022, 11.98 billion COVID-19 vaccine doses have been administered worldwide, with 66.3 percent of the global population having received at least one dose. While 18.7 million vaccines were then being administered daily, only 17.8 percent of people in low-income countries had received at least a first vaccine by March 2022, according to official reports from national health agencies, which are collated by Our World in Data.[226]

During a pandemic on the rapid timeline and scale of COVID-19 cases in 2020, international organizations like the World Health Organization (WHO) and Coalition for Epidemic Preparedness Innovations (CEPI), vaccine developers, governments, and industry evaluated the distribution of the eventual vaccine(s).[227] Individual countries producing a vaccine may be persuaded to favor the highest bidder for manufacturing or provide first-service to their own country.[228][229][230][231][excessive citations] Experts emphasize that licensed vaccines should be available and affordable for people at the frontline of healthcare and having the most need.[228][229][231]

In April 2020, it was reported that the UK agreed to work with 20 other countries and global organizations including France, Germany, and Italy to find a vaccine and to share the results and that UK citizens would not get preferential access to any new COVID‑19 vaccines developed by taxpayer-funded UK universities.[232] Several companies planned to initially manufacture a vaccine at artificially low pricing, then increase prices for profitability later if annual vaccinations are needed and as countries build stock for future needs.[231]

An April 2020 CEPI report stated: "Strong international coordination and cooperation between vaccine developers, regulators, policymakers, funders, public health bodies, and governments will be needed to ensure that promising late-stage vaccine candidates can be manufactured in sufficient quantities and equitably supplied to all affected areas, particularly low-resource regions."[233] The WHO and CEPI are developing financial resources and guidelines for the global deployment of several safe, effective COVID‑19 vaccines, recognizing the need are different across countries and population segments.[227][234][235][236][excessive citations] For example, successful COVID‑19 vaccines would be allocated early to healthcare personnel and populations at greatest risk of severe illness and death from COVID‑19 infection, such as the elderly or densely-populated impoverished people.[237][238]

The WHO had set out the target to vaccinate 40% of the population of all countries by the end-2021 and 70% by mid-2022,[239] but many countries missed the 40% target at the end of 2021.[240][241]

Access

Countries have extremely unequal access to the COVID-19 vaccine. Vaccine equity has not been achieved, or even approximated. The inequity has harmed both countries with poor access and countries with good access.[21][22][242]

Nations pledged to buy doses of the COVID-19 vaccine before the doses were available. Though high-income nations represent only 14% of the global population, as of 15 November 2020, they had contracted to buy 51% of all pre-sold doses. Some high-income nations bought more doses than would be necessary to vaccinate their entire populations.[20]

Production of Sputnik V vaccine in Brazil, January 2021.
An elderly man receiving second dose of CoronaVac vaccine in Brazil, April 2021.
Covid vaccination for children aged 12–14 in Bhopal, India

In January 2021, WHO Director-General Tedros Adhanom Ghebreyesus warned of problems with equitable distribution: "More than 39 million doses of vaccine have now been administered in at least 49 higher-income countries. Just 25 doses have been given in one lowest-income country. Not 25 million; not 25 thousand; just 25."[243]

In March 2021, it was revealed the US attempted to convince Brazil not to purchase the Sputnik V COVID-19 vaccine, fearing "Russian influence" in Latin America.[244] Some nations involved in long-standing territorial disputes have reportedly had their access to vaccines blocked by competing nations; Palestine has accused Israel of blocking vaccine delivery to Gaza, while Taiwan has suggested that China has hampered its efforts to procure vaccine doses.[245][246][247]

A single dose of the COVID-19 vaccine by AstraZeneca would cost 47 Egyptian pounds (EGP), and the authorities are selling it between 100 and 200 EGP. A report by Carnegie Endowment for International Peace cited the poverty rate in Egypt as around 29.7 percent, which constitutes approximately 30.5 million people, and claimed that about 15 million of the Egyptians would be unable to gain access to the luxury of vaccination. A human rights lawyer, Khaled Ali, launched a lawsuit against the government, forcing them to provide vaccination free of cost to all members of the public.[248]

According to immunologist Dr. Anthony Fauci, mutant strains of the virus and limited vaccine distribution pose continuing risks and he said: "we have to get the entire world vaccinated, not just our own country."[249] Edward Bergmark and Arick Wierson are calling for a global vaccination effort and wrote that the wealthier nations' "me-first" mentality could ultimately backfire because the spread of the virus in poorer countries would lead to more variants, against which the vaccines could be less effective.[250]

In March 2021, the United States, Britain, European Union member states and some other members of the World Trade Organization (WTO) blocked a push by more than eighty developing countries to waive COVID-19 vaccine patent rights in an effort to boost production of vaccines for poor nations.[251] On 5 May 2021, the US government under President Joe Biden announced that it supports waiving intellectual property protections for COVID-19 vaccines.[252] The Members of the European Parliament have backed a motion demanding the temporary lifting of intellectual properties rights for COVID-19 vaccines.[253]

COVID-19 mass vaccination queue in Finland, June 2021.
A drive-through COVID-19 vaccination center in Iran, August 2021.

