Vaccines are available under temporary emergency-use or conditional marketing authorizations in various countries. This is not a full marketing authorization or approval.
Immunization programs are generally prioritizing people who are at highest risk from serious disease or death (e.g., residents and staff in care homes, older people, healthcare workers, and those with underlying health conditions). However, priorities differ between countries and you should consult local guidance.
Protection starts around 14 days after vaccination, and vaccination may not protect all vaccine recipients. It is unknown whether vaccines prevent asymptomatic infection or transmission from individuals who are infected despite vaccination. Vaccinated people should continue to follow public health recommendations. Safety and efficacy, including duration of immunity, beyond 2 months is unknown. Advice will be updated as information on the impact of vaccination on virus transmission and indirect protection in the community is assessed. See Vaccine efficacy real world data below for more information.
Surveillance of adverse events is extremely important, and may reveal additional, less frequent serious adverse events not detected in clinical trials.
Safety signals regarding thrombotic events with thrombocytopenia and anaphylaxis have been reported outside of clinical trials so far. See specific sections below for more detailed information.
The mRNA vaccines have not been authorized for use in humans previously, so there is no long-term safety and efficacy data available for these types of vaccines.
Report all suspected adverse reactions via your local reporting system.
Laboratory-confirmed cases of COVID-19 have been reported after vaccination.
Symptoms can be mistaken for vaccine-related adverse effects in the initial days after vaccination. Have a high level of suspicion of reported symptoms and avoid dismissing complaints as vaccine-related until vaccine recipients are tested and true infection is ruled out.
Vaccine dose schedules may differ across locations.
The World Health Organization (WHO) recommends that countries experiencing exceptional epidemiologic circumstances may consider delaying the administration of the second dose of mRNA vaccines for a short period (up to 42 days based on currently available clinical trial data) as a pragmatic approach to maximizing the number of individuals benefiting from a first dose while vaccine supply continues to increase. However, evidence for this extension is not strong. Countries should ensure that any such program adjustments to dose intervals do not affect the likelihood of receiving the second dose. The WHO does not support altering doses. The WHO recommends an interval of 8 to 12 weeks (rather than 4-12 weeks as the manufacturer recommends) between the two doses of the AstraZeneca vaccine, in light of the observation that two-dose efficacy and immunogenicity increase with a longer interdose interval.
In the UK, the Joint Committee on Vaccination and Immunisation recommends that delivery of the first dose of any vaccine to as many eligible individuals as possible should be initially prioritized over delivery of a second dose. However, there is a lack of evidence to support an extended dose interval between the first and second dose, and this is outside of the manufacturer's authorized dose recommendations.
In the US, the Centers for Disease Control and Prevention recommends that the second dose of an mRNA vaccine can be scheduled for up to 6 weeks after the first dose if the recommended dosing interval cannot be met. The agency continues to emphasize that the second dose should be given as close to the recommended interval as possible, and states that the two mRNA vaccines that are available in the US may be considered interchangeable in exceptional circumstances.
There have been suggestions about extending the length of time between doses, reducing the number of doses, changing the dose (half-dose), or mixing and matching different COVID-19 vaccines in order to vaccinate more people. However, there is no evidence to support these strategies as yet. Clinical trials have started in the UK to determine whether different vaccines may be used for the 2-dose regimen.
Consult local guidelines before administering vaccines. Patients must give free and voluntary informed consent prior to vaccination.
The tables below compare the vaccines that have been authorized for use in the US.
In addition to these, the AstraZeneca COVID-19 vaccine (a chimpanzee adenovirus vector vaccine that carries the genetic code for the severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] spike protein) has been authorized in many countries, CoronaVac® and Covilo® (inactivated version of the SARS-CoV-2 virus) have been authorized in China, Covaxin® (inactivated version of the SARS-CoV-2 virus) has been authorized in India, and Sputnik V® (an adenovirus vector vaccine) has been authorized in Russia and is 91.6% effective.
Sinopharm’s Covilo® vaccine has also been authorized by the World Health Organization for global use in adults ≥18 years of age (two-dose regimen with an interval of 3 to 4 weeks between doses). A large multi-country phase 3 trial has shown that two doses, administered at an interval of 21 days, have an efficacy of 79% against symptomatic infection 14 or more days after the second dose.
Several other vaccine candidates are still in development including mRNA vaccines, DNA vaccines, viral vector vaccines, protein subunit vaccines, live-attenuated vaccines, inactivated virus vaccines, and intranasal delivery systems.
Thrombosis with thrombocytopenia syndrome (TTS)
Thromboembolic events with thrombocytopenia have been reported in a small number of people after receiving the AstraZeneca and Janssen vaccines during post-authorization use.
Regulatory agencies have confirmed that a causal relationship between the vaccines and the occurrence of TTS is plausible based on current information. However, this is yet to be confirmed, and further research is required. Both vaccines use an adenovirus vector system. Evidence to date does not suggest that these vaccines cause venous thromboembolism without thrombocytopenia.
Several countries temporarily paused the use of these vaccines while the safety signal was investigated. While use of the AstraZeneca vaccine has now resumed in most countries, some countries have permanently stopped its use in their immunization programs (e.g., Norway). Use of the Janssen vaccine has now resumed in Europe and the US, with a warning added to the vaccine’s labels about the risk of TTS, particularly in women ages 18 to 49 years. However, some countries have permanently stopped the use of the Janssen vaccine in their immunization programs (e.g., Norway).
There has been no safety signal for TTS following receipt of mRNA COVID-19 vaccines, although a small number of cases have been reported and the European Medicines Agency continues to closely monitor the situation.
Also known as vaccine-induced prothrombotic immune thrombocytopenia (VIPIT), vaccine-induced immune thrombotic thrombocytopenia (VITT), and vaccine-induced thrombosis and thrombocytopenia (VITT).
Blood clots occur in unusual sites.
The very rare types of thrombosis reported include cerebral venous sinus thrombosis, splanchnic vein thrombosis, and arterial thrombosis, together with thrombocytopenia and sometimes bleeding. Multifocal venous and arterial thromboses have also been reported in serious cases. Although rare, these events can rapidly progress and may be life-threatening or fatal.
Most cases occur in younger people after the first dose.
Data suggest that there is a slightly higher incidence reported in younger adult age groups.
Risk factors have not been identified, and there is limited experience with the second dose.
These events are very rare.
Monitoring of the Yellow Card reporting system in the UK has detected 242 reports of TSS mostly after the first dose of the AstraZeneca vaccine, including 93 cases of cerebral venous sinus thrombosis and 149 cases of thrombosis in other major veins, with 49 deaths (as of 28 April 2021). The overall risk in the UK has currently been estimated to be 10.5 per million people who receive the vaccine.
A total of 17 cases of TTS have been reported with the Janssen vaccine to VAERS (as of 21 April 2021). All of these cases occurred in women between the ages of 18 and 59, with a symptom onset between 6 and 15 days after vaccination. The overall risk has currently been estimated to be 1.9 per million people who receive the vaccine, with the risk increasing to 7 per million in women ages 18 to 49 years.
A study in Denmark and Norway reported 11 excess venous thromboembolic events per 100,000 vaccinations, including 2.5 excess cerebral venous thrombosis events per 100,000 vaccinations with the AstraZeneca vaccine.
It is thought to be triggered by an immune response.
There are now age-related prescribing restrictions for the vaccines in some countries.
The Joint Committee on Vaccination and Immunisation (JCVI) in the UK advises that it is preferable for adults ages 30 to 39 years without underlying health conditions to receive an alternative to the AstraZeneca vaccine, where available, and only if this does not cause substantial delays in being vaccinated. The JCVI also advises that it is preferable for adults ages <30 years without underlying health conditions that put them at higher risk of severe disease to be offered an alternative vaccine. All recipients should be fully informed about the benefits and risks of vaccination.
Consult local guidelines for more information on prescribing restrictions in your country.
There are now additional contraindications, warnings, and cautions to using the vaccines in some countries.
The AstraZeneca vaccine is contraindicated in patients with a history of heparin-induced thrombocytopenia and thrombosis (HITT or HIT type 2). Only consider administration of the AstraZeneca vaccine in patients with a history of cerebral venous sinus thrombosis or antiphospholipid syndrome when the potential benefits outweigh the potential risks. Patients who have experienced major venous and arterial thrombosis occurring with thrombocytopenia following vaccination with any COVID-19 vaccine should not receive a second dose of the AstraZeneca vaccine.
The European Medicines Agency and the US Centers for Disease Control and Prevention have recommended that a warning about the risk of TTS be added to the product information for the Janssen vaccine, particularly in women ages 18 to 49 years. However, there are no new contraindications or cautions at this point in time.
Pregnancy predisposes to thrombosis; therefore, women should discuss whether the benefits of having the vaccine outweigh the risks for them with their healthcare professional.
Be alert to the signs and symptoms of TTS.
Advise vaccine recipients who experience any severe symptoms (e.g., dyspnea, chest pain, leg swelling, persistent abdominal pain, neurologic symptoms such as severe and persistent headaches or blurred vision, tiny blood spots under the skin beyond the site of the injection) from around 4 to 20 days after vaccination to seek urgent medical attention.
Promptly treat patients who develop TTS according to local guidelines.
There is limited information about the optimal treatment of this condition; however, management is similar to heparin-induced thrombocytopenia. Consult a hematologist.
Guidelines generally recommend ordering a complete blood count (with platelets), coagulation screen (including fibrinogen and D-dimer), blood film/peripheral smear, and platelet factor 4 enzyme-linked immunosorbent assay for any patient presenting with acute thrombosis or new-onset thrombocytopenia within 28 to 30 days of receiving a COVID-19 vaccination. Typical laboratory features include thrombocytopenia, raised D-dimer levels above the level expected for venous thromboembolism, and low fibrinogen. Antibodies to platelet factor 4 have also been identified. Imaging studies may also be required (e.g., suspected cerebral venous sinus thrombosis).
First-line treatment is urgent administration of intravenous immune globulin. Some experts also recommend the use of corticosteroids. Anticoagulate with a nonheparin-based therapy such as a direct oral anticoagulant, fondaparinux, danaparoid, or argatroban, depending on the clinical picture. Heparin and platelet transfusions are best avoided. Plasma exchange may be considered under certain circumstances. Replace fibrinogen if needed.
Consult local guidelines for more detailed information on the diagnosis and management of this condition. All cases must be reported to local authorities.
The benefits of the vaccines continue to outweigh the risks.
The World Health Organization, the European Medicines Agency, and the Medicines and Healthcare products Regulatory Agency in the UK state that the benefits of the AstraZeneca vaccine continue to outweigh the risks.
Vaccines and allergic or vasovagal reactions
Severe allergic reactions, including anaphylaxis, have been reported outside of clinical trials in the general population after vaccination.
In the US, monitoring by the VAERS detected 4.7 cases of anaphylaxis per million doses of the Pfizer/BioNTech vaccine, and 2.5 cases per million doses of the Moderna vaccine as of 18 January 2021.
In the UK, monitoring of the Yellow Card reporting system has detected 283 cases of anaphylaxis with the Pfizer/BioNTech vaccine, and 590 cases of anaphylaxis with the AstraZeneca vaccine (as of 28 April 2021).
It has been suggested that reactions after vaccines may be due to the presence of lipid pegylated ethylene glycol (PEG), or PEG derivatives such as polysorbates.
