The World Health Organization (WHO) has authorized the use of the following six vaccines for global use below. Other vaccines have also been authorized in specific countries (e.g., Sputnik V® in Russia, Covaxin® in India, Convidecia® in Latin America).
AstraZeneca (adenovirus vector)
Janssen (adenovirus vector)
Sinopharm’s Covilo® (inactivated SARS-CoV-2 virus)
Sinovac’s CoronaVac® (inactivated SARS-CoV-2 virus)
Vaccine availability and immunization programs differ between countries.
Vaccines are generally available under emergency-use, provisional, or conditional marketing authorizations, but may be approved in some countries.
Consult your local guidance for information.
Patients must give informed consent prior to vaccination.
For consent to immunization to be valid, it must be given freely, voluntarily, and without coercion by an appropriately informed person.
Protection starts around 14 days after full vaccination.
Vaccination may not protect all vaccine recipients.
Have a high level of suspicion of reported symptoms post-vaccination, and avoid dismissing complaints as vaccine-related until vaccine recipients are tested and true infection is ruled out.
Duration of protection after vaccination is unknown and is still being assessed in ongoing clinical trials.
Breakthrough infections are possible.
Risk factors for breakthrough infection after the first dose may include frailty in older adults ≥60 years, living in deprived areas, and obesity. Older age, male sex, increasing number of comorbidities, hospitalization in the previous 4 weeks, high-risk occupation, care home residence, socioeconomic deprivation, and smoking history were all associated with an increased risk of hospitalization or death in patients with breakthrough infections after the first dose.
In the US, 30,177 cases of hospitalized or fatal vaccine breakthrough cases have been reported (as of 4 October 2021) with 6617 deaths. However, breakthrough cases who are not hospitalized or fatal are no longer reported in the US, which means the true incidence of breakthrough infection is unknown.
One small observational study in patients admitted to hospital with a positive test found that 46% of fully vaccinated people with breakthrough infection were asymptomatic, while 26% had severe or critical disease, 20% had moderate disease, and 7% had mild disease. In another study, the rate of severe disease or death per 1000 person-days was 4.08 among those with breakthrough infections and 3.6 among unvaccinated matched controls with infection.
Emerging data from the US and UK indicates that fully vaccinated people with breakthrough infections have similar viral loads of the Delta variant compared with unvaccinated people, and are therefore equally likely to transmit the infection.
Vaccinated people should continue to follow local public health recommendations.
Vaccines: dose schedules
Dose schedules may differ between countries depending on vaccine coverage rates and supply constraints.
The WHO recommends that countries that have not yet achieved high vaccine coverage rates in high-priority groups and who are experiencing a high incidence of cases combined with vaccine supply constraints should focus on achieving a high first-dose coverage in the high-priority groups by extending the interdose interval of mRNA vaccines by up to 12 weeks. The WHO recommends an interval of 8 to 12 weeks between the two doses of the AstraZeneca vaccine (rather than 4 to 12 weeks as the manufacturer recommends) as two-dose efficacy and immunogenicity increase with a longer interdose interval.
In the UK, the Joint Committee on Vaccination and Immunisation (JCVI) recommends that the second dose of a vaccine should be routinely scheduled between 8 and 12 weeks after the first dose for all available vaccines. The main exception to the 8-week lower interval would be those about to commence immunosuppressive treatment. Evidence shows that delaying the second dose to 12 weeks after the first improves the boosting effect.
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.
Use the same vaccine product for both doses.
There is a lack of data on using two different vaccines to complete a two-dose schedule. However, recommendations will be updated as further information becomes available on interchangeability between vaccines.
Heterologous vaccination schedules have been found to induce a robust humoral and cellular immune response after a second dose of an mRNA vaccine in people primed with the AstraZeneca vaccine 8 to 12 weeks earlier, and were associated with an acceptable and manageable reactogenicity profile in small cohort studies. However, an interim analysis of a UK multicenter, participant-masked, randomized heterologous prime-boost vaccination study found an increase in systemic reactogenicity after the boost dose in heterologous vaccine schedules in comparison to homologous vaccine schedules in participants ages 50 years and older. The difference between studies may be explained, in part, by the difference in administration intervals used between the studies (i.e., 28 days versus 8 to 12 weeks).