In a meeting in April 2021, the World Health Organization's emergency committee addressed concerns of persistent inequity in the global vaccine distribution.[254] Although 9 percent of the world's population lives in the 29 poorest countries, these countries had received only 0.3% of all vaccines administered as of May 2021.[255] On 15 March, Brazilian journalism agency Agência Pública reported that the country vaccinated about twice as many people who declare themselves white than black and noted that mortality from COVID-19 is higher in the black population.[256]

In May 2021, UNICEF made an urgent appeal to industrialised nations to pool their excess COVID-19 vaccine capacity to make up for a 125-million-dose gap in the COVAX program. The program mostly relied on the Oxford–AstraZeneca COVID-19 vaccine produced by Serum Institute of India, which faced serious supply problems due to increased domestic vaccine needs in India from March to June 2021. Only a limited amount of vaccines can be distributed efficiently, and the shortfall of vaccines in South America and parts of Asia are due to a lack of expedient donations by richer nations. International aid organisations have pointed at Nepal, Sri Lanka, and Maldives as well as Argentina and Brazil, and some parts of the Caribbean as problem areas, where vaccines are in short supply. In mid-May 2021, UNICEF was also critical of the fact that most proposed donations of Moderna and Pfizer vaccines were not slated for delivery until the second half of 2021, or early in 2022.[257]

In July 2021, the heads of the World Bank Group, the International Monetary Fund, the World Health Organization, and the World Trade Organization said in a joint statement: "As many countries are struggling with new variants and a third wave of COVID-19 infections, accelerating access to vaccines becomes even more critical to ending the pandemic everywhere and achieving broad-based growth. We are deeply concerned about the limited vaccines, therapeutics, diagnostics, and support for deliveries available to developing countries."[258][259] In July 2021, The BMJ reported that countries have thrown out over 250,000 vaccine doses as supply exceeded demand and strict laws prevented the sharing of vaccines.[260] A survey by The New York Times found that over a million doses of vaccine had been thrown away in ten U.S. states because federal regulations prohibit recalling them, preventing their redistribution abroad.[261] Furthermore, doses donated close to expiration often cannot be administered quickly enough by recipient countries and end up having to be discarded.[262] To help overcome this problem, the Prime Minister of India, Narendra Modi announced that they would make their digital vaccination management platform CoWIN open to the global community. He also announced that India would also release the source code for contact tracing app Aarogya Setu for developers around the world. Around 142 countries including Afghanistan, Bangladesh, Bhutan, Maldives, Guyana, Antigua & Barbuda, St. Kitts & Nevis and Zambia expressed their interest in the application for COVID management.[263][264]

Amnesty International and Oxfam International have criticized the support of vaccine monopolies by the governments of producing countries, noting that this is dramatically increasing the dose price by five times and often much more, creating an economic barrier to access for poor countries.[265][266] Médecins Sans Frontières (Doctors without Borders) has also criticized vaccine monopolies and repeatedly called from their suspension, supporting the TRIPS Waiver. The waiver was first proposed in October 2020, and has support from most countries, but delayed by opposition from EU (especially Germany - major EU countries such as France, Italy and Spain support the exemption),[267] UK, Norway, and Switzerland, among others. MSF called for a Day of Action in September 2021 to put pressure on the WTO Minister's meeting in November, which was expected to discuss the TRIPS IP waiver.[268][269][270]

Inside of a vaccination center in Brussels, Belgium, February 2021.

In August 2021, to reduce unequal distribution between rich and poor countries, the WHO called for a moratorium on a booster dose at least until the end of September. However, on 18 August, the United States government announced plans to offer booster doses 8 months after the initial course to the general population, starting with priority groups. Before the announcement, the WHO harshly criticized this type of decision, citing the lack of evidence for the need for boosters, except for patients with specific conditions. At this time, vaccine coverage of at least one dose was 58% in high-income countries and only 1.3% in low-income countries, and 1.14 million Americans already received an unauthorized booster dose. US officials argued that waning efficacy against mild and moderate disease might indicate reduced protection against severe disease in the coming months. Israel, France, Germany, and the United Kingdom have also started planning boosters for specific groups.[271][272][273] On 14 September 2021, more than 140 former world leaders, and Nobel laureates, including former President of France François Hollande, former Prime Minister of the United Kingdom Gordon Brown, former Prime Minister of New Zealand Helen Clark, and Professor Joseph Stiglitz, called on the candidates to be the next German chancellor to declare themselves in favour of waiving intellectual property rules for COVID-19 vaccines and transferring vaccine technologies.[274] In November 2021, nursing unions in 28 countries have filed a formal appeal with the United Nations over the refusal of the UK, EU, Norway, Switzerland, and Singapore to temporarily waive patents for Covid vaccines.[275]