The WHO recommends that a history of anaphylaxis to any component of the vaccine is a contraindication to vaccination for all vaccines. People with an immediate anaphylactic allergic reaction to the first dose of two-dose regimens should not receive additional doses. Administer vaccines only in settings where anaphylaxis can be treated, and observe for at least 15 minutes after vaccination.
The WHO recommends people with an immediate nonanaphylactic allergic reaction to the first dose of an mRNA vaccine (i.e. urticaria, angioedema, or respiratory symptoms such as cough, stridor, or wheezing without any other symptoms within 4 hours of administration) should not receive additional doses unless recommended after review by a health professional with specialist expertise. A history of any immediate allergic reaction to any other vaccine or injectable therapy is considered a precaution, but not a contraindication, to vaccination. Perform a risk assessment to determine the type and severity of reaction and the reliability of the information. These people may still be vaccinated, but the risks should be weighed against the benefits of vaccination, and the recipient should be observed for 30 minutes after vaccination in healthcare settings where anaphylaxis can be treated immediately. Anaphylactic reactions have also been reported in people without a history of severe allergic reactions. Food, insect venom, contact, or seasonal allergies, and allergic rhinitis, eczema, and asthma are not considered a precaution. There is no contraindication or precaution to vaccination for people with latex, egg, or gelatin allergies.
The UK-based Medicines and Healthcare products Regulatory Agency recommends that anyone with a previous history of allergic reactions to the ingredients of the vaccine should not receive it, but those with any other allergies such as a food allergy can have the vaccine.
In the US, the Centers for Disease Control and Prevention recommends that people with a contraindication to one type of the currently authorized vaccines (e.g., an mRNA vaccine) have a precaution to the other (e.g., viral vector vaccine). However, because of potential cross-reactive hypersensitivity between ingredients in mRNA and viral vector vaccines, an allergist/immunologist should be consulted to help determine whether the patient can safely receive vaccination.
Guidelines on vaccinating people with a history of allergy or anaphylaxis may differ across locations; consult local guidance.
People with a history of receiving dermal fillers may develop swelling at or near the site of filler injection (e.g., lips, face) following administration of an mRNA vaccine. This appears to be temporary and may be treated with corticosteroids. The European Medicines Agency found that there is at least a reasonable possibility of a causal association between the vaccine and the reported cases of facial swelling.
Anxiety-related reactions, including vasovagal reactions and hyperventilation, may occur. Ensure precautions are in place to avoid injury from fainting.
Vaccines and Bell palsy
There have been case reports of isolated facial paralysis after vaccination for decades with almost all viral vaccines, and it is thought to be immune-mediated or induced by viral reactivations. However, pharmacoepidemiologic studies have so far failed to identify a higher risk of facial paralysis after vaccination. When compared with other viral vaccines, mRNA COVID-19 vaccines do not appear to display a safety signal of facial paralysis, although cases have been rarely reported.
Vaccines and Guillain-Barre syndrome
The European Medicines Agency is currently assessing safety signals of Guillain-Barre syndrome with the AstraZeneca vaccine.
Vaccines and myocarditis/pericarditis
The European Medicines Agency is currently assessing safety signals of myocarditis and pericarditis with the mRNA vaccines (mainly the Pfizer/BioNTech vaccine).
Vaccines and capillary leak syndrome
The European Medicines Agency is currently reviewing a safety signal to assess reports of capillary leak syndrome in people who received the AstraZeneca vaccine.
In the UK, monitoring of the Yellow Card reporting system has detected 4 cases of capillary leak syndrome with the AstraZeneca vaccine (as of 21 April 2021).
Vaccines and specific patient populations
There are limited or no data available from clinical trials about the use of vaccines in specific patient populations. Despite this, the WHO recommends that the following populations may be vaccinated, depending on the vaccine used:
Older people (without an upper age limit)
People with comorbidities that have been identified as increasing the risk for severe disease
Immunocompromised people who are part of a group recommended for vaccination
People living with HIV who are part of a group recommended for vaccination
People with autoimmune conditions who have no contraindications to vaccination and who are part of a group recommended for vaccination
People with a history of Bell palsy who have no contraindications to vaccination
People with a history of symptomatic or asymptomatic SARS-CoV-2 infection.
Delayed vaccination is recommended in people with an acute febrile illness or current acute COVID-19 (until they are afebrile and have recovered from acute illness), and in people who previously received passive antibody therapy for COVID-19 (for at least 90 days).
Delayed vaccination may be considered in people who have had confirmed SARS-CoV-2 infection in the preceding 6 months (until near the end of this period) if, for example, there is limited vaccine supply. Emerging data indicate that symptomatic reinfection after natural infection may occur in settings where variants of concerns with evidence of immune escape are circulating. In these settings, earlier immunization after infection may be advisable.
A single dose of an mRNA vaccine has been found to elicit a rapid immune response in seropositive participants, with post-vaccination antibody titers that were similar to (or exceeded) titers found in seronegative participants who received two vaccinations.
People with previous infection have been shown to generate strong humoral and cellular responses to one dose of the Pfizer/BioNTech COVID-19 vaccine with evidence of high titers of in vitro live virus neutralization.
A preprint study found that one dose of the vaccine may be sufficient for people who have already been infected with SARS-CoV-2; however, further research is required.
The WHO recommends an individual risk–benefit assessment for very frail older people with a life expectancy anticipated to be less than 3 months. The Norwegian Medicines Agency recommends conducting more thorough evaluations of very frail older patients before vaccination, after 23 patients died shortly after receiving the Pfizer/BioNTech vaccine. However, it is currently unknown whether there is a connection between these deaths and the vaccine. The agency has investigated 13 of the deaths so far and has concluded that common adverse reactions of mRNA vaccines, such as fever, nausea, and diarrhea, may have contributed to fatal outcomes in some of the frail patients.
