Primary prevention

Vaccines

  • The World Health Organization (WHO) has authorized the use of the following monovalent vaccines (based on the original wild-type virus) for global use:

    • mRNA vaccines: Comirnaty® (Pfizer/BioNTech); Spikevax® (Moderna)

    • Adenovirus vector vaccines: Vaxzevria® (AstraZeneca); Jcovden® (Janssen); Convidecia® (Cansino)

    • Protein subunit vaccines: Nuvaxoid® (Novavax); Covovax® (Serum Institute of India)

    • Inactivated virus vaccines: Covilo® (Sinopharm); CoronaVac® (Sinovac); VLA2001 (Valneva)

    • WHO: COVID-19 vaccines technical documents Opens in new window

  • Vaccine availability and immunization programs differ between countries.

    • Other vaccines may be authorized in specific countries.

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

    • Novel formulations may be available in some countries (e.g., an inhaled vaccine is available in China).

    • Consult your local COVID-19 vaccination schedule for more information.

  • Vaccine efficacy depends on the vaccine used, the predominant circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, and time since vaccination.

    • Initial authorization of vaccines was based on interim analyses of ongoing phase 3 clinical trials with a median follow-up of 2 months. Overall initial vaccine efficacy for preventing symptomatic infection was reported as 95% (Pfizer/BioNTech), 94.1% (Moderna), 74% (AstraZeneca), and 66.9% (Janssen).[360][361][362][363]

    • Observational evidence from the initial global vaccine rollout suggested real-world efficacy in reducing the rate of symptomatic or asymptomatic infection, disease severity, hospitalization, death, and possibly even reinfection. However, evidence indicates a minimal to modest reduction of vaccine protection against severe disease over the 6 months after the primary series, while waning efficacy against all clinical disease and infection is more pronounced. Vaccine efficacy against severe disease decreased by about 8% over a 6-month period in all age groups (10% in those ages >50 years), and vaccine efficacy against symptomatic disease decreased by 32% in those ages >50 years.[364] Waning of immunity after vaccination begins as early as the first month and continues to decline until the sixth month, where the level of immunity may not provide adequate protection.[365]

    • Efficacy is highest for the Alpha variant, with lower efficacy reported for Beta, Gamma, and Delta variants.[366] Efficacy against severe outcomes (e.g., hospitalization) are lower for Omicron compared with Delta, but mostly remain >50% after the primary series and improve with a booster dose to >80%.[12] It is uncertain how long this protection lasts for, although one study suggests 4 to 6 months.[367] There is no reported difference in vaccine efficacy between Omicron subvariants.[3][368] 

    • While current monovalent vaccines continue to perform well in preventing severe disease and death due to the Omicron variant (and its subvariants), particularly with the use of a booster dose(s), protection against infection and symptomatic illness due to the Omicron variant is lower than other variants and declines rapidly, even after a third (booster) dose.[369][370]

    • Some immune evasion/escape has been observed in the context of the Omicron subvariants that are currently circulating (e.g., BA.2.75, BA.4, and BA.5).[371][372][373]

  • Bivalent mRNA vaccines are available in some countries, and may be recommended as part of booster programs.

    • Bivalent vaccines target two SARS-CoV-2 variants: the original wild-type virus, and the Omicron variant. Some bivalent vaccines are based on the Omicron BA.1 subvariant, while others are based on the Omicron BA.4 and BA.5 subvariants. Availability differs between countries.

    • Studies indicate that BA.1-based bivalent vaccines produce a marginally higher immune response against Omicron variants compared with the original wild-type vaccine.[374] However, the clinical relevance of these small differences is uncertain, and there is a lack of published safety and efficacy data available.[375][376] There are no human data available for the BA.4/BA.5 vaccine, and approval was based on studies in mice.[377]

    • The World Health Organization recommends that variant-containing vaccines should not be used for the primary series until supportive evidence or regulatory approval become available. Variant-containing vaccines may be used for the first or second booster doses. However, there are currently insufficient data to support a preferential recommendation for bivalent vaccines over monovalent vaccines. Immunogenicity data comparing bivalent boosters to the monovalent boosters demonstrate only modest superiority, and the impact on vaccine effectiveness remains to be demonstrated.[373] Despite this recommendation, bivalent vaccines may be used in the primary vaccination series in some countries.[378]

    • Consult your local COVID-19 vaccination schedule for more information.

  • WHO: draft landscape and tracker of COVID-19 candidate vaccines Opens in new window

Vaccines: dose schedules

  • Administer the primary vaccination series according to local public health authority recommendations.

    • One-, two-, or three-dose schedules may be recommended depending on the vaccine used and the patient’s age.

    • Some vaccines may only be authorized for use in adults ≥18 years of age, while others may be approved for use in children ≥6 months of age and adults. Authorizations may differ between countries.

    • Doses in children ≥12 years of age and adolescents are typically the same as doses for people ≥18 years of age. However, lower doses are recommended in children <12 years of age and depend on the vaccine brand used.

    • Vaccine vials may have different colored caps to help identify the correct formulation and dose for a particular age group, and therefore help to reduce the risk of dose administration errors.

    • Intervals between doses depend on the vaccine used and may differ between countries. Some countries may recommend longer intervals between doses as it has been associated with higher vaccine efficacy and a lower risk of myocarditis (e.g., in young men).

  • Additional doses may be recommended as part of the primary vaccination series for moderately to severely immunocompromised people.

    • The WHO recommends that the primary vaccination series for all vaccines should be extended to include an additional dose in moderately to severely immunocompromised people.[379] 

    • There are no vaccine efficacy studies following a third dose in immunocompromised people.[380] Although there is no direct evidence that the ability to produce antibodies in these patients offers protection, it is expected that the extra dose increases protection, at least in some patients.[381]

  • Administer booster doses according to local public health authority recommendations. The booster dose may differ from the dose used for the primary series for some vaccines.

    • The WHO recommends an initial booster dose for the highest priority-use groups 4 to 6 months after the completion of the primary vaccination series. Once high booster dose coverage has been achieved in these groups, a booster may be considered for other lower priority-use groups.[382]

    • Evidence for the benefit of an initial booster dose is inferred through immunogenicity, and the overall level of certainty is very low for prevention of symptomatic disease, hospitalization, and death, as well as serious adverse events and reactogenicity.[383] Observational data to support the safety and efficacy of an initial booster dose are available, but their follow-up periods are generally too short to assess long-term effectiveness, the number of trial participants is small, and studies focus on plasma neutralizing antibodies and don’t take into account the protection provided by cellular immunity.[384][385][386][387][388][389][390][391] 

    • The WHO recommends considering a second booster dose 4 to 6 months after the last dose for the following groups: older people; moderately to severely immunocompromised; adults with comorbidities that put them at higher risk for severe disease; pregnant women; and healthcare workers.[392]

    • Evidence for the benefit of a second booster dose is limited and largely comes from Israel.[393][394][395] There is no clear evidence to support giving a second booster dose to people <60 years of age who are not at higher risk of severe disease.[396]

    • Bivalent vaccines are available in some countries, and may be recommended as part of booster programs in certain age groups or those with underlying health conditions. Monovalent vaccines may no longer be recommended for booster doses. Consult your local COVID-19 vaccination schedule for more information.

    • A monovalent vaccine based on the SARS-CoV-2 Beta variant is available in some countries as a booster in patients who have previously received an mRNA or adenovirus-vector vaccine.[397]

  • Heterologous vaccination schedules may be recommended in some countries.

    • The WHO recommends that homologous schedules should be considered standard practice. However, a flexible approach is supported, and two heterologous doses of any authorized vaccine may be used to complete a primary series.[398] Heterologous regimens may also be used for booster doses.[392]

    • A systematic review and network meta-analysis found that different heterologous and homologous three-dose regimens worked comparably well in preventing infection, even against different variants. However, the effectiveness against death remains uncertain.[399]

  • COVID-19 and influenza vaccines may be administered together.

    • The WHO recommends that coadministration of any dose of a COVID-19 vaccine with an inactivated seasonal influenza vaccine is acceptable and may be considered during the same visit (in contralateral limbs). Only limited evidence exists to support this recommendation, but available evidence does not show increased adverse events. No coadministration data are available for other live or inactivated vaccines.[400] 

    • A multicenter randomized controlled phase 4 trial found that concomitant COVID-19 and influenza vaccine administration raised no safety concerns, most systemic reactions were mild or moderate, and the immune response was not adversely affected.[401] However, a retrospective cohort study found that simultaneous administration of a COVID-19 mRNA booster and seasonal influenza vaccines was associated with significant increases in reports of systemic reactions 0 to 7 days following vaccination, although most reactions were generally mild.[402]

  • Consult your local COVID-19 vaccination schedule for detailed information on choice of vaccine, dose schedule, contraindications, warnings, and cautions.

Vaccines: special patient populations

  • Pregnancy

    • The WHO recommends offering vaccination to all pregnant women. Pregnancy testing is not recommended prior to vaccination. Delaying pregnancy or terminating a pregnancy because of vaccination is not recommended.[403]

    • There are limited safety and efficacy data available in pregnant women. However, available data do not support an increased risk of adverse outcomes following vaccination in pregnancy.[404] Systematic reviews and meta-analyses have found no evidence of a higher risk of adverse outcomes in pregnant women including miscarriage, earlier gestation at birth, placental abruption, pulmonary embolism, postpartum hemorrhage, maternal death, intensive care unit admission, lower birthweight Z-score, Apgar score ≤7 at 5 minutes, or neonatal intensive care unit admission with mRNA vaccines.[405][406][407][408] However, these data have limitations, and continued monitoring is needed to further assess the risk. Additional data on vaccination early in pregnancy, non-mRNA vaccines, and longer-term infant outcomes are needed.

    • Emerging observational evidence suggests that vaccination during pregnancy may protect the infant against infection during the first 4 months of life, and reduce the risk of hospitalization among infants <6 months of age.[409][410] However, the optimal timing of vaccination in pregnancy for neonatal benefit remains uncertain.[404]

  • Breastfeeding

    • The WHO recommends offering vaccination to all breastfeeding women. Discontinuing breastfeeding because of vaccination is not recommended.[411]

    • There are limited safety and efficacy data available in breastfeeding women. Vaccine-derived mRNA has been detected in the breast milk of women who received vaccination within 6 months of delivery. The implications of this are currently unknown, and further research is required.[412]

    • Studies have found robust secretion of SARS-CoV-2 specific immunoglobulin A (IgA) and IgG antibodies in breast milk after vaccination.[413] However, it is unclear how long antibodies persist in the breast milk after vaccination, and their impact on the prevention of infection in infants is also unclear.

  • Children and adolescents

    • The WHO recommends offering vaccination to children with comorbidities and severe immunocompromising conditions.[414]

    • Vaccines are authorized for infants from 6 months of age in some countries. Available evidence suggests that the safety and efficacy of vaccines are acceptable in children and adolescents. Older children and adolescents were at significantly increased risk of adverse reactions after vaccination compared with younger children. There is a need for additional multicenter, large-sample studies and long-term follow-up data.[415]

    • Due to the limited number of children included in the original clinical trials, studies could not have detected rare adverse effects such as myocarditis. However, safety monitoring of the Vaccine Adverse Event Reporting System (VAERS) noted over 9000 reports of adverse events post-vaccination in adolescents ages 12 to 17 years (as of 16 July 2021), 9.3% of which were for serious adverse events including myocarditis (4.3%).[416] Preliminary real world data has not picked up an increased risk of myocarditis in children ages 5 to 11 years as yet.[417][418] No data is available for children <5 years of age as yet.

  • Immunocompromised

    • Seroconversion rates were significantly lower in immunocompromised people, especially solid organ transplant recipients, but increased after the second dose. However, seroconversion remained severely reduced in solid organ transplant recipients even after second and third doses compared with the general population.[419][420] Approximately 20% to 40% of solid organ transplant recipients did not mount an antibody response despite receiving multiple doses of mRNA vaccines.[421]

    • Immunosuppressive medication was the most prominent risk factor associated with seroconversion failure in transplant patients, although this was dependent on the specific drug regimen used. Calcineurin inhibitors, corticosteroids, and mycophenolate were associated with an increased risk of seroconversion failure, while azathioprine and mTOR inhibitors were not.[420] Other risk factors include older age, short interval from receiving the vaccine to the time of transplantation, or comorbidities (e.g., diabetes, kidney disease).[420][422]

    • Available evidence suggests that seroconversion rates in people with HIV infection are similar to healthy controls.[423]

    • Interrupting methotrexate treatment for 2 weeks after a vaccine booster dose has been shown to double the antibody response in people with immune-mediated inflammatory diseases after 4 weeks, and this improvement in antibody response was maintained for 12 weeks. However, there was a temporary deterioration in self-reported disease activity and control at 4 weeks that resolved by 12 weeks.[424]

    • Further research is needed to understand vaccine efficacy among this group.

  • Autoimmune disease

    • Data suggests that vaccine efficacy may be lower in patients with autoimmune disease.[425][426] It is uncertain whether vaccines may cause an exacerbation of preexisting autoimmune diseases; however, there are case reports of new autoimmune conditions or flares of existing autoimmune conditions (e.g., multiple sclerosis) post vaccination.[427][428][429][430][431] Further research is needed to understand vaccine efficacy among this group.

  • Malignancy

    • Data suggests that vaccine efficacy may be lower in cancer patients compared with the general population. Antibody response was lower in hematologic malignancies compared with solid tumors. Antibody response was also lower for allogeneic and autologous hematopoietic stem cell transplant recipients, and those receiving active treatment. The response varied depending on the treatment; lower responses were reported for anti-CD20 therapies, Bruton kinase inhibitors, venetoclax, ruxolitinib, and chimeric antigen receptor T-cell therapy.[432] Further research is needed to understand vaccine efficacy among this group.

Vaccines: breakthrough infections

  • Breakthrough infections are possible after vaccination.

    • Breakthrough infections that have resulted in hospitalization or death, as well as mild or asymptomatic infections, have been reported in fully vaccinated people.[433][434]

    • One observational study 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.[435] 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.[436]

    • One systematic review and meta-analysis of 18 studies found that there were no statistically significant differences in the risk of hospitalization, invasive mechanical ventilation, or mortality between unvaccinated people and fully vaccinated people with breakthrough infections (during the Delta variant-dominant period). However, unvaccinated people showed an increased need for oxygen supplementation. There was a limited number of studies included in the meta-analysis and a high level of heterogeneity across studies; therefore, these results should be interpreted with caution. Further prospective studies that adjust for the baseline characteristics of patients are necessary to evaluate vaccine efficacy more precisely.[437] 

  • Vaccinated people should be considered a possible source of transmission and continue to follow local public health recommendations.

    • Limited evidence suggests that fully vaccinated people with breakthrough infections have similar viral loads compared with unvaccinated people, and therefore may be equally likely to transmit the infection, including to fully vaccinated contacts.[438][439] 

    • Secondary attack rates among household contacts exposed to fully vaccinated index cases were similar to household contacts exposed to unvaccinated index cases (25% for vaccinated versus 23% for unvaccinated).[440]

  • Risk factors for breakthrough infections and progression to severe disease are similar to those for unvaccinated people.

    • Risk factors for breakthrough infection include frailty in older adults ages ≥60 years, dementia, living in deprived areas, immune dysfunction (including HIV infection), cancer (especially hematologic malignancies and those undergoing active cancer care), and obesity.[441][442][443][444][445] 

    • Older age, male sex, increasing number of comorbidities, hospitalization in the previous 4 weeks, high-risk occupation, care home residence, socioeconomic deprivation, and smoking history were all associated with an increased risk of hospitalization or death in patients with breakthrough infections.[446] 

    • Prior SARS-CoV-2 infection may be associated with a lower risk for breakthrough infection.[447]

  • Breakthrough infections have been reported with the Omicron variant, including people who have received a booster dose.

    • While breakthrough infections with the Omicron variant are more frequent compared with the Delta variant, hospital admissions were less frequent with Omicron.[448][449]

Vaccines: adverse events

  • Consult the prescribing information for detailed information about the adverse events associated with a specific vaccine. Adverse events may vary depending on the type of vaccine used and include, but are not limited to, the following:

    • Common: injection-site reactions, fatigue, headache, myalgia, arthralgia, chills, fever, rash, nausea/vomiting, and diarrhea; these are usually mild or moderate, and generally resolve a few days after vaccination

    • Uncommon: lymphadenopathy, hypersensitivity reactions including anaphylaxis, hyperhidrosis, night sweats, insomnia, dizziness, lethargy, asthenia, malaise, abdominal pain, pain in vaccinated arm, tremor

    • Rare: transverse myelitis (mainly adenovirus-vector vaccines), Guillain-Barre syndrome (mainly adenovirus-vector vaccines), acute peripheral facial paralysis, myocarditis/pericarditis (mainly mRNA and protein subunit vaccines), vaccine-induced immune thrombocytopenia and thrombosis and other thromboembolic events (mainly adenovirus-vector vaccines), immune thrombocytopenia (mainly adenovirus-vector vaccines), paresthesia/hypoesthesia, erythema multiforme, extensive swelling of the vaccinated limb, facial swelling (in people with a history of dermatologic fillers)

    • For information on the diagnosis and management of myocarditis/pericarditis and vaccine-induced immune thrombocytopenia and thrombosis see Complications.

