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COVID-19 (coronavirus disease 2019)

Last updated: June 7, 2021

Summarytoggle arrow icon

COVID-19 is an acute infectious respiratory disease caused by infection with the coronavirus subtype SARS-CoV-2, first detected in Wuhan, China, in December 2019. It is currently spreading worldwide and is considered a pandemic disease. Transmission occurs primarily via respiratory droplets (sneezing and coughing). Following an incubation period of 2–14 days (average ∼ 5 days), COVID-19 usually presents with fever and upper respiratory symptoms, especially dry cough and often dyspnea; asymptomatic courses and certain other symptoms can also occur. Clinical courses range from very mild to developing into severe with pneumonia and even critical with life-threatening complications such as ARDS, shock, and organ dysfunction. Recommendations for infection control and preventive measures vary according to the appropriate health department/agency, but generally involve personal hygiene (e.g., washing hands), avoiding exposure/public places, quarantines/isolation, and wearing suitable personal protective equipment (PPE). Diagnosis is confirmed by RT-qPCR of SARS-CoV-2 RNA isolated from patient specimens, preferably from at least a nasopharyngeal swab. In some cases of mild symptoms and depending on local recommendations, diagnostic testing may not be warranted. In mild clinical courses, patients should self-isolate with supportive care and monitoring at home. Patients with clinical manifestations of severe courses (i.e., dyspnea, cyanosis, chest discomfort, or mental status change), signs of respiratory distress (SpO2 ≤ 93%, respiratory rate > 22/min), or possibly at high-risk for severe course (≥ 65 years or certain underlying conditions) should be admitted. Hospitalized patients should receive supportive and oxygen therapy while being regularly monitored with supporting laboratory and imaging studies (Chest x-ray, Chest CT, possibly POCUS). Notable findings indicative of progression to pneumonia include lymphocytopenia, elevated CRP, and CT scans showing ground-glass opacities (can progress to solid white consolidation in severe infection) and inter- and/or intralobular septal thickening (indicating swelling of the interstitial space). POCUS can assist in monitoring of pneumonia and possibly screening for cardiomyopathy. Intensive care and airway management are indicated for patients displaying signs of respiratory failure (e.g., dyspnea with hypoxemia, respiratory rate > 30/min). Endotracheal intubation should be initiated early, preferably by rapid-sequence induction and avoid virus aerosol-generating procedures (AGPs), such as noninvasive ventilation, high-flow oxygen therapy, bronchoscopy, and nebulizer treatment, whenever feasible. Mechanical ventilation should consist of lower tidal volumes and PEEP and FiO2 settings in line with ARDS protocols (e.g., ARDSnet protocol). There is currently no effective treatment; any antiviral treatments should only be considered case-by-case as part of research studies and compassionate use programs. The overall mortality rate ranges from ∼ 0.5–3%, and greatly increases for elderly (∼ 15% for > 80 years) as well as those with certain underlying conditions (e.g., cardiac, pulmonary, diabetes mellitus).

Given the severity of the situation, we at AMBOSS are doing our best to accurately update and expand the content as quickly as possible. Considering that information about COVID-19 is changing daily, we greatly appreciate your understanding of potential delays and hiccups during our development process.

Additional free AMBOSS resources for COVID-19

In addition to this article, the AMBOSS team offers further articles in the library that are relevant for the management of severe COVID-19. Access to the following articles is possible without a paid AMBOSS subscription:

  • Incidence and prevalence
    • Refer to the Johns Hopkins University & Medicine Coronavirus Resource Center (https://coronavirus.jhu.edu/map.html) for up-to-date statistics. [1]
    • Countries with most confirmed cases: US, India, Brazil, United Kingdom, Russia, and France
    • Countries with most deaths: US, Brazil, Mexico, India, United Kingdom, and Italy
  • Outbreak status
    • WHO declared the COVID-19 outbreak a Public Health Emergency of International Concern on January 30, 2020.
    • WHO classified COVID-19 as a pandemic on March 11, 2020.
  • Infectivity
    • Basic reproduction number (R0): ∼ 2–4 [2][3][4]
    • “Flattening the curve”
      • Efforts to prevent the spread of infection (e.g., social distancing, quarantine) decrease the R0, i.e., “flatten the curve” of the number of new cases.
      • The total number of cases may not decrease, but the number of new cases is distributed over a longer period of time.
    • ∼ 31–43% attack rate of family members in China [5]

  • Demographics [6]
    • ♂ = ♀
    • Affects people of all ages
    • In the US, the median age has declined from 40.8 years in March–April, to 35.8 years in June–July. [7]
  • Fatality rate [6]
    • ∼ 0.5–3%
    • Greatly increases > 60 years of age, and for individuals > 80 years reaching ∼ 15%

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

  • Like other coronaviruses, SARS-CoV-2 is an enveloped, nonsegmented, positive-sense, ssRNA virus.
  • The viral genome is packaged into a helical ribonucleocapsid; by the N protein: plays an essential role during viral self-assembly.
  • Genome encodes
    • Four structural proteins
      • Spike (S): allows entry by attaching to the ACE2 receptor of the host cell
      • Envelope (E)
      • Membrane (M)
      • Nucleocapsid (N)
    • 16 nonstructural proteins: form the replicase–transcriptase complex
  • Specifically, it is a β-coronavirus. The other two β-coronaviruses were SARS-CoV and MERS-CoV, which both also caused outbreaks of potentially fatal respiratory tract infections in 2003 and 2012, respectively. [8]
  • The virus was first reported in Wuhan, China. Its origin is still under investigation
    • Genome sequencing shows 96.2% identity to a bat coronavirus RaTG13, making bats the most likely natural host of the SARS-CoV-2 origin. [9]
    • SARS-CoV-2 may be a recombinant virus between a bat coronavirus and an unknown coronavirus strain; homologous recombination may have contributed to the ability of the virus to infect different species (i.e., humans and certain animals). [10]

SARS-CoV-2 variants

  • A population genetic analysis conducted in January 2020 concluded there are two prevalent genotypes of SARS-CoV-2, an L-type (∼ 70%) and an S-type (∼ 30%), with very minor differences. [11]
    • L-type evolved from the S-type and is somewhat more contagious and aggressive.
    • S-type was the original type transmitted to humans from the animal host and is less contagious and aggressive.
  • By now thousands of variants detected worldwide
  • Potential risks of emerging SARS-CoV-2 variants
  • As of April 2021, the most concerning variants are:
    • B.1.1.7 (501Y.V1, United Kingdom)
      • Increased transmissibility compared with the original strain [12][13][14]
      • Possible increased disease severity and mortality [13][15]
    • B.1.351 (501Y.V2, South Africa)
      • Increased transmissibility compared with the original strain [16]
      • Not associated with increased disease severity [15]
      • Spike protein mutation (E484K) might lead to decreased neutralization by antibodies, potentially impacting immunity from vaccination or prior infection. [17][18][19]
    • B.1.1.28 P.1 (501Y.V3, Brazil)
      • Also contains the spike protein mutation E484K, therefore the potential of impacting immunity seems to be similar to B.1.351 variant.
    • B.1.427/B.1.429 (US, California) [20]
      • Increased transmissibility compared with the original strain
      • Spike protein mutation (L452R) leads to decreased neutralization by antibodies

Viral life cycle

  • Invasion of host cells [21]
    • Entry point: Angiotensin-converting enzyme 2 (ACE2) via the spike protein [22][23][24][25][26][27]
    • Transmembrane protease, serine 2 (TMPRSS2): The virus uses TMPRSS2 to invade host cells. It then fuses with the membrane and enters the cell via endosomes.

