• Clinical science

COVID-19 (coronavirus disease 2019)


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

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

Additional free AMBOSS resources for COVID-19

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  • The disease is currently spreading worldwide. Refer to the Johns Hopkins University & Medicine Coronavirus Resource Center (https://coronavirus.jhu.edu/map.html) for up-to-date statistics. [3]
  • To date, the greatest number of confirmed cases has been reported from the US, mainland China, Italy, and Spain. The greatest number of deaths have been reported from Italy, Spain, and China.
  • WHO declared the COVID-19 outbreak a Public Health Emergency of International Concern on January 30, 2020.
  • WHO classified the disease as a pandemic on March 11, 2020.
  • Men and women are equally affected. [4]
  • The median age of patients is ∼ 47 years in China. [5]
  • Mortality rate ranges from ∼ 0.5 to 3%.
  • The mortality rate greatly increases > 60 years of age, with the most lethal rates for individuals > 80 years reaching ∼ 15%. [4]


  • The virus
    • SARS-CoV-2 is a potentially lethal type of coronavirus, a subfamily of enveloped nonsegmented positive-sense RNA viruses that usually cause mild respiratory tract infections.
    • 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]
    • Genome sequencing shows 96.2% identity to a bat coronavirus RaTG13, making bats the most likely natural host of the SARS-CoV-2 origin. [7]
      • The initial animal-to-human transmission likely occurred via direct exposure to an unknown intermediate host at the Huanan Seafood Wholesale Market in Wuhan, China, a live animal and seafood market (“wet market”) that was identified as the point of origin. [8]
    • 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]
      • The authors suggested:
        • S-type was the original type transmitted to humans from the animal host and is less contagious and aggressive.
        • L-type evolved from the S-type and is somewhat more contagious and aggressive.
      • However, the WHO currently does not believe the genetic diversity observed in the study means that virus activity is changing. [10]
      • Because of limited data, more research is needed to better understand the implications of genetic diversity on virulence and lethality.
  • Invasion of host cells [11]
    • Entry point: ACE2, which catalyzes the conversion of angiotensin II, is expressed in the surface epithelium of the lungs and other organs. ACE2 receptors have been identified as the binding site for SARS-CoV-2 in animals and humans. [12][13][14][15][16]
    • 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.
  • Direct cytopathic effects
    • Virus-induced damage, particularly to the alveolar epithelium
    • Other organs, especially the liver and heart, can also be affected.
  • Dysregulated immune response: As in sepsis, there is an immune response involving the release of cytokines (IL-6) and the triggering of an acute inflammatory response. However, COVID-19 usually does not lead to hypotension, a defining feature of septic shock.

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!

Initial infection

  • Transmission: person-to-person, primarily via respiratory droplets (sneezing and coughing)
    • Direct contact transmission: especially hand-to-face contact
    • Fomite transmission: not documented but conceivably possible, especially with objects and surfaces that may have recently come into contact with infected individuals
      • Transmission via mail and packaged (imported) goods: There is no evidence to suggest that mail and packaged (imported) goods pose a risk for the spread of COVID-19.
    • Fecal-oral transmission: Evidence that both SARS-CoV and MERS-CoV are excreted fecally suggests that fecal-oral transmission is possible. [17]
  • Incubation period: 2–14 days, usually ∼ 5 days [18][19]

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

Clinical features

  • Symptoms
    • Often asymptomatic
    • Symptomatic cases [20][21][22]
  • Course: The disease has a wide spectrum of severity, ranging from mild to critical.

Differential diagnoses

COVID-19 Influenza Common cold Allergic rhinitis
Fever +++ +++ - -
Cough +++ +++ +++ ++
Fatigue +++ +++ + -
Anorexia ++ ++ - -
Dyspnea ++ - - -
Myalgia ++ +++ + -
Loss of smell/taste ++ - ++ ++
Rhinitis + + +++ +++
Sneezing - - +++ +++
Sore throat + + +++ -
Diarrhea + + - -
Headache - +++ ++ -
Itchy eyes - - - +++

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

Infection control and preventive measures

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.

The CDC has recommended that organizers cancel or postpone in-person events with ≥ 50 people in the US for the next 8 weeks.