  • Menstrual changes have also been reported following vaccination.[450] However, further research is required.

    • One prospective cohort study found that vaccination was associated with a small change in cycle length (one-day change), but not menses length.[451] Another large cohort study found that 42% of people with regular menstrual cycles bled more heavily than usual, while breakthrough bleeding was reported in people on long-acting reversible contraceptives (71%), postmenopausal women (66%), and people on gender-affirming hormones (39%).[452]

    • A systematic review found that 52% of women reported some form of menstrual problem after vaccination including menorrhagia, metrorrhagia, and polymenorrhea being the most common.[453] 

    • The European Medicines Agency has recommended that heavy menstrual bleeding be added to the product information as an adverse effect of mRNA vaccines.[454]

  • Serious adverse events, including fatal adverse events, have been reported in clinical trials, case reports, case studies, and observational studies (e.g., neurologic disorders, cutaneous manifestations, varicella zoster virus reactivation, autoimmune disorders, myocardial infarction).[455][456][457][458][459] However, a causal link may not have been confirmed for some. A detailed discussion of adverse events is beyond the scope of this topic.

    • A secondary analysis of phase 3 randomized clinical trials of mRNA vaccines in adults found an excess risk of serious adverse events of special interest of 12.5 per 10,000 vaccinated, which suggests a higher risk than initially estimated at the time of emergency authorization.[460]

    • Medicines and Healthcare products Regulatory Agency: coronavirus vaccine - summary of Yellow card reporting Opens in new window

  • Report all suspected adverse events after vaccination via your local reporting system. This is mandatory in some countries. Surveillance of adverse events is extremely important, and may reveal additional, less frequent serious adverse events not detected in clinical trials. The mRNA vaccines have not been authorized for use in humans previously, so there is no long-term safety and efficacy data available for these types of vaccines.

Monoclonal antibodies: pre-exposure prophylaxis

  • Tixagevimab/cilgavimab is authorized in some countries for pre-exposure prophylaxis.

    • Tixagevimab/cilgavimab is a long-acting, neutralizing monoclonal antibody combination with activity against SARS-CoV-2. It is designed to attach to the spike protein of the virus at two different sites.

    • It is authorized for use in the US, the UK, and Europe.[461][462][463] However, the UK government has not procured the drug due to insufficient data on the duration of protection it provides against the Omicron variant and its subvariants.[464]

  • Guideline recommendations for the use of tixagevimab/cilgavimab vary. Consult your local guidance.

    • In the US, the National Institutes of Health guidelines panel recommends tixagevimab/cilgavimab for pre-exposure prophylaxis in children ages ≥12 years (weighing ≥40 kg) and adults who do not have SARS-CoV-2 infection, who have not been recently exposed to an individual with SARS-CoV-2 infection, AND who are moderately to severely immunocompromised and may have an inadequate immune response to vaccination, or are not able to be fully vaccinated with any available COVID-19 vaccines due to a documented history of severe reactions. This includes people with advanced or untreated HIV infection. The decision to use tixagevimab/cilgavimab should be based on the regional prevalence of resistant subvariants and the individual patient’s risks for infection and severe disease. Precautions to avoid SARS-CoV-2 exposure are still recommended.[465]  

    • The Infectious Diseases Society of America supports the use of tixagevimab/cilgavimab for pre-exposure prophylaxis when predominant regional variants are susceptible. It suggests against the use of tixagevimab/cilgavimab for post-exposure prophylaxis, unless predominal regional variants are susceptible.[466] 

  • Consult your local drug formulary for information about contraindications, cautions, adverse effects, and drug interactions before prescribing this treatment.

    • Tixagevimab/cilgavimab is given as a single dose administered as two separate consecutive intramuscular injections.

    • Serious hypersensitivity reactions including anaphylaxis have been reported. Monitor and observe patients for at least 1 hour after administration.

    • There is a risk of cross-hypersensitivity with COVID-19 vaccines, and people with a history of a severe hypersensitivity reaction to a COVID-19 vaccine should consider consultation with an allergist/immunologist prior to administration of tixagevimab/cilgavimab.

    • Serious cardiac adverse events were reported infrequently in the clinical trial; however, it is unknown whether these events were caused by the drug.