Further safety and efficacy data are required before heterologous schedules can be recommended.
Booster doses may be recommended in some countries.
Observational data to support the safety and efficacy of booster doses are emerging, but their follow-up periods are too short to assess long-term effectiveness, and the number of trial participants is small. The studies also focus on plasma neutralizing antibodies and don’t take into account the protection provided by cellular immunity.
In the US, the Food and Drug Administration has authorized an additional (third) dose of the Pfizer/BioNTech and Moderna mRNA vaccines in moderately to severely immunocompromised people at least 28 days after the completion of the initial vaccine series. It has also authorized a single booster dose of the Pfizer/BioNTech vaccine to be administered at least 6 months after the completion of the primary series in certain people. The Centers for Disease Control and Prevention recommends that the following groups should receive a booster dose: people ages ≥65 years and residents in long-term care settings; and people ages 50 to 64 years with underlying medical conditions. It recommends that the following groups may receive a booster dose: people ages 18 to 49 years with underlying medical conditions based on their individual benefits and risks; and people ages 18 to 64 years who are at increased risk for exposure and transmission because of occupational or institutional setting based on their individual benefits and risks.
In the UK, the JCVI advises that a third primary dose be offered to people ages ≥12 years with severe immunosuppression. The third primary dose should ideally be given at least 8 weeks after the second dose, with special attention paid to current or planned immunosuppressive therapies. Choice of vaccine depends on age and the previous vaccine used. The JCVI has also advised that people who were vaccinated during phase 1 of the vaccination program in priority groups 1 to 9 (i.e., adults ≥50 years of age, frontline health and social care workers, people living in residential care homes, people ages 16 to 49 years with underlying conditions that put them at higher risk and their adult caregivers, adult household contacts of immunosuppressed people) should be offered a booster dose no earlier than 6 months after completion of their primary course. Influenza and COVID-19 vaccines may be administered together where operationally practical, although there are a lack of data to support this.
In Europe, the European Medicines Agency recommends that a booster dose of an mRNA vaccine may be given to people with severely weakened immune systems, at least 28 days after their second dose. Although there is no direct evidence that the ability to produce antibodies in these patients offered protection, it is expected that the extra dose would increase protection at least in some patients. The risk of side effects after a booster is not known and is being carefully monitored.
Consult your local guidance for information.
Vaccines: safety signals
Vaccine-induced immune thrombocytopenia and thrombosis (VITT)
VITT has been reported after vaccination with the adenovirus vector-based COVID-19 vaccines (e.g., AstraZeneca, Janssen). Regulatory agencies have confirmed that a causal relationship is plausible. There has been no safety signal for VITT following receipt of mRNA vaccines, although a small number of cases have been reported.
In the UK, monitoring of the Yellow Card reporting system has detected 421 reports of VITT after administration of the AstraZeneca vaccine, with 72 deaths, an overall case fatality rate of 17% (as of 29 September 2021). The overall risk has been estimated to be 15.1 cases per million doses after first or unknown doses (20.5 per million in people ages 18-49 years), and 1.9 cases per million doses after the second dose.
In the US, the overall risk of VITT with the Janssen vaccine has currently been estimated to be 3 cases per million people who receive the vaccine, with the reporting rate highest among women ages 30 to 49 years (8.8 cases per million doses).
Some countries have permanently stopped the use of these vaccines in their immunization program. Other countries have implemented age-related prescribing restrictions. For example, in the UK, the JCVI advises that it is preferable for adults ages <40 years without underlying health conditions that put them at higher risk of severe disease to receive an alternative to the AstraZeneca vaccine, where available. Age cut-offs vary widely between countries so it is important to consult your local guidance.
The World Health Organization recommends that people who have had VITT following the first dose of the AstraZeneca vaccine should not receive a second dose of the same vaccine.