Vaccines and pregnant/breastfeeding women
Use caution in pregnant and breastfeeding women as there are limited safety and efficacy data available.
Preliminary data from the v-safe pregnancy registry and VAERS in the US did not show any obvious safety signals among pregnant women who received mRNA vaccines. These data have many limitations, and continued monitoring is needed to further assess the risk. Among 221 pregnancy-related adverse events reported to the VAERS, the most frequently reported event was spontaneous abortion (46 cases), followed by stillbirth, premature rupture of membranes, and vaginal bleeding (3 reports for each). No congenital anomalies were reported to the VAERS.
A small prospective study found robust secretion of SARS-CoV-2 specific immunoglobulin A (IgA) and IgG antibodies in breast milk for 6 weeks after vaccination.
Recommendations for use in pregnant and breastfeeding women vary. Consult your local guidance.
The WHO recommends not using vaccines in pregnant women, unless the benefits outweigh the potential risks (e.g., healthcare workers at high risk of exposure, women with comorbidities that place them in a high-risk group for severe disease). It recommends that women who are breastfeeding, and who are part of a group recommended for vaccination, should be offered vaccination on an equivalent basis. It does not recommend delaying pregnancy or discontinuing breastfeeding after vaccination.
Public Health England recommends that pregnant women should not routinely be vaccinated; however, vaccination may be considered when the potential benefits outweigh the potential risks for the mother and fetus. It recommends that women who are breastfeeding can receive the vaccine.
The Joint Committee on Vaccination and Immunisation (JCVI) advises that pregnant women in the UK should be offered the COVID-19 vaccine, preferably an mRNA vaccine, at the same time as the rest of the population, based on their age and clinical risk group. However, the JCVI acknowledges that more research is needed, and advises pregnant women to discuss the risk and benefits with their clinician.
The US Centers for Disease Control and Prevention recommends that pregnant women are eligible for and can receive a COVID-19 vaccine. Pregnant women who choose to receive a vaccine are encouraged to enroll in the v-safe program. CDC: v-safe COVID-19 vaccine pregnancy registry external link opens in a new window
The American College of Obstetricians and Gynecologists recommends that COVID-19 vaccines should not be withheld from pregnant or breastfeeding women who meet criteria for vaccination based on recommended priority groups. Discuss the risks and benefits with the person before vaccination. Pregnant and breastfeeding women who decline vaccination should be supported in their decision.
Vaccines and children
Vaccines are not currently authorized for use in children <12 years of age.
The US Food and Drug Administration has authorized the Pfizer/BioNTech vaccine for emergency use in adolescents ages 12 to 15 years. Authorization was based on an ongoing randomized, placebo-controlled clinical trial in the US of over 2000 participants. More than half of the participants were followed for safety for at least 2 months following the second dose. Data are yet to be published.
The European Medicines Agency is currently evaluating an application to extend the use of the Pfizer/BioNTech vaccine in young people ages 12 to 15 years.
Vaccine efficacy: real world data
Emerging observational evidence suggests real-world efficacy in reducing the rate of symptomatic or asymptomatic infection, disease severity, hospitalization, and death; however, further research is required.
A prospective cohort study (preprint) in the UK found that people ages ≥70 years who received a single dose of either the Pfizer/BioNTech or AstraZeneca vaccine had a 44% and 55% reduced risk of death, respectively, compared with unvaccinated people. There was a 69% reduced risk of death after the second dose of the Pfizer/BioNTech vaccine.
A prospective cohort study (preprint) in the UK found that effectiveness in preventing hospitalization was high in people ages ≥70 years who received a single dose of either the AstraZeneca or Pfizer/BioNTech vaccines (73% and 81%, respectively, in patients ≥80 years; 84% and 81%, respectively, in patients 70-79 years), and especially after two doses of the Pfizer/BioNTech vaccine (93% in patients ≥80 years) compared with unvaccinated people. A study in Scotland found that the first dose of the Pfizer/BioNTech vaccine was associated with a 91% reduction in hospital admissions at 28 to 34 days post-vaccination (an 88% reduction for the AstraZeneca vaccine).
A prospective cohort study (preprint) in the UK found that odds of new infection were reduced by 65% after the first dose of either the Pfizer/BioNTech or AstraZeneca vaccine compared with unvaccinated people without prior evidence of infection. A larger reduction in odds of infection was seen after the second dose (70%). There was no evidence that the benefits varied between the two vaccines.
A prospective cohort study in UK healthcare workers found that a single dose of the Pfizer/BioNTech vaccine showed effectiveness at preventing both symptomatic and asymptomatic infection of 70% at 21 days after the first dose and 85% at 7 days after two doses compared with an unvaccinated cohort. The study population was exposed to the B.1.1.7 variant.
A prospective cohort study (preprint) in the UK found that the Pfizer/BioNTech and AstraZeneca vaccines are associated with reduced likelihood of household transmission from individuals diagnosed with COVID-19 after vaccination. The secondary attack rate was reduced from 10.1% when the index case was an unvaccinated person, to 5.7% to 6.25% (depending on the vaccine) when the contact was vaccinated.
Observational studies from Israel have found that the Pfizer/BioNTech vaccine was highly effective in preventing symptomatic and asymptomatic infection, as well as hospitalizations, severe disease, need for mechanical ventilation, and death, including those caused by the B.1.1.7 variant.
Observational studies from the US have found that the Pfizer/BioNTech and Moderna vaccines were highly effective in preventing symptomatic and asymptomatic infection, as well as hospitalizations.
