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COVID-19 (coronavirus disease 2019)

Last updated: September 13, 2021

Summarytoggle arrow icon

COVID-19 is a pandemic acute infectious respiratory disease caused by infection with the coronavirus subtype SARS-CoV-2, first detected in Wuhan, China, in December 2019. Transmission occurs primarily via respiratory droplets. 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 other symptoms can also occur. Clinical courses range from very mild to severe with pneumonia and life-threatening complications such as ARDS, shock, and organ dysfunction. Recommendations for infection control and preventive measures vary but generally involve personal hygiene (e.g., washing hands), avoiding exposure/public places, quarantine/isolation, and wearing suitable personal protective equipment (PPE). Diagnosis is confirmed by RT-qPCR of SARS-CoV-2 RNA isolated from a nasopharyngeal swab. In mild clinical cases, patients should self-isolate with supportive care and monitoring at home. Patients with severe disease (i.e., dyspnea, cyanosis, chest discomfort, or mental status change), signs of respiratory distress (SpO2 ≤ 93%, respiratory rate > 22/min), or at high risk of severe disease (≥ 65 years, presence of certain comorbidities) should be admitted. Hospitalized patients should receive supportive and oxygen therapy and be 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) and inter- and/or intralobular septal thickening (indicating swelling of the interstitial space). POCUS can assist in monitoring 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. Mechanical ventilation should be according to ARDS protocols (e.g., ARDSnet protocol). 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 any potential delays.

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]
  • 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.

  • Demographics [5]
    • =
    • Affects people of all ages
  • Fatality rate [5]
    • ∼ 5%
    • 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. [6]
  • The virus was first reported in Wuhan, China. Its origin is still under investigation

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. [9]
    • 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 June 2021, the most concerning variants are:
    • B.1.1.7 (501Y.V1, United Kingdom)
      • Increased transmissibility compared with the original strain [10][11][12]
      • Possible increased disease severity and mortality [11][13]
    • B.1.351 (501Y.V2, South Africa)
      • Increased transmissibility compared with the original strain [14]
      • Not associated with increased disease severity [13]
      • Spike protein mutation (E484K) might lead to decreased neutralization by antibodies, potentially impacting immunity from vaccination or prior infection. [15][16][17]
    • 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) [18]
      • Increased transmissibility compared with the original strain
      • Spike protein mutation (L452R) leads to decreased neutralization by antibodies
    • B.1.617.2 (Delta variant, India) [18]
      • Increased transmissibility compared with the original strain
      • Decreased neutralization antibodies

Viral life cycle

  • Invasion of host cells [19]
    • Entry point: Angiotensin-converting enzyme 2 (ACE2) via the spike protein [20][21][22][23][24][25]
    • 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 [30][31]
    • Primarily via respiratory droplets: can be emitted during sneezing and coughing as well as loud speech [32]
    • 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 [33]
      • 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 [34][35][36]
    • Vertical transmission: see “COVID-19: pregnancy and breastfeeding
  • Incubation period: 2–14 days, usually ∼ 5 days [37][38][39]
  • 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. [40][41][42]
    • Viral RNA has been found in respiratory samples long after initial infection, [43] 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 [42][44][45] or exposure to viral components [46].
    • But the duration of immunity and its efficacy on the prevention of reinfection is still uncertain. [47][48] [49][50][51]
    • Some studies suggest that the magnitude of the immune response might be dependent on the severity of the disease. [52][53]
    • Cases of reinfection are possible but rare [54][55][56][57]

The transmission of SARS-CoV-2 by asymptomatic individuals can occur, but individuals are most contagious when they are symptomatic. [58]

Overview

  • Often asymptomatic
  • Children are more likely to be asymptomatic [59]

Symptoms [60][61][62]

Patients with the Delta variant (B.1.617.2) often present with milder symptoms such as headache, rhinitis, fever, and sore throat.

Course [59][62][72][73][74]

Postacute COVID-19 syndrome (“long COVID”) [76]

COVID-19 Influenza Common cold Allergic rhinitis
Fever +++ +++ - -
Cough +++ +++ +++ ++
Fatigue +++ +++ + -
Shortness of breath ++ + - -
Loss of appetite ++ ++ - -
Myalgia ++ +++ + -
Loss of smell/taste ++ + ++ ++
Headache ++ +++ ++ -
Runny nose ++ + +++ +++
Sneezing ++ - +++ +++
Sore throat ++ + +++ -
Diarrhea + + - -
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. [77] Patients with COVID-19 also have a higher proportion of extrapulmonary complications. [78]

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). [79]
    • 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 [80]
    • Face shields generally do not replace the use of a mask but may be used in addition
  • Cloth face coverings [80][81]
    • 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 [82]
    • 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 [83]
    • The CDC offers free “Sew and No Sew Instructions” for self-made cloth face coverings on their website: [84]
  • 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 [85]
    • 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 [83]
    • 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). [86]
    • 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). [79][80]

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”). [81]

Public health measures [87]

  • 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 [88][89]

  • 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 [91]
  • Individuals with a recent high-risk exposure are advised to:

Infection prevention and control in healthcare settings

Recommendations vary according to the appropriate health department/agency. Some recommendations from the CDC include: [92]

  • 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) [92][93]

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: [94]
      • 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: [95]
      • 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) [96]

  • 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.
    • 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). [97][98][99]
    • 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 [100]
  • 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 [101][102][103]
      • 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 [34]
        • Performing simultaneous antibody testing
  • Limitations: does not detect antibodies against SARS-CoV-2 [100]
    • 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. [101]

Antigen testing [104][105]

  • 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 [106][107]

  • 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. [108]
      • 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, [42][44][45] but the duration of immunity and its efficacy on the prevention of reinfection is still uncertain. [47][48] [49][50][51]
  • 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 [109]
  • 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 [110][111]

  • 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. [112] 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”.) [113]

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. [114]

Initial steps and determining the site of care

Initial triage should take place via telemedicine, if possible. Management depends on vital signs, physical exam findings

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: [89]
    • 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
    • Antipyretic and anti-inflammatory therapy for controlling fever and pain (if required)
      • Acetaminophen (paracetamol): drug of choice in most patients, unless contraindications are present (e.g., liver disease)
      • Alternative: ibuprofen or other NSAIDS, but limit use in elderly patients and those with cardiovascular or renal disease
    • For patients at high risk of disease progression: casirivimab plus imdevimab
  • Monitor symptoms carefully: Individuals should seek medical care immediately if symptoms worsen or any emergency warning signs develop, including: [94]
  • 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 [60]

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 [60][118]

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 [119][120]
  • Point-of-care ultrasound (POCUS): better results than chest x-ray and easily repeatable for reevaluation [121]
    • 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 [118][122][123]
    • Can initially be normal in up to 60% of hospitalized patients [123]
    • 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 [124]

  • 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

  • Supportive care and symptomatic management
  • For patients at high risk of disease progression, use one of the following:
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 [124]

Outpatient 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: [124]

  • Casirivimab plus imdevimab
  • Sotrovimab
  • Bamlanivimab plus etesevimab is NOT recommended anymore due to the lower susceptibility of new SARS-CoV-2 variants.