  • Circulating SARS-CoV-2 variants may be associated with resistance to monoclonal antibodies.

    • In vitro data show that the Omicron BA.1, BA.4, and BA.5 subvariants have decreased susceptibility to tixagevimab/cilgavimab, while there is no change with the BA.2 subvariant.[465] However, according to the manufacturer, in vivo data suggests that tixagevimab/cilgavimab retains neutralizing activity against Omicron subvariants.[467]

    • Dose recommendations may depend on the local circulating variant and whether the patient has had the treatment previously. Repeat dosing may be required every 6 months.[465]

    • Consult local guidance for details regarding specific variants and resistance.

  • Evidence is limited.

    • In an ongoing multicenter, double-blind, parallel-group, randomized, placebo-controlled trial, tixagevimab/cilgavimab reduced the risk of developing symptomatic disease by 76.7% (relative risk reduction) compared with placebo at the primary analysis (median 83 days after administration), with an 82.8% relative risk reduction reported at the median 6-month follow-up. All cases of severe or critical disease were reported in the placebo group. The most common adverse event was injection-site reactions.[468]

    • A small cohort study found that pre-exposure administration of tixagevimab/cilgavimab was associated with a lower risk of infection in severely immunocompromised patients with immune-mediated inflammatory diseases who were fully vaccinated. However, due to the limitations of the study, these results should be interpreted with caution.[469]

Infection prevention and control for healthcare professionals

  • Consult local infection prevention and control protocols; only basic principles from the World Health Organization (WHO) guidelines are detailed here.[470][471]

  • Screen all people, including patients, visitors, and others entering the facility, for COVID-19 at the first point of contact with the health facility to allow for early recognition.

  • Immediately isolate all suspected or confirmed cases in a well-ventilated area that is separate from other patients. Place patients in adequately ventilated single rooms if possible. When single rooms are not available, place all cases together in the same adequately ventilated room and ensure there is at least 3 feet (1 meter) between patients.

  • Implement standard precautions at all times:

    • Practice hand and respiratory hygiene

    • Give patients a medical mask to wear

    • Wear appropriate personal protective equipment

    • Practice safe waste management and environmental cleaning.

  • Implement additional contact and droplet precautions before entering a room where suspected or confirmed cases are admitted.

    • A respirator or medical mask should be worn along with other personal protective equipment (i.e., gown, gloves, eye protection) before entering a room with a suspected or confirmed case.

    • A respirator should be worn in the following situations: in care settings where ventilation is known to be poor or cannot be assessed, or the ventilation system is not properly maintained; based on the worker’s values and preferences and on their perception of what offers the highest protection possible to prevent infection.

    • Appropriate mask fitting should always be ensured, as should compliance with appropriate use of personal protective equipment and other precautions.

    • Universal masking is strongly recommended in health facilities in areas of known or suspected community or cluster transmission.

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

    • A respirator should always be worn along with other personal protective equipment while performing aerosol-generating procedures, and in settings where these procedures are regularly performed on patients with suspected or confirmed disease (e.g., intensive care units, emergency departments).

    • Some countries and organizations recommend airborne precautions for any situation involving the care of a COVID-19 patient.

  • All specimens collected for laboratory investigations should be regarded as potentially infectious.

  • Appropriate personal protective equipment gives healthcare workers a high level of protection.

    • A rapid review and meta-analysis found that wearing personal protective equipment conferred significant protection against infection compared with not wearing it. High-certainty evidence indicates that using N95 masks significantly reduces the risk of infection. No effect was found for wearing gloves and gowns. There is a lack of evidence for different combinations of personal protective equipment.[472]

  • 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.[473]

  • Detailed infection prevention and control guidance is available:

Infection prevention and control for the general public

  • Public health recommendations vary between countries and you should consult your local guidance.

    • It is generally recommended that people stay at least 3 to 6 feet (1-2 meters) away from others (recommendations vary between countries), wash their hands often with soap and water (or hand sanitizer that contains at least 60% alcohol), cover coughs and sneezes, 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.[474][475]

    • WHO: advice for the public – coronavirus disease (COVID-19) Opens in new window

  • Countries may sometimes implement nonpharmaceutical interventions in order to reduce and delay viral transmission (e.g., social distancing, city lockdowns, stay-at-home orders, curfews, nonessential business closures, bans on gatherings, school and university closures, remote working, quarantine of exposed people).

