• COVID-19 (coronavirus disease 2019) is a respiratory tract infection with a newly recognized coronavirus, SARS-CoV-2

    • Illness ranges in severity from asymptomatic or mild to severe; a significant proportion of patients with clinically evident infection develop severe disease, which may be complicated by acute respiratory distress syndrome and shock


    COVID-19 disease severity (1)

    • Mild disease: symptomatic patients with suspected, probable, or confirmed SARS-CoV-2 infection without evidence of viral pneumonia or hypoxia

    • Moderate disease: requires presence of pneumonia (diagnosis for which typically entails chest imaging)

      • Adolescent or adult with clinical signs of pneumonia (eg, fever, cough, dyspnea, fast breathing) but no signs of severe pneumonia, including SpO₂ greater than or equal to 90% on room air

      • Child with clinical signs of non-severe pneumonia (eg, cough or difficulty breathing plus fast breathing and/or chest indrawing) and no signs of severe pneumonia

      • Severe disease: requires presence of severe pneumonia (diagnosis for which typically entails chest imaging)

      • Adolescent or adult with clinical signs of pneumonia (eg, fever, cough, dyspnea, fast breathing) plus one of the following: respiratory rate greater than 30 breaths per minute, severe respiratory distress, or SpO₂ less than 90% on room air

      • Child with clinical signs of pneumonia (cough or difficulty in breathing) plus at least one of the following: Central cyanosis or SpO₂ less than 90%, severe respiratory distress (eg, fast breathing, grunting, very severe chest indrawing), general danger sign (eg, inability to breastfeed or drink, lethargy or unconsciousness, or convulsions)



    • Clinical spectrum of COVID-19 ranges from asymptomatic infection to critical illness; illness may evolve over the course of a week or longer, beginning with mild symptoms that progress (in some cases) to the point of respiratory distress and shock 2, 3

    • Among patients who are symptomatic, the median incubation period is approximately 4 to 5 days, and about 98% have symptoms within 11 days after infection 4

    • History

      • Most common complaints are fever (more than 80%) and cough, which may or may not be productive 5, 3

      • Other common symptoms include upper respiratory symptoms (rhinorrhea, sneezing, sore throat), myalgias and fatigue, the latter of which may be profound 3

      • Alteration in smell and/or taste is widely reported, often as an early symptom, and is highly suggestive; absence of these symptoms does not exclude the diagnosis 6

      • Less common manifestations include headache and gastrointestinal symptoms (nausea, vomiting, diarrhea) 3, 7

    • Physical examination

      • For mild disease, the following signs are common: fever (often exceeding 39 °C) 3, conjunctival secretions/injection,chemosis 8

      • Described cutaneous manifestations include: erythematous rashes, purpura, petechiae, and vesicles 9, 10, 11, 12


    • Testing indications

      • CDC and WHO have slightly different criteria for whom to test but both support testing hospitalized patients with a clinically compatible illness 13, 14, 15


    Testing indications for SARS-CoV-2 (COVID-19)

    1. Test patients with acute onset of fever and cough or acute onset of any 3 or more of a specified list of symptoms (eg, fever, cough, general weakness/fatigue, headache, myalgia, sore throat, coryza,dyspnea, anorexia/nausea/vomiting, diarrhea, altered mental status) plus one of the following:Living or working in a setting with high risk of transmission of SARS-CoV-2 (eg, closed residential facilities, refugee camps) at any time during the 14 days preceding symptom onsetA history of travel to or residence in an area reporting local transmission of COVID-19 during the 14 days preceding symptom onsetWorking in any health care setting at any time during the 14 days preceding symptom onset

    2. Onset within the last 10 days of a severe acute respiratory tract infection requiring hospital admission without an alternative etiologic diagnosis

    3. In situations where testing must be prioritized, test the following:Patients at high risk for severe disease and hospitalizationSymptomatic health care workersFirst symptomatic persons in closed-space environments (eg, schools, long-term care facilities, hospitals, prisons), representing possible index cases WHO: World Health Organization 1. WHO: Clinical Management of COVID-19: Interim Guidance. WHO website. Updated May 27, 2020. Accessed April 20, 2021. 2.