The US Centers for Disease Control and Prevention recommends that people with a history of an episode of an immune-mediated syndrome characterized by thrombosis and thrombocytopenia, such as heparin-induced thrombocytopenia, should be offered an mRNA vaccine instead of the Janssen vaccine (the AstraZeneca vaccine is not currently available in the US) if it has been ≤90 days since their illness resolved. After 90 days, patients may be vaccinated with any authorized vaccine.
Pregnancy predisposes to thrombosis; therefore, women should discuss with their healthcare professional whether the benefits of having these vaccines outweigh the risks.
The European Medicines Agency’s safety committee has also concluded that there is a possible link to rare cases of venous thromboembolism that is distinct from VITT with the Janssen vaccine.
See the Complications section for more information on this condition, including diagnosis and management.
Myocarditis and pericarditis
Cases occurred predominantly in adolescents and young adults 12 to 29 years of age, more often in males than in females, more often following dose 2 than dose 1, and typically within 7 days after vaccination.
In the UK, monitoring of the Yellow Card reporting system estimates the overall risk of myocarditis to be 7.6 cases per million people (Pfizer/BioNTech vaccine), 29.8 cases per million people (Moderna vaccine), and 2.4 cases per million people (AstraZeneca vaccine) who receive the vaccine. The overall risk of pericarditis has been estimated to be 5.9 cases per million people (Pfizer/BioNTech vaccine), 17.7 cases per million people (Moderna vaccine), and 3.7 cases per million people (AstraZeneca vaccine) who receive the vaccine.
In the US, monitoring by the Vaccine Adverse Event Reporting System (VAERS) detected 40.6 cases per million second doses of vaccine in males ages 12 to 29 years, and 2.4 per million in males aged ≥30 years.
In Israel, a large study estimates the incidence to be 2.13 cases per 100,000 people, with the highest incidence between the ages of 16 to 29 years (10.7 cases per 100,000 people).
The Centers for Disease Control and Prevention recommends that people with a history of myocarditis or pericarditis may receive any vaccine after the episode has completely resolved. People with a history of myocarditis or pericarditis after their first dose of an mRNA vaccine should defer receiving their second dose, or may consider it under certain circumstances provided the episode has fully resolved.
Consider myocarditis and pericarditis in adolescents or young adults with acute chest pain, shortness of breath, or palpitations.
The short-term clinical course appears to be mild in most patients; however, the long-term risks remain unknown.
Some countries have suspended the use of the Moderna vaccine in their immunization program following the detection of signals of an increased risk of side effects such as myocarditis and pericarditis.
Severe allergic reactions, including anaphylaxis, have been reported after vaccination. Reactions may be due to the presence of lipid pegylated ethylene glycol (PEG), or PEG derivatives such as polysorbates.
In the UK, monitoring of the Yellow Card reporting system has detected 486 cases of anaphylaxis with the Pfizer/BioNTech vaccine, 820 cases with the AstraZeneca vaccine, and 40 cases with the Moderna vaccine (as of 29 September 2021).
In the US, monitoring by 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.
Globally, the incidence of anaphylaxis post-vaccination has been reported to be 7.91 cases per million based on available data.
A history of anaphylaxis to any component of the vaccine is a contraindication to vaccination. People who have an anaphylactic reaction following the first dose of the vaccine should not receive a second dose of the same vaccine. Observe people for 15 to 30 minutes after vaccination in healthcare settings where anaphylaxis can be immediately treated. Consult local guidelines for recommendations on vaccinating people with a history of allergies or anaphylaxis as guidance may differ across locations.
A small retrospective study found that most patients who have immediate and potentially allergic reactions to the first dose of an mRNA vaccine tolerate the second dose; however, further research is required.
Capillary leak syndrome
Capillary leak syndrome has been reported after vaccination with the AstraZeneca vaccine. Most cases occurred in women within 4 days of vaccination, and half of the patients had a history of capillary leak syndrome.