Vaccine efficacy: clinical trial data
Pfizer/BioNTech COVID-19 vaccine
Efficacy is based on an interim analysis of results from a phase 3 trial of 43,448 participants (with randomization to vaccine and placebo arms in a 1:1 ratio). The vaccine is reported to be 95% effective in preventing symptomatic COVID-19 after 2 doses compared with placebo (saline), in people ages 16 years and older (data on adolescents ages 12 to 15 years is yet to be published). This is based on an analysis of 170 confirmed cases of COVID-19 with an onset at least 7 days after the second dose among recipients with no evidence of existing or prior SARS-CoV-2 infection (8 cases in the vaccine arm versus 162 cases in the placebo arm). Efficacy was 52% after the first dose. Among 10 cases of severe disease with onset after the first dose, 9 cases occurred in the placebo arm and 1 case occurred in the vaccine arm. This only provides preliminary evidence of vaccine-mediated protection against severe disease.
The manufacturer reports an efficacy of 91.3% against symptomatic illness diagnosed from 1 week to 6 months after the second dose.
Preliminary studies suggest that the vaccine may be effective against new SARS-CoV-2 variants with spike protein mutations (i.e.,B.1.1.7 and B.1.351 lineages and N501Y mutations); however, neutralization of the B.1.351 variant may be weaker. Further research is required.
The manufacturer has started testing whether a third dose (booster) is safe and effective against currently circulating and emerging SARS-CoV-2 variants.
Moderna COVID-19 vaccine
Efficacy is based on an interim analysis of results from a phase 3 trial of 30,420 participants (with randomization to vaccine and placebo arms in a 1:1 ratio). The vaccine is reported to be 94.1% effective in preventing symptomatic COVID-19 after 2 doses compared with placebo (saline) in people ages 18 years and older. This is based on an analysis of 196 confirmed cases of COVID-19 with an onset at least 14 days after the second dose among recipients with no evidence of existing or prior SARS-CoV-2 infection (11 cases in the vaccine arm versus 185 cases in the placebo arm). Among 30 cases of severe disease (including one fatality) with onset after the first dose, all cases occurred in the placebo arm and none in the vaccine arm.
Antibody levels remained high in 33 adults at approximately 200 days after receiving the second dose of the vaccine in an ongoing phase 1 trial.
Preliminary studies suggest that the vaccine may be effective against new SARS-CoV-2 variants with spike protein mutations (i.e., B.1.351 and B.1.1.7 lineages). Although neutralizing antibody titers were lower for the B.1.351 variant compared with earlier SARS-CoV-2 variants, levels were expected to be protective, although this is yet to be confirmed. Further research is required. The manufacturer will test an additional booster dose to study the ability to further increase neutralizing titers against emerging strains beyond the existing primary vaccination series. It has also started clinical trials of a variant booster candidate against the B.1.351 lineage variant (known as mRNA-1273.351).
AstraZeneca COVID-19 vaccine
Efficacy is based on an interim analysis of pooled data from four ongoing randomized controlled clinical trials with 11,636 participants conducted in the UK, Brazil, and South Africa. The vaccine is reported to be 70.4% effective in preventing symptomatic COVID-19 after 2 doses compared with control (meningococcal vaccine or saline) in people ages 18 years and older. This is based on an analysis of 131 confirmed cases of COVID-19 with an onset at least 15 days after the second dose among recipients with no evidence of existing or prior SARS-CoV-2 infection (30 cases in the vaccine arm versus 101 cases in the placebo arm). Trial results are yet to be published. Among 2 cases of severe disease, all cases occurred in the control arm and none in the vaccine arm.
Vaccine efficacy appears to be higher when the interval between doses is longer. Data from a primary analysis of the clinical trials were consistent with those seen in the interim analysis, and includes results of a further month of data collection with 332 cases of symptomatic disease reported. The study found that a single standard dose provides 76% protection overall against symptomatic disease in the first 90 days after vaccination. Efficacy reached 80% after the second dose in those with a dosing interval of 12 weeks or more. However, the efficacy was only 55.1% if the two doses were given less than 6 weeks apart.
Data from the US phase 3 trial has been reported by the manufacturer. Based on an interim analysis of 32,449 participants and 141 symptomatic cases, vaccine efficacy at preventing symptomatic disease has been reported as 79%. However, the National Institutes of Health queried the accuracy of the data. The manufacturer has now presented further updated data that found an overall efficacy rate of 76%.
A study suggests that the vaccine may be effective against symptomatic infection caused by the B.1.1.7 SARS-CoV-2 variant. However, a randomized controlled trial found that a two-dose regimen did not show protection against mild to moderate disease due to the B.1.351 variant, reporting an efficacy rate of 21.9%.
Janssen COVID-19 vaccine
Efficacy is based on an interim analysis of pooled data from an ongoing randomized controlled clinical trial with 43,783 participants conducted in South Africa, South America, Mexico, and the US. The vaccine is reported to be 66.9% and 66.1% effective in preventing moderate to severe/critical disease at least 14 days and 28 days after vaccination, respectively, compared with placebo (saline) in people ages 18 years and older. Efficacy for prevention of severe/critical disease was 76.7% and 85.4% at least 14 days and 28 days after vaccination, respectively. These figures are based on an analysis of 464 confirmed cases of COVID-19 with an onset at least 14 days after vaccination among recipients with no evidence of existing or prior SARS-CoV-2 infection (116 cases in the vaccine arm versus 348 cases in the placebo arm), and 259 confirmed cases of COVID-19 with an onset at least 28 days after vaccination (66 cases in the vaccine arm versus 193 cases in the placebo arm). Vaccine efficacy was higher in the US (74%) compared with South Africa (52%). Trial results are yet to be published.
Vaccine safety: clinical trial data
Pfizer/BioNTech COVID-19 vaccine
Safety is based on an interim analysis of results from a phase 3 trial of 43,448 participants. The reactogenicity subset included 8183 participants.
