Elsevier Logo




  • COVID-19 (coronavirus disease 2019) is a respiratory tract infection due to a novel coronavirus, SARS-CoV-21

  • 5% of diagnosed cases require critical care to manage severe manifestations and complications, with reported mortality rates among ICU patients with COVID-19 ranging from 39% to 72%  2

  • Most patients with severe COVID-19 experience a bimodal illness, with initial improvement before severe worsening and critical illness. This may be related to the immunologic role in the sepsis seen with COVID-19 ("cytokine storm")



  • History ○In symptomatic patients, median time from symptom onset to pneumonia is 5 days; time to severe hypoxemia is 7 to 12 days 3 ○In patients with progression to severe disease, deterioration is typically rapid and characterized by progressive hypoxemia which may or may not be associated with symptoms of dyspnea 4, 5 ○Cardiac, vascular, and neurologic manifestations may accompany pulmonary disease, resulting in localized symptoms (eg, pain, including headache) as well as alterations in cognition and level of consciousness

  • Physical examination

○ Tachypnea, labored respirations ○ Silent or "happy" hypoxemia: COVID-19-related phenomena of asymptomatic hypoxemia ○ Fever, often exceeding 39 °C6

○Tachyarrhythmias 7

○ Signs/symptoms of arterial or deep vein thrombosis, including large-vessel stroke, as the presenting clinical event 8 ○ Positive neurologic findings, including hyperactive deep tendon reflexes, ankle clonus, and positive Babinski sign9

○Agitation, confusion, decreased responsiveness 9

○Skin changes, including purpura, petechiae, vesicular rashes; nonspecific erythematous exanthems 10, 11, 12, 13, 14 ○ Findings of shock, including hypotension, tachycardia, cool/clammy extremities, altered mental status


  • Risk factors and/or associations ○ Age – Risk of severe disease increases with age 15, 2 ○ Sex – Male sex may be a risk factor for severe disease 16 ○ Other risk factors/associations – Medical conditions associated with increased risk for severe disease include chronic kidney disease, chronic obstructive pulmonary disease, diabetes type 2, cardiovascular disease, severe obesity, immunosuppression, malignancy 17 – Residents of nursing homes and long-term care facilities are at high risk for acquiring infection and severe disease 18, 19


  • Primary diagnostic tools ○ Polymerase chain reaction tests are the standard for diagnosis; antigen testing has also received emergency use authorization in the United States 20, 21, 22, 23, 3, 24, 25

  • Laboratory ○ Routine blood work is not diagnostic, but a pattern of typical abnormalities has emerged, particularly in patients with severe illness: 26, 27 – Leukopenia and anemia 6, 27, 26 – Coagulopathy 26 – Elevated levels of lactate dehydrogenase and liver enzymes (ALT and AST) are common6, 26 –Serum procalcitonin levels are usually within reference range; elevated levels have been seen in patients with –secondary infection6 – Serum levels of acute phase reactants (eg, C-reactive protein, ferritin) are elevated in most patients, as is the erythrocyte sedimentation rate 26 – Cardiac biomarkers (troponin, B-type natriuretic peptides) may be elevated28 – Serum lactate levels are elevated in the setting of shock 3

  • Imaging ○ Chest imaging (eg, plain radiography, CT, ultrasonography) is abnormal with bilateral involvement in most patients; varies from ground glass opacities to consolidation in more severely ill patients 27, 26, 29, 30, 6 ○ CT appears to be more sensitive than plain radiographs and can distinguish progression of infection from heart failure due to myocarditis or from pulmonary embolism (both commonly associated with COVID-19) 31, 32, 33 ○ Bedside ultrasonography is widely used to monitor progression of pulmonary infiltrates, assess cardiac function and volume status, and detect deep vein or vascular catheter thrombosis 3, 34



  • Ensure adequate oxygenation and hemodynamic support and prevent complications


  • Admission criteria ○ Criteria for ICU admission – Evidence of critical respiratory tract disease: tachypnea, severe respiratory distress, and inadequate oxygenation35 – – Presence of severe complications (eg, septic shock, acute respiratory distress syndrome)

  • Recommendations for specialist referral ○ All patients should be managed in consultation with public health authorities ○ Consultation of specialists, including infectious disease, pulmonology, and critical care, is recommended


  • Standard, contact, and (at least) droplet precautions should be implemented as soon as the diagnosis is suspected; airborne precautions are recommended if resources allow, especially for aerosol-generating procedures 36

  • Drug therapy

    ○ Remdesivir, an antiviral agent, is the only FDA-approved antiviral drug recommended specifically for treatment of hospitalized COVID-19 patients who require supplemental oxygen37, 38, 39, 40, 41 ○ Corticosteroid therapy is recommended for patients with COVID-19 who have refractory shock or respiratory insufficiency necessitating oxygen administration42 –Dexamethasone has shown efficacy in patients with severe disease and hypoxemia 32, 26, 43 □ Typical duration up to 10 days in patients with severe or critical COVID-1937, 41 □

    □ In the absence of dexamethasone, another glucocorticoid (eg, prednisone, methylprednisolone, hydrocortisone) may be used ○ Studies on the therapeutic efficacy of convalescent plasma are underway in various countries – Early administration (eg, before mechanical ventilation is required) appears more likely to be beneficial

    – FDA has produced a fact sheet for providers with labeling criteria, suggested dosing/infusion practices, and potential adverse effects 44 – ○ Immunomodulators for the mitigation of cytokine release syndrome ("cytokine storm") in severe acute respiratory distress syndrome and shock in COVID-19 are being investigated (eg, tocilizumab and sarilumab, both monoclonal antibodies against interleukin-6 receptor; baricitinib and other Janus kinase inhibitors) 41, 45, 46 – Baricitinib may be added to remdesivir in severely ill patients, under emergency use authorization45 – The Surviving Sepsis Campaign guideline, Infectious Disease Society of America, and NIH COVID-19 treatment guideline do not recommend tocilizumab at this time for routine use, although it may be considered in patients with progressive severe or critical COVID-19 who have elevated levels of markers of systemic inflammation38, 42, 47, 40, 41 –

    ○ Appropriate antimicrobial therapy should be administered until a diagnosis of COVID-19 is confirmed, in accordance with the severity of clinical disease, site of acquisition (hospital or community), epidemiologic risk factors, and local antimicrobial susceptibility patterns 41, 42

    ○ The NIH and Infectious Diseases Society of America recommend against hydroxychloroquine or chloroquine and against the combination of either of these drugs with azithromycin in hospitalized patients for the treatment of COVID-19 due to risk of QT prolongation and cardiac arrhythmias 38, 41, 48, 49, 37 ○ Published guidelines do not recommend therapeutic anticoagulation for hospitalized patients with COVID-19 (unless there is  documented thrombosis or other accepted indication) but do recommend usual prophylactic regimens in any hospitalized patient with COVID-19, including pregnant patients 50, 40, 51, 52, 37 ○ Pharmacologic (vasopressor) support may be necessary in patients with COVID-19 and evidence of septic shock whose hemodynamic parameters do not respond to initial fluid support and oxygen supplementation3, 40, 41, 42

  • Nondrug and supportive care ○ Oxygenation and ventilation  – High-flow nasal oxygen or noninvasive positive pressure ventilation has been used to achieve adequate oxygenation in some COVID-19 patients who develop hypoxemