Primary prevention

Vaccines

  • Vaccines are available under emergency-use or conditional marketing authorisations.

    • This is not a full marketing authorisation or approval.

  • The World Health Organization (WHO) has authorised the use of the following six vaccines for global use below.[356][357][358][359][360][361] Other vaccines have also been authorised in specific countries (e.g., Sputnik V® in Russia, Covaxin® in India).[362][363]

  • Vaccine availability and immunisation programmes differ between 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.[364]

  • Protection starts around 14 days after full vaccination.

    • Vaccination may not protect all vaccine recipients. Breakthrough infections that have resulted in hospitalisation or death, as well as asymptomatic infections, have been reported in fully vaccinated people.[365][366][367][368]

    • 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.[369]

    • Duration of protection after vaccination is unknown and is still being assessed in ongoing clinical trials. There is emerging evidence of a durable humoral and cellular immune response for at least 8 months after vaccination with a viral vector vaccine.[370]

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

    • There is insufficient evidence on the extent of vaccine impact on virus transmission.[356][357][358][359][360][361]

    • 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

COVID-19 vaccine mRNA-1273; Elasomeran

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

Ad26.COV2.S; JNJ-78436725

Vaccine type

Lipid nanoparticle-formulated mRNA vaccine that encodes the SARS-CoV-2 spike protein

Replication-incompetent adenovirus (chimpanzee) vector vaccine that carries the genetic code for the SARS-CoV-2 spike protein

Replication-incompetent adenovirus type 26 (human) vector vaccine that carries the genetic code for the SARS-CoV-2 spike protein

Overall efficacy*

95%

94.1%

66.7% to 76% (depending on trial)

66.9%

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

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

Different brands of the AstraZeneca vaccine are considered equivalent and interchangeable

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

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

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

Uncommon: lymphadenopathy; malaise; anaphylaxis; hypersensitivity; acute peripheral facial paralysis; insomnia; pain in extremity; influenza-like illness; myocarditis/pericarditis

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

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

Common: headache; arthralgia; myalgia; injection-site reactions; pain in extremity; 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

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)

Information for healthcare professionals

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. *Efficacy in preventing symptomatic infection in people aged 16 or 18 years and older (depending on vaccine) according to clinical trials. **Dose schedules may differ in some locations. Last updated: 22 July 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.[356][357] 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.[358]

    • 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.[356][357][358][359][360][361]

    • 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.[371][372] 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.[373] 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.

Vaccines: safety signals

  • Thrombosis with thrombocytopenia syndrome (TTS)

    • TTS has been reported after vaccination with the AstraZeneca and Janssen vaccines.[374][375] Regulatory agencies have confirmed that a causal relationship is plausible.[376][377][378][379][380][381] There has been no safety signal for TTS following receipt of mRNA vaccines, although a small number of cases have been reported.[382]

    • In the UK, monitoring of the Yellow Card reporting system has detected 405 reports of TSS after administration of the AstraZeneca vaccine, including 147 cases of cerebral venous sinus thrombosis and 258 cases of thrombosis in other major veins, with 74 deaths, an overall case fatality rate of 18% (as of 7 July 2021). Most cases occurred after the first dose; however, 39 cases have been reported after the second dose. The overall risk has been estimated to be 14.8 cases per million people who receive the vaccine.[383]

    • In the US, a total of 17 cases have been reported with the Janssen vaccine (as of 21 April 2021). All of these cases occurred in women between the ages of 18 and 59, with a symptom onset between 6 and 15 days after vaccination. The overall risk has currently been estimated to be 0.9 cases per million people who receive the vaccine, with the risk increasing to 7 per million in women aged 18 to 49 years.[384][385][386]

    • Some countries have permanently stopped the use of these vaccines in their immunisation programme.[387][388] 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.[389][390] Age cut-offs vary widely between countries so it is important to consult your local guidance.

    • 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.[391]

    • Pregnancy predisposes to thrombosis; therefore, women should discuss with their healthcare professional whether the benefits of having these vaccines outweigh the risks.[377]

    • Regulatory agencies state that the benefits of these vaccines continue to outweigh the risks.[376][377][378][381][384]

    • See the Complications section for more information on this condition, including diagnosis and management.

  • Myocarditis and pericarditis

    • Myocarditis and pericarditis have been reported after vaccination.[392][393][394][395] Regulatory agencies have concluded that myocarditis and pericarditis can occur in very rare cases following vaccination with mRNA vaccines and have updated the prescribing information for these 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 a case series of 23 previously healthy male military members, myocarditis was identified within 4 days of vaccination. For most patients, the diagnosis was made after the second dose of an mRNA vaccine.[400]

    • In the UK, monitoring of the Yellow Card reporting system has detected 81 cases of myocarditis and 63 reports of pericarditis with the Pfizer/BioNTech vaccine, 69 cases of myocarditis and 107 reports of pericarditis with the AstraZeneca vaccine, and 9 cases of myocarditis and 9 reports of pericarditis with the Moderna vaccine (as of 7 July 2021).[383]

    • In the US, monitoring by the Vaccine Adverse Event Reporting System (VAERS) detected 1226 reports of myocarditis after vaccination with an mRNA vaccine. This equates to 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]

    • 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.[391]

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

  • 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.[402]

    • In the UK, monitoring of the Yellow Card reporting system has detected 428 cases of anaphylaxis with the Pfizer/BioNTech vaccine, 781 cases with the AstraZeneca vaccine, and 26 cases with the Moderna vaccine (as of 7 July 2021).[383]

    • 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.[403]

    • Globally, the incidence of anaphylaxis post-vaccination has been reported to be 7.91 cases per million based on available data.[404]

    • 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.[356][357][358][359][360][361] Consult local guidelines for recommendations on vaccinating people with a history of allergies or anaphylaxis as guidance may differ across locations.

  • 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.[405]

    • The European Medicines Agency advises that the AstraZeneca and Janssen vaccines are contraindicated in people with a history of capillary leak syndrome.[405][406]

    • Severe, life-threatening flares have also been reported with mRNA vaccines.[407] Cases of capillary leak syndrome have also been reported in patients with COVID-19.[408]

    • In the UK, monitoring of the Yellow Card reporting system has detected 8 cases of capillary leak syndrome with the AstraZeneca vaccine (as of 7 July 2021).[383]

  • 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.[409]

    • 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.[410]

    • A case-control study also failed to identify a higher risk after recent vaccination with the Pfizer/BioNTech vaccine.[411]

    • 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.[412]

    • 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.[383]

  • 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.[413]

    • 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.[414]

  • Guillain-Barre syndrome

    • Guillain-Barre syndrome has been reported after vaccination.[415][416]

    • The European Medicines Agency has recommended adding a warning to the prescribing information of the AstraZeneca vaccine as available data neither confirm nor rule out a possible association with the vaccine.[417]

    • In the UK, monitoring of the Yellow Card reporting system has detected 344 cases of Guillain-Barre syndrome and 20 cases of Miller Fisher syndrome with the AstraZeneca vaccine, 41 cases of Guillain-Barre syndrome with the Pfizer/BioNTech vaccine, and 2 reports of Guillain-Barre syndrome with the Moderna vaccine (as of 7 July 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.[383]

  • Vaccines and menstrual disorders/unexpected vaginal bleeding

    • Menstrual disorders including heavier than usual periods, delayed periods, and unexpected vaginal bleeding have been reported after vaccination (22,981 reports as of 7 July 2021).[383]

    • 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.[383]

  • Immune thrombocytopenic purpura

    • Immune thrombocytopenic purpura has been reported after vaccination with the AstraZeneca vaccine.[418]

  • Facial swelling

    • 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.[419]

  • 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.[420][421]

  • 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.[422]