    • Implementing any nonpharmaceutical interventions was associated with a significant reduction in case growth when comparing countries with more restrictive nonpharmaceutical interventions to countries with less restrictive nonpharmaceutical interventions. However, there was no clear, significant beneficial effect of more restrictive nonpharmaceutical interventions compared with less restrictive nonpharmaceutical interventions in any of the countries studied.[476] 

    • 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.[477]

  • Some countries have published guidance to support the next stage of the pandemic, living with COVID-19. This new phase focuses on protecting those who are most at risk from the virus. Consult your local guidance.

  • The following guidance has been published in the UK:

Face masks

  • Public health recommendations on wearing face masks vary between countries and you should consult your local guidance. Many countries have ended mask mandates, except in certain high-risk situations.

  • The WHO recommends wearing a mask, regardless of vaccination status or history of prior infection, in settings where there is community or cluster transmission when interacting with nonhousehold members in the following circumstances:[471]

    • Indoor settings where ventilation is poor or cannot be assessed, regardless of whether physical distancing of at least 3 feet (1 meter) can be maintained

    • Indoor settings with adequate ventilation if physical distancing cannot be maintained

    • Outdoor settings if physical distancing cannot be maintained

    • For people who are at higher risk of severe complications from infection, if physical distancing cannot be maintained in any setting.

  • Masks are not recommended:

    • During vigorous-intensity physical activity

    • In children ages <5 years for source control (a risk-based approach should be applied to children ages 6-11 years)

    • In children with severe cognitive or respiratory impairments, developmental disorders, disabilities, or other specific health conditions who experience difficulties wearing a mask or have health conditions that interfere with mask-wearing.

  • There is no high-quality or direct scientific evidence to support the widespread use of masks by healthy people in the community setting. Data on effectiveness is based on limited and inconsistent observational and epidemiologic studies.

    • The only randomized controlled trial to investigate the efficacy of masks in the community found that the recommendation to wear surgical masks when outside the home did not reduce infection compared with a no mask recommendation. However, the study did not assess whether masks could decrease disease transmission from mask wearers to others (source control).[478] Evidence from randomized controlled trials for other respiratory viral illnesses shows no significant benefit of masks in limiting transmission but is of poor-quality and not SARS-CoV-2-specific.[479]

    • 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.[480] 

    • A living rapid review found that the evidence for mask effectiveness for respiratory tract infection prevention is stronger in healthcare settings compared with community settings; however, direct evidence on comparative effectiveness in SARS-CoV-2 infection is insufficient. The strength of evidence for any mask use versus nonuse in community settings is low-moderate and is based mainly on observational studies with methodological limitations.[481][482]

    • 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.[483][484]

  • There are harms and disadvantages of wearing masks including headache, breathing difficulties, facial skin lesions, irritant dermatitis, worsening acne, difficulty wearing masks by certain members of the population (e.g., children, people with learning disabilities, mental illness or cognitive impairment, asthma, chronic respiratory or breathing problems, facial trauma or recent oral maxillofacial surgery, living in hot and humid environments), psychological issues, difficulty communicating, poor compliance, waste disposal issues, and increased viral load. There are insufficient data to quantify all of the adverse effects that might reduce the acceptability, adherence, and effectiveness of face masks.[471][485][486]

    • Overall prevalence of facial dermatoses has been reported to be 55%.[487]

    • Consensus recommendations suggest taking a break from mask wearing after 1 to 2 hours of continuous use, particularly certain groups of people (e.g., pregnant women, children, people with respiratory conditions or epilepsy).[488]

    • BMJ: mask related acne (“maskne”) and other facial dermatoses Opens in new window

Travel-related control measures

  • Many countries implemented measures including complete or partial closure of borders, entry or exit screening, and/or quarantine of travelers; however, these measures are no longer in place in most countries. Consult your local guidance.

    • 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).[489] 

    • 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.[490] 

    • A Cochrane review found quarantine to be important in reducing the number of people infected and deaths, especially when started earlier and when used in combination with other prevention and control measures. However, the current evidence is limited because most studies are based on mathematical modeling studies that make assumptions on important model parameters.[491] 

  • The psychosocial effects of enforced quarantine may have long-lasting repercussions.[492][493]

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.[494]

  • The WHO recommends that tobacco users stop using tobacco given the well-established harms associated with tobacco use and second-hand smoke exposure.[225] 

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