Primary prevention

Vaccines

  • The World Health Organization (WHO) has authorised the use of the following six vaccines for global use below.[342][343][344][345][346][347] Other vaccines have also been authorised in specific countries (e.g., Sputnik V® in Russia, Covaxin® in India, Convidecia® in Latin America).[348][349]

    • Pfizer/BioNTech (mRNA) [350]

    • Moderna (mRNA)

    • AstraZeneca (adenovirus vector)

    • Janssen (adenovirus vector)

    • Sinopharm’s Covilo® (inactivated SARS-CoV-2 virus)

    • Sinovac’s CoronaVac® (inactivated SARS-CoV-2 virus)

    • WHO: COVID-19 vaccines technical documents external link opens in a new window

  • Vaccine availability and immunisation programmes differ between countries.

    • Vaccines are generally available under emergency-use, provisional, or conditional marketing authorisations, but may be approved in some countries.

    • Consult your local guidance for information.

  • Patients must give informed consent prior to vaccination.

    • For consent to immunisation to be valid, it must be given freely, voluntarily, and without coercion by an appropriately informed person.[351]

  • 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.[352]

    • Duration of protection after vaccination is unknown and is still being assessed in ongoing clinical trials.

  • Breakthrough infections are possible.

    • Breakthrough infections that have resulted in hospitalisation or death, as well as mild or asymptomatic infections, have been reported in fully vaccinated people.[353][354][355][356]

    • Risk factors for breakthrough infection after the first dose may include frailty in older adults ≥60 years, living in deprived areas, and obesity.[357] Older age, male sex, increasing number of comorbidities, hospitalisation in the previous 4 weeks, high-risk occupation, care home residence, socioeconomic deprivation, and smoking history were all associated with an increased risk of hospitalisation or death in patients with breakthrough infections after the first dose.[358]

    • In the US, 30,177 cases of hospitalised or fatal vaccine breakthrough cases have been reported (as of 4 October 2021) with 6617 deaths. However, breakthrough cases who are not hospitalised or fatal are no longer reported in the US, which means the true incidence of breakthrough infection is unknown.[359]

    • 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.[360] 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.[361]

    • 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.[362][363]

  • Vaccinated people should continue to follow local public health recommendations.

    • There is insufficient evidence on the extent of vaccine impact on virus transmission.[342][343][344][345][346][347]

    • Evidence of efficacy in the real world is emerging (see Vaccines: real world efficacy data below).

Pfizer/BioNTech COVID-19 vaccine

Moderna COVID-19 vaccine

AstraZeneca COVID-19 vaccine

Janssen COVID-19 vaccine

Brand name

Comirnaty®

Spikevax®

Vaxzevria®

To be confirmed

Synonyms

COVID-19 mRNA vaccine BNT162b2; tozinameran

COVID-19 vaccine mRNA-1273; elasomeran

COVID-19 vaccine ChAdOx1 S recombinant; AZD 1222; SII Covishield®

Ad26.COV2.S; JNJ-78436725

Vaccine type

mRNA vaccine

Adenovirus vector vaccine

Indication

Active immunisation of individuals ≥12 years of age

Active immunisation of individuals ≥18 years of age

Authorised dose*

TWO-DOSE REGIMEN

0.3 mL (30 micrograms) IM; second dose at least 21 days after first dose

A third booster dose may be administered at least 8 weeks after the second dose in certain people (e.g., immunocompromised)

TWO-DOSE REGIMEN

0.5 mL (100 micrograms) IM; second dose at least 28 days after first dose

TWO-DOSE REGIMEN

0.5 mL IM (5 × 1010 viral particles); second dose 4-12 weeks after first dose

A third booster dose may be administered at least 8 weeks after the second dose in certain people (e.g., immunocompromised)

Different brands of the AstraZeneca vaccine are considered equivalent and interchangeable

SINGLE-DOSE REGIMEN

0.5 mL IM (5 × 1010 viral particles)

Contraindications

Hypersensitivity to active substance or any excipients; immediate allergic reaction to first dose of two-dose regimens (should not get second dose)