  • Replication cycle
    • Enzymes, such as RNA polymerase or proteases, that are virally induced by endosomal viral RNA release replicate viral components.
    • Endosomes with newly constituted viruses are released via exocytosis.

Effects

There are currently many hypotheses founded on the research conducted on previous coronavirus outbreaks (MERS, SARS); the viability of these hypotheses and the application of past research to the present situation has yet to be determined!

  • Transmission: mainly person-to-person [32][33]
    • Primarily via respiratory droplets: can be emitted during sneezing and coughing as well as loud speech [34]
    • Via aerosols: infectious concentrations of viral particles were detected in aerosols for a duration of 3 hours and could last even longer
    • Direct contact transmission: especially hand-to-face contact
    • Fomite (surface) transmission: viral particles remain infectious on surfaces outside a host for up to a few days depending on the material [35]
      • Latex, aluminum, copper: ∼ 8 hours
      • Cardboard: ∼ 24 hours
      • Countertops, plastic, stainless steel: ∼ 1–3 days
      • Wood, glass: ∼ 5 days
    • Fecal-oral transmission: unlikely as it has not yet been documented to date [36][37][38]
    • Vertical transmission: see “COVID-19: pregnancy and breastfeeding”
  • Incubation period: 2–14 days, usually ∼ 5 days [39][40][41]
  • Duration of infectiousness
    • It is estimated that infected individuals:
      • Become infectious 2.5 days before the onset of symptoms
      • Cease to be infectious 8 days after the onset of symptoms.
    • The period of greatest infectiousness is at the beginning of symptoms. [42][43][44]
    • Viral RNA has been found in respiratory samples long after initial infection, [45] but the presence of detectable viral RNA does not mean that the individual is still infectious.
  • Immunity and reinfection
    • There is evidence of immune responses to SARS-CoV-2 following initial infection [44][46][47] or exposure to viral components [48].
    • But the duration of immunity and its efficacy on the prevention of reinfection is still uncertain. [49][50] [51][52][53]
    • Some studies suggest that the magnitude of the immune response might be dependent on the severity of the disease. [54][55]
    • Cases of reinfection are possible but rare [56][57][58][59]

The transmission of SARS-CoV-2 by asymptomatic individuals can occur, but individuals are most contagious when they are symptomatic. [60]

Overview

  • Often asymptomatic
  • Children are more likely to be asymptomatic [61]

Symptoms [62][63][64]

Course [61][64][74][75][76]

Postacute COVID-19 syndrome (“long COVID”) [78]

COVID-19 Influenza Common cold Allergic rhinitis
Fever +++ +++ - -
Cough +++ +++ +++ ++
Fatigue +++ +++ + -
Shortness of breath ++ + - -
Loss of appetite ++ ++ - -
Myalgia ++ +++ + -
Loss of smell/taste ++ - ++ ++
Runny nose + + +++ +++
Sneezing - - +++ +++
Sore throat + + +++ -
Diarrhea + + - -
Headache + +++ ++ -
Itchy eyes - - - +++

+++ = very common, ++ = common, + = less common, - = rare

Compared to influenza, a higher proportion of patients with COVID-19 require mechanical ventilation and longer ventilation periods. [79] Patients with COVID-19 also have a higher proportion of extrapulmonary complications![80]

General protective measures

  • Hand hygiene
    • Hands should be washed with soap and water or disinfected with a virucidal hand disinfectant after contact with potentially virus-contaminated objects and infected persons
    • Avoid touching the face: i.e., the eyes, nose, and mouth.

  • Respiratory hygiene and cough etiquette
    • Avoid coughing or sneezing in the direction of others!
    • Use tissues and discard these after use.
      • If tissues are unavailable, coughing and sneezing into the crook of the arm can help keep hands free of contamination.
    • Maintain 3–6 ft (at least an arm's length) distance to coughing or sneezing persons.
  • Avoid exposure
    • Avoid crowds of people (public transport, train stations, airports, mass events).
    • Avoid travel to areas of outbreak.
    • Follow local health agency recommendations regarding attendance of events and gatherings.

Masks

  • General considerations
    • Respirators and masks should be used resourcefully with special consideration for HCF needs.
    • Sufficient supplies are currently at risk due to the high global demand for personal protective equipment (PPE). [81]
    • If not handled correctly (e.g., by bringing infectious material near the airways when touching the mask to adjust it), face coverings and masks might pose an additional risk of infection to the user.
    • Not recommended: masks with valves or vents, scarves, ski masks, balaclavas [82]
    • Face shields generally do not replace the use of a mask but may be used in addition
  • Cloth face coverings [82][83]
    • Indications: Recommendations vary. The following points are based on CDC recommendations:
      • Unvaccinated individuals should wear masks in public settings.
      • Fully vaccinated individuals are not required to wear masks in many public settings.
      • Certain areas or activities (e.g., during flights) may still require masks regardless of vaccination or past infection status.
    • Explicitly recommended in some regions (e.g., the US) for public settings in which physical distancing of 2 meters (∼ 6 feet) cannot be maintained sufficiently (e.g., grocery stores, pharmacies)
    • Might prevent transmission from asymptomatic infected individuals who are unaware of their infectious status [84]
    • Might help reduce the diffusion of viral particles and the range of contamination when exhaling, speaking, coughing, or sneezing
    • May not reliably prevent the dissemination of viral particles to the outside of the mask when an infected individual is coughing [85]
    • The CDC offers free “Sew and No Sew Instructions” for self-made cloth face coverings on their website: [86]
  • Surgical masks
    • Indication: individuals with confirmed or suspected infection
    • Might be efficient in preventing the transmission of viral particles from symptomatic patients by filtering the exhaled breath [87]
    • Might reduce the diffusion of respiratory secretions (via droplets and aerosols) and the range of contamination, e.g., during patient transports
    • May not reliably prevent the dissemination of viral particles to the outside of the mask when an infected individual is coughing [85]
    • Do not provide adequate protection for the user especially during high-risk exposures (e.g., invasive diagnostics, close contact)
  • N95 respirators
    • Indication: health workers and persons taking care of an infected individual in close settings, such as HCFs or home care settings
    • N95 respirators and protective eyewear are recommended for health care personnel that are potentially exposed to airborne and fluid hazards (e.g., during invasive procedures). [88]
    • If N95 respirator bottlenecks occur, unvalved N95 respirators may be used with a face shield.