  • 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 did not show any obvious safety signals among pregnant women who received mRNA vaccines. These data have many limitations, and continued monitoring is needed to further assess the risk. Among 221 pregnancy-related adverse events reported to VAERS, the most frequently reported event was spontaneous abortion (46 cases), followed by stillbirth, premature rupture of membranes, and vaginal bleeding (3 reports for each). No congenital anomalies were reported to VAERS.[423]

    • 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.[356][357][358][359][360][361]

    • 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.[424][425]

    • The US Centers for Disease Control and Prevention recommends that pregnant women are eligible for and can receive a vaccine. 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 agency also recommends that women who are trying to become pregnant can receive a vaccine, although it acknowledges that there are no safety data available.[391]

    • 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.[426]

  • Breastfeeding

    • Use caution in breastfeeding women as there are limited safety and efficacy data available. A small prospective study found robust secretion of SARS-CoV-2 specific immunoglobulin A (IgA) and IgG antibodies in breast milk for 6 weeks after vaccination.[427] Vaccine-associated mRNA was not detected in 13 milk samples collected 4 to 48 hours after vaccination from 7 breastfeeding individuals.[428] 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.[356][357][358][359][360][361]

    • The US Centers for Disease Control and Prevention recommends that lactating women can receive a vaccine, although it acknowledges that there are no safety data available.[391]

    • The American College of Obstetricians and Gynecologists recommends that vaccines should be offered to lactating individuals similar to non-lactating individuals.[426]

  • 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.[429][430][431][432] 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.[433] Due to the limited number of children included in the study, the trial could not have detected rare adverse effects.

    • The WHO recommends considering 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.[356]

    • 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. Routine vaccination of children outside of these groups is not recommended, based on the current evidence.[434]

    • The European Medicines Agency and the US Food and Drug Administration are evaluating an application to extend the use of the Moderna vaccine to include young people aged 12 to 17 years.[435]

    • There are currently no efficacy or safety data for children <12 years of age.

  • 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.[356][357][358][359][360][361]

  • 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.[356][357][358][359][360][361]

    • Delayed vaccination is recommended in people who previously received passive antibody therapy for COVID-19 (for at least 90 days).[356][357][358][359][360][361]

    • 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.[356][357][358][359][360][361]

    • Emerging evidence suggests that one dose of the vaccine may be sufficient for people who have already been infected with SARS-CoV-2.[436][437][438][439] People who have had previous SARS-CoV-2 infection are unlikely to become reinfected whether or not they receive the vaccine.[440]

  • Immunocompromised

    • The WHO recommends that immunocompromised people, people living with HIV, and people with autoimmune conditions who have no contraindications to vaccination may be vaccinated if they are part of a group recommended for vaccination.[356][357][358][359][360][361]

    • Emerging preprint 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. Further research is needed to understand vaccine efficacy against severe disease among immunosuppressed groups.[441]

    • A small study found that the AstraZeneca vaccine was safe and immunogenic in people with HIV infection with we-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.[442]

  • Autoimmune disease

    • It is uncertain whether vaccines may cause an exacerbation of pre-existing autoimmune diseases.

    • A case of reactivation of IgA vasculitis has been reported.[443]

    • 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.[444]

  • 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.[445][446][447][448][449][450][451][452][453][454]

    • Frequent and high levels of humoral responses have been identified in allogeneic haematopoietic stem cell transplant recipients after two vaccine doses.[455]

    • Patients with lymphoma can develop a robust serological response as early as 6 months after treatment.[456]

    • 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.[457]

    • A third dose of the Pfizer/BioNTech vaccine significantly improved the immunogenicity of the vaccine in a small group of solid organ transplant recipients.[458]

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.[459][460][461][462][463]

  • Emerging observational evidence suggests real-world efficacy in reducing the rate of symptomatic or asymptomatic infection, disease severity, hospitalisation, and death; however, further research is required.

    • The interim results of a living systematic review in Europe found a vaccine efficacy of 80% to 90% in preventing infection (including asymptomatic infection) for vaccines approved in Europe.[464]

    • A meta-analysis of 19 observational studies found that the Pfizer/BioNTech vaccine provided a significant protective effect against testing positive on reverse transcription polymerase chain reaction (regardless of the presence of symptoms) 14 days or more after the first dose (vaccine efficacy 53%), and 7 days or more after the second dose (vaccine efficacy 95%).[465]

    • A case control study of over 150,000 adults aged ≥70 years who were vaccinated with either the Pfizer/BioNTech or AstraZeneca vaccines and who reported symptoms between 8 December 2020 and 19 February 2021 found that vaccination with one dose of either vaccine was associated with a 60% to 70% protection against symptomatic disease, an 80% protection against hospital admission, and an 85% protection against death. Protection was maintained for at least 6 weeks, and vaccines were effective against the B.1.1.7 variant.[466]

      Early effectiveness of covid-19 vaccination[Figure caption and citation for the preceding image starts]: Early effectiveness of covid-19 vaccinationBMJ. 2021 May 13;373:n1088 [Citation ends].

    • A prospective cohort study (preprint) in the UK found that people aged ≥70 years who received a single dose of either the Pfizer/BioNTech or AstraZeneca vaccine had a 44% and 55% reduced risk of death, respectively, compared with unvaccinated people. There was a 69% reduced risk of death after the second dose of the Pfizer/BioNTech vaccine.[467]

    • A prospective cohort study (preprint) in the UK found that effectiveness in preventing hospitalisation was high in people aged ≥70 years who received a single dose of either the AstraZeneca or Pfizer/BioNTech vaccines (73% and 81%, respectively, in patients ≥80 years; 84% and 81%, respectively, in patients 70-79 years), and especially after two doses of the Pfizer/BioNTech vaccine (93% in patients ≥80 years) compared with unvaccinated people.[468] A study in Scotland found that the first dose of the Pfizer/BioNTech vaccine was associated with a 91% reduction in hospital admissions at 28 to 34 days post-vaccination (an 88% reduction for the AstraZeneca vaccine).[469]

    • A prospective cohort study (preprint) in the UK found that odds of new infection were reduced by 65% after the first dose of either the Pfizer/BioNTech or AstraZeneca vaccine compared with unvaccinated people without prior evidence of infection. A larger reduction in odds of infection was seen after the second dose (70%). There was no evidence that the benefits varied between the two vaccines.[470]

    • A prospective cohort study in UK healthcare workers found that a single dose of the Pfizer/BioNTech vaccine showed effectiveness at preventing both symptomatic and asymptomatic infection of 70% at 21 days after the first dose and 85% at 7 days after two doses compared with an unvaccinated cohort. The study population was exposed to the B.1.1.7 variant.[471]

    • A prospective cohort study (preprint) in the UK found that the Pfizer/BioNTech and AstraZeneca vaccines are associated with reduced likelihood of household transmission from individuals diagnosed with COVID-19 after vaccination. The secondary attack rate was reduced from 10.1% when the index case was an unvaccinated person, to 5.7% to 6.25% (depending on the vaccine) when the contact was vaccinated.[472]

    • A prospective cohort study in the over 10,000 older adults living in long-term care facilities in the UK found that the Pfizer/BioNTech and AstraZeneca vaccines are associated with a substantially reduced risk of infection from 28 days after a single dose, and this effect was maintained for at least 7 weeks.[473]

    • A prospective test-negative case-control study in adults aged at least 80 years who were admitted to hospital in the UK found that one dose of either the Pfizer/BioNTech and AstraZeneca vaccines resulted in a substantial risk reduction in hospitalisation.[474]

    • Observational studies from Israel have found that the Pfizer/BioNTech vaccine was highly effective in preventing symptomatic and asymptomatic infection, as well as hospitalisations, severe disease, need for mechanical ventilation, and death, including those caused by the B.1.1.7 variant.[475][476][477][478][479][480] However, concerns have been raised about the studies.[481]

    • Observational studies from the US have found that the Pfizer/BioNTech and Moderna vaccines were highly effective in preventing symptomatic and asymptomatic infection, as well as hospitalisations.[482][483][484][485][486][487]