In the UK, monitoring of the Yellow Card reporting system has detected 12 cases of capillary leak syndrome with the AstraZeneca vaccine (as of 29 September 2021). Of these reports, 2 people had a history of capillary leak syndrome.
Clinical trials of the mRNA vaccines showed an imbalance in the incidence of Bell palsy following vaccination compared with the placebo arm of each trial, suggesting vaccination may be associated with Bell palsy. Cases have also been reported outside of clinical trials. A case of two discrete episodes in one patient shortly after receiving both the first and second doses of the Pfizer/BioNTech vaccine has been reported.
Analysis of data from the World Health Organization’s pharmacovigilance database up until early March 2021 failed to identify a higher risk of facial paralysis after vaccination.
A case-control study also failed to identify a higher risk after recent vaccination with the Pfizer/BioNTech vaccine.
EudraVigilance data indicate a much higher frequency of facial paralysis after the Pfizer/BioNTech vaccine (13.6 cases per million doses) compared with the AstraZeneca vaccine (4.1 cases per million doses), indicating that the risk may be higher with mRNA vaccines.
In the UK, the Yellow Card system has found that the number of reports of facial paralysis received so far is similar to the expected natural rate and does not currently suggest an increased risk following vaccination.
An increased risk of Bell palsy has been reported after vaccination with Sinovac’s CoronaVac® (inactivated SARS-CoV-2 virus) vaccine compared with the Pfizer/BioNTech vaccine.
Ipsilateral axillary/supraclavicular lymphadenopathy has been reported within 2 to 4 days after vaccination. It occurs more commonly after the second dose, and more commonly with the Moderna vaccine compared with the Pfizer/BioNTech vaccine.
The incidence has been reported to be 3% in one small cohort of vaccinated people. A large study from Israel identified an excess risk of lymphadenopathy among vaccinated people (78.4 events per 100,000 people).
Although UK guidelines currently recommend a 2-week suspected-cancer referral for unexplained axillary lymphadenopathy in those ages >30 years, a watchful wait approach may be appropriate in patients who have been vaccinated in the past week, provided that they have a normal breast exam and no history of breast cancer. Further examination up to 2 weeks later is recommended, with referral to secondary care for those with nonresolving lymphadenopathy. An urgent referral to the breast clinic is advisable in patients with current or previous history of breast cancer.
In the UK, monitoring of the Yellow Card reporting system has detected 428 cases of Guillain-Barre syndrome and 26 cases of Miller Fisher syndrome with the AstraZeneca vaccine, 53 cases of Guillain-Barre syndrome with the Pfizer/BioNTech vaccine, and 3 reports of Guillain-Barre syndrome with the Moderna vaccine (as of 29 September 2021). The UK Medicines and Healthcare products Regulatory Agency is reviewing these cases to assess whether there is an increased risk of Guillain-Barre syndrome after vaccination. Based on the available evidence at this stage, the agency is not able to confirm or rule out a causal relationship with the vaccine.
In the US, monitoring by VAERS detected 1 case of Guillain-Barre syndrome per 100,000 doses of the Janssen vaccine as of 24 July 2021. The median time to onset following vaccination was 13 days (range 10-42 days), and 93% of cases were serious.
The Centers for Disease Control and Prevention recommends that people with a history of Guillain-Barre syndrome should consider an mRNA vaccine instead of the Janssen vaccine (the AstraZeneca vaccine is not currently available in the US).
Menstrual disorders/unexpected vaginal bleeding
Menstrual disorders including heavier than usual periods, delayed periods, and unexpected vaginal bleeding have been reported after vaccination (39,330 reports as of 29 September 2021).
Current evidence does not suggest an increased risk of either menstrual disorders or unexpected vaginal bleeding following the vaccines; however, the UK Medicines and Healthcare products Regulatory Agency is closely monitoring the situation.
Immune thrombocytopenic purpura
The European Medicines Agency’s safety committee has concluded that immune thrombocytopenia is a possible adverse effect of both vaccines, and that people with a history of a thrombocytopenic disorder should have their platelets monitored for the first 4 weeks following vaccination.