  • Masks
    • In PUIs and individuals with confirmed infection: useful for preventing the diffusion of respiratory secretions, e.g., during patient transports
    • In healthcare facilities (HCFs) or home care settings: crucial for health workers and persons taking care of an infected individual in close settings (in a HCF or at home)
      • Surgical masks do not provide adequate protection in the setting of invasive diagnostics or those at high risk of exposure.
        • 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). [24]
        • Confirmed COVID-19 patients and PUIs can use standard N95 respirators.
        • If N95 respirator bottlenecks occur, unvalved N95 respirators may be used with a face shield.
        • Respirators and masks should be used resourcefully with special consideration for HCF needs.
    • In the general population: Surgical masks are most likely ineffective and may even pose an additional risk of infection.

Exposure risk management [25]

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.

  • Public health measures
    • Social distancing means individuals should avoid:
      • Mass gatherings
      • Congregate settings: crowded public places where close contact may occur (movie theater, shopping center)
      • Maintain a distance of ∼ 6 feet (2 meters) from others
    • 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 categories (adapted from the CDC)
    • High: Living with, having intimate contact with, or providing home care for a person with symptomatic laboratory-confirmed COVID-19 without following recommended precautions for home isolation and care.
    • Medium
      • Travel from a country with sustained transmission or on a cruise ship/riverboat
      • Close contact (within ∼ 6 feet or 2 meters) with or direct contact with infections secretions from a person with symptomatic laboratory-confirmed COVID-19
      • Living with, having intimate contact with, or providing home care for a person with symptomatic laboratory-confirmed COVID-19 while following recommended precautions for home isolation and care.
    • Low: being in the same indoor environment as a person with symptomatic laboratory-confirmed COVID-19 for a prolonged period
    • No identifiable risk: any interaction with a person with symptomatic laboratory-confirmed COVID-19 that does not meet the criteria above
  • Recommendations for exposure risk management vary according to state and local authorities. Some measures based upon some of the CDC recommendations include:
Risk level If asymptomatic If symptomatic
Low or no identifiable risk
  • N/A
  • Self-isolation, social distancing
  • No travel until asymptomatic
  • Seek health advice (via phone call preferred) to determine need for medical evaluation or controlled travel
Medium risk
  • Self-isolation
  • No public activities
  • Public health assessment (via phone call preferred) to determine need for medical evaluation or controlled travel
  • If medical evaluation or travel is needed, all infection control precautions should be followed.
High risk
  • Quarantine in a location determined by public health authorities
  • No public activities
  • Only controlled travel
  • Active monitoring

Infection prevention and control in healthcare settings

Recommendations vary according to the appropriate health department/agency. Some recommendations from the CDC include: [26]

  • 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 door
    • 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) for COVID-19

  • PPE recommendations for individuals in close contact with COVID-19 cases or PUIs consists of the following items in this order: [26][27]
    1. Long-sleeved isolation gown: Fully cover torso, extending from the neck to knees and end of wrists; then close the backside.
    2. N95 respirator or facemask: secure and fit
    3. Eye protection (e.g., goggles or disposable full-face shield): place and adjust
    4. Clean nonsterile gloves: cover wrist of isolation gown
  • Safely removing PPE [27]
    • There are a variety of ways to remove PPE without contamination.
    • Any part of the PPE directly exposed to the patient (especially the front and sleeves) is contaminated and should not be touched with ungloved hands during removal.
    • All PPE (except for a respirator if worn) should be removed before leaving the contaminated space (e.g., patient room).
    • Anytime hands are contaminated, immediately wash them or use an alcohol-based hand sanitizer between steps.
    • Example 1 (in order):
      1. Gloves:
        1. Using a gloved hand, grasp the palm area of the other gloved hand and peel it off.
        2. Hold removed gland in gloved hand.
        3. Slide fingers of ungloved hand under remaining glove at wrist (do not touch the gown!) and slide it inside out over the first glove.
        4. Discard gloves in a waste container.
      2. Goggles or face shield:
        1. Remove from the back by lifting the head band or ear pieces.
        2. If reusable: Place in designated receptacle; Otherwise, discard in a waste container.
      3. Gown:
        1. Unfasten ties without contacting body with sleeves.
        2. While only touching the inside, pull gown away from neck and shoulders.
        3. Turn it inside out over the arms.
        4. Roll into a bundle and discard in a waste container.
      4. Mask or respirator
        1. Grasp bottom ties or elastics, then together the top ones, and remove upwards without touching the front.
        2. Discard in a waste container.
      5. Immediately wash hands or use an alcohol-based hand sanitizer.
    • Example 2 (in order):
      1. Gown and gloves together:
        1. Grasp the gown in front and pull away from the body until the ties break (only touch outside of gown with gloved hands).
        2. While removing the gown over the arms, roll the gown inside-out.
        3. Before the gown is removed from the wrists, using a gloved hand to grasp a portion of the glove of the other hand and sleeve of the gown together.
        4. With the glove and sleeve secured together, pull the arm of this side back, allowing the naked hand to exit the glove while only being exposed to the inside of the gown.
        5. Now using the ungloved hand, slide the remaining part of the gown and glove from the other side off, only touching the inside, in an inside-out manner and into the bundle.
        6. Place the gown and gloves into a waste container.
      2. Goggles or face shield:
        1. Remove from the back by lifting the head band or ear pieces.
        2. If reusable: Place in designated receptacle; Otherwise, discard in a waste container.
      3. Mask or respirator
        1. Grasp bottom ties or elastics, then together the top ones, and remove upwards without touching the front.
        2. Discard in a waste container.
      4. Immediately wash hands or use an alcohol-based hand sanitizer

Evaluation and testing

Real-time polymerase chain reaction (RT-PCR) of DNA 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 healthcare facility (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 states that not everyone needs testing for COVID-19, and defers decisions about testing to respective health departments and/or individual clinicians. [28]
      • Exception: Older adults or individuals with certain underlying conditions, including cardiovascular, pulmonary, renal, or metabolic (diabetes mellitus) conditions should seek medical care for testing as soon as symptoms begin.
    • In general, clinicians are urged to make judgment calls if a patient's signs, symptoms, and risk factors warrant COVID-19 testing.
    • In some cases (e.g., if testing is limited), predetermined priorities should be considered to maximize the benefits of testing. The CDC has set priorities for testing, consisting of: [29]
      • Priority 1: Ensure optimal care options for all hospitalized patients, lessen the risk of nosocomial infections, and maintain the integrity of the healthcare system
        • Hospitalized patients
        • Symptomatic healthcare workers
      • Priority 2: Ensure that those who are at highest risk of complication of infection are rapidly identified and appropriately triaged
        • Patients in long-term care facilities with symptoms
        • Patients 65 years of age and older with symptoms
        • Patients with underlying conditions with symptoms
        • First responders with symptoms
      • Priority 3: As resources allow, test individuals in the surrounding community of rapidly increasing hospital cases to decrease community spread, and ensure health of essential workers
        • Critical infrastructure workers with symptoms
        • Individuals who do not meet any of the above categories with symptoms
        • Health care workers and first responders
        • Individuals with mild symptoms in communities experiencing high COVID-19 hospitalizations
      • Non-priority: Individuals without symptoms
    • Some health agencies and departments (e.g., in the United Kingdom) directly recommend that individuals suspected of COVID-19 not be tested for the virus if they only have mild symptoms and instead, should remain at home in isolation. [30]
  • 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) [31]

  • General measures
    • Specimens should be collected at a clinical or public health laboratory for routine testing of respiratory pathogens.
    • Testing should only be conducted for individuals demonstrating symptomatic disease in consultation with a clinician.
    • Close contact with PUIs should be avoided; anytime it is required, health care personnel should wear all recommended personal protective equipment (PPE) for COVID-19.
  • Collection of specimens
    • For all individuals, conduct on an upper respiratory specimen.
      • Preferred method by the CDC: nasopharyngeal specimen (NPS) using a single synthetic fiber swab with a plastic shaft that is gently inserted through the nostril to the posterior nasopharynx , where it is left for several seconds to absorb secretions before slowly removing while rotating
      • Alternative methods
        • Oropharyngeal (OP) swab (throat swab): swab the posterior pharynx while avoiding the tongue
        • Nasal mid-turbinate (NMT) swab
        • Anterior nares specimen (NS)
        • Possibly nasopharyngeal wash/aspirate or nasal aspirate
      • Handling
        • Swabs should be placed immediately into sterile transport tubes containing 2–3 ml of viral transport media
        • If both NP and OP swabs: combine in a single tube
    • When feasible, lower respiratory tract specimens should also be collected.
      • If productive coughing: from sputum
        • After rinsing the mouth with water, the patient should spit deep cough sputum into a sterile sputum collection cup or sterile dry container.
      • If undergoing mechanical breathing: lower respiratory tract aspirate or bronchoalveolar lavage
        • 2–3 mL should be placed in a sterile sputum collection cup or sterile dry container.
    • Many locations have necessary materials already prepared in respiratory virus swab collection kits.
  • 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 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 “Stephen Lindstrom: 2019-nCoV PUI”.
      • Ship overnight to CDC on ice pack.