During his first international trip, President of Peru Pedro Castillo spoke at the seventy-sixth session of the United Nations General Assembly on 21 September 2021, proposing the creation of an international treaty signed by world leaders and pharmaceutical companies to guarantee universal vaccine access, arguing "The battle against the pandemic has shown us the failure of the international community to cooperate under the principle of solidarity".[276][277]

Optimizing the societal benefit of vaccination may benefit from a strategy that is tailored to the state of the pandemic, the demographics of a country, the age of the recipients, the availability of vaccines, and the individual risk for severe disease: In the UK, the interval between prime and boost dose was extended to vaccinate as many persons as early as possible,[278] many countries are starting to give an additional booster shot to the immunosuppressed[279][280] and the elderly,[281] and research predicts an additional benefit of personalizing vaccine dose in the setting of limited vaccine availability when a wave of virus Variants of Concern hits a country.[282]

Despite the extremely rapid development of effective mRNA and viral vector vaccines, vaccine equity has not been achieved.[21] The World Health Organization called for 70 per cent of the global population to be vaccinated by mid-2022, but as of March 2022 it was estimated that only one per cent of the 10 billion doses given worldwide had been administered in low-income countries.[283] An additional 6 billion vaccinations may be needed to fill vaccine access gaps, particularly in developing countries. Given the projected availability of the newer vaccines, the development and use of whole inactivated virus (WIV) and protein-based vaccines are also recommended. Organizations such as the Developing Countries Vaccine Manufacturers Network could help to support the production of such vaccines in developing countries, with lower production costs and greater ease of deployment.[21][284]

While vaccines substantially reduce the probability and severity of infection, it is still possible for fully vaccinated people to contract and spread COVID-19.[285] Public health agencies have recommended that vaccinated people continue using preventive measures (wear face masks, social distance, wash hands) to avoid infecting others, especially vulnerable people, particularly in areas with high community spread. Governments have indicated that such recommendations will be reduced as vaccination rates increase and community spread declines.[286]

Economics

Moreover, an unequal distribution of vaccines will deepen inequality and exaggerate the gap between rich and poor and will reverse decades of hard-won progress on human development.
— United Nations, COVID vaccines: Widening inequality and millions vulnerable[287]

Vaccine inequity damages the global economy, disrupting the global supply chain.[242] Most vaccines were being reserved for wealthy countries, as of September 2021,[287] some of which have more vaccine than is needed to fully vaccinate their populations.[20] When people, undervaccinated, needlessly die, experience disability, and live under lockdown restrictions, they cannot supply the same goods and services. This harms the economies of undervaccinated and overvaccinated countries alike. Since rich countries have larger economies, rich countries may lose more money to vaccine inequity than poor ones,[242] though the poor ones will lose a higher percentage of GDP and suffer longer-term effects.[288] High-income countries would profit an estimated US$4.80 for every $1 spent on giving vaccines to lower-income countries.[242]

The International Monetary Fund sees the vaccine divide between rich and poor nations as a serious obstacle to a global economic recovery.[289] Vaccine inequity disproportionately affects refuge-providing states, as they tend to be poorer, and refugees and displaced people are economically more vulnerable even within those low-income states, so they have suffered more economically from vaccine inequity.[290][21]

Liability

Several governments agreed to shield pharmaceutical companies like Pfizer and Moderna from negligence claims related to COVID-19 vaccines (and treatments), as in previous pandemics, when governments also took on liability for such claims.