Facial swelling and eruptions
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.
Facial pustular neutrophilic eruptions have been reported after vaccination with mRNA vaccines.
Delayed-onset local reactions
Delayed-onset local reactions around the injection site have been reported with the Moderna vaccine (median 7-8 days after first vaccination), and are sometimes quite large (e.g., at least 10 cm in diameter). Most people who had a reaction to the first dose also developed a similar reaction to the second dose, and developed it much sooner compared with the first dose.
Anxiety-related reactions, including vasovagal reactions and hyperventilation, have been reported after vaccination. Ensure precautions are in place to avoid injury from fainting.
The following adverse effects have also been added to the European prescribing information: paresthesia and hypoesthesia, asthenia, lethargy, decreased appetite, and nocturnal hyperhidrosis (Pfizer/BioNTech); erythema multiforme (Pfizer/BioNTech and Moderna); transverse myelitis, tinnitus, and dizziness (Janssen).
Cases of Stevens-Johnson syndrome, cutaneous vasculitis, glomerulonephritis, nephrotic syndrome, multisystem inflammatory syndrome, immune myositis, adult-onset Still disease, appendicitis, necrotizing pancreatitis, varicella zoster virus reactivation, and Graves disease have been reported after vaccination; however, causality is yet to be established.
Report all suspected adverse reactions after vaccination via your local reporting system. This is mandatory in some countries.
Surveillance of adverse events is extremely important, and may reveal additional, less frequent serious adverse events not detected in clinical trials. 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.
Vaccines: special patient populations
There are limited or no data available from clinical trials about the use of vaccines in specific patient populations.
Use caution in pregnant women as there are limited safety and efficacy data available. Preliminary data from the v-safe pregnancy registry and VAERS in the US have not shown 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.
The WHO recommends vaccines in pregnant women when the benefits outweigh the potential risks. The WHO does not recommend pregnancy testing prior to vaccination, or delaying pregnancy or terminating a pregnancy because of vaccination.
The UK Joint Committee on Vaccination and Immunisation (JCVI) advises that pregnant women should be offered the 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 Royal College of Obstetricians and Gynaecologists in the UK recommends that vaccination should be offered to pregnant women at the same time as the rest of the population, based on age and clinical risk. Pregnant women should be offered the Pfizer/BioNTech or Moderna vaccines unless they have already had one dose of the AstraZeneca vaccine, in which case they should complete the course with the AstraZeneca vaccine.
The US Centers for Disease Control and Prevention recommends that all pregnant women or women who are thinking about or trying to become pregnant should be vaccinated. 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 pregnant women have access to vaccines. Women should have access to available information about the safety and efficacy of the vaccine, including information about data that are not available. A conversation between the patient and the clinical team may assist with the decision. Pregnant women who decline vaccination should be supported in their decision.
Use caution in breastfeeding women as there are limited safety and efficacy data available. Studies have found robust secretion of SARS-CoV-2 specific immunoglobulin A (IgA) and IgG antibodies in breast milk after vaccination. Vaccine-associated mRNA was not detected in 13 milk samples collected 4 to 48 hours after vaccination from 7 breastfeeding individuals. However, further research is required.
The Royal College of Obstetricians and Gynaecologists in the UK recommends that breastfeeding women can receive a vaccine and there is no need to stop breastfeeding to have the vaccine.
The US Centers for Disease Control and Prevention recommends that all lactating women should be vaccinated, although it acknowledges that there are limited safety data available in lactating women and the infant.
The American College of Obstetricians and Gynecologists recommends that vaccines should be offered to lactating individuals similar to nonlactating individuals.
Children and adolescents
The Pfizer/BioNTech vaccine has been authorized for use in young people ages 12 to 15 years in many countries, including the UK, Europe, and the US. Authorization was based on an ongoing randomized, placebo-controlled clinical trial in the US of over 2000 participants that reports 100% efficacy from 7 days after the second dose. Due to the limited number of children included in the study, the trial could not have detected rare adverse effects. Safety monitoring of VAERS noted over 9000 reports of adverse events post-vaccination in adolescents ages 12 to 17 years (as of 16 July 2021), 9.3% of which were for serious adverse events including myocarditis (4.3%).