    1. Reasonable to test patients with a clinically compatible illness; however, clinicians should use judgement, informed by knowledge of local COVID-19 activity and other risk factors, to determine the need for diagnostic testing

    2. Maintain a low threshold for testing persons with extensive or close contact with people at high risk for severe disease in their home or employment setting

    3. Testing may also be recommended in other circumstances:Any person (even if asymptomatic) with recent close contact with a person known or suspected to have COVID-19Asymptomatic persons without known or suspected exposure in certain settings (eg, closequarters community, preoperative setting)To document resolution of infection (not routine but may be appropriate in certain circumstances)Public health surveillance CDC: Centers for Disease Control CDC: COVID-19: Overview of Testing for SARS-CoV-2 (COVID-19). Updated March 17, 2021. Accessed April 25, 2021.


    • Primary diagnostic tools

      • Diagnosis of COVID-19 is commonly made through detection of SARS-CoV-2 RNA by means of a PCR assay

      • Alternative methods for diagnosis are antigen tests or serology

        • Antigen tests are generally less sensitive than PCR tests but are less expensive and can be used at the point of care with rapid results 16

        • Antibody (serologic) testing is not recommended for diagnostic purposes 17, 14, 18, 19

      • Chest imaging is recommended for patients with clinical signs of pneumonia (fever, cough, dyspnea, tachypnea) to determine if patients have pneumonia and to assess severity 1, 5

    • Repeat testing after initial negative result

      • Infectious Diseases Society of America guidelines provide additional guidance and an algorithm, including indications for repeated testing when suspicion for disease is high but initial test result is negative 20

      • For patients with high likelihood of disease but negative initial result, repeated testing is recommended; in patients with lower respiratory tract symptoms, sputum or other lower respiratory tract specimen is recommended for repeated testing 20

    • Adjunct testing is generally unnecessary for cases of mild COVID-19

    • Laboratory

      • PCR assay for detection of SARS-CoV-2 nucleic acid

        • Specimen sources for PCR include secretions from nasopharynx, midturbinate, anterior nares, oropharynx, or saliva 14, 21

        • A systematic review and meta-analysis compared frequency with which SARS-CoV-2 RNA was detected in sputum, nasopharyngeal swabs, and oropharyngeal swabs in patients with documented COVID-19. Overall positivity was 71% for sputum, 54% for nasopharyngeal swabs, and 43% for oropharyngeal swabs. 22 Sensitivity of PCR testing of nasopharyngeal swabs is high just before and soon after symptom onset 2

      • Antigen testing to identify SARS-CoV-2

        • Antigen tests are less sensitive than polymerase chain reaction, although specificity is equivalent and may be as high as 100% 16

        • False-positive results are uncommon, but a negative result may warrant retesting (preferably within 2 days) with polymerase chain reaction if there is a high suspicion for infection 16

        • A Cochrane review noted wide-ranging sensitivity and specificity of antigen tests (average sensitivity, 56.2%; average specificity, 99.5%) 23

      • Serology (antibody testing)

        • Serology is not recommended for routine use in diagnosis, but it may be useful under some circumstances (eg, high suspicion for disease with persistently negative results on viral RNA tests) 17

        • Antibody tests are most likely to be clinically useful 15 days or more into the course of infection; data are scarce regarding antibody tests beyond 35 days 24

      • Other laboratory findings are variable but typically include lymphopenia and elevated lactate dehydrogenase and transaminase levels

    • Imaging Chest radiograph Chest imaging in symptomatic patients almost always shows abnormal findings, usually including bilateral infiltrates; ground-glass opacities are usually



    • Treatment of mild COVID-19 largely involves isolation precautions and supportive care

      • Patients with mild COVID-19, who are not hypoxemic and do not require oxygen, may not require emergency interventions or hospitalization and may be managed at home; however, isolation is necessary for all suspect or confirmed cases to contain virus transmission. 1

    • Isolation precautions 26

      • Patients with mild COVID-19 who are treated at home should stay in a specific "sick room" if at all possible, avoid contact with other household members, and use good hand hygiene (soap and water or hand sanitizer with at least 60% alcohol)

      • Restrict contact to a minimum number of caregivers. Ensure that persons with underlying medical conditions are not exposed to the patient