Hypersensitivity to active substance or any excipients; immediate allergic reaction to first dose (should not get second dose)

Individuals who have experienced thrombosis with with thrombocytopenia syndrome following vaccination with the AstraZeneca vaccine

History of capillary leak syndrome

Hypersensitivity to active substance or any excipients

Cautions

History of anaphylaxis/allergic reactions

Acute severe febrile illness or acute infection

Bleeding disorders or anticoagulation

Immunocompromised

Pregnancy and breastfeeding

History of anaphylaxis/allergic reactions

Acute severe febrile illness or acute infection

Bleeding disorders or anticoagulation

Immunocompromised

Pregnancy and breastfeeding

History of heparin-induced thrombocytopenia and thrombosis (HITT or HIT type 2) or cerebral venous sinus thrombosis

Use may be restricted (or restricted in some age groups) in some countries

History of anaphylaxis/allergic reactions

Acute severe febrile illness or acute infection

Bleeding disorders or anticoagulation

Immunocompromised

Pregnancy and breastfeeding

History of heparin-induced thrombocytopenia and thrombosis (HITT or HIT type 2)

Adverse events

Common: headache; arthralgia; myalgia; injection-site reactions; fatigue; fever; chills; nausea; vomiting; diarrhoea; influenza-like illness

Uncommon: lymphadenopathy; malaise; anaphylaxis; hypersensitivity; acute peripheral facial paralysis; insomnia; pain in extremity (vaccinated arm); extensive swelling of vaccinated limb; face swelling (if dermatological fillers present); myocarditis/pericarditis

Common: headache; arthralgia; myalgia; injection-site reactions; fatigue; fever; chills; nausea; vomiting; rash; axillary lymphadenopathy (on same side as injection site); delayed injection-site reaction

Uncommon: acute peripheral facial paralysis; hypoaesthesia; anaphylaxis; hypersensitivity; face swelling (if dermatological fillers present); myocarditis/pericarditis; dizziness

Common: headache; arthralgia; myalgia; injection-site reactions; pain in extremity (vaccinated arm); fatigue; malaise; fever; chills; nausea; vomiting; diarrhoea; influenza-like illness

Uncommon: lymphadenopathy; dizziness; somnolence; decreased appetite; abdominal pain; hyperhidrosis; pruritus; rash; urticaria; angioedema; anaphylaxis; hypersensitivity; neuroinflammatory disorders; thrombosis with thrombocytopenia syndrome; thrombocytopenia; capillary leak syndrome; Guillain-Barre syndrome

Common: injection-site reactions; headache; cough; fatigue; myalgia; arthralgia; nausea; fever; chills

Uncommon: anaphylaxis; urticaria; hypersensitivity; tremor; hyperhidrosis; rash; sneezing; oropharyngeal pain; pain in extremity; back pain; muscular weakness; asthenia; malaise; thrombosis with thrombocytopenia syndrome

Interactions

Interactions with other vaccines/drugs have not been studied (WHO recommends a minimum of 14 days between COVID-19 vaccines and other vaccines; however, the US Food and Drug Administration recommends that COVID-19 vaccines and other vaccines may now be administered without regard to timing)

UK Summary of Product Characteristics

Pfizer/BioNTech COVID-19 vaccine external link opens in a new window

Moderna COVID-19 vaccine external link opens in a new window

AstraZeneca COVID-19 vaccine external link opens in a new window

Janssen COVID-19 vaccine external link opens in a new window

Comparison of vaccines authorised for use in the UK. Information is based on the Summary of Product Characteristics (see links in tables). Consult your local drug formulary or guidelines for the prescribing information for your location. *Dose schedules may differ in some locations. Last updated: 13 October 2021

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.[342][343] 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.[344]

    • 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.

    • Public Health England: COVID-19 vaccination information for healthcare practitioners external link opens in a new window

    • 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 emphasise 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.