Inpatient management

Remdesivir [125][126]

Corticosteroids

  • Dexamethasone is recommended for use in hospitalized patients who require: [124]
  • 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.

Kinase inhibitors [127]

  • Baricitinib
    • Selective JAK1 and JAK2 inhibitor that blocks cytokine signaling/activity
    • If corticosteroids are contraindicated, 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.
  • Tofacitinib
    • Selective JAK1 and JAK3 inhibitor that blocks cytokine signaling/activity
    • Can be used if baricitinib is unavailable

Anticoagulation [124]

  • 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.

Postexposure prophylaxis [124]

Casirivimab and imdevimab may be administered as postexposure prophylaxis in patients at high risk for progression to severe disease who:

  • Are ≥ 12 years of age and weigh ≥ 40 kg
  • Are not fully vaccinated or not expected to build a good immune response after vaccination (e.g., patients taking immunosuppressive medications)
  • Have been in close contact with an individual with COVID-19 or are at high risk of exposure due to the presence of COVID-19 infections in individuals in the same institutional settings (e.g., prisons)

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. [124][128][129]

RNA polymerase inhibitors and nucleotide analogs

Inhibition of adhesion and invasion

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). [136][137]

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.

Indications

Mechanical breathing

  • Recommended settings for ventilated patients with COVID-19: [73]
  • Effect/indications: The effects and indications of mechanical ventilation for patients with COVID-19 are currently subject to discussion. [143]
    • High mortality rates among ventilated patients have been reported and could be due to a variety of factors: [144] [145]
      • Lung injury from COVID-19 might manifest differently from typical ARDS, and adjustments in ventilation management may be necessary. [146]
      • 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. [147]
    • 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. [148]
  • 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. [149][150]
      • The procedure is discouraged by some medical societies. [151]
      • The FDA granted an Emergency Use Authorization for ventilator expansion devices to facilitate the treatment of up to four patients with one ventilator [152]
    • 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 [153]
    • 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) [154]
    • 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. [154][155]
  • Currently (December 2020), the CDC and WHO do not recommend discontinuing isolation according to test-based strategies [155]

Discharging patients from healthcare facility

Recommendations based on CDC guidance: [156]

  • 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%. [157]
    • Individuals considered at high-risk for a severe course (and thus a higher mortality rate) include those with: [115]
  • Pediatric patients: See “COVID-19: children” below for more details.
    • Most children with COVID-19 experience a mild course and some are asymptomatic. [158][159]
    • The CDC reports: [160]
      • 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: [159]
      • 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: 18 June 2021

COVID-19 vaccines
Name Manufacturer Type Administration Common side effects Storage FDA emergency use authorization (EUA) Contraindications
Pfizer-BioNtech COVID-19 vaccine [161]
  • Pfizer Inc.
  • Intramuscular injection
  • 2 doses administered 3 weeks apart
  • - 70ºC
  • Individuals aged ≥ 12 years
Moderna COVID-19 vaccine [162]
  • ModernaTX, Inc.
  • Intramuscular injection
  • 2 doses administered 1 month apart
  • -20ºC
  • Individuals aged ≥ 18 years

Janssen COVID-19 vaccine (Johnson & Johnson vaccine) [163]

  • Janssen Biotech Inc.
  • Intramuscular injection
  • Single dose
  • 2–8ºC
  • Individuals aged ≥ 18 years

Vaxzevria [164]

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

Sputnik V vaccine [165]

  • 2 doses administered 21 days apart
  • 2–8ºC
  • Not authorized for use in the US

Administering the vaccine

Immunized individuals can still contract and spread COVID-19. However, the risk of severe disease, admission to ICU, and death is significantly less. It is also likely that they are less infectious than nonvaccinated individuals.

  • 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 [166][167]

  • 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 [168]

  • General approach [166]
    • 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) [169]
    • 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 [170]
    • 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: [171]

Transmission [124]

Current evidence (August 2021) indicates the following, but note that this might change as more data becomes available.

Management [124][174]

  • 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.
  • In severe cases, early birth via cesarean delivery may be warranted.
  • 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
      • Infection prevention measures (e.g., washing hands, cleaning objects, wearing a face mask) are crucial in preventing viral transmission while in close contact with the newborn. [175]
  • Medical treatment: may be considered if severe disease

Imaging [174]

  • 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 [124]

Vaccination [124]

Risk assessment [158][159][160]

  • 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. [177]
      • However, there is increasing evidence that the probability of transmission from children is lower than from adults. [178]
      • The effectiveness of school closures in controlling SARS-CoV-2 community transmission is controversial [179]
        • 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) [70]
      • 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. [69][180]
      • 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. [181]
      • Diagnostic criteria: apply to patients currently or previously positive for COVID-19 and without an alternative diagnosis

Management [160][182]

  • 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 [183]
  • World Health Organization [184]
  • Johns Hopkins CSSE real-time tracking of COVID-19 spread [185]
  • COVID-19 Projections (by IHME) [186]
  • U.S. Food and Drug Administration [187]
  • COVID-19 Open Research Dataset (CORD-19) [188]
  • COVID-19 Open Patent Dataset (by Lens.org) [189]
  • LitCovid literature hub (by the NCBI/NLM) [190][191]
  • COVID-19 Clinical Trials Tracker (by TranspariMED) [192]