The CDC recommends the use of cloth face coverings for everyone in public settings (e.g., grocery stores) to reduce the spread of SARS-CoV-2 by asymptomatic infected individuals. Surgical masks and N95 respirators should be reserved for health care workers as a response to the current global shortage of personal protective equipment (PPE). [81][82]

Exposure risk management

  • Depending on official risk assessments, public health measures intended to prevent the spread of COVID-19 include social distancing, home isolation, quarantine, and lockdown of entire communities or countries. The information here is primarily based on CDC recommendations.
  • Individuals who have been fully vaccinated against COVID-19 are exempt from certain rules and regulations (see “https://www.cdc.gov/coronavirus/2019-ncov/vaccines/fully-vaccinated-guidance.html”). [83]

Public health measures [89]

  • Social distancing means individuals should maintain a distance of ∼ 6 feet (2 meters) from others and avoid:
    • Mass gatherings
    • Congregate settings: crowded public places where close contact may occur (e.g., movie theaters, shopping centers)
  • Quarantine: separation of a person or group of people who were exposed to the virus but are not yet symptomatic
  • Isolation: separation of a person or group of people who are infected or reasonably believed to be infected with SARS-CoV-2

Exposure risk assessment and management recommendations [90][91]

  • All U.S. residents are currently at risk of being exposed to SARS-CoV-2 and are advised to:
  • Specific recommendations apply to people with high-risk exposures, such as:
    • Everyone with prolonged (> 15 min) close contact (< 6 feet apart) with an infectious individual , e.g., a household member, an intimate partner, or a person in need of care
    • Travelers returning from another country or a cruise ship [93]
  • Individuals with a recent high-risk exposure are advised to:
    • Isolate at home for 14 days and practice social distancing in regard to other household members
    • Avoid any contact with individuals with risk factors for severe courses of COVID-19
    • Monitor themselves for symptoms of COVID-19 (especially fever, cough, shortness of breath)
    • Check their body temperature to monitor for fever twice daily
    • Contact a health care provider to get advice on their specific situation

Infection prevention and control in healthcare settings

Recommendations vary according to the appropriate health department/agency. Some recommendations from the CDC include: [94]

  • Limit how germs enter HCF
    • Use telemedicine when possible
    • Manage visitor access and movement
    • Cancel elective procedures
    • Screen patients for respiratory symptoms
    • Encourage respiratory hygiene
  • Isolate symptomatic patients with suspected or confirmed COVID-19
    • Set up suitable triage areas
    • Place in private rooms with bathroom (if possible) with closed doors
    • Prioritize airborne infection isolation rooms (AIIRs) for patients requiring aerosol-generating procedures (AGPs)
  • Protect health care personnel
    • Emphasize hand hygiene
    • Limit contact with patients with suspected or confirmed COVID-19: respect barriers, limit staff providing care
    • Prioritize respirators
    • Avoid AGPs
    • Follow recommendations for PPE for COVID-19 (see below) and optimize supply

Personal protective equipment (PPE) [94][95]

Quantitative reverse transcription real-time polymerase chain reaction (RT-qPCR) of RNA collected from patient specimens is conducted to confirm infection with SARS-CoV-2. It is important to follow health department policies for collecting clinical specimens to minimize the risk of spreading infection and ensure quick and accurate test results.

Initial medical evaluation

  • Calling ahead
    • Individuals with mild COVID-19 symptoms and/or exposure to the virus who think they should be medically evaluated for COVID-19 should first call their HCF before visiting to determine if there are special directions (e.g., visit a specific site for testing).
    • If emergency medical services (EMS) are required (COVID-19 related or not), EMS should be notified if the individual is at risk of having COVID-19.
  • Recommendations for COVID-19 testing: vary according to health departments
    • Guiding factors consider epidemiological data and availability of diagnostic testing resources and health care personnel.
    • The CDC recommends testing in the following scenarios: [96]
      • All individuals with COVID-19 symptoms
      • Individuals who had close contact with a confirmed COVID-19 case, except:
        • Fully vaccinated individuals who are asymptomatic
        • Individuals who had COVID-19 in the past 3 months and are asymptomatic
      • Individuals at high risk for COVID-19 infection due to recent activities in which physical distancing was impossible, e.g., travel, mass gatherings, being crowded in poorly-ventilated indoor areas
    • In general, clinicians are urged to make judgment calls if a patient's signs, symptoms, and risk factors warrant COVID-19 testing.
    • The CDC recommends screening certain groups to minimize community transmission, such as: [97]
      • Race and ethnic minority groups and other populations disproportionately affected by COVID-19
      • Staff in schools and childcare settings
      • Students and staff at institutions of higher education
      • Workers with regular close contact to coworkers or customers
      • First responders and health care workers
      • Residents and staff in congregate settings: shelters, correctional facilities, residential settings (e.g., nursing homes), workplaces that provide congregate housing (e.g., farmworker housing), military training facilities (e.g., barracks)
      • Individuals who recently traveled (domestic or international)
      • Individuals who attended mass gatherings
      • Patients in healthcare settings
      • Specific age groups in which the incidence of infection is high
  • Notify authorities: All measures should be consistent with appropriate health department regulations. In the US, health care personnel should immediately notify state or local health departments of patients with fever and/or respiratory symptoms suspected of COVID-19 (i.e., person under investigation, or PUI) to determine:
    • If criteria are met for testing
    • To receive support in collecting, storing, and shipping specimens

Collecting and handling clinical specimens (recommendations based upon CDC guidelines) [98]

  • General measures
  • Collection of specimens
    • For all individuals, conduct on an upper respiratory specimen.
      • Preferred method by the CDC: nasopharyngeal specimen (NPS) using a single synthetic fiber swab with a plastic shaft that is gently inserted through the nostril to the posterior nasopharynx , where it is left for several seconds to absorb secretions before slowly removing while rotating
      • Alternative methods
        • Oropharyngeal (OP) swab (throat swab): swab the posterior pharynx while avoiding the tongue
        • Nasal mid-turbinate (NMT) swab
        • Anterior nares specimen (NS)
        • Possibly nasopharyngeal wash/aspirate or nasal aspirate
      • Handling
        • Swabs should be placed immediately into sterile transport tubes containing 2–3 ml of viral transport media
        • If both NP and OP swabs: combine in a single tube
    • When feasible, lower respiratory tract specimens should also be collected.
      • If productive coughing: from sputum
        • After rinsing the mouth with water, the patient should spit deep cough sputum into a sterile sputum collection cup or sterile dry container.
      • If undergoing mechanical breathing: lower respiratory tract aspirate or bronchoalveolar lavage
        • 2–3 mL should be placed in a sterile sputum collection cup or sterile dry container.
    • Many locations have necessary materials already prepared in respiratory virus swab collection kits.

For patients in late, severe stages of infection (pneumonia, ARDS, sepsis), swab specimens from the upper respiratory tract may be negative, while the lower respiratory tract is positive.

  • Storage and transport of specimens
    • Store specimens at 2–8°C up to 72 hours after collection.
      • If there is a delay in shipping or testing, specimens should be stored at -70°C.
    • Label and transport immediately as requested by the appropriate government health agency/departments.
    • In the US, the CDC requests the following:
      • Label each specimen container with the patient’s ID number (e.g., medical record number), unique CDC or state-generated nCov specimen ID (e.g., laboratory requisition number), specimen type (e.g., serum) and the date the sample was collected.
      • Complete a CDC Form 50.34 for each specimen submitted. In the upper left box of the form,
        1. for test requested select “Respiratory virus molecular detection (non-influenza) CDC-10401” and
        2. for At CDC, bring to the attention of enter “Unit 84 (Non-flu Resp Virus)”.

  • At-home sample collection
    • Several at-home sample collection kits have been granted an Emergency Use Authorization by the FDA (November 2020). [99][100][101]
    • Should only be conducted if a patient is suspected to have COVID-19 and has been screened by a health care professional.

Quantitative reverse transcription PCR (RT-qPCR)

Confirms active infection with SARS-CoV-2 from patient specimens.

  • Method: detection of viral genome regions specific to SARS-CoV-2
    • Viral RNA is transcribed (via reverse transcription) into complementary DNA (cDNA) and then amplified with qPCR
    • Positive test result: positive amplification of the viral genome indicates presence of viral particles in patient specimen.
    • Negative test result: negative amplification of the viral genome indicates no viral particles in patient specimen [102]
  • Specimen: e.g., nasal or pharyngeal swabs or aspirates, sputum, bronchoalveolar lavage
  • Advantages
    • Results should be available within a few hours
    • Has both high sensitivity and specificity for identifying the SARS-CoV-2 genome in a specimen [103][104][105]
      • The specificity is close to 100% because the primers used for the PCR only bind to a unique sequence within the genome of SARS-CoV-2.
      • The chance of identifying infected individuals can likely be increased by:
        • Testing specimens from multiple sites [36]
        • Performing simultaneous antibody testing
  • Limitations: does not detect antibodies against SARS-CoV-2 [102]
    • Cannot determine if an individual is immune to COVID-19
    • Cannot provide information regarding prior infections

PCR can still be negative early in the disease or may produce a false-negative test result due to technical errors (e.g., inaccurate specimen collection). In such cases, if there is still concern that a patient is infected, consider repeating PCR testing every 2–3 days (potentially with both upper and lower respiratory tract specimens) and performing simultaneous antibody testing. [103]

Antigen testing [106][107]

  • Method: direct detection of SARS-CoV-2 antigens (protein fragments)
  • Specimen: nasal swabs, saliva
  • Advantages
    • Very quick: results available within 15 minutes
    • Very specific
    • Can be used as a point-of-care test, making it easier for the general public to get tested
    • Lower costs compared to PCR
    • Can be used to screen asymptomatic individuals
    • Widely available in many countries
  • Limitations
    • Less sensitive than PCR testing
    • The following scenarios require subsequent confirmatory RT-qPCR testing:
      • Negative antigen test results in patients whose clinical presentation is strongly suspicious for SARS-CoV-2 infection
      • Positive results in asymptomatic individuals

Serological studies [108][109]

  • Current situation (November 2020)
    • Antibodies specific to SARS-CoV-2 can confirm previous exposure of an individual to the virus for either symptomatic or asymptomatic infection.
    • There are currently many efforts to develop effective antibody testing and ensure correct interpretation of test results. [110]
      • Further research is necessary, e.g., to ensure test specificity for SARS-CoV-2
      • The interpretation of a diagnostic test result depends on the properties of the test (e.g., sensitivity, specificity) as well as the prevalence of the disease in the target population.
    • There is evidence of immune responses to SARS-CoV-2 following initial infection, [44][46][47] but the duration of immunity and its efficacy on the prevention of reinfection is still uncertain. [49][50] [51][52][53]
  • Advantages of serological studies
    • To collect epidemiological data (large-area screening)
      • Estimate the spread in the population by testing large numbers of people
      • Identifies individuals who have previously been exposed to SARS-CoV-2 and have acquired specific antibodies through asymptomatic infections
    • To help develop treatments: neutralizing antibodies in blood serum donations from immune individuals are being tested as immunotherapy in severe cases [111]
  • Limitations of serological studies
    • Not as sensitive or specific as PCR: should not serve as the sole test to diagnose or exclude COVID-19
      • Antibodies are not detectable until a few days after infection (seroconversion), which may lead to negative test results during early infection.
      • Positive results may be due to past or present infection with other coronavirus strains
      • Conducting antibody tests for SARS-CoV-2 in a population with a low prevalence of COVID-19 cases can lead to high numbers of false-positives results.
      • False-positives can be dangerous because individuals might abandon exposure risk management measures (e.g., social distancing) based on a false sense of security from having previously been exposed to the SARS-CoV-2.

Testing for SARS-CoV-2 in a population with a low prevalence of COVID-19 can lead to high numbers of false-positive test results, which can convey a false sense of security in situations where individuals consider themselves immune to the virus but, in fact, have not been infected.

Serological tests that can show previous exposure to SARS-CoV-2 antigens from infection or potential future vaccinations are expected to become highly relevant over the course of the pandemic!

Rapid IgM-IgG antibody tests [112][113]

  • Method: point-of-care detection of antibodies against SARS-CoV-2 (IgM and IgG antibodies)
  • Specimen: serum, plasma, or whole blood
  • Advantages: Results are usually available within a few minutes.
    • Support in identifying COVID-19 quickly at point of care
    • Quickly help identify individuals who had a recent or past infection

The high demand for testing modalities and the potential seen by some companies to profit from the situation has led some to falsely advertise FDA approval/authorization or claim they can diagnose COVID-19. [114] We recommend that individuals refer only to statements published directly by reliable sources, e.g., the FDA (see “Reliable sources of information” below).

ELISA (Enzyme-Linked Immunosorbent Assay)

  • Method: detection of antibodies against SARS-CoV-2 (IgM, IgA, and IgG antibodies)
  • Specimen: serum, plasma, or whole blood
  • Limitations: Not suitable in all settings because it takes several hours and usually requires a lab.

For any management steps involving close contact with patients with confirmed or suspected COVID-19, observe all hygiene and isolation measures in accordance with state or local health department recommendations and regulations. (See “Infection prevention and control in healthcare settings” and “PPE for COVID-19”.) [115]

Reporting

  • All measures should be consistent with state or local health department regulations.
  • Generally, this involves notifying state and/or local health departments as well as HCF infection control personnel of PUIs and confirmed cases. [116]

Initial steps and determining the site of care

Management of asymptomatic or mild courses consists primarily of supportive self-care at home (home care) and isolation in accordance with health department regulations. Antiviral treatment should be administered to patients at high risk of disease progression.

  • Minimize spread of infection: [91]
    • Stay in a designated “sick room” away from other people.
    • Use a separate bathroom if possible.
    • Do not leave home except to get medical care.
    • If going out is necessary, avoid public places, public transportation, ridesharing, and taxis.
    • Call before seeking medical care.
    • Wear a facemask.
    • Follow general protective measures as described above.
    • Avoid sharing personal household items and wash any used items thoroughly.
    • Clean “high-touch” surfaces daily.
  • Management of close contacts: notifiable in accordance with state or local health department regulations
  • Supportive care: rest, adequate hydration, and nutrition
  • Pharmacological treatment
  • Monitor symptoms carefully: Individuals should seek medical care immediately if symptoms worsen or any emergency warning signs develop, including: [96]
  • Discontinuing home isolation: Determining when to end home isolation is approached from different strategies, which can vary according to health departments and testing resources. See “Discontinuation of isolation and other transmission-based precautions” below.

General approach

Laboratory studies [62]

Regular laboratory monitoring of hospitalized patients should include: ABG/VBG, CBC, electrolyte panel, inflammatory markers (CRP, LDH, procalcitonin), organ function (creatinine, urea nitrogen, urine volume, LFTs, cardiac enzymes), coagulation tests, and D-dimer. Blood culture should also initially be considered.

Imaging [62][120]

All hospitalized patients should undergo initial and follow-up imaging according to the clinical course.

  • Chest x-ray: usually bilateral, peripheral opacities in multiple lobes [121][122]
  • Point-of-care ultrasound (POCUS): better results than chest x-ray and easily repeatable for reevaluation [123]
    • Thickened and irregular pleural lines
    • B lines as an early sign indicate a need for intensifying care
    • Consolidation (both translobar or non-translobar) indicates progression of the pulmonary disease
    • Should also screen for cardiomyopathy
  • Chest CT: recommended for hospitalized patients [120][124][125]
    • Can initially be normal in up to 60% of hospitalized patients [125]
    • CT findings are sometimes already present before clinical manifestation.
    • Findings: generally bilateral, but a minority are unilateral
      • Ground glass opacities that can progress to solid white consolidation in severe infection
      • Inter- and/or intralobular septal thickening
      • Mixed “crazy-paving” pattern = combination of ground-glass opacity with superimposed interlobular septal thickening and/or intralobular septal thickening

Overview [126]

  • Recommendations vary based on the patient's condition and oxygen supplementation needs.
  • Based on the course of disease, when indicated, consider administering remdesivir early (to decrease viral replication) and corticosteroids later (to counter cytokine storm).
  • See “https://www.covid19treatmentguidelines.nih.gov/therapeutic-management”
Disease Severity Recommended treatment
Not hospitalized

Mild to moderate, not hospitalized
Hospitalized Does not require O2 therapy
  • Consider remdesivir for patients at high risk of disease progression.
Requires O2 therapy
Requires high-flow O2 therapy or noninvasive ventilation
Requires mechanical ventilation or ECMO

Currently recommended therapies [126]

Outpatient pharmacological management

For patients with mild to moderate COVID-19 who are at increased risk of disease progression and hospitalization, combination treatment with neutralizing monoclonal antibodies that bind to an epitope of the SARS-CoV-2 spike protein receptor-binding domain (thereby blocking the entry of SARS-CoV-2 into host cells) is recommended: [126]

  • Bamlanivimab plus etesevimab
  • Casirivimab plus imdevimab

Inpatient management

Remdesivir [127][128]

  • Mechanism of action
    • Phosphoramidate prodrug: metabolized in the cells to produce an active neucleotide analogue
    • Active form: acts as a neucleotide analogue that inhibits viral RNA-dependent RNA polymerase → impairment of viral exoribonuclease (ExoN) proofreading → inhibition of viral RNA production
  • Recommended for: [126]
    • Hospitalized adults and pediatric patients (aged ≥ 12 years old and weighing ≥ 40 kg) with COVID-19 who require supplemental oxygen
    • Available through an FDA EUA for hospitalized pediatric patients weighing 3.5 kg – < 40kg or aged < 12 years
  • There is insufficient data to recommend remdesivir for patients who:
  • The effectiveness and safety of remdesivir for the treatment of children aged < 12 years and weighing < 40 kg and pregnant women have not been evaluated. Its use may be considered after weighing the risks and benefits.

Corticosteroids

  • Dexamethasone is recommended for use in hospitalized patients who require: [126]
  • Believed to reduce the severity of cytokine storm
  • Patients already on oral or inhaled corticosteroids for preexisting medical conditions should continue treatment as usual unless discontinuation is warranted by the clinical condition.
  • Baricitinib [129]
    • Selective JAK1 and JAK2 inhibitor that blocks cytokine signaling/activity
    • Used in combination with remdesivir in the treatment of hospitalized adult and pediatric (aged ≥ 2 years) patients with COVID-19 who require oxygen supplementation, mechanical ventilation, or ECMO, but only when corticosteroids are contraindicated.

Anticoagulation [126]

  • Patients on anticoagulation and antiplatelet therapies for preexisting medical conditions: Continue treatment.
  • For hospitalized nonpregnant adults with no findings suggestive of a thromboembolic event: Administer prophylactic anticoagulation (e.g., with LMWH or fondaparinux).
  • Extended venous thromboembolism prophylaxis: Consider after discharge in patients with a high risk of thrombotic events (risk measurement should follow the same recommendations used for patients without COVID-19) and a low risk of bleeding.
  • Venous thromboembolism prophylaxis: Indications are the same in children with and without COVID-19.
  • Hospitalized pregnant women with severe COVID-19: Administer prophylactic anticoagulation unless contraindicated.
  • Patients with findings suggestive of a thromboembolic event: Manage the same as patients without COVID-19.
  • There is currently no evidence supporting the use of prophylactic anticoagulation therapy in nonhospitalized patients.

Antimicrobial therapy

There are insufficient data to recommended antimicrobial therapy treatment of COVID-19 in the absence of another indication.

Experimental drugs

A variety of agents are being tested, and clinical studies are being conducted. The use of these drugs can be considered in the context of research studies, compassionate use programs, and individual cases after weighing the risks and benefits. [126][130][131]

RNA polymerase inhibitors and nucleotide analogs

Inhibition of adhesion and invasion

  • Serine protease inhibitor (inhibits TMPRSS2): camostat [24]
  • Inhibition of fusion
    • Umifenovir [134]
    • Chloroquine and less toxic hydroxychloroquine (± azithromycin): not recommended for the treatment of patients with COVID-19, or as postexposure prophylaxis to prevent COVID-19 infection. [126]
  • Protease inhibitors
  • Nuclear import inhibitors: ivermectin [135]
    • Commonly used anti-parasitic drug
    • Has been shown to reduce viral load in cell cultures infected with SARS-CoV-2
  • IL-6 pathway inhibitors
  • Recombinant ACE2 (rhACE2, APN01) [25]
  • Passive immunization through serum therapy [136]
    • The FDA issued a EUA on August 23, 2020, for COVID-19 convalescent plasma to treat hospitalized patients with COVID-19 [137]
    • However, as of September 2020, the NIH COVID-19 Treatment Guidelines Panel states that there is still not enough available clinical evidence to support the use of COVID-19 convalescent plasma for the treatment of patients with COVID-19. [126]

There are no proven benefits of hydroxychloroquine for COVID-19 treatment, which is the main reason for the FDA revoking the EUA of this usage. Hydroxychloroquine and other drugs under investigation should only be used in COVID-19 treatment in the context of clinical studies. Otherwise, they should be reserved for individuals who depend on these drugs for other reasons (e.g., hydroxychloroquine for rheumatic diseases). [138][139]

When a drug is administered during the course of the disease is likely a decisive factor. While drugs that inhibit the invasion and replication of the virus (e.g., camostat, rhACE2) would have to be administered as early as possible, other approaches, which aim to control immune response dysregulation in severe courses (e.g., tocilizumab), could also be effective in later stages of the disease.

No evidence that ACE inhibitors and NSAIDs aggravate COVID-19

  • Unconfirmed reports and published hypotheses about the pathophysiology of COVID-19 raised suspicions that RAAS antagonists (esp. ACE inhibitors and angiotensin II receptor blockers), NSAIDs, and thiazolidinediones may facilitate infection with and exacerbate the course of COVID-19.
  • Although these medications may increase ACE2 receptor expression, there is currently (May 2021) no evidence supporting the association between the treatment with these agents and severe courses of the disease. [126][140][141][142]

Regardless of COVID-19, NSAIDs may have nephrotoxic and cardiotoxic effects in individuals with cardiovascular and/or renal conditions.

Indications

Mechanical breathing

  • Recommended settings for ventilated patients with COVID-19: [75]
  • Effect/indications: The effects and indications of mechanical ventilation for patients with COVID-19 are currently subject to discussion. [148]
    • High mortality rates among ventilated patients have been reported and could be due to a variety of factors: [149] [150]
      • Lung injury from COVID-19 might manifest differently from typical ARDS, and adjustments in ventilation management may be necessary. [151]
      • Lack of ventilation experts and personnel trained to operate ventilation machines could contribute to worse outcomes among severely ill patients.
      • Strains on many health care systems worldwide, high levels of stress among health care providers, and insecurity about treatment strategies and management for COVID-19 might affect the quality of care for some patients:
        • Physicians might favor drastic measures (e.g., intubation) over restrictive approaches (e.g., breathing masks) early in disease progression.
        • Higher rates of intubated and ventilated patients might result from concerns among health-care professionals about contracting COVID-19 through potentially aerosol-generating methods like nasal tubes and breathing masks.
    • The effects of COVID-19 on the respiratory system are not yet fully understood, prompting some physicians to advise against changing established protocols regarding ventilation management in COVID-19 patients presenting with ARDS. [152]
    • In patients with confirmed COVID-19 and relatively mild signs of ARDS, high-flow nasal cannula therapy could be considered initially. However, mechanical ventilation might still be necessary at a later point in the course of disease. [153]
  • Limited ventilator availability: High volumes of patients with critical conditions due to COVID-19 have raised concerns regarding ventilator shortages in hospitals during the pandemic.
    • Ventilator sharing: a controversial, off-label procedure in response to ventilation capacity shortages
      • Pros and cons should be carefully considered in the context of a specific situation.
      • Some institutions are already experimenting with sharing ventilators to compensate for short supplies. [154][155]
      • The procedure is discouraged by some medical societies. [156]
      • The FDA granted an Emergency Use Authorization for ventilator expansion devices to facilitate the treatment of up to four patients with one ventilator [157]
    • New inventions: Mechanical devices have been designed to compress a bag valve mask (BVM) and serve as a temporary ventilator during emergencies and times of ventilator shortages, specifically the COVID-19 pandemic.
      • MIT E-Vent (Massachusetts Institute of Technology Emergency Ventilator)
      • AmboVent by the Israeli Air Force (IAF)
      • Pandemic Ventilator Project

Extracorporeal blood purification therapy

  • Can be used to filter inflammatory cytokines from the blood of patients with severe courses of COVID-19 [158]
    • Use is based on the hypothesis that cytokine storms are important in the etiology of severe courses
    • The treatment is invasive, so it should only be considered for patients with respiratory failure who are in the ICU.
    • A special filter, which can be used with standard extracorporeal purification machines (e.g., for hemodialysis), has been granted an Emergency Use Authorization by the FDA (April 10, 2020).

Discontinuation of isolation

  • CDC recommends to end home isolation according to a strategy based on clinical criteria (December 2020) [159]
    • For patients with symptomatic COVID-19:
      • 10 days after the onset of symptoms AND
      • No fever for at least 24 hours without antipyretics AND
      • Respiratory symptoms have improved
    • For patients with asymptomatic COVID-19: 10 days have passed without illness since the date of the positive COVID-19 test. [159][160]
  • Currently (December 2020), the CDC and WHO do not recommend discontinuing isolation according to test-based strategies [160]

Discharging patients from healthcare facility

Recommendations based on CDC guidance: [161]