  • Current data on the real world effectiveness and the impact of vaccines is published each week in the UK. As of 15 July 2021, vaccine effectiveness has been estimated as follows (evidence varies from low to high depending on the outcome and the vaccine):

    • Symptomatic disease: 85% to 95% (after 2 doses of Pfizer/BioNTech); 70% to 85% (after 2 doses of AstraZeneca)

    • Hospitalisation: 90% to 99% (after 2 doses of Pfizer/BioNTech); 80% to 99% (after 2 doses of AstraZeneca)

    • Mortality: 95% to 99% (after 2 doses of Pfizer/BioNTech); 75% to 99% (after 2 doses of AstraZeneca)

    • Infection: 70% to 90% (after 2 doses of Pfizer/BioNTech); 65% to 90% (after 2 doses of AstraZeneca)

    • Transmission: no data available as yet.

    • Public Health England: COVID-19 vaccine surveillance reports external link opens in a new window

  • Previous trials of coronavirus vaccines identified cellular immunopathology and antibody-dependent enhancement as potential safety issues.[488][489]

    • 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.[459][460]

Vaccines: efficacy against SARS-CoV-2 variants

  • Pfizer/BioNTech: preliminary studies suggest that the Pfizer/BioNTech vaccine may be effective against the following variants, although the neutralisation effect may be reduced compared with the wild-type virus:[44][45][46][47][490][491][492][493][494][495][496][497]

    • B.1.1.7 (and B.1.1.7 + E484K)

    • B.1.351

    • B.1.526

    • B.1.429

    • B.1.617.1 and B.1.617.2.

  • Moderna: preliminary studies suggest that the Moderna vaccine may be effective against the following variants, although the neutralisation effect may be reduced compared with the wild-type virus:[44][493][498][499][500]

    • B.1.1.7

    • B.1.351

    • B.1.617.1 and B.1.617.2.

  • AstraZeneca: preliminary studies suggest that the AstraZeneca vaccine may be effective against the following variants, although the neutralisation effect may be reduced compared with the wild-type virus:[44][46][47][501]

    • B.1.1.7

    • B.1.617.2.

  • Manufacturers are currently testing booster doses against emerging variants.[497][502][503]

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.[504]

  • 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 cases are admitted:

    • Wear a medical mask, gloves, an appropriate gown, and eye/facial protection (e.g., goggles or a face shield)

    • Use single-use or disposable equipment.

  • Implement airborne precautions when performing aerosol-generating procedures, including placing patients in a negative pressure room.

    • Some countries and 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.[505]

    • 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.[506]

  • 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.[507]

  • 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.[508][509]

  • 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:[510][511][512][513]

    • 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.[92]

    • 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.[92]

    • 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).[514] 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.[515]

    • 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.[516]

    • 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.[517][518]

    • 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.[519][520]

    • There are harms and disadvantages of wearing masks (e.g., headache, breathing difficulties, facial skin lesions, psychological issues, difficulty communicating, increased viral load).[92] There are insufficient data to quantify all of the adverse effects that might reduce the acceptability, adherence, and effectiveness of face masks.[521][522]

    • 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.[523]

    • 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.[524]

  • 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.

    • Shielding is currently paused in the UK, and the government recommends that clinically extremely vulnerable people follow national restrictions for the general population, and continue to take extra precautions to protect themselves.[525]

    • 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).[526]

    • 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.[527] 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.[528]

    • 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.[529]

    • The psychosocial effects of enforced quarantine may have long-lasting repercussions.[530][531]

    • 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.[532]

  • The WHO recommends that tobacco users stop using tobacco given the well-established harms associated with tobacco use and second-hand smoke exposure.[246] Public Health England also recommends stopping smoking.

Pre-exposure or post-exposure prophylaxis

  • There are no treatments recommended for pre-exposure prophylaxis or post-exposure prophylaxis, except in the context of a clinical trial.[3] See the Emerging external link opens in a new windowsection for more information.

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