Local adverse reactions were more common in the vaccine group compared with placebo, with the most common reaction being injection-site pain within 7 days after injection (83% after the first dose and 78% after the second dose in younger participants; 71% after the first dose and 66% after the second dose in older participants). Less than 1% of participants reported severe pain. Local adverse reactions were similar after the first and second doses.
Systemic adverse reactions were more common in the vaccine group compared with placebo, and were reported more often by younger patients and after the second dose. The most commonly reported systemic adverse reactions after the second dose were fatigue (59% in younger participants; 51% in older participants), headache (52% in younger participants; 39% in older participants), and fever (16% in younger participants; 11% in older participants). Severe systemic events were reported in <2% of participants after either dose, except for fatigue and headache after the second dose.
Other rare adverse events included lymphadenopathy, shoulder injury (related to vaccine administration), paroxysmal ventricular arrhythmia, and right leg paresthesia.
Moderna COVID-19 vaccine
Safety is based on an interim analysis of results from a phase 3 trial of 30,420 participants.
Solicited local and systemic adverse reactions were reported in 87.8% of participants within 7 days after the first dose in the vaccine group compared with 48% in the placebo group, and 92.2% of participants within 7 days after the second dose in the vaccine group compared with 42.8% in the placebo group. The most commonly reported solicited adverse reactions included injection-site reactions, fatigue, headache, myalgia, and arthralgia. These reactions were more commonly reported and were more severe after the second dose. Solicited adverse reactions were more common among participants ages 18 to 64 years compared with adults ages ≥65 years.
Unsolicited adverse events related to vaccination (up to 28 days after any injection) were reported in 8.2% of participants in the vaccine group compared with 4.5% in the placebo group. The incidence of severe adverse events was higher in the vaccine group compared with the placebo group (0.5% versus 0.2%). The most commonly reported unsolicited adverse events (reported in at least 1% of participants) were fatigue and headache. The relative incidence of these events was not affected by age.
Bell palsy occurred more commonly in the vaccine group (three cases) compared with the placebo group (one case), suggesting that it may be more than a chance event. This will require close monitoring as larger populations are vaccinated outside of clinical trials.
AstraZeneca COVID-19 vaccine
Safety is based on an interim analysis of pooled data from four ongoing randomized controlled clinical trials with 23,745 participants conducted in the UK, Brazil, and South Africa (trial results are yet to be published).
The most frequently reported adverse events were: injection-site reactions (>60%); headache, fatigue (>50%); myalgia, malaise (>40%); fever, chills (>30%); arthralgia, nausea (>20%). Adverse reactions were milder and reported less frequently after the second dose and in adults ages ≥65 years.
Janssen COVID-19 vaccine
Safety is based on an interim analysis of pooled data from an ongoing randomized controlled clinical trial with 43,783 participants conducted in South Africa, South America, Mexico, and the US (trial results are yet to be published). The reactogenicity subset included 6736 participants.
The most frequently reported adverse events were: injection-site reactions (48.6%); headache (38.9%); fatigue (38.2%); and myalgia (33.2%). Approximately 0.7% and 1.8% of local and systemic solicited adverse reactions, respectively, were reported as grade 3. Reports of solicited reactions were less common among participants ≥60 years of age. Other adverse reactions possibly related to the vaccine included urticaria, thromboembolic events, and tinnitus. One serious event of a hypersensitivity reaction (not classified as anaphylaxis) and one case of severe systemic reactogenicity were likely related to the vaccine.
Vaccine trial limitations
A key limitation of the data is the short duration of safety and efficacy follow-up. Trials were not sufficiently powered to detect less common adverse events reliably, and the median follow-up time was only 2 months after the second dose. Trials do not address whether the vaccine prevents transmission or affects infectiousness, and the duration of protection is yet to be determined. There are no data on children or younger adolescents, pregnant or breastfeeding women, or immunocompromised people. There are also no data to assess efficacy in populations at high risk of severe disease, in people previously infected with SARS-CoV-2, against long-term effects of disease, or against mortality.
There are concerns that the trials were not designed to detect a reduction in any serious outcome such as hospital admissions, use of intensive care, or deaths, or whether the vaccines can interrupt transmission of the virus – two key primary end points in vaccine efficacy trials. Also, since the trials have been published, important questions about final efficacy data exclusions, as well as concerns about the use of pain and fever medications, unblinding, and primary event adjudication committees have been raised.
Planned long-term follow-up of participants is unlikely to occur in the context of trials due to the ethics of following a placebo recipient long-term without offering the vaccine. This could inadvertently threaten ongoing vaccine research that is yet to define immunologic correlates of protection against COVID-19, which could vary according to the vaccine platform, individual characteristics, age groups, and population subset.
Previous trials of coronavirus vaccines identified cellular immunopathology and antibody-dependent enhancement (ADE) as potential safety issues. There are concerns over ADE of SARS-CoV-2 due to subsequent exposure to wild-type SARS-CoV-2 post vaccination and prior exposure to other coronaviruses (such as those that cause the common cold). Available data do not indicate a risk of vaccine-enhanced disease with the mRNA vaccines; however, data are limited and the risk over time, potentially associated with waning immunity, remains unknown and needs to be evaluated further.
Infection prevention and control for healthcare professionals
Always consult local infection prevention and control protocols; only basic principles are detailed here.
Immediately isolate all suspected or confirmed cases in an area that is separate from other patients. Place patients in adequately ventilated single rooms if possible. When single rooms are not available, place all cases together in the same room and ensure there is at least 3 feet (1 meter) between patients.
Implement standard precautions at all times:
Practice hand and respiratory hygiene
Give patients a medical mask to wear
Wear appropriate personal protective equipment
Practice safe waste management and environmental cleaning.