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

  1. Coronavirus Disease 2019 (COVID-19). https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-disabilities.html. Updated: April 7, 2020. Accessed: April 9, 2020.
  2. Chang D, Xu H, Rebaza A, Sharma L, Dela Cruz CS. Protecting health-care workers from subclinical coronavirus infection. The Lancet Respiratory Medicine. 2020; 8 (3): p.e13. doi: 10.1016/s2213-2600(20)30066-7 . | Open in Read by QxMD
  3. Cheung JC-H, Ho LT, Cheng JV, Cham EYK, Lam KN. Staff safety during emergency airway management for COVID-19 in Hong Kong. The Lancet Respiratory Medicine. 2020 . doi: 10.1016/s2213-2600(20)30084-9 . | Open in Read by QxMD
  4. Wax RS, Christian MD. Practical recommendations for critical care and anesthesiology teams caring for novel coronavirus (2019-nCoV) patients. Canadian Journal of Anesthesia/Journal canadien d'anesthésie. 2020 . doi: 10.1007/s12630-020-01591-x . | Open in Read by QxMD
  5. Features, Evaluation and Treatment Coronavirus (COVID-19) [Updated 2020 Mar 8].
  6. Acute Respiratory Distress Syndrome Network, Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A.. Ventilation with Lower Tidal Volumes as Compared with Traditional Tidal Volumes for Acute Lung Injury and the Acute Respiratory Distress Syndrome. N Engl J Med. 2000; 342 (18): p.1301-1308. doi: 10.1056/nejm200005043421801 . | Open in Read by QxMD
  7. ARDSnet Clinical Network Mechanical Ventilation Protocol Summary.
  8. Why Ventilators May Not Be Working as Well for COVID-19 Patients as Doctors Hoped. https://time.com/5820556/ventilators-covid-19/. Updated: April 16, 2020. Accessed: April 27, 2020.
  9. Yang X, Yu Y, Xu J, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. The Lancet Respiratory Medicine. 2020 . doi: 10.1016/s2213-2600(20)30079-5 . | Open in Read by QxMD
  10. Bhatraju PK, Ghassemieh BJ, Nichols M, et al. Covid-19 in Critically Ill Patients in the Seattle Region — Case Series. N Engl J Med. 2020 . doi: 10.1056/nejmoa2004500 . | Open in Read by QxMD
  11. Gattinoni L, Coppola S, Cressoni M, Busana M, Rossi S, Chiumello D. Covid-19 Does Not Lead to a “Typical” Acute Respiratory Distress Syndrome. Am J Respir Crit Care Med. 2020 . doi: 10.1164/rccm.202003-0817le . | Open in Read by QxMD
  12. Xu Z, Shi L, Wang Y, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. The Lancet Respiratory Medicine. 2020; 8 (4): p.420-422. doi: 10.1016/s2213-2600(20)30076-x . | Open in Read by QxMD
  13. Wang K, Zhao W, Li J, Shu W, Duan J. The experience of high-flow nasal cannula in hospitalized patients with 2019 novel coronavirus-infected pneumonia in two hospitals of Chongqing, China. Annals of Intensive Care. 2020; 10 (1). doi: 10.1186/s13613-020-00653-z . | Open in Read by QxMD
  14. COVID-19 How to Use One Ventilator to Save Multiple Lives. https://www.youtube.com/watch?v=uClq978oohY&feature=emb_logo. Updated: March 14, 2020. Accessed: April 11, 2020.
  15. Neyman G, Irvin CB. A Single Ventilator for Multiple Simulated Patients to Meet Disaster Surge. Academic Emergency Medicine. 2006; 13 (11): p.1246-1249. doi: 10.1197/j.aem.2006.05.009 . | Open in Read by QxMD
  16. Consensus Statement on Multiple Patients Per Ventilator.
  17. Emergency Use Authorization (EUA) relating to insufficient supply and availability of FDA-cleared ventilators for use in healthcare settings to treat patients during the COVID-19 pandemic.
  18. CytoSorbent, Inc. Extracorporeal Blood Purification (EBP) Device - Letter of Authorization.
  19. Dong Y, Mo X, Hu Y, et al. Epidemiological Characteristics of 2143 Pediatric Patients With 2019 Coronavirus Disease in China. Pediatrics. 2020 : p.e20200702. doi: 10.1542/peds.2020-0702 . | Open in Read by QxMD
  20. Lu X, Zhang L, Du H, et al. SARS-CoV-2 Infection in Children. N Engl J Med. 2020 . doi: 10.1056/nejmc2005073 . | Open in Read by QxMD
  21. Bialek S, Gierke R, et al. Coronavirus Disease 2019 in Children — United States, February 12–April 2, 2020. MMWR Morb Mortal Wkly Rep. 2020; 69 (14): p.422-426. doi: 10.15585/mmwr.mm6914e4 . | Open in Read by QxMD
  22. An analysis of SARS-CoV-2 viral load by patient age.
  23. Munro, Faust. Children are not COVID-19 super spreaders: time to go back to school. Archives of Disease in Childhood. 2020; 105 (7): p.618-619.
  24. Viner et al.. School closure and management practices during coronavirus outbreaks including COVID-19: a rapid systematic review. The Lancet Child & Adolescent Health. 2020; 4 (5): p.397-404.
  25. Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with Coronavirus Disease 2019 (COVID-19). https://emergency.cdc.gov/han/2020/han00432.asp. Updated: May 14, 2020. Accessed: May 19, 2020.
  26. Exclusive: National alert as ‘coronavirus-related condition may be emerging in children’. https://www.hsj.co.uk/acute-care/exclusive-national-alert-as-coronavirus-related-condition-may-be-emerging-in-children/7027496.article. Updated: April 27, 2020. Accessed: April 27, 2020.
  27. Verdoni L, Mazza A, Gervasoni A, et al. An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study. Lancet. 2020 . doi: 10.1016/s0140-6736(20)31103-x . | Open in Read by QxMD
  28. Riphagen S, Gomez X, Gonzalez-Martinez C, Wilkinson N, Theocharis P. Hyperinflammatory shock in children during COVID-19 pandemic. Lancet. 2020 . doi: 10.1016/s0140-6736(20)31094-1 . | Open in Read by QxMD
  29. Is it safe to see the pediatrician for vaccines and medical visits?. https://www.health.harvard.edu/blog/when-to-see-the-pediatrician-deciding-about-vaccines-and-medical-visits-right-now-2020033119384. Updated: March 31, 2020. Accessed: April 13, 2020.
  30. COVID-19: Recommendations for Management of Elective Surgical Procedures. https://www.facs.org/covid-19/clinical-guidance/elective-surgery. Updated: March 13, 2020. Accessed: April 20, 2020.
  31. Interim Clinical Guidance for Management of Patients with Confirmed Coronavirus Disease (COVID-19). https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-guidance-management-patients.html. Updated: April 6, 2020. Accessed: April 20, 2020.
  32. Outpatient and Ambulatory Care Settings: Responding to Community Transmission of COVID-19 in the United States. https://www.cdc.gov/coronavirus/2019-ncov/hcp/ambulatory-care-settings.html. Updated: April 7, 2020. Accessed: April 20, 2020.
  33. Telehealth Coding and Billing During COVID-19. https://www.acponline.org/practice-resources/covid-19-practice-management-resources/telehealth-coding-and-billing-during-covid-19. Updated: April 17, 2020. Accessed: April 20, 2020.