    • CDC: interim clinical considerations for use of COVID-19 vaccines currently authorized in the United States external link opens in a new window

  • 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.[342][343][344][345][346][347]

    • 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.[364][365][366][367] However, an interim analysis of a UK multicentre, participant-masked, randomised 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 aged 50 years and older.[368][369] 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.[370]

  • 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.[371][372][373] The studies also focus on plasma neutralising antibodies and don’t take into account the protection provided by cellular immunity.

    • In the US, the Food and Drug Administration has authorised 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.[374] It has also authorised 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.[375] The US Centers for Disease Control and Prevention recommends that the following groups should receive a booster dose: people aged ≥65 years and residents in long-term care settings; and people aged 50 to 64 years with underlying medical conditions. It recommends that the following groups may receive a booster dose: people aged 18 to 49 years with underlying medical conditions based on their individual benefits and risks; and people aged 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.[376]

    • In the UK, the JCVI advises that a third primary dose be offered to people aged ≥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.[377] The JCVI has also advised that people who were vaccinated during phase 1 of the vaccination programme 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 aged 16 to 49 years with underlying conditions that put them at higher risk and their adult carers, adult household contacts of immunosuppressed people) should be offered a booster dose no earlier than 6 months after completion of their primary course.[378] Influenza and COVID-19 vaccines may be administered together where operationally practical, although there are a lack of data to support this.[379]

    • 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.[380]

    • 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).[381] Regulatory agencies have confirmed that a causal relationship is plausible.[382][383][384][385][386][387] There has been no safety signal for VITT following receipt of mRNA vaccines, although a small number of cases have been reported.[388] 

    • 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 aged 18-49 years), and 1.9 cases per million doses after the second dose.[389]

    • 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 aged 30 to 49 years (8.8 cases per million doses).[390]

    • Some countries have permanently stopped the use of these vaccines in their immunisation programme.[391][392] Other countries have implemented age-related prescribing restrictions. For example, in the UK, the JCVI advises that it is preferable for adults aged <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.[393][394] 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.[344]

    • The US Centers for Disease Control and Prevention recommends that people with a history of an episode of an immune-mediated syndrome characterised 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 authorised vaccine.[376]

    • Pregnancy predisposes to thrombosis; therefore, women should discuss with their healthcare professional whether the benefits of having these vaccines outweigh the risks.[383]

    • 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.[395]

    • See the Complications external link opens in a new window section for more information on this condition, including diagnosis and management.

  • Myocarditis and pericarditis

    • Myocarditis and pericarditis can occur in very rare cases following vaccination with mRNA vaccines.[396][397][398]

    • 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.[399]

    • 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.[389]

    • In the US, monitoring by the Vaccine Adverse Event Reporting System (VAERS) detected 40.6 cases per million second doses of vaccine in males aged 12 to 29 years, and 2.4 per million in males aged ≥30 years.[399]

    • 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).[400]

    • The US 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.[376]

    • Consider myocarditis and pericarditis in adolescents or young adults with acute chest pain, shortness of breath, or palpitations.[401]

    • The short-term clinical course appears to be mild in most patients; however, the long-term risks remain unknown.[402]

    • Some countries have suspended the use of the Moderna vaccine in their immunisation programme following the detection of signals of an increased risk of side effects such as myocarditis and pericarditis.[403]

  • Anaphylaxis

    • 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.[404][405]

    • 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).[389]

    • 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.[406]

    • Globally, the incidence of anaphylaxis post-vaccination has been reported to be 7.91 cases per million based on available data.[407]

    • 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.[342][343][344][345][346][347] 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.[408]

  • 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.[409]

    • The European Medicines Agency advises that the AstraZeneca and Janssen vaccines are contraindicated in people with a history of capillary leak syndrome.[409][410]

    • Severe, life-threatening flares have also been reported with mRNA vaccines.[411] Cases of capillary leak syndrome have also been reported in patients with COVID-19.[412]

    • 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.[389]

  • Bell's palsy

    • Clinical trials of the mRNA vaccines showed an imbalance in the incidence of Bell's palsy following vaccination compared with the placebo arm of each trial, suggesting vaccination may be associated with Bell's palsy.[413] 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.[414]

    • 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.[415]

    • A case-control study also failed to identify a higher risk after recent vaccination with the Pfizer/BioNTech vaccine.[416]

    • 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.[417]

    • 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.[389]

    • An increased risk of Bell's palsy has been reported after vaccination with Sinovac’s CoronaVac® (inactivated SARS-CoV-2 virus) vaccine compared with the Pfizer/BioNTech vaccine.[418]

  • Lymphadenopathy

    • 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.[419]

    • The incidence has been reported to be 3% in one small cohort of vaccinated people.[420] A large study from Israel identified an excess risk of lymphadenopathy among vaccinated people (78.4 events per 100,000 people).[421]

    • Although UK guidelines currently recommend a 2-week suspected-cancer referral for unexplained axillary lymphadenopathy in those aged >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 examination and no history of breast cancer. Further examination up to 2 weeks later is recommended, with referral to secondary care for those with non-resolving lymphadenopathy. An urgent referral to the breast clinic is advisable in patients with current or previous history of breast cancer.[422]

  • Guillain-Barre syndrome

    • Guillain-Barre syndrome has been reported after vaccination and a casual relationship is possible.[423][424][425][426]

    • 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.[389]

    • 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.[427]

    • The US 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).[376]

  • 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).[389]

    • 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.[389]

  • Immune thrombocytopenic purpura

    • Immune thrombocytopenic purpura has been reported after vaccination with the AstraZeneca and Janssen vaccines.[428][429]

    • 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.[395]

  • 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.[430]

    • Facial pustular neutrophilic eruptions have been reported after vaccination with mRNA vaccines.[431]

  • 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.[432][433]

  • Vasovagal reactions

    • Anxiety-related reactions, including vasovagal reactions and hyperventilation, have been reported after vaccination. Ensure precautions are in place to avoid injury from fainting.[434]

  • Other

    • The following adverse effects have also been added to the European prescribing information: paraesthesia and hypoaesthesia, asthenia, lethargy, decreased appetite, and nocturnal hyperhidrosis (Pfizer/BioNTech); erythema multiforme (Pfizer/BioNTech and Moderna); transverse myelitis, tinnitus, and dizziness (Janssen).[429][435][436][437]

    • Cases of Stevens-Johnson syndrome, cutaneous vasculitis, glomerulonephritis, nephrotic syndrome, multisystem inflammatory syndrome, immune myositis, adult-onset Still's disease, appendicitis, necrotising pancreatitis, varicella zoster virus reactivation, and Graves' disease have been reported after vaccination; however, causality is yet to be established.[438][421][439][440][441][442][443][444][445][446][447]

  • 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 authorised 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.

  • Pregnancy

    • 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.[448]

    • 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.[342][343][344][345][346][347]

    • 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.[449][450]

    • 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.[451]

    • 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.[376] Pregnant women who choose to receive a vaccine are encouraged to enroll in the v-safe programme. 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.[452]

  • Breastfeeding

    • 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.[453][454] Vaccine-associated mRNA was not detected in 13 milk samples collected 4 to 48 hours after vaccination from 7 breastfeeding individuals.[455] However, further research is required.

    • The WHO recommends that vaccines may be used in lactating women as in other adults. The WHO does not recommend discontinuing breastfeeding because of vaccination.[342][343][344][345][346][347]

    • 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.[451]

    • 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.[376]

    • The American College of Obstetricians and Gynecologists recommends that vaccines should be offered to lactating individuals similar to non-lactating individuals.[452]

  • Children and adolescents

    • The Pfizer/BioNTech vaccine has been authorised for use in young people aged 12 to 15 years in many countries, including the UK, Europe, and the US.[456][457][458][459] Authorisation was based on an ongoing randomised, placebo-controlled clinical trial in the US of over 2000 participants that reports 100% efficacy from 7 days after the second dose.[460] 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 aged 12 to 17 years (as of 16 July 2021), 9.3% of which were for serious adverse events including myocarditis (4.3%).[461]

    • The WHO recommends considering the use of the Pfizer/BioNTech vaccine in children aged 12 to 15 years only when high vaccine coverage with 2 doses has been achieved in high-priority groups. Children aged 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.[342]

    • The UK’s JCVI recommends that children who are at increased risk of serious disease are offered the Pfizer/BioNTech vaccine, including children aged 12 to 15 years with severe neurodisabilities, Down's syndrome, immunosuppression, and multiple or severe learning disabilities. The JCVI also recommends that children aged 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.[462] The JCVI does not recommend vaccination in young people aged 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.[463] Despite this, the UK government recommends offering a vaccine to all 12- to 15-year-olds.[378]

    • The European Medicines Agency has also approved the Moderna vaccine in young people aged 12 to 17 years.[464] An ongoing phase 2/3 randomised controlled trial found that the Moderna vaccine has an acceptable safety profile in adolescents aged 12 to 17 years, and the immune response was similar to that in young adults.[465]

    • 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

    • The WHO recommends that older people (without an upper age limit) and people with comorbidities that have been identified as increasing the risk for severe disease may be vaccinated.[342][343][344][345][346][347]

  • 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.[342][343][344][345][346][347]

    • Delayed vaccination is recommended in people who previously received passive antibody therapy for COVID-19 (for at least 90 days).[342][343][344][345][346][347]

    • 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 immunisation after infection may be advisable.[342][343][344][345][346][347]

    • Emerging evidence suggests that one dose of the vaccine may be sufficient for people who have already been infected with SARS-CoV-2.[466][467] 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.[468] 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.[469]

  • Immunocompromised

    • 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.[342][343][344][345][346][347]

    • 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 non-significant reduction in vaccine efficacy.[470] 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.[471] A third (booster) dose is now being tested in these patients.[472] 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 viraemia and good CD4 cell counts. Further data are required to test the durability of this response and in those who are viraemic or have low CD4 cell counts.[473]

    • A third/booster dose of an mRNA vaccine may be recommended in certain immunocompromised patients (see above).

  • Autoimmune disease

    • 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.[342][343][344][345][346][347]

    • It is uncertain whether vaccines may cause an exacerbation of pre-existing autoimmune diseases; however, there are case reports of new or flares of existing autoimmune conditions in Israel.[474] 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.[475] 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).[476] A case of reactivation of IgA vasculitis has been reported.[477]

    • 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.[478] In patients with psoriasis, seroconversion rates after vaccination were lower in patients receiving immunosuppressants, with the lowest rate in those receiving methotrexate. Neutralising activity was preserved in those receiving targeted biological agents.[479] Patients with a history of taking CD20 B-cell-depleting treatments may have blunted humoral and cell-mediated immune responses elicited by mRNA vaccines.[480]

    • 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

    • Emerging data suggest that vaccine efficacy may be lower in cancer patients and solid organ transplant recipients.[481][482][483][484][485][486][487][488][489][490]

    • Frequent and high levels of humoral responses have been identified in allogeneic haematopoietic stem cell transplant recipients after two vaccine doses.[491][492]

    • Patients with lymphoma can develop a robust serological response as early as 6 months after treatment.[493]

    • Patients with haematological 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.[494][495]

    • A third/booster dose of an mRNA vaccine may be recommended in certain immunocompromised patients (see above).

Vaccines: real world efficacy data

  • Initial authorisation 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).[496][497][498][499]

  • Observational evidence from the initial global vaccine rollout suggested real-world efficacy in reducing the rate of symptomatic or asymptomatic infection, disease severity, hospitalisation, death, and possibly even reinfection.[500][501][502][503][504][505][506][507][508][509][510][511][512][513][514][515][516][517][518][519]

  • 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 hospitalisation from the Alpha variant, but may be less effective against infection compared with the Alpha variant.[520][521][522][523]

  • 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 aged ≥65 years, and immunosuppressed people.[524][525][526][527][528][529]

    • Recent data from the UK estimated vaccine efficacy to be 49% to 58% in late July 2021.[530]