Implement additional contact and droplet precautions before entering a room where cases are admitted:
Wear a medical mask, gloves, an appropriate gown, and eye/facial protection (e.g., goggles or a face shield)
Use single-use or disposable equipment.
Implement airborne precautions when performing aerosol-generating procedures, including placing patients in a negative pressure room.
Some countries and organizations recommend airborne precautions for any situation involving the care of a COVID-19 patient.
All specimens collected for laboratory investigations should be regarded as potentially infectious.
Appropriate personal protective equipment gives healthcare workers a high level of protection against COVID-19. A cross-sectional study of 420 healthcare workers deployed to Wuhan with appropriate personal protective equipment tested negative for SARS-CoV-2 on molecular and serologic testing when they returned home, despite all participants having direct contact with COVID-19 patients and performing at least one aerosol-generating procedure. Standard surgical masks are as effective as respirator masks for preventing infection of healthcare workers in outbreaks of viral respiratory illnesses such as influenza, but it is unknown whether this applies to COVID-19.
Detailed infection prevention and control guidance is available:
Telehealth for primary care physicians
It is important that primary care physicians avoid in-person assessment of patients with suspected COVID-19 in primary care when possible to avoid infection. Most patients can be managed remotely by telephone or video consultations. Algorithms for dealing with these patients are available:
General prevention measures for the general public
Wash hands often with soap and water for at least 20 seconds or an alcohol-based hand sanitizer (that contains at least 60% alcohol), especially after being in a public place, blowing their nose, or coughing/sneezing. Avoid touching the eyes, nose, and mouth with unwashed hands
Avoid close contact with people (i.e., maintain a distance of at least 3 feet [1 meter]) including shaking hands, particularly those who are sick, have a fever, or are coughing or sneezing. Avoid going to crowded and poorly ventilated places. It is important to note that recommended distances differ between countries (for example, 6 feet [2 meters] is recommended in the US and UK) and you should consult local guidance. However, there is no evidence to support a distance of 6 feet (2 meters)
Practice respiratory hygiene (i.e., cover mouth and nose when coughing or sneezing, discard tissue immediately in a closed bin, and wash hands)
Seek medical care early if they have a fever, cough, and difficulty breathing, and share their previous travel and contact history (travelers or suspected/confirmed cases) with their healthcare provider
Stay at home and self-isolate if they are sick, even with mild symptoms, until they recover (except to get medical care)
Clean and disinfect frequently touched surfaces daily (e.g., light switches, door knobs, countertops, handles, phones).
Face masks in community settings
Recommendations on the use of face masks in community settings vary between countries. It is mandatory to wear a mask in public in certain countries or in certain situations, and masks may be worn in some countries according to local cultural habits. Consult local public health guidance for more information.
There is no high-quality or direct scientific evidence to support the widespread use of masks by healthy people in the community setting, and there are risks and benefits that must be considered. Data on effectiveness is based on limited and inconsistent observational and epidemiologic studies. The first randomized controlled trial to investigate the efficacy of masks in the community (in addition to other public health measures such as social distancing) found that the recommendation to wear surgical masks when outside the home among others did not reduce incident SARS-CoV-2 infection compared with no mask recommendation. However, the study did not assess whether masks could decrease disease transmission from mask wearers to others. A Cochrane review found that wearing a mask may make little to no difference in how many people caught influenza-like illnesses; however, this is based on low-certainty evidence, and does not include results of studies from the current COVID-19 pandemic. Evidence for mask effectiveness for respiratory tract infection prevention is stronger in healthcare settings compared with community settings; direct evidence on comparative effectiveness in SARS-CoV-2 infection is insufficient. The strength of evidence for any mask use versus nonuse in community settings is low. Randomized trials have not addressed the question of source control.
Despite the lack of good-quality evidence, the WHO advises that in areas of known or suspected community or cluster transmission, people should wear a nonmedical mask in the following circumstances: indoor or outdoor settings where physical distancing cannot be maintained; indoor settings with inadequate ventilation, regardless of whether physical distancing can be maintained; and in situations when physical distancing cannot be maintained and the person has a higher risk of severe complications (e.g., older age, underlying condition). Caregivers and those living with suspected or confirmed cases should wear a medical mask when in the same room, regardless of whether the case has symptoms. Children ages up to 5 years should not wear masks for source control. A risk-based approach is recommended for children ages 6 to 11 years. Special considerations are required for immunocompromised children, or children with certain diseases, developmental disorders, or disabilities. The WHO advises that people should not wear masks during vigorous-intensity physical activity. Use of a mask alone is insufficient to provide adequate protection, and they should be used in conjunction with other infection prevention and control measures such as frequent hand hygiene and social distancing.
Potential harms and disadvantages of wearing masks include: potential increased risk of self-contamination due to manipulation of face mask and touching face/eyes, or when nonmedical masks are not changed when wet or soiled; headache and/or breathing difficulties; facial skin lesions, irritant dermatitis, or worsening acne; discomfort; difficulty communicating; social and psychological acceptance; false sense of security; poor compliance; waste management issues; and difficulties for patients with chronic respiratory conditions or breathing problems. Masks may also create a humid habitat where the virus can remain active and this may increase viral load in the respiratory tract; deeper breathing caused by wearing a mask may push the virus deeper into the lungs. There are insufficient data to quantify all of the adverse effects that might reduce the acceptability, adherence, and effectiveness of face masks.
Cloth masks have limited efficacy in preventing viral transmission compared with medical-grade masks. Efficacy depends on the type of material used, the number of layers, the degree of moisture in the mask, and the fitting of the mask on the face. In a study comparing the use of cloth masks to surgical masks in healthcare workers, the rates of all infection outcomes were highest in the cloth mask arm, with the rate of influenza-like illness statistically significantly higher in this group. Moisture retention, reuse of cloth masks, and poor filtration may result in increased risk of infection.