      • Both patient(s) and household members should wear a face mask when in the same room. The caregiver should wear disposable gloves when there is potential for contact with the patient's saliva, mucus, vomit, blood, urine or stool

      • Regularly use a disinfectant (diluted household bleach or other product) on household surfaces, especially high-touch areas; if surfaces have visible dirt, clean first with soap or detergent

    • Other supportive care

      • Antipyretics (NSAIDs, acetaminophen) may be used for fever and pain; at present there is no convincing evidence that the disease worsens or severe adverse events occur in patients who use NSAIDs 27, 28

      • Adequate nutrition and appropriate rehydration should be encouraged 29 Individuals who are not admitted to a health facility should be monitored (by trained community workers or outreach teams through telephone or email) in the event that deterioration occurs

        • Monitor for new or worsening of lightheadedness, dyspnea, chest pain; should these occur, direct the patient to seek urgent care 29, 30

        • In children, monitor for difficulty breathing/fast or shallow breathing, blue lips or face, chest pain or pressure, new confusion as well as an inability to wake up, interact when awake, drink or keep liquids down 29

        • In infants, monitor for grunting and inability to breastfeed

        • Be especially alert for patients with known risk factors for rapid deterioration, severe disease, and/or increased mortality; these include older age (>60 years) and chronic diseases such as cardiovascular disease, diabetes mellitus, chronic lung disease, cancer and cerebrovascular disease 3

        • Consider using home pulse oximetry to assess oxygen saturation in the blood for the early identification of low oxygen levels in patients with initially mild or moderate COVID-19 or silent hypoxia, when a patient does not appear to be short of breath but oxygen levels are low 31

        • Be aware that pulse oximetry may produce falsely high results in persons with very dark skin pigmentation 32

        • COVID-19 patients with other chronic non-communicable diseases should have an adequate supply (at least 2 weeks) of medications to treat these conditions 29

    Complications and Progrnosis


    Patients who have mild illness usually recover at home, with supportive care and isolation Whether recovery from infection is associated with protective immunity is unknown; reinfection has been documented, and the risk of reinfection may be increased with exposure to variant strains that have emerged in the United Kingdom, South Africa, and Brazil (32) Mortality rate among diagnosed cases (case fatality rate) is generally about 3% globally but varies by country; true overall mortality rate is uncertain, as the total number of cases (including undiagnosed persons with milder illness) is unknown (35,36)

    Screening and Prevention


    Several vaccines against SARS-CoV-2 have entered use in various countries, and more are in development (37) Existing vaccines have received emergency or temporary authorizations from various national regulatory authorities under the emergency conditions of the pandemic, and future authorizations in more countries are pending Existing vaccines have been shown to be safe and effective and vaccination is recommended for all adults



    Knowledge of this disease is incomplete and evolving; moreover, several variants with potential impact on transmission, clinical disease, and immune protection have been recognized


    1. WHO: Clinical Management of COVID-19: Interim Guidance. WHO website. Updated May 27, 2020. Accessed April 20, 2021.

    2. Gandhi RT et al: Mild or moderate Covid-19. N Engl J Med. 383(18):1757-66, 2020

    3. Huang C et al: Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 395(10223):497-506, 2020

    4. Lauer SA et al: The Incubation Period of Coronavirus Disease 2019 (COVID-19) From Publicly Reported Confirmed Cases: Estimation and Application. Ann Intern Med. 172(9):577-582, 2020

    5. Chen N et al: Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. ePub, January 30, 2020

    6. Spinato G et al: Alterations in smell or taste in mildly symptomatic outpatients with SARS-CoV-2 infection. JAMA. ePub, April 22, 2020

    7. Chan JFW et al: A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet. 395(10223):514-23, 2020

    8. Wu P et al: Characteristics of ocular findings of patients with coronavirus disease 2019 (COVID-19) in Hubei Province, China. JAMA Ophthalmol. ePub, March 31, 2020

    9. Joob B et al: COVID-19 can present with a rash and be mistaken for dengue. J Am Acad Dermatol. 82(5):e177, 2020

    10. Marzano AV et al: Varicella-like exanthem as a specific COVID-19-associated skin manifestation: multicenter case series of 22 patients. J Am Acad Dermatol. ePub, April 16, 2020

    11. Recalcati S: Cutaneous manifestations in COVID-19: a first perspective. J Eur Acad Dermatol Venereol. ePub, March 26, 2020

    12. Magro C et al: Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: a report of five cases. Transl Res. ePub, April 15, 2020

    13. WHO: Laboratory Testing for 2019 Novel Coronavirus (2019-nCoV) in Suspected Human Cases: Interim guidance. WHO website. Updated March 19, 2020. Accessed April 20, 2021.