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.

Laboratory testing

  • Real-time polymerase chain reaction (RT-PCR): confirms infection with SARS-CoV-2 from patient specimens
    • Results should be available within a few hours
    • Has both high sensitivity and specificity
    • Sensitivity likely increases when testing specimens from multiple sites. [32]

A PCR can initially be negative. In such cases, if there is still concern that a patient is infected, repeating PCR testing every 2–3 days should be considered, potentially with both upper and lower respiratory tract specimens.


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” above.) [33]


  • 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 healthcare facility (HCF) infection control personnel of persons under investigation (PUI) and confirmed cases. [34]

Initial steps and site of care

  • Measure vital signs (BT, BP, HR, RR) and SpO2
  • Consider ambulant management with watchful waiting for patients with:
    • Low fever (< 100.4°F or 38.3°C)
    • No signs of respiratory distress
    • Normal SpO2
    • Negative qSOFA score
  • Admit symptomatic patients with the following signs:
    • Difficulty breathing
    • Persistent pain or pressure in the chest
    • Change in mental status (e.g., confused, nonresponsive)
    • Signs of cyanosis (e.g., bluish lips)
    • SpO2 ≤ 93%
    • Respiratory rate > 22/min
    • Fever > 37.5°C
    • Systolic BP: ≤ 100 mmHg
  • Depending on clinical status, consider admitting high-risk patients who show any COVID-19 symptoms to closely monitor for developing a severe course and complications. Individuals considered at high-risk for a severe course (and thus a higher mortality rate) include those with: [35]
  • Especially for hospitalized patients, obtain patient preferences for the following:

Management of asymptomatic or mild courses

There is no effective antiviral treatment; management consists of supportive self-care at home (home care) and isolation in accordance with health department regulations.

  • Minimize spread of infection: [36]
    • 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” surfaced daily.
  • Management of close contacts: notifiable in accordance with state or local health department regulations
  • Supportive care: Get rest and stay hydrated.
  • Fever management: Antipyretic therapy for controlling fever in patients with COVID-19 is usually not necessary.
    • When to consider antipyretic therapy:
      • High-grade fever (e.g., > 39.4°C/103°F)
      • Increased risk of dehydration or circulatory dysregulation
    • Agents: both acetaminophen and NSAIDS are safe options (despite controversy; see “Do ACE inhibitors and NSAIDs aggravate COVID-19?” for more information)
      • 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
  • Monitor symptoms carefully: Individuals should seek medical care immediately if symptoms worsen or any emergency warning signs develop, including: [28]
    • Difficulty breathing
    • Persistent pain or pressure in the chest
    • Change in mental status (e.g., confused, nonresponsive)
    • Signs of cyanosis (e.g., bluish lips)
  • 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.

Management of hospitalized patients

  • Administer O2 therapy via nasal canula: 1–6 L O2/min if SpO2 ≤ 93%
    • Careful with patients with COPD: a SpO2 of 90–93% is appropriate
  • Supportive care:
    • Stay hydrated and plenty of rest
    • Fever management
    • Fluid-sparing resuscitation and electrolyte balance as needed
  • Empiric antibiotic therapy: consider
  • Evaluation and monitoring: Vital signs, SpO2, laboratory studies, and imaging should regularly be conducted to help guide management and monitor progression. The following studies should be considered:

Laboratory studies [20]

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 [38][20]

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 [39][40]
  • Point-of-care ultrasound (POCUS): better results than chest x-ray and easily repeatable for reevaluation [41]
    • 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 [38][42][43]
    • Can initially be normal in up to 60% of hospitalized patients [43]
    • 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

Intensive care

  • Indications: Admit to ICU and initiate intubation if any of the following are present:
  • Airway management: Considering health-care workers have an increased risk of developing COVID-19, especially during high-risk procedures such as intubation, aerosol-generating procedures should be avoided whenever possible! [44][45][46]
    • Endotracheal intubation: Rapid-sequence induction is preferred, especially as it minimizes the spreading of infectious aerosols.
    • To avoid aerosolizing the virus, noninvasive ventilation, high-flow oxygen therapy, bronchoscopy, and nebulizer treatment should be avoided unless there is an absolute indication.
      • If NIPPV is indicated (e.g., COPD, asthma, DNI status): attempt with a helmet (vs. face mask) interface
  • Mechanical breathing: ventilation with lower tidal volumes (LTV) as with ARDS [47]

Medical therapy

  • General information
    • To date, no therapy has proven effective. Any approach is experimental.
    • The use of drugs:[16][49]
      • May be considered in individual cases after weighing the risks and benefits.
      • Is recommended in the context of research studies and compassionate use programs.
  • Potential target structures and agents: A variety of agents are being tested, and clinical studies are being conducted. [50][51]
    • Inhibition of adhesion and invasion
    • Inhibition of fusion
      • Chloroquine or less toxic hydroxychloroquine [52][53][54][55]
        • Hydroxychloroquine In combination with azithromycin is being intensely tested [56]
      • Umifenovir [57]
    • Inhibition of protease
    • RNA polymerase inhibitors and nucleotide analogs
      • Favipiravir [63] (brand name: Avigan®; approved in Japan)
      • Remdesivir [61][62]
      • Baloxavir marboxil
    • Antibody therapy and biologicals [64]
      • Tocilizumab, especially in the phase of ARDS when IL-6 and CRP are increased [65]
      • Recombinant ACE2 (rhACE2, APN01) [15][66]
    • Passive immunization through serum therapy: [67]
      • Immunized individuals (already had COVID-19) donate serum
      • Especially a potential option for risk groups
  • Interactions between the drugs listed: numerous; this must be kept in mind when considering administration (prescribing information!) or use according to information provided by the Liverpool Drug Interaction Group! [68]

The point in time at which a drug is administered during the course of the disease is likely to be 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!

Discontinuation of isolation and other transmission-based precautions

  • Determining when to end home isolation is approached from different strategies, which can vary according to health departments and testing resources.
  • CDC guidance consists of: [69]
    • For patients with symptomatic COVID-19
      • Non-test-based strategy (time-since-illness-onset and time-since-recovery strategy) consisting of:
        • At least 3 days (72 hours) since recovery, meaning:
          • Resolution of fever without antipyretics AND
          • Respiratory symptoms have improved AND
        • AND at least 7 days since onset of symptoms
      • Test-based strategy (if ample testing resources and convenient access) consisting of:
        • No fever (without antipyretics) AND
        • Respiratory symptoms have improved AND
        • Two negative tests in a row, 24 hours apart
    • For patients with asymptomatic COVID-19: at least 7 days have passed without illness since date of COVID-19 test

Discharging patients from healthcare facility

Recommendations based on CDC guidance: [70]

  • Considered infectious (requirements for discontinuation transmission-based precautions are not met): If clinically indicated, patients may be discharged without meeting 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%. [4]
    • Individuals considered at high-risk for a severe course (and thus a higher mortality rate) include those with: [35]
  • Pediatric patients
    • Most children with COVID-19 experience a mild course and some are asymptomatic. [71][72]
    • A study evaluating 2143 pediatric patients with COVID-19 in China showed: [72]
      • 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).

Although most children with COVID-19 appear to experience a milder course, measures for infection control and prevention should be followed.

Do ACE inhibitors and NSAIDs aggravate COVID-19?

ACE inhibitor and NSAID use as an aggravating factor in COVID-19

Unconfirmed reports and published hypotheses about the pathophysiology of COVID-19 have raised suspicions that RAAS antagonists (esp. ACE inhibitors and angiotensin II receptor blockers), NSAIDs, and thiazolidinediones may facilitate infection with and exacerbate the course of COVID-19.

Fact check

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

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last updated 03/29/2020
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