  • Considered infectious (requirements for discontinuation transmission-based precautions are not met): If clinically indicated, patients may be discharged without meeting the criteria for discontinuation of transmission-based precautions.
    • If discharged home: They should follow guidance for home care and isolation as described above in “Management of asymptomatic or mild courses.”
    • If discharged to long-term care or assisted-living facility: Transmission-based precautions should still be followed.
  • Considered noninfectious (requirements for discontinuation transmission-based precautions are met): If clinically indicated, patients may be discharged without COVID-19-associated restrictions.
    • Exceptions: Some patients may have recovered but have persistent symptoms (e.g., cough). Additional precautions are recommended for such individuals (such as wearing a facemask and staying in a single room) until symptoms completely resolve or 14 days after onset of symptoms, whichever is longer.
  • Mortality rate: ranges from ∼ 0.5 to 3%
    • The mortality rate greatly increases for individuals with certain underlying medical conditions or > 60 years of age, with the most lethal rates for individuals > 80 years reaching ∼ 15%. [6]
    • Individuals considered at high-risk for a severe course (and thus a higher mortality rate) include those with: [117]
  • Pediatric patients: See “COVID-19: children” below for more details.
    • Most children with COVID-19 experience a mild course and some are asymptomatic. [162][163]
    • The CDC reports: [164]
      • Up to 20% of children were hospitalized, which is lower than adults (up to 33%)
        • Children aged < 1 year were much more likely to be hospitalized (up to 62%)
        • For children aged 1–17 years, up to 15% were hospitalized
      • Severe courses requiring ICU admittance only occurred in ∼ 2% of children with COVID-19, whereas adults required ICU admittance in up to 4.5% of cases.
        • Children aged < 1 year were more likely to have a severe course that required ICU admittance (5.3%)
      • Three deaths were reported among pediatric cases; further investigation continue to determine if COVID-19 was the cause of death.
    • A study evaluating 2143 pediatric patients with COVID-19 in China showed: [163]
      • Severe course occurred in 5.9% of cases (vs. 18.5% for adults from the same population study), and only one died.
      • Younger children, especially infants, were more vulnerable to severe or critical course (infants < 11% vs. 7% for ages 1–5 years and less for older pediatric groups).

Overview of common vaccines

Last updated: 9 April 2021

COVID-19 vaccines
Name Manufacturer Type Administration Common side effects Storage FDA emergency use authorization (EUA) Contraindications
Pfizer-BioNtech COVID-19 vaccine [165]
  • Pfizer Inc.
  • Intramuscular injection
  • 2 doses administered 3 weeks apart
  • - 70ºC
  • Individuals aged ≥ 18 years
Moderna COVID-19 vaccine [166]
  • ModernaTX, Inc.
  • Intramuscular injection
  • 2 doses administered 1 month apart
  • -20ºC
  • Individuals aged ≥ 18 years

Janssen COVID-19 vaccine (Johnson & Johnson vaccine) [167]
  • Janssen Biotech Inc.
  • Intramuscular injection
  • Single dose
  • 2–8ºC
  • Individuals aged ≥ 18 years

Vaxzevria [168]
  • AstraZeneca
  • Intramuscular injection
  • 2 doses administered 4–12 weeks apart
  • 2–8ºC
  • Not authorized for use in the US

Sputnik V vaccine [169]
  • 2 doses administered 21 days apart
  • 2–8ºC
  • Not authorized for use in the US

Administering the vaccine

  • The COVID-19 pandemic has complicated many patient interactions, especially in places where the pandemic may be more profound and equipment, resources, space, and personnel are limited. During the pandemic, certain procedures may need to be delayed or only conducted under certain circumstances. Similarly, special considerations may need to be considered for patient groups that normally have regular check-ups. Some groups that may be affected include:
    • People with disabilities
    • Pregnant and breastfeeding patients
    • Children (including immunizations and other appointments)
    • Health care provider appointments and telemedicine, including:
      • Check-up visits
      • Gynecology visits
      • Elective surgeries and procedures
  • Patients should call their health care providers to determine how COVID-19 may affect operations.

Risk assessment [170][171]

  • Health care workers and other professionals at health care facilities are at increased risk of exposure to SARS-CoV-2.
  • In-person health care appointments pose a risk of infection with SARS-CoV-2.
  • Individuals with follow-up appointments for underlying health conditions are generally at higher risk of severe courses of COVID-19.
  • Asymptomatic patients can transmit SARS-CoV-2 to other patients and medical personal.
  • Delaying nonurgent procedures and surgeries can save critical medical supplies (e.g., PPE, ICU beds, ventilators) and medical personnel that are needed for the care of patients with COVID-19.

Management [172]

  • General approach [170]
    • In-person appointments should be minimized as much as possible.
      • Elective in-person appointments (e.g., general check-up visits, follow-up appointments) should be delayed or conducted via telemedicine (e.g., phone or video calls).
      • Elective surgeries should be delayed and rescheduled when possible.
    • Acutely ill patients, with or without COVID-19, have to be admitted.
    • Patients with mild symptoms or suspicion of COVID-19 (e.g., via recent contact) should be:
      • Assessed for the ability to self-isolate and monitor their symptoms at home
      • Asked about their living situation and risk of transmission to others
      • Followed up closely (using telemedicine) to adjust the medical approach as needed (e.g., admitting patients if symptoms worsen)
  • Before approaching a health care facility
    • Patients should call their health care provider for advice and assess the risks and benefits associated with a particular in-person appointment (e.g., the benefits of receiving an infusion for a chronic disease might outweigh the risk of contracting SARS-CoV-2).
    • Algorithms should be used when assessing patients via telemedicine to determine their need to call 911, go to the emergency department, or come in for an appointment.
  • At the health care facility
    • All patients who require in-person appointments should be:
      • Assessed for symptoms of COVID-19, ideally before entering a health care facility (e.g., via telemedicine) or upon entry
      • Triaged according to the severity of their symptoms
      • Distributed to either a COVID-19 unit or COVID-19-free unit depending on previous test results and/or COVID-19 related symptoms (e.g., respiratory symptoms)
    • Follow appropriate infection control and preventive measures (see above).
  • Telemedicine (or telehealth) [173]
    • Allows health care providers to offer medical care and advise to patients without in-person contact
    • Methods: advice telephone lines, telephone appointments, video conferences, text messaging, email exchange, etc.
    • Use is especially encouraged during the COVID-19 pandemic
      • To reduce the risk of transmission of SARS-CoV-2 between patients and health care workers
      • To decrease the number of patients in health care facilities and spare PPE and clinic space for critically ill patients
    • Billing for telemedicine appointments is not standardized in the US health care system. This might lead to an inconsistency in the availability of specific methods between different health care providers.
  • Workers at health care facilities [174]
    • All personnel should follow standard recommendations like hand hygiene before and after any patient contact, wearing disposable masks, and physical distancing whenever possible (see “Infection control and preventive measures” for more info).
    • Additional PPE for specific circumstances:
      • Includes eye protection or face shields, gowns, and gloves (in addition to masks)
      • Recommended when caring (e.g., bedside care, operative procedures) for a patient who is either positive for SARS-CoV-2 or has symptoms of COVID-19
      • N95 respirators should be used instead of simple masks when:
        • Performing aerosol-generating procedures (e.g., intubation, CPR) on a patient who is either positive for SARS-CoV-2 or has symptoms of COVID-19
        • Performing airway procedures on any patient

Risk assessment

  • No increased risk of contracting COVID-19 from disabilities alone
  • People with disabilities are more likely to have medical comorbidities that impose an increased risk for severe courses (see “Management” above).
  • The risk of infection might be increased compared to the general population when:
    • A support person is needed (especially when coming from outside the household), e.g., due to decreased mobility
    • Personal protective measures cannot be understood or followed, e.g., due to cognitive impairment
    • Symptoms cannot be communicated, e.g., due to impaired speech or cognition

Management

  • Develop a personal plan/strategy with the patient
  • Safety net: organize backup support in case the current support person becomes sick or is quarantined
  • Emergency communication: set up multiple reliable ways to quickly call for help (e.g., speed-dial in phone, carrying a cell phone and a note with important contacts)
  • Stockpiling: ensure sufficient supplies of household items, medication, and medical equipment that can last for about 30 days
  • Specific contact precautions
    • Support persons: transparent about symptoms and sick contacts
    • Hand hygiene: should be followed by everyone entering the home, and before and after close personal contact
    • Frequently used surfaces, medical devices, and other objects: clean and disinfect regularly

Reference: [175]

Risk assessment [176][177][178]

Only a few studies with small cohorts have been conducted so far, making recommendations difficult at this time. [179]

  • Affect of pregnancy: Pregnant women appear to have the same risk of infection and severity as non-pregnant adults
  • Transmission

Management [182]

  • Contact patient gynecologist if nasopharyngeal swab tests positive or the patient has had contact with a symptomatic individual.
  • In the event of home quarantine, the necessity of prenatal visits should be discussed with the patient's gynecologist.
  • Prenatal ultrasounds are recommended for surveillance (e.g., screening for intrauterine growth restriction or possible malformations)
  • In mothers who have tested positive or have a high degree of suspicion for infection, birth should take place in a hospital.
  • There is currently no contraindication for vaginal delivery.
  • Independent of the status of infection, all women have the same rights during childbirth, including: [183]
    • Be addressed with dignity and clear communication by all maternity staff
    • Choosing the preferred birth position
    • Receiving adequate pain control
    • Having a companion of choice during labor
  • Separation of the newborn from the mother: physical distancing is the most effective measure to prevent infection
    • Severe cases: Physical separation immediately after birth to avoid postnatal infection might be the best option if feasible in the hospital.
    • Mild cases or high suspicion of infection: Breastfeeding is encouraged, but hygiene measures (i.e., washing hands, cleaning objects) and wearing a face mask are crucial in preventing viral transmission while in close contact with the newborn. [183]
  • Medical treatment: may be considered case-by-case if severe disease

Imaging [182]

  • Chest imaging can be crucial in diagnosing COVID-19 but might put the fetus at risk for radiation exposure.
    • Chest x-ray: can be performed without increased risk for the fetus
    • CT scan: can be considered for severe courses in the mother (informed consent should be acquired, and a radiation shield can be used to reduce radiation exposure for the fetus)

Complications

Risk assessment [162][163][164]

  • Milder disease: SARS-CoV-2 infection in children (< 18 years) generally manifest with less severe features than in adults.
    • Asymptomatic cases seem to be common in children.
    • Hospitalization rates are lower than in adults.
    • Young children, especially infants, appear to be more vulnerable to severe or critical courses than older children.
    • Children are not immune to infections with SARS-CoV-2: Severe cases and deaths have been reported.
    • To date, there are different hypotheses why children might be less vulnerable than adults:
      • There are fewer ACE2 receptors (where virus attaches to cells) in the lungs of children.
      • Greater resilience to viral infections due to a more effective immune response and fewer comorbidities than the elderly
      • Immaturity of the immune system in children might prevent the occurrence of cytokine storms (an overshooting immune response), which can lead to organ failure and death.
    • Transmission of SARS-CoV-2 through children
      • Infected children (symptomatic and asymptomatic) seem to have similar viral loads to other age groups and could therefore be equally infectious. [185]
      • However, there is increasing evidence that the probability of transmission from children is lower than from adults. [186]
      • The effectiveness of school closures in controlling SARS-CoV-2 community transmission is controversial [187]
        • Researchers currently warn about reopening schools and daycare facilities in an unregulated manner as this could accelerate the spread of SARS-CoV-2 among children and their families.
  • More atypical clinical presentations
    • Fewer classical symptoms, such as fever, cough, shortness of breath, compared to adult populations
    • Common cold symptoms (e.g., pharyngitis, rhinitis) are seen more often.
    • Multisystem inflammatory syndrome in children (MIS-C) [72]
      • Background: Features of toxic shock syndrome and Kawasaki disease have been described in children in the context of active and previous infections with SARS-CoV-2. [71][188]
      • Description: MIS-C is a new syndrome seen in children in the context of COVID-19, which manifests with features of severe inflammation, organ failure, and potentially lethal outcome. [189]
      • Diagnostic criteria: apply to patients currently or previously positive for COVID-19 and without an alternative diagnosis

Management [164][190]

  • Precautionary measures
    • Observe infection control and preventive measures as described above.
      • To avoid exposure and possible illness
      • To reduce transmission from asymptomatic infected children to other individuals
    • Suspicion for COVID-19 should be high during the pandemic
      • Primary caretakers: self-isolate and contact health care provider (e.g., via call or email) when classic symptoms (e.g., fever, cough), or other signs of illness occur or when in doubt
      • Clinicians: monitor symptoms and progression of illness closely, especially in infants and children with underlying health conditions
    • Mental health
      • Reassure children that they will not die from COVID-19.
      • Encourage articulation of feelings/fears and openly address any concerns.
    Immunizations
    • Although vaccinations protect against certain organisms that can cause serious illnesses, every clinical appointment potentially increases the risk of exposure to SARS-CoV-2.
    • The decision if a specific vaccine should be administered at this time should be discussed with the responsible health care provider.
    • General considerations are:
      • Protection provided by certain vaccines (e.g., against pertussis, or pneumococcus) might outweigh the risk of exposure to the public, especially in:
      • Children > 2 years: vaccination can usually be delayed for some time
  • Well-child visits and follow-up appointments
    • The decision of whether a patient should be brought into the office at this time should be discussed with the responsible health care provider.
    • Can often be delayed or conducted using telemedicine (e.g., phone or video calls), especially if patient is doing well
    • In-person visits are often still required for:

Although most children with COVID-19 appear to experience a milder course of disease, measures for infection control and prevention should be followed in order to avoid infections with SARS-CoV-2 and slow viral transmission to others.

  • Centers for Disease Control and Prevention [191]
  • World Health Organization [192]
  • Johns Hopkins CSSE real-time tracking of COVID-19 spread [193]
  • COVID-19 Projections (by IHME) [194]
  • U.S. Food and Drug Administration [195]
  • COVID-19 Open Research Dataset (CORD-19) [196]
  • COVID-19 Open Patent Dataset (by Lens.org) [197]
  • LitCovid literature hub (by the NCBI/NLM) [198][199]
  • COVID-19 Clinical Trials Tracker (by TranspariMED) [200]

Interested in the newest medical research, distilled down to just one minute? Sign up for the One-Minute Telegram in “Tips and links” below.

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