  34. COVID-19: Considerations for Optimum Surgeon Protection Before, During, and After Operation. https://www.facs.org/covid-19/clinical-guidance/surgeon-protection. Updated: April 1, 2020. Accessed: April 21, 2020.
  35. Pfizer-BioNTech COVID-19 Vaccine. https://www.fda.gov/emergency-preparedness-and-response/coronavirus-disease-2019-covid-19/pfizer-biontech-covid-19-vaccine. Updated: December 11, 2020. Accessed: December 31, 2020.
  36. Moderna COVID-19 Vaccine. https://www.fda.gov/emergency-preparedness-and-response/coronavirus-disease-2019-covid-19/moderna-covid-19-vaccine. Updated: December 18, 2020. Accessed: December 31, 2020.
  37. Janssen COVID-19 Vaccine. https://www.fda.gov/emergency-preparedness-and-response/coronavirus-disease-2019-covid-19/janssen-covid-19-vaccine. Updated: February 27, 2021. Accessed: March 17, 2021.
  38. Vaxzevria (previously COVID-19 Vaccine AstraZeneca). https://www.ema.europa.eu/en/medicines/human/EPAR/vaxzevria-previously-covid-19-vaccine-astrazeneca#product-information-section. . Accessed: April 9, 2021.
  39. Logunov DY, Dolzhikova IV, Shcheblyakov DV, et al. Safety and efficacy of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine: an interim analysis of a randomised controlled phase 3 trial in Russia. The Lancet. 2021; 397 (10275): p.671-681. doi: 10.1016/s0140-6736(21)00234-8 . | Open in Read by QxMD
  40. Rodriguez-Morales AJ, Cardona-Ospina JA, Gutiérrez-Ocampo E, et al. Clinical, laboratory and imaging features of COVID-19: A systematic review and meta-analysis. Travel Med Infect Dis. 2020 : p.101623. doi: 10.1016/j.tmaid.2020.101623 . | Open in Read by QxMD
  41. Guan W, Ni Z, Hu Y, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020 . doi: 10.1056/nejmoa2002032 . | Open in Read by QxMD
  42. Wang D, Hu B, Hu C, et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China. JAMA. 2020; 323 (11): p.1061. doi: 10.1001/jama.2020.1585 . | Open in Read by QxMD
  43. Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The Lancet. 2020 . doi: 10.1016/s0140-6736(20)30566-3 . | Open in Read by QxMD
  44. Salehi S, Abedi A, Balakrishnan S, Gholamrezanezhad A. Coronavirus Disease 2019 (COVID-19): A Systematic Review of Imaging Findings in 919 Patients. American Journal of Roentgenology. 2020 : p.1-7. doi: 10.2214/ajr.20.23034 . | Open in Read by QxMD
  45. Qian L, Yu J, Shi H. Severe Acute Respiratory Disease in a Huanan Seafood Market Worker: Images of an Early Casualty. Radiology: Cardiothoracic Imaging. 2020; 2 (1): p.e200033. doi: 10.1148/ryct.2020200033 . | Open in Read by QxMD
  46. Ai T, Yang Z, Hou H, et al. Correlation of Chest CT and RT-PCR Testing in Coronavirus Disease 2019 (COVID-19) in China: A Report of 1014 Cases. Radiology. 2020 : p.200642. doi: 10.1148/radiol.2020200642 . | Open in Read by QxMD
  47. Peng Q-Y, Wang X-T, Zhang L-N. Findings of lung ultrasonography of novel corona virus pneumonia during the 2019–2020 epidemic. Intensive Care Med. 2020 . doi: 10.1007/s00134-020-05996-6 . | Open in Read by QxMD
  48. RSNA Journals - Radiology of Coronavirus: Spectrum of imaging findings. https://pubs.rsna.org/2019-ncov. . Accessed: March 24, 2020.
  49. Wang Y, Dong C, Hu Y, et al. Temporal Changes of CT Findings in 90 Patients with COVID-19 Pneumonia: A Longitudinal Study. Radiology. 2020 : p.200843. doi: 10.1148/radiol.2020200843 . | Open in Read by QxMD
  50. Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China. JAMA. 2020; 323 (13): p.1239. doi: 10.1001/jama.2020.2648 . | Open in Read by QxMD
  51. Xu X-W, Wu X-X, Jiang X-G, et al. Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series. BMJ. 2020 : p.m606. doi: 10.1136/bmj.m606 . | Open in Read by QxMD
  52. Loss of sense of smell as marker of COVID-19 infection.
  53. Giacomelli A, Pezzati L, Conti F, et al. Self-reported olfactory and taste disorders in SARS-CoV-2 patients: a cross-sectional study. Clinical Infectious Diseases. 2020 . doi: 10.1093/cid/ciaa330 . | Open in Read by QxMD
  54. AAO-HNS: Anosmia, Hyposmia, and Dysgeusia Symptoms of Coronavirus Disease. https://www.entnet.org/content/aao-hns-anosmia-hyposmia-and-dysgeusia-symptoms-coronavirus-disease. Updated: March 22, 2020. Accessed: March 29, 2020.
  55. Huang N, Pérez P, et al. SARS-CoV-2 infection of the oral cavity and saliva. Nat Med. 2021 . doi: 10.1038/s41591-021-01296-8 . | Open in Read by QxMD
  56. Wichmann D, Sperhake J-P, Lütgehetmann M, et al. Autopsy Findings and Venous Thromboembolism in Patients With COVID-19. Ann Intern Med. 2020 . doi: 10.7326/m20-2003 . | Open in Read by QxMD
  57. Klok FA, Kruip MJHA, van der Meer NJM, et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res. 2020 . doi: 10.1016/j.thromres.2020.04.013 . | Open in Read by QxMD
  58. Clinical characteristics of COVID-19 patients with digestive symptoms in Hubei, China: a descriptive, cross-sectional, multicenter study.
  59. Michael Dreher, Alexander Kersten, Johannes Bickenbach, et al. The characteristics of 50 hospitalized COVID-19 patients with and without ARDS. Dtsch Arztebl Int. 2020 . doi: 10.3238/arztebl.2020.0271 . | Open in Read by QxMD
  60. Myers LC, Parodi SM, Escobar GJ, Liu VX. Characteristics of Hospitalized Adults With COVID-19 in an Integrated Health Care System in California. JAMA. 2020 . doi: 10.1001/jama.2020.7202 . | Open in Read by QxMD
  61. Arentz M, Yim E, Klaff L, et al. Characteristics and Outcomes of 21 Critically Ill Patients With COVID-19 in Washington State. JAMA. 2020; 323 (16): p.1612. doi: 10.1001/jama.2020.4326 . | Open in Read by QxMD
  62. Clinical Spectrum of SARS-CoV-2 Infection. https://www.covid19treatmentguidelines.nih.gov/overview/clinical-spectrum/. . Accessed: April 12, 2021.
  63. Testing for COVID-19. https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/testing.html. Updated: March 21, 2020. Accessed: March 27, 2020.
  64. Evaluating and Testing Persons for Coronavirus Disease 2019 (COVID-19). https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-criteria.html. Updated: March 14, 2020. Accessed: March 27, 2020.
  65. Interim Guidelines for Collecting, Handling, and Testing Clinical Specimens from Persons for Coronavirus Disease 2019 (COVID-19). https://www.cdc.gov/coronavirus/2019-nCoV/lab/guidelines-clinical-specimens.html. Updated: March 25, 2020. Accessed: March 26, 2020.
  66. LabCorp COVID-19 RT-PCR Letter of Authorization.
  67. Everlywell COVID-19 Test Home Collection Kit.