Alcohol-based hand sanitizers
The Centers for Disease Control and Prevention has issued a warning about alcohol-based sanitizers containing methanol (which may be labeled as containing ethanol). Methanol poisoning should be considered in patients who present with relevant signs and symptoms (e.g., headache, impaired vision, nausea/vomiting, abdominal pain, loss of coordination, decreased level of consciousness) who report ingestion of hand sanitizer or frequent repeated topical use. Cases of permanent blindness and death have been reported.
Travel-related control measures
Many countries have implemented travel-related control measures including complete closure of borders, partial travel restrictions, entry or exit screening, and/or quarantine of travelers. Overall, low to very low evidence suggests that travel-related control measures may help to limit the spread of infection across national borders. Cross-border travel restrictions are likely to be more effective than entry and exit screening, and screening is likely to be more effective in combination with other measures (e.g., quarantine, observation).
Entry/exit screening: people traveling from areas with a high risk of infection may be screened using questionnaires about their travel, contact with ill people, symptoms of infection, and/or measurement of their temperature. Low-certainty evidence suggests that screening at travel hubs may slightly slow the importation of infected cases; however, the evidence base comes from two mathematical model studies and is limited by their assumptions. Evidence suggests that one-time screening in apparently healthy people may miss between 40% and 100% of people who are infected, although the certainty of this ranges from very low to moderate. In very low‐prevalence settings, screening for symptoms or temperature may result in few false negatives and many true negatives, despite low overall accuracy. Repeated screenings may result in more cases being identified eventually and reduced harm from false reassurance. Entry screening at three major US airports found a low yield of laboratory-diagnosed cases (one case per 85,000 travelers) between January and September 2020.
Quarantine: enforced quarantine is being used to isolate easily identifiable cohorts of people at potential risk of recent exposure. Despite limited evidence, a Cochrane review found quarantine to be important in reducing the number of people infected and deaths, especially when started earlier and when used in combination with other prevention and control measures. However, the current evidence is limited because most studies are based on mathematical modeling studies that make assumptions on important model parameters. The psychosocial effects of enforced quarantine may have long-lasting repercussions.
Travelers who arrive in the UK are required to self-isolate for 10 days unless they have traveled from an exempt country. Travelers who have visited a country with a travel ban in the 10 days before arrival must self-isolate, along with their household, for 10 days from the day of departure from these countries. Public Health England: how to quarantine when you arrive in England external link opens in a new window
Many countries have implemented mandatory social distancing measures in order to reduce and delay transmission (e.g., city lockdowns, stay-at-home orders, curfews, nonessential business closures, bans on gatherings, school and university closures, travel restrictions and bans, remote working, quarantine of exposed people).
Although the evidence for social distancing for COVID-19 is limited, it is emerging, and the best available evidence appears to support social distancing measures to reduce the transmission and delay spread. The timing and duration of these measures appears to be critical. When comparing countries with more restrictive nonpharmaceutical interventions (e.g., mandatory stay-at-home and business closure orders) to countries with less restrictive nonpharmaceutical interventions, implementing any nonpharmaceutical interventions was associated with a significant reduction in case growth. However, there was no clear, significant beneficial effect of more restrictive nonpharmaceutical interventions compared with less restrictive nonpharmaceutical interventions in any of the countries studied. It should be noted that the study has important limitations.
Researchers in Singapore found that social distancing measures (isolation of infected individuals and family quarantine, school closures, and workplace distancing) significantly decreased the number of infections in simulation models.
Harms must also be considered. Public health policies mostly rely on models and these models often ignore potential harms including excess death and inequalities arising from economic damage, negative health effects, and effects on vulnerable populations. Negative consequences of community-based mass quarantine include psychological distress, food insecurity, economic challenges, diminished healthcare access, heightened communication inequalities, alternative delivery of education, and gender-based violence.
Shielding extremely vulnerable people
Shielding is a measure used to protect vulnerable people (including children) who are at very high risk of severe illness from COVID-19 because they have an underlying health condition. Shielding involves minimizing all interactions between those who are extremely vulnerable and other people to protect them from coming into contact with the virus.
Extremely vulnerable groups include:
Solid organ transplant recipients
People with specific cancers
People with severe respiratory conditions (e.g., cystic fibrosis, severe asthma, or severe COPD)
People with rare diseases that significantly increase the risk of infections (e.g., homozygous sickle cell disease, severe combined immunodeficiency)
People on immunosuppression therapies sufficient to significantly increase the risk of infection
People with spleen problems (e.g., prior splenectomy)
Adults with Down syndrome
Adults on dialysis or with chronic kidney disease
Women who are pregnant with significant heart disease (congenital or acquired)
Other people who have also been classed as clinically extremely vulnerable based on clinical judgment and an assessment of their needs.
The UK government recommends that clinically extremely vulnerable people follow national restrictions for the general population:
Consult current guidance for specific recommendations (recommendations may differ between countries).
Shielding advice for children and young adults is available. Consult current guidance for specific recommendations (recommendations may differ between countries).
Lifestyle modifications (e.g., smoking cessation, weight loss) may help to reduce the risk of COVID-19, and may be a useful adjunct to other interventions.
The WHO recommends that tobacco users stop using tobacco given the well-established harms associated with tobacco use and second-hand smoke exposure. Public Health England also recommends stopping smoking. Public Health England: COVID-19 – advice for smokers and vapers external link opens in a new window
Pre-exposure or postexposure prophylaxis
There are no drugs recommended for pre-exposure prophylaxis or postexposure prophylaxis, except in the context of a clinical trial. See the Emerging section for more information.
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