The WHO recommends considering the use of the Pfizer/BioNTech vaccine in children ages 12 to 15 years only when high vaccine coverage with 2 doses has been achieved in high-priority groups. Children ages 12 to 15 years with comorbidities that put them at significantly higher risk of serious disease, alongside other high-risk groups, may be offered vaccination.
The UK’s JCVI recommends that children who are at increased risk of serious disease are offered the Pfizer/BioNTech vaccine, including children ages 12 to 15 years with severe neurodisabilities, Down syndrome, immunosuppression, and multiple or severe learning disabilities. The JCVI also recommends that children ages 12 to 17 years who live with an immunosuppressed person should be offered the vaccine. The JCVI advises that all 16- to 17-year-olds should now be offered a first dose of the Pfizer/BioNTech vaccine. This is in addition to the existing offer of 2 doses of vaccine to 16- to 17-year-olds who are in at-risk groups. Pending further evidence on effectiveness and safety in this age group, a second vaccine dose is anticipated to be offered later to increase the level of protection and contribute towards longer-term protection. The JCVI does not recommend vaccination in young people ages 12 to 15 years who do not have underlying health conditions as the health benefits of vaccination were only marginally greater than the potential known harms. Despite this, the UK government recommends offering a vaccine to all 12- to 15-year-olds.
The European Medicines Agency has also approved the Moderna vaccine in young people ages 12 to 17 years. An ongoing phase 2/3 randomized controlled trial found that the Moderna vaccine has an acceptable safety profile in adolescents ages 12 to 17 years, and the immune response was similar to that in young adults.
There are currently no efficacy or safety data for children <12 years of age; however, clinical trials are in progress, and a decision about the 5- to 11-year-old age group is expected soon.
Recommendations on vaccinating children and adolescents vary; check your local guidance.
Older people and people with comorbidities
Current or previous SARS-CoV-2 infection
Delayed vaccination is recommended in people with current acute COVID-19 (or any other acute febrile illness) until they have recovered from the acute illness and the criteria for discontinuation of isolation have been met.
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.
Emerging evidence suggests that one dose of the vaccine may be sufficient for people who have already been infected with SARS-CoV-2. Emerging preprint (not peer reviewed) data suggests that people who have had previous SARS-CoV-2 infection are unlikely to become reinfected whether or not they receive the vaccine. A higher rate of adverse effects has been reported after the first dose of the vaccine in people with a history of SARS-CoV-2 infection compared with participants who had not previously been infected, but not after the second dose.
The WHO recommends that immunocompromised people and people living with HIV who have no contraindications to vaccination may be vaccinated if they are part of a group recommended for vaccination.
Emerging preprint (not peer reviewed) data from the UK indicate that the Pfizer/BioNTech and AstraZeneca vaccines are effective at preventing symptomatic disease in the majority of people with underlying health conditions who are clinically vulnerable. Efficacy was reduced in immunocompromised patients after one dose; however, after a second dose there was only a small and nonsignificant reduction in vaccine efficacy. Another preprint (not peer reviewed) study (the OCTAVE trial) found that 11% of immune vulnerable patient groups failed to generate SARS-CoV-2 spike protein antibodies 4 weeks after two doses. A third (booster) dose is now being tested in these patients. Further research is needed to understand vaccine efficacy among immunosuppressed groups.
A small study found that the AstraZeneca vaccine was safe and immunogenic in people with HIV infection with well-suppressed viremia and good CD4 cell counts. Further data are required to test the durability of this response and in those who are viremic or have low CD4 cell counts.
A third/booster dose of an mRNA vaccine may be recommended in certain immunocompromised patients (see above).
The WHO recommends that people with autoimmune conditions who have no contraindications to vaccination may be vaccinated if they are part of a group recommended for vaccination.
It is uncertain whether vaccines may cause an exacerbation of preexisting autoimmune diseases; however, there are case reports of new or flares of existing autoimmune conditions in Israel. Available evidence suggests that vaccination does not trigger disease exacerbation or relapse or vaccine failure in patients with multiple sclerosis; however, evidence is limited and vaccine timing may need to be individually tailored depending on the disease-modifying agent the patient is taking. A small study in patients with systemic lupus erythematosus found that the risk of disease flare was approximately 3%; however, the study had limitations (no control group, self-reporting). A case of reactivation of IgA vasculitis has been reported.
Seroconversion rates after vaccination are lower in patients with immune-mediated inflammatory disease, and some therapies (e.g., anti-CD20 therapies such as rituximab and anticytotoxic T-lymphocyte associated antigen therapies such as abatacept) may result in poorer responses. In patients with psoriasis, seroconversion rates after vaccination were lower in patients receiving immunosuppressants, with the lowest rate in those receiving methotrexate. Neutralizing activity was preserved in those receiving targeted biologic agents. Patients with a history of taking CD20 B-cell-depleting treatments may have blunted humoral and cell-mediated immune responses elicited by mRNA vaccines.
A third/booster dose of an mRNA vaccine may be recommended in certain immunocompromised patients (see above).
Malignancy and solid organ or stem cell transplant recipients
Patients with lymphoma can develop a robust serologic response as early as 6 months after treatment.
Patients with hematologic malignancies mount blunted and heterogeneous antibody responses. People treated with Bruton tyrosine kinase inhibitors, ruxolitinib, venetoclax, and anti-CD20 antibody therapies appear to be most affected.
Vaccines: real world efficacy data
Initial authorization of vaccines was based on interim analyses of ongoing phase 3 clinical trials with a median follow-up of 2 months. Overall vaccine efficacy for preventing symptomatic infection was reported as 95% (Pfizer/BioNTech), 94.1% (Moderna), 74% (AstraZeneca), and 66.9% (Janssen).
Observational evidence from the initial global vaccine rollout suggested real-world efficacy in reducing the rate of symptomatic or asymptomatic infection, disease severity, hospitalization, death, and possibly even reinfection.
Evidence suggests that current vaccines may be effective against the Delta variant after two doses, but with reduced efficacy after one dose. Efficacy is comparable to vaccine efficacy against hospitalization from the Alpha variant, but may be less effective against infection compared with the Alpha variant.
Evidence suggests that vaccine efficacy decreases over time following initial vaccination and immunity wanes, especially against the Delta variant. Humoral response appears to be substantially decreased among men, people ages ≥65 years, and immunosuppressed people.
Recent data from the UK estimated vaccine efficacy to be 49% to 58% in late July 2021.
Recent data from Israel estimated vaccine efficacy to be 39% in late July 2021.
Recent data from the US estimates that vaccine efficacy against infection declined from 88% during the first month after full vaccination to 47% after 5 months, based on data up to August 2021. However, vaccine efficacy against hospitalization was high (93%) overall up to 6 months. Data from Qatar show a similar trend.
Emerging evidence (including preprint data that has not been peer reviewed) suggests that natural immunity may confer longer-lasting and stronger protection against infection, symptomatic disease, and hospitalization caused by the Delta variant, or other variants of concern, compared with vaccine-induced immunity.
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. The possibility of antibody-dependent enhancement in people receiving vaccines based on the original virus strain spike sequence who are then exposed to the Delta variant has not been studied.
Infection prevention and control for healthcare professionals
Screen all people, including patients, visitors, and others entering the facility, for COVID-19 at the first point of contact with the health facility to allow for early recognition.
Immediately isolate all suspected or confirmed cases in a well-ventilated 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 adequately ventilated 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 suspected or confirmed cases are admitted:
Wear a medical mask, gloves, an appropriate gown, and eye/facial protection (e.g., goggles or a face shield)
Respirators may be used instead of medical masks in all settings based on health workers’ values and preferences (including settings where aerosol-generating procedures are not performed)
Appropriate mask fitting should always be ensured
Use single-use or disposable equipment.