  68. Infinity BiologiX TaqPath SARS-CoV-2 Assay.
  69. COVID-19 Test (At-Home Kit). https://www.pixel.labcorp.com/at-home-test-kits/covid-19-test. Updated: April 26, 2020. Accessed: April 26, 2020.
  70. Sethuraman N, Jeremiah SS, Ryo A. Interpreting Diagnostic Tests for SARS-CoV-2. JAMA. 2020 . doi: 10.1001/jama.2020.8259 . | Open in Read by QxMD
  71. Udugama B, Kadhiresan P, Kozlowski HN, et al. Diagnosing COVID-19: The Disease and Tools for Detection. ACS Nano. 2020; 14 (4): p.3822-3835. doi: 10.1021/acsnano.0c02624 . | Open in Read by QxMD
  72. CDC 2019-Novel Coronavirus (2019-nCoV) Real-Time RT-PCR Diagnostic Panel.
  73. Wang W, Xu Y, Gao R, et al. Detection of SARS-CoV-2 in Different Types of Clinical Specimens. JAMA. 2020 . doi: 10.1001/jama.2020.3786 . | Open in Read by QxMD
  74. Coronavirus (COVID-19) Update: FDA Authorizes First Antigen Test to Help in the Rapid Detection of the Virus that Causes COVID-19 in Patients. https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-first-antigen-test-help-rapid-detection-virus-causes. Updated: May 9, 2020. Accessed: May 11, 2020.
  75. Interim Guidance for Antigen Testing for SARS-CoV-2. https://www.cdc.gov/coronavirus/2019-ncov/lab/resources/antigen-tests-guidelines.html. Updated: December 16, 2020. Accessed: April 13, 2021.
  76. Serology-based tests for COVID-19. http://www.centerforhealthsecurity.org/resources/COVID-19/Serology-based-tests-for-COVID-19.html. . Accessed: April 9, 2020.
  77. Guo L, Ren L, Yang S, et al. Profiling Early Humoral Response to Diagnose Novel Coronavirus Disease (COVID-19). Clinical Infectious Diseases. 2020 . doi: 10.1093/cid/ciaa310 . | Open in Read by QxMD
  78. Zhao J, Yuan Q, Wang H, et al. Antibody responses to SARS-CoV-2 in patients of novel coronavirus disease 2019. Clinical Infectious Diseases. 2020 . doi: 10.1093/cid/ciaa344 . | Open in Read by QxMD
  79. Kai-Wang To et al.. Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study. The Lancet. 2020 .
  80. Wolfel et al.. Virological assessment of hospitalized patients with COVID-2019. Nature. 2020 .
  81. Grifoni et al.. Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals. Cell. 2020 .
  82. Long et al.. Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections. Nature Medicine. 2020 .
  83. Wang et al.. Longitudinal dynamics of the neutralizing antibody response to SARS-CoV-2 infection. Clinical Infectious Diseases. 2020 .
  84. Chandrashekar et al.. SARS-CoV-2 infection protects against rechallenge in rhesus macaques. Science. 2020 .
  85. Deng et al.. Primary exposure to SARS-CoV-2 protects against reinfection in rhesus macaques. Science. 2020 .
  86. Yu et al.. DNA vaccine protection against SARS-CoV-2 in rhesus macaques. Science. 2020 .
  87. Shen C, Wang Z, Zhao F, et al. Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma. JAMA. 2020 . doi: 10.1001/jama.2020.4783 . | Open in Read by QxMD
  88. Coronavirus (COVID-19) Update: Serological Tests. https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-serological-tests. Updated: April 7, 2020. Accessed: April 10, 2020.
  89. Li Z, Yi Y, Luo X, et al. Development and Clinical Application of A Rapid IgM‐IgG Combined Antibody Test for SARS‐CoV‐2 Infection Diagnosis. J Med Virol. 2020 . doi: 10.1002/jmv.25727 . | Open in Read by QxMD
  90. The 'game changer' that wasn't: Company falsely claimed FDA authorization for coronavirus blood test. https://edition.cnn.com/2020/04/02/health/coronavirus-test-false-fda-authorization/index.html. Updated: April 2, 2020. Accessed: April 11, 2020.
  91. Prevention & Treatment. https://www.cdc.gov/coronavirus/2019-ncov/about/prevention-treatment.html. Updated: February 15, 2020. Accessed: March 5, 2020.
  92. Information for Health Departments on Reporting a Person Under Investigation (PUI), or Presumptive Positive and Laboratory-Confirmed Cases of COVID-19. https://www.cdc.gov/coronavirus/2019-ncov/hcp/guidance-home-care.html. Updated: March 1, 2020. Accessed: March 5, 2020.
  93. People who are at higher risk for severe illness. https://www.cdc.gov/coronavirus/2019-ncov/specific-groups/people-at-higher-risk.html. Updated: March 26, 2020. Accessed: March 27, 2020.
  94. Novel Coronavirus Pneumonia Emergency Response Epidemiology Team.. [The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19) in China].. Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi. 2020; 41 (2): p.145-151. doi: 10.3760/cma.j.issn.0254-6450.2020.02.003 . | Open in Read by QxMD
  95. FAQs on Shortages of Surgical Masks and Gowns. https://www.fda.gov/medical-devices/personal-protective-equipment-infection-control/faqs-shortages-surgical-masks-and-gowns. Updated: April 8, 2020. Accessed: April 9, 2020.
  96. Coronavirus Disease 2019 (COVID-19). https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/cloth-face-cover.html. Updated: April 3, 2020. Accessed: April 9, 2020.
  97. Interim Public Health Recommendations for Fully Vaccinated People. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/fully-vaccinated-guidance.html. Updated: May 13, 2021. Accessed: May 17, 2021.
  98. Rothe C, Schunk M, Sothmann P, et al. Transmission of 2019-nCoV Infection from an Asymptomatic Contact in Germany. N Engl J Med. 2020; 382 (10): p.970-971. doi: 10.1056/nejmc2001468 . | Open in Read by QxMD
  99. Bae S, Kim M-C, Kim JY, et al. Effectiveness of Surgical and Cotton Masks in Blocking SARS–CoV-2: A Controlled Comparison in 4 Patients. Ann Intern Med. 2020 . doi: 10.7326/m20-1342 . | Open in Read by QxMD
  100. Use of Cloth Face Coverings to Help Slow the Spread of COVID-19. https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/diy-cloth-face-coverings.html. Updated: April 13, 2020. Accessed: April 23, 2020.
  101. Leung NHL, Chu DKW, Shiu EYC, et al. Respiratory virus shedding in exhaled breath and efficacy of face masks. Nat Med. 2020 . doi: 10.1038/s41591-020-0843-2 . | Open in Read by QxMD
  102. Frequently Asked Questions about Personal Protective Equipment. https://www.cdc.gov/coronavirus/2019-ncov/hcp/respirator-use-faq.html. Updated: February 29, 2020. Accessed: March 5, 2020.
  103. Social Distancing, Quarantine, and Isolation. https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/social-distancing.html. Updated: April 4, 2020. Accessed: May 5, 2020.
  104. Public Health Recommendations for Community-Related Exposure. https://www.cdc.gov/coronavirus/2019-ncov/php/public-health-recommendations.html. Updated: March 30, 2020. Accessed: May 5, 2020.
  105. What To Do if You Are Sick. https://www.cdc.gov/coronavirus/2019-ncov/if-you-are-sick/steps-when-sick.html. Updated: March 25, 2020. Accessed: March 27, 2020.
  106. How to Protect Yourself & Others. https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/prevention.html. Updated: April 24, 2020. Accessed: May 6, 2020.
  107. Public Health Guidance for Potential COVID-19 Exposure Associated with International Travel or Cruise Travel. https://www.cdc.gov/coronavirus/2019-ncov/php/risk-assessment.html. Updated: May 3, 2020. Accessed: May 6, 2020.
  108. Interim Infection Prevention and Control Recommendations for Patients with Suspected or Confirmed Coronavirus Disease 2019 (COVID-19) in Healthcare Settings. https://www.cdc.gov/coronavirus/2019-ncov/infection-control/control-recommendations.html. Updated: March 19, 2020. Accessed: March 27, 2020.
  109. Sequence for Donning and Removing Personal Protective Equipment.
  110. Coronavirus Disease 2019 (COVID-19). https://www.cdc.gov/coronavirus/2019-ncov/index.html. Updated: March 2, 2020. Accessed: March 5, 2020.
  111. Q&A on coronaviruses (COVID-19). https://www.who.int/news-room/q-a-detail/q-a-coronaviruses. Updated: February 23, 2020. Accessed: March 5, 2020.
  112. Coronavirus COVID-19 Global Cases by Johns Hopkins CSSE. https://www.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6. Updated: February 11, 2020. Accessed: March 5, 2020.
  113. COVID-19 Projections. https://covid19.healthdata.org/united-states-of-america. . Accessed: April 11, 2020.
  114. Coronavirus Disease 2019 (COVID-19). https://www.fda.gov/emergency-preparedness-and-response/counterterrorism-and-emerging-threats/coronavirus-disease-2019-covid-19. Updated: April 8, 2020. Accessed: April 9, 2020.
  115. COVID-19 Open Research Dataset (CORD-19). https://pages.semanticscholar.org/coronavirus-research. . Accessed: April 11, 2020.
  116. Human Coronaviruses Data Initiative. https://about.lens.org/covid-19/. . Accessed: April 11, 2020.
  117. LitCovid. https://www.ncbi.nlm.nih.gov/research/coronavirus/. . Accessed: April 11, 2020.
  118. Chen Q, Allot A, Lu Z. Keep up with the latest coronavirus research. Nature. 2020; 579 (7798): p.193-193. doi: 10.1038/d41586-020-00694-1 . | Open in Read by QxMD
  119. All COVID-19 clinical trials at a glance. https://www.transparimed.org/single-post/2020/03/27/COVID-19-clinical-trials-information-sources. Updated: April 9, 2020. Accessed: April 11, 2020.
  120. Zhu N, Zhang D, Wang W, et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019.. N Engl J Med. 2020; 382 (8): p.727-733. doi: 10.1056/NEJMoa2001017 . | Open in Read by QxMD
  121. Guo YR, Cao QD, Hong ZS, et al. The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak - an update on the status.. Military Medical Research. 2020; 7 (1): p.11. doi: 10.1186/s40779-020-00240-0 . | Open in Read by QxMD
  122. WHO-convened Global Study of Origins of SARS-CoV-2: China Part. https://www.who.int/publications/i/item/who-convened-global-study-of-origins-of-sars-cov-2-china-part. Updated: April 6, 2021. Accessed: April 17, 2021.
  123. Ji W, Wang W, Zhao X, Zai J, Li X. Cross‐species transmission of the newly identified coronavirus 2019‐nCoV. J Med Virol. 2020; 92 (4): p.433-440. doi: 10.1002/jmv.25682 . | Open in Read by QxMD
  124. Tang X, Wu C, Li X, et al. On the origin and continuing evolution of SARS-CoV-2. National Science Review. 2020 . doi: 10.1093/nsr/nwaa036 . | Open in Read by QxMD
  125. Rapid increase of a SARS-CoV-2 variant with multiple spike protein mutations observed in the United Kingdom. https://www.ecdc.europa.eu/sites/default/files/documents/SARS-CoV-2-variant-multiple-spike-protein-mutations-United-Kingdom.pdf. Updated: December 20, 2020. Accessed: February 21, 2021.
  126. Transmission of SARS-CoV-2 Lineage B.1.1.7 in England: Insights from linking epidemiological and genetic data. https://www.imperial.ac.uk/media/imperial-college/medicine/mrc-gida/2020-12-31-COVID19-Report-42-Preprint-VOC.pdf. Updated: December 31, 2020. Accessed: February 21, 2021.
  127. NERVTAG note on B.1.1.7 severity. https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/955239/NERVTAG_paper_on_variant_of_concern__VOC__B.1.1.7.pdf. Updated: January 21, 2021. Accessed: February 21, 2021.
  128. Emerging SARS-CoV-2 Variants. https://www.cdc.gov/coronavirus/2019-ncov/more/science-and-research/scientific-brief-emerging-variants.html#ref1. Updated: January 28, 2021. Accessed: February 21, 2021.
  129. SARS-CoV-2 Variants. https://www.who.int/csr/don/31-december-2020-sars-cov2-variants/en/. Updated: December 31, 2020. Accessed: February 26, 2021.
  130. Weisblum et al.. Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants. eLife. 2020 .
  131. Wibmer et al.. SARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma. bioRxiv. 2021 .
  132. Spike E484K mutation in the first SARS-CoV-2 reinfection case confirmed in Brazil. https://virological.org/t/spike-e484k-mutation-in-the-first-sars-cov-2-reinfection-case-confirmed-in-brazil-2020/584. Updated: January 10, 2021. Accessed: February 26, 2021.
  133. SARS-CoV-2 Variant Classifications and Definitions. https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/variant-surveillance/variant-info.html. . Accessed: April 12, 2021.
  134. Gralinski LE, Menachery VD. Return of the Coronavirus: 2019-nCoV.. Viruses. 2020; 12 (2). doi: 10.3390/v12020135 . | Open in Read by QxMD
  135. Wan Y, Shang J, Graham R, Baric RS, Li F. Receptor Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on Decade-Long Structural Studies of SARS Coronavirus.. J Virol. 2020; 94 (7). doi: 10.1128/JVI.00127-20 . | Open in Read by QxMD
  136. Nicholls J, Peiris M. Good ACE, bad ACE do battle in lung injury, SARS. Nat Med. 2005; 11 (8): p.821-822. doi: 10.1038/nm0805-821 . | Open in Read by QxMD
  137. Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020 . doi: 10.1016/j.cell.2020.02.052 . | Open in Read by QxMD
  138. Zhang H, Penninger JM, Li Y, Zhong N, Slutsky AS. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med. 2020 . doi: 10.1007/s00134-020-05985-9 . | Open in Read by QxMD
  139. Li W, Moore MJ, Vasilieva N, et al. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003; 426 (6965): p.450-454. doi: 10.1038/nature02145 . | Open in Read by QxMD
  140. Yuki et al.. COVID-19 pathophysiology: A review. Clinical Immunology. 2020 .
  141. Zheng Y-Y, Ma Y-T, Zhang J-Y, Xie X. COVID-19 and the cardiovascular system. Nat Rev Cardiol. 2020; 17 (5): p.259-260. doi: 10.1038/s41569-020-0360-5 . | Open in Read by QxMD
  142. Leung JM, Yang CX, Tam A, et al. ACE-2 Expression in the Small Airway Epithelia of Smokers and COPD Patients: Implications for COVID-19. European Respiratory Journal. 2020 : p.2000688. doi: 10.1183/13993003.00688-2020 . | Open in Read by QxMD
  143. Jose RJ, Manuel A. COVID-19 cytokine storm: the interplay between inflammation and coagulation. The Lancet Respiratory Medicine. 2020 . doi: 10.1016/s2213-2600(20)30216-2 . | Open in Read by QxMD
  144. Qing Ye, Bili Wang, Jianhua Mao. The pathogenesis and treatment of the `Cytokine Storm' in COVID-19. J Infect. 2020 . doi: 10.1016/j.jinf.2020.03.037 . | Open in Read by QxMD
  145. Piroth et al.. Comparison of the characteristics, morbidity, and mortality of COVID-19 and seasonal influenza: a nationwide, population-based retrospective cohort study. The Lancet Respiratory Medicine. 2020 .
  146. Xie et al.. Comparative evaluation of clinical manifestations and risk of death in patients admitted to hospital with covid-19 and seasonal influenza: cohort study. BMJ. 2020 .
  147. COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. https://www.covid19treatmentguidelines.nih.gov/. Updated: September 1, 2020. Accessed: October 2, 2020.
  148. Zeng H, Xu C, Fan J, et al. Antibodies in Infants Born to Mothers With COVID-19 Pneumonia. JAMA. 2020 . doi: 10.1001/jama.2020.4861 . | Open in Read by QxMD
  149. Dong L, Tian J, He S, et al. Possible Vertical Transmission of SARS-CoV-2 From an Infected Mother to Her Newborn. JAMA. 2020 . doi: 10.1001/jama.2020.4621 . | Open in Read by QxMD
  150. Poon LC, Yang H, Lee JCS, et al. ISUOG Interim Guidance on 2019 novel coronavirus infection during pregnancy and puerperium: information for healthcare professionals. Ultrasound in Obstetrics & Gynecology. 2020 . doi: 10.1002/uog.22013 . | Open in Read by QxMD
  151. Coronavirus disease (COVID-19) advice for the public. https://www.who.int/emergencies/diseases/novel-coronavirus-2019/advice-for-public. Updated: March 31, 2020. Accessed: April 13, 2020.
  152. Dashraath P, Jing Lin Jeslyn W, Mei Xian Karen L, et al. Coronavirus Disease 2019 (COVID-19) Pandemic and Pregnancy. Am J Obstet Gynecol. 2020 . doi: 10.1016/j.ajog.2020.03.021 . | Open in Read by QxMD
  153. Coronavirus COVID-19 Global Cases. https://coronavirus.jhu.edu/map.html. . Accessed: March 28, 2020.
  154. Liu Y, Gayle AA, Wilder-Smith A, Rocklöv J. The reproductive number of COVID-19 is higher compared to SARS coronavirus. Journal of Travel Medicine. 2020; 27 (2). doi: 10.1093/jtm/taaa021 . | Open in Read by QxMD
  155. Novel coronavirus disease 2019 (COVID-19) pandemic: increased transmission in the EU/EEA and the UK – sixth update.
  156. Viceconte G, Petrosillo N. COVID-19 R0: Magic number or conundrum?. Infectious Disease Reports. 2020; 12 (1). doi: 10.4081/idr.2020.8516 . | Open in Read by QxMD
  157. Sun WW, Ling F, Pan JR, et al. [Epidemiological characteristics of 2019 novel coronavirus family clustering in Zhejiang Province].. Zhonghua Yu Fang Yi Xue Za Zhi. 2020; 54 : p.E027. doi: 10.3760/cma.j.cn112150-20200227-00199 . | Open in Read by QxMD
  158. Overview of COVID-19. https://www.covid19treatmentguidelines.nih.gov/overview/overview-of-covid-19/ . Updated: July 8, 2021. Accessed: August 31, 2021.
  159. Decreasing median age of COVID-19 cases in the United States: changing epidemiology or changing surveillance?. http://dx.doi.org/10.1101/2020.07.22.20160119. Updated: July 24, 2020. Accessed: August 25, 2020.
  160. Bourouiba L. Turbulent Gas Clouds and Respiratory Pathogen Emissions. JAMA. 2020 . doi: 10.1001/jama.2020.4756 . | Open in Read by QxMD
  161. Van Doremalen N, Bushmaker T, Morris DH, et al. Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1. N Engl J Med. 2020 . doi: 10.1056/nejmc2004973 . | Open in Read by QxMD
  162. Stadnytskyi V, Bax CE, Bax A, Anfinrud P. The airborne lifetime of small speech droplets and their potential importance in SARS-CoV-2 transmission. Proceedings of the National Academy of Sciences. 2020 : p.202006874. doi: 10.1073/pnas.2006874117 . | Open in Read by QxMD
  163. Ong SWX, Tan YK, Chia PY, et al. Air, Surface Environmental, and Personal Protective Equipment Contamination by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) From a Symptomatic Patient. JAMA. 2020 . doi: 10.1001/jama.2020.3227 . | Open in Read by QxMD
  164. Clinical presentation and virological assessment of hospitalized cases of coronavirus disease 2019 in a travel-associated transmission cluster. http://dx.doi.org/10.1101/2020.03.05.20030502. Updated: March 8, 2020. Accessed: December 28, 2020.
  165. Lan et al.. Positive RT-PCR Test Results in Patients Recovered From COVID-19. JAMA. 2020 .
  166. Incubation Period and Other Epidemiological Characteristics of 2019 Novel Coronavirus Infections with Right Truncation: A Statistical Analysis of Publicly Available Case Data. http://dx.doi.org/10.1101/2020.01.26.20018754. Updated: January 28, 2020. Accessed: March 27, 2020.
  167. Q&A on coronaviruses (COVID-19). https://www.who.int/news-room/q-a-detail/q-a-coronaviruses. Updated: March 9, 2020. Accessed: March 27, 2020.
  168. Lauer SA, Grantz KH, Bi Q, et al. The Incubation Period of Coronavirus Disease 2019 (COVID-19) From Publicly Reported Confirmed Cases: Estimation and Application. Ann Intern Med. 2020 . doi: 10.7326/m20-0504 . | Open in Read by QxMD
  169. Bullard et al.. Predicting infectious SARS-CoV-2 from diagnostic samples. Clinical Infectious Diseases. 2020 .
  170. Perera et al.. SARS-CoV-2 Virus Culture and Subgenomic RNA for Respiratory Specimens from Patients with Mild Coronavirus Disease. Emerging Infectious Diseases. 2020 .
  171. Cheng et al.. Contact Tracing Assessment of COVID-19 Transmission Dynamics in Taiwan and Risk at Different Exposure Periods Before and After Symptom Onset. JAMA Internal Medicine. 2020 .
  172. Xiao et al.. Profile of RT-PCR for SARS-CoV-2: a preliminary study from 56 COVID-19 patients. Clinical Infectious Diseases. 2020 .
  173. Feng-Cai Zhu et al.. Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial. The Lancet. 2020 .
  174. Lynch et al.. Magnitude and kinetics of anti-SARS-CoV-2 antibody responses and their relationship to disease severity. Clinical Infectious Diseases. 2020 .
  175. Rijkers et al.. Differences in Antibody Kinetics and Functionality Between Severe and Mild Severe Acute Respiratory Syndrome Coronavirus 2 Infections. The Journal of Infectious Diseases. 2020 .
  176. Kelvin Kai-Wang To, Ivan Fan-Ngai Hung. COVID-19 re-infection by a phylogenetically distinct SARS-coronavirus-2 strain confirmed by whole genome sequencing. Clinical Infectious Diseases. 2020 .
  177. Liotti et al.. Assessment of SARS-CoV-2 RNA Test Results Among Patients Who Recovered From COVID-19 With Prior Negative Results. JAMA Internal Medicine. 2020 .
  178. Tillett et al.. Genomic evidence for reinfection with SARS-CoV-2: a case study. The Lancet Infectious Diseases. 2020 .
  179. Iwasaki. What reinfections mean for COVID-19. The Lancet Infectious Diseases. 2020 .
  180. Bai Y, Yao L, Wei T, et al. Presumed Asymptomatic Carrier Transmission of COVID-19. JAMA. 2020 . doi: 10.1001/jama.2020.2565 . | Open in Read by QxMD
  181. Duration of Isolation and Precautions for Adults with COVID-19. https://www.cdc.gov/coronavirus/2019-ncov/hcp/duration-isolation.html. Updated: July 22, 2020. Accessed: August 10, 2020.
  182. Criteria for releasing COVID-19 patients from isolation. https://www.who.int/news-room/commentaries/detail/criteria-for-releasing-covid-19-patients-from-isolation. Updated: June 17, 2020. Accessed: August 10, 2020.
  183. Discontinuation of Transmission-Based Precautions and Disposition of Patients with COVID-19 in Healthcare Settings (Interim Guidance). https://www.cdc.gov/coronavirus/2019-ncov/hcp/disposition-hospitalized-patients.html. Updated: March 23, 2020. Accessed: March 28, 2020.
  184. Coronavirus (COVID-19) Update: FDA Issues Emergency Use Authorization for Potential COVID-19 Treatment. https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-issues-emergency-use-authorization-potential-covid-19-treatment. Updated: May 1, 2020. Accessed: May 2, 2020.
  185. Remdesivir EUA Letter of Authorization.
  186. NIH Clinical Trial Shows Remdesivir Accelerates Recovery from Advanced COVID-19. https://www.niaid.nih.gov/news-events/nih-clinical-trial-shows-remdesivir-accelerates-recovery-advanced-covid-19?fbclid=IwAR0XHEy6MMXGrTtv_kpJq7TTjT7G4cxgRrIurazAzKfj1OUo7o41s_C76aI. Updated: April 29, 2020. Accessed: April 30, 2020.
  187. NIH Clinical Trial of Remdesivir to Treat COVID-19 Begins. https://www.niaid.nih.gov/news-events/nih-clinical-trial-remdesivir-treat-covid-19-begins. Updated: February 25, 2020. Accessed: April 30, 2020.
  188. Sheahan TP, Sims AC, Leist SR, et al. Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV. Nature Communications. 2020; 11 (1). doi: 10.1038/s41467-019-13940-6 . | Open in Read by QxMD
  189. Agostini ML, Andres EL, Sims AC, et al. Coronavirus Susceptibility to the Antiviral Remdesivir (GS-5734) Is Mediated by the Viral Polymerase and the Proofreading Exoribonuclease. mBio. 2018; 9 (2). doi: 10.1128/mbio.00221-18 . | Open in Read by QxMD
  190. The COVID-19 Treatment Guidelines Panel’s Statement on Baricitinib for the Treatment of Adults with COVID-19. https://www.covid19treatmentguidelines.nih.gov/therapies/statement-on-baricitinib/. Updated: May 27, 2021. Accessed: June 23, 2021.
  191. Xie J, Tong Z, Guan X, Du B, Qiu H, Slutsky AS. Critical care crisis and some recommendations during the COVID-19 epidemic in China. Intensive Care Med. 2020 . doi: 10.1007/s00134-020-05979-7 . | Open in Read by QxMD
  192. Lu H. Drug treatment options for the 2019-new coronavirus (2019-nCoV).. Bioscience trends. 2020; 14 (1): p.69-71. doi: 10.5582/bst.2020.01020 . | Open in Read by QxMD
  193. Noshi T, Kitano M, Taniguchi K, et al. In vitro characterization of baloxavir acid, a first-in-class cap-dependent endonuclease inhibitor of the influenza virus polymerase PA subunit. Antiviral Res. 2018; 160 : p.109-117. doi: 10.1016/j.antiviral.2018.10.008 . | Open in Read by QxMD
  194. FURUTA Y, KOMENO T, NAKAMURA T. Favipiravir (T-705), a broad spectrum inhibitor of viral RNA polymerase. Proceedings of the Japan Academy, Series B. 2017; 93 (7): p.449-463. doi: 10.2183/pjab.93.027 . | Open in Read by QxMD
  195. Xu et al.. Clinical Efficacy of Arbidol in Patients with 2019 Novel Coronavirus-Infected Pneumonia: A Retrospective Cohort Study. The Lancet. 2020 .
  196. Outcomes of hydroxychloroquine usage in United States veterans hospitalized with Covid-19. http://dx.doi.org/10.1101/2020.04.16.20065920. Updated: April 21, 2020. Accessed: April 23, 2020.
  197. Therapeutic Options for COVID-19 Currently Under Investigation. https://covid19treatmentguidelines.nih.gov/therapeutic-options-under-investigation/. Updated: April 21, 2020. Accessed: April 23, 2020.
  198. Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM. The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Res. 2020; 178 : p.104787. doi: 10.1016/j.antiviral.2020.104787 . | Open in Read by QxMD
  199. Casadevall A, Pirofski L. The convalescent sera option for containing COVID-19. J Clin Invest. 2020 . doi: 10.1172/jci138003 . | Open in Read by QxMD
  200. FDA EUA for COVID-19 convalescent plasma for the treatment of hospitalized patients with COVID-19. https://www.fda.gov/media/141477/download. Updated: August 23, 2020. Accessed: October 2, 2020.
  201. Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19. https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management. Updated: April 13, 2020. Accessed: April 15, 2020.
  202. Yazdany J, Kim AHJ. Use of Hydroxychloroquine and Chloroquine During the COVID-19 Pandemic: What Every Clinician Should Know. Ann Intern Med. 2020 . doi: 10.7326/m20-1334 . | Open in Read by QxMD
  203. Interim US Guidance for Risk Assessment and Public Health Management of Persons with Potential Coronavirus Disease 2019 (COVID-19) Exposures: Geographic Risk and Contacts of Laboratory-confirmed Cases. https://www.cdc.gov/coronavirus/2019-ncov/php/risk-assessment.html. Updated: March 22, 2020. Accessed: March 26, 2020.
  204. Discontinuation of Home Isolation for Persons with COVID-19 (Interim Guidance). https://www.cdc.gov/coronavirus/2019-ncov/hcp/disposition-in-home-patients.html. Updated: March 16, 2020. Accessed: March 28, 2020.
  205. Emergency Use Authorization (EUA) for qSARS-CoV-2 IgG/IgM Rapid Test.
  206. COVID-19 IgM/IgG Rapid Test. https://www.biomedomics.com/products/infectious-disease/covid-19-rt/. . Accessed: April 10, 2020.
  207. Qin Y-Y, Zhou Y-H, Lu Y-Q, et al. Effectiveness of glucocorticoid therapy in patients with severe coronavirus disease 2019. Chin Med J (Engl). 2020; 133 (9): p.1080-1086. doi: 10.1097/cm9.0000000000000791 . | Open in Read by QxMD