In the US, these liability shields took effect on 4 February 2020, when the US Secretary of Health and Human Services Alex Azar published a notice of declaration under the Public Readiness and Emergency Preparedness Act (PREP Act) for medical countermeasures against COVID-19, covering "any vaccine, used to treat, diagnose, cure, prevent, or mitigate COVID-19, or the transmission of SARS-CoV-2 or a virus mutating therefrom". The declaration precludes "liability claims alleging negligence by a manufacturer in creating a vaccine, or negligence by a health care provider in prescribing the wrong dose, absent willful misconduct." In other words, absent "willful misconduct", these companies can not be sued for money damages for any injuries that occur between 2020 and 2024 from the administration of vaccines and treatments related to COVID-19.[291] The declaration is effective in the United States through 1 October 2024.[291]

In December 2020, the UK government granted Pfizer legal indemnity for its COVID-19 vaccine.[292]

In the European Union, the COVID-19 vaccines are licensed under a conditional marketing authorization which does not exempt manufacturers from civil and administrative liability claims.[293] While the purchasing contracts with vaccine manufacturers remain secret, they do not contain liability exemptions even for side-effects not known at the time of licensure.[294]

The Bureau of Investigative Journalism, a nonprofit news organization, reported in an investigation that unnamed officials in some countries, such as Argentina and Brazil, said that Pfizer demanded guarantees against costs of legal cases due to adverse effects in the form of liability waivers and sovereign assets such as federal bank reserves, embassy buildings or military bases, going beyond the expected from other countries such as the US.[295] During the pandemic parliamentary inquiry in Brazil, Pfizer's representative said that its terms for Brazil are the same as for all other countries with which it has signed deals.[296]

Controversy

In June 2021, a report revealed that the UB-612 vaccine, developed by the US-based COVAXX, was a for-profit venture initiated by the Blackwater founder Erik Prince. In a series of text messages to Paul Behrends, the close associate recruited for the COVAXX project, Prince described the profit-making possibilities in selling the COVID-19 vaccines. COVAXX provided no data from the clinical trials on safety or efficacy it conducted in Taiwan. The responsibility of creating distribution networks was assigned to an Abu Dhabi-based entity, which was mentioned as "Windward Capital" on the COVAXX letterhead but was actually Windward Holdings. The firm's sole shareholder, which handled "professional, scientific and technical activities", was Erik Prince. In March 2021, COVAXX raised $1.35 billion in a private placement.[297]

Misinformation and hesitancy

A protest against COVID-19 vaccination in London, United Kingdom
Anti-vaccination activists and other people in many countries have spread a variety of unfounded conspiracy theories and other misinformation about COVID-19 vaccines based on misunderstood or misrepresented science, religion, exaggerated claims about side effects, a story about COVID-19 being spread by 5G , misrepresentations about how the immune system works and when and how COVID-19 vaccines are made, and other false or distorted information. This misinformation has proliferated and may have made many people averse to vaccination.[298] This has led to governments and private organizations around the world introducing measures to incentivize/coerce vaccination, such as lotteries,[299] mandates[300] and free entry to events,[301] which has in turn led to further misinformation about the legality and effect of these measures themselves.[302]

See also

Notes

  1. ^ Our World in Data (OWID) vaccination maps. Click on the download tab to download the map. The table tab has a table of the exact data by country. The source tab says the data is from verifiable public official sources Archived 21 December 2021 at the Wayback Machine collated by Our World in Data. The map at the source is interactive and provides more detail. Run your cursor over the color bar legend to see the countries that apply to that point in the legend. There is an OWID vaccination info FAQ Archived 10 March 2021 at the Wayback Machine.
  2. ^ The table data is automatically updated daily by a bot; see Template:COVID-19 data for more information. Scroll down past the table to find the documentation and the main reference. See also: Category:Automatically updated COVID-19 pandemic table templates.

References

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  2. ^ Subbarao K (July 2021). "The success of SARS-CoV-2 vaccines and challenges ahead". Cell Host & Microbe. 29 (7): 1111–1123. doi:10.1016/j.chom.2021.06.016. PMC 8279572. PMID 34265245.
  3. ^ Padilla TB (24 February 2021). "No one is safe unless everyone is safe". BusinessWorld. Archived from the original on 23 February 2021. Retrieved 24 February 2021.
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  5. ^ Vergano D (5 June 2021). "COVID-19 Vaccines Work Way Better Than We Had Ever Expected. Scientists Are Still Figuring Out Why". BuzzFeed News. Archived from the original on 6 October 2021. Retrieved 24 June 2021.
  6. ^ Mallapaty S, Callaway E, Kozlov M, Ledford H, Pickrell J, Van Noorden R (December 2021). "How COVID vaccines shaped 2021 in eight powerful charts". Nature. 600 (7890): 580–583. Bibcode:2021Natur.600..580M. doi:10.1038/d41586-021-03686-x. PMID 34916666. S2CID 245262732.
  7. ^ Watson OJ, Barnsley G, Toor J, Hogan AB, Winskill P, Ghani AC (23 June 2022). "Global impact of the first year of COVID-19 vaccination: a mathematical modelling study". The Lancet Infectious Diseases. doi:10.1016/s1473-3099(22)00320-6. ISSN 1473-3099. PMC 9225255.
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