Implement airborne precautions when performing aerosol-generating procedures, including placing patients in a negative pressure room and wearing a particulate respirator.
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.
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.
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.
Detailed infection prevention and control guidance is available:
Infection prevention and control for the general public
Public health recommendations vary between countries and you should consult your local guidance. It is generally recommended that people stay at least 3 to 6 feet (1-2 meters) away from others (recommendations vary between countries), wash their hands often with soap and water (or hand sanitizer that contains at least 60% alcohol), cover coughs and sneezes, wear a mask, avoid crowds and poorly ventilated spaces, clean and disinfect high touch surfaces, monitor their health and self-isolate or seek medical attention if necessary, and get vaccinated.
Headache, nausea, and dizziness due to inhalation of vapors, especially in enclosed or poorly ventilated spaces
Methanol poisoning (including cases of permanent blindness and death) due to ingestion or frequent repeated topical use
Accidental ingestion and unintentional ocular exposures, especially by children
Face masks: 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; 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 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, while 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.
There is no high-quality or direct scientific evidence to support the widespread use of masks by healthy people in the community setting. Data on effectiveness is based on limited and inconsistent observational and epidemiologic studies.
The only randomized controlled trial to investigate the efficacy of masks in the community found that the recommendation to wear surgical masks when outside the home did not reduce infection compared with a no mask recommendation. However, the study did not assess whether masks could decrease disease transmission from mask wearers to others (source control). Evidence from randomized controlled trials for other respiratory viral illnesses shows no significant benefit of masks in limiting transmission but is of poor-quality and not SARS-CoV-2-specific.
A Cochrane review found that wearing a mask may make little to no difference in how many people caught influenza-like illnesses. However, this was based on low-certainty evidence, and does not include results of studies from the current pandemic.
A living rapid review found that the evidence for mask effectiveness for respiratory tract infection prevention is stronger in healthcare settings compared with community settings; however, 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.
Cloth masks have limited efficacy in preventing viral transmission compared with medical-grade masks and the efficacy is dependent on numerous factors (e.g., material type, number of layers, fitting, moisture level), and may result in increased risk of infection.
There are harms and disadvantages of wearing masks (e.g., headache, breathing difficulties, facial skin lesions, psychological issues, difficulty communicating, increased viral load). There are insufficient data to quantify all of the adverse effects that might reduce the acceptability, adherence, and effectiveness of face masks.
Nonpharmaceutical interventions: many countries have implemented nonpharmaceutical interventions in order to reduce and delay viral transmission (e.g., social distancing, city lockdowns, stay-at-home orders, curfews, nonessential business closures, bans on gatherings, school and university closures, remote working, quarantine of exposed people).
Implementing any nonpharmaceutical interventions was associated with a significant reduction in case growth when comparing countries with more restrictive nonpharmaceutical interventions to countries with less restrictive nonpharmaceutical interventions. 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.
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 (e.g., cancer, severe respiratory condition, chronic kidney disease, immunosuppression). Shielding involves minimizing all interactions between those who are extremely vulnerable and other people to protect them from coming into contact with the virus.
The UK shielding program ended in September 2021. The guidance for clinically extremely vulnerable people is to follow the same advice as the rest of the population, with any additional precautions determined by the individual and their healthcare professional.
Shielding advice may be available in other countries; consult local public health guidance.
Travel-related control measures: many countries have implemented measures including complete or partial closure of borders, entry or exit screening, and/or quarantine of travelers.
Low- to very low-certainty 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).
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.
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.
Lifestyle modifications (e.g., smoking cessation, weight loss) may help to reduce the risk of infection, 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.
Pre-exposure or postexposure prophylaxis
There are no treatments recommended for pre-exposure prophylaxis, except in the context of a clinical trial.
Casirivimab/imdevimab has been granted an emergency-use authorization/conditional marketing authorization for postexposure prophylaxis in select people in some countries. See the Emerging section for more information.
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