    • Recent data from Israel estimated vaccine efficacy to be 39% in late July 2021.[531]

    • 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 hospitalisation was high (93%) overall up to 6 months.[532] Data from Qatar show a similar trend.[533]

    • 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 hospitalisation caused by the Delta variant, or other variants of concern, compared with vaccine-induced immunity.[350][534]

  • Previous trials of coronavirus vaccines identified cellular immunopathology and antibody-dependent enhancement as potential safety issues.[535][536]

    • 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.[496][497] 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.[537]

Infection prevention and control for healthcare professionals

  • Consult local infection prevention and control protocols; only basic principles from the World Health Organization guidelines are detailed here.[538][539]

  • 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 1 metre (3 feet) 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 organisations 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 serological testing when they returned home, despite all participants having direct contact with COVID-19 patients and performing at least one aerosol-generating procedure.[540]

    • 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.[541]

  • 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.[542]

  • 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 1 to 2 metres (3-6 feet) away from others (recommendations vary between countries), wash their hands often with soap and water (or hand sanitiser 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.[543][544]

  • Alcohol-based hand sanitiser: may be recommended in situations where it is not possible to use soap and water; however, adverse events have been reported including:[545][546][547][548]

    • Headache, nausea, and dizziness due to inhalation of vapours, 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

    • Antimicrobial resistance.

  • Face masks: the WHO advises that in areas of known or suspected community or cluster transmission, people should wear a non-medical 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); carers and those living with suspected or confirmed cases when in the same room, regardless of whether the case has symptoms. Children aged up to 5 years should not wear masks for source control, while a risk-based approach is recommended for children aged 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.[77]

    • 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 epidemiological studies.[77]

    • The only randomised 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).[549] Evidence from randomised 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.[550]

    • 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.[551]

    • 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 non-use in community settings is low.[552][553]

    • 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.[554][555]

    • There are harms and disadvantages of wearing masks (e.g., headache, breathing difficulties, facial skin lesions, psychological issues, difficulty communicating, increased viral load).[77] There are insufficient data to quantify all of the adverse effects that might reduce the acceptability, adherence, and effectiveness of face masks.[556][557]

    • BMJ: mask related acne ('maskne') and other facial dermatoses external link opens in a new window

  • Non-pharmaceutical interventions: many countries have implemented non-pharmaceutical interventions in order to reduce and delay viral transmission (e.g., social distancing, city lockdowns, stay-at-home orders, curfews, non-essential business closures, bans on gatherings, school and university closures, remote working, quarantine of exposed people).

    • Implementing any non-pharmaceutical interventions was associated with a significant reduction in case growth when comparing countries with more restrictive non-pharmaceutical interventions to countries with less restrictive non-pharmaceutical interventions. However, there was no clear, significant beneficial effect of more restrictive non-pharmaceutical interventions compared with less restrictive nonpharmaceutical interventions in any of the countries studied.[558]

    • 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.[559]

  • 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 minimising all interactions between those who are extremely vulnerable and other people to protect them from coming into contact with the virus.

    • The UK shielding programme 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.[560]

    • 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 travellers.

    • 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).[561]

    • 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.[562] Entry screening at three major US airports found a low yield of laboratory-diagnosed cases (one case per 85,000 travellers) between January and September 2020.[563]

    • 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 modelling studies that make assumptions on important model parameters.[564]

    • The psychosocial effects of enforced quarantine may have long-lasting repercussions.[565][566]

    • Public Health England: travel abroad - step by step external link opens in a new window

Lifestyle modifications

  • 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.[567]

  • The WHO recommends that tobacco users stop using tobacco given the well-established harms associated with tobacco use and second-hand smoke exposure.[238] Public Health England also recommends stopping smoking.

Pre-exposure or post-exposure prophylaxis

  • There are no treatments recommended for pre-exposure prophylaxis, except in the context of a clinical trial.[568]

  • Casirivimab/imdevimab has been granted an emergency-use authorisation/conditional marketing authorisation for post-exposure prophylaxis in select people in some countries. See the Emerging external link opens in a new windowsection for more information.

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