    14. CDC: COVID-19: Overview of Testing for SARS-CoV-2 (COVID-19). Updated March 17, 2021. Accessed April 25, 2021.

    15. WHO: Laboratory Testing Strategy Recommendations for COVID-19: Interim Guidance. WHO website. Updated March 21, 2020. Accessed April 20, 2021.

    16. CDC: Interim Guidance for Antigen Testing for SARS-CoV-2. CDC website. Updated December 16, 2020. Accessed April 20, 2021.

    17. Hanson KE et al: Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19: Serologic Testing. IDSA website. Published August 18, 2020. Accessed April 20, 2021.

    18. La Marca A et al: Testing for SARS-CoV-2 (COVID-19): a systematic review and clinical guide to molecular and serological in-vitro diagnostic assays. Reprod Biomed Online. ePub, June 14, 2020

    19. Babiker A et al: SARS-CoV-2 testing. Am J Clin Pathol. ePub, May 5, 2020

    20. Hanson KE et al: Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19. IDSA website. Published May 6, 2020. Updated December 23, 2020. Accessed April 20, 2021.

    21. CDC: COVID-19: Interim Guidelines for Collecting, Handling, and Testing Clinical Specimens for COVID-CDC website. Updated February 26, 2021. Accessed April 20, 2021.

    22. Mohammadi A et al: SARS-CoV-2 detection in different respiratory sites: A systematic review and meta-analysis. EBioMedicine. 102903, 2020

    23. Dinnes J et al: Rapid, point-of-care antigen and molecular-based tests for diagnosis of SARS-CoV-2 infection. Cochrane Database Syst Rev. 8:CD013705, 2020

    24. Deeks JJ et al: Antibody tests for identification of current and past infection with SARS-CoV-2. Cochrane Database Syst Rev. 6:CD013652, 2020

    25. Shi H et al: Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study. Lancet Infect Dis. 20(4):425-434, 2020

    26. CDC: COVID-19: If You Are Sick or Caring for Someone. CDC website. Updated November 20, 2020. Accessed April 20, 2021.

    27. NIH: COVID-19 Treatment Guidelines. NIH website. Updated April 21, 2021. Accessed April 25, 2021.

    28. Rinott E et al: Ibuprofen use and clinical outcomes in COVID-19 patients. Clin Microbiol Infect. ePub, June 12, 2020

    29. WHO: Home Care for Patients With COVID-19 Presenting With Mild Symptoms and Management of Their Contacts: Interim Guidance. WHO website. Updated March 17, 2020. Accessed April 20, 2021.

    30. Macgregor H, Hrynick T. COVID-19: Strategies to support home and community-based care. Social Science in Humanitarian Action Platform: 2020. Accessed April 29, 2021.

    31. Jouffroy R et al: Prehospital pulse oximetry: a red flag for early detection of silent hypoxemia in COVID-19 patients. Crit Care. 24(1):313, 2020

    32. CDC: COVID-19: Interim Clinical Guidance for Management of Patients with Confirmed Coronavirus Disease (COVID-19). CDC website. Updated February 16, 2021. Accessed April 20, 2021.

    33. Greenhalgh T et al: Management of post-acute covid-19 in primary care. BMJ. 370:m3026, 2020

    34. Carfì A et al: Persistent Symptoms in Patients After Acute COVID-19. JAMA. ePub, 2020

    35. WHO: WHO Coronavirus Disease (COVID-19) Dashboard. WHO website. Updated daily. Accessed April 20, 2021.

    36. Johns Hopkins University Coronavirus Resource Center: Mortality Analyses. JHU website. Updated daily. Accessed April 20, 2021.

    37. CDC: COVID-19: COVID-19 Vaccination. CDC website. Accessed April 29, 2021 Published April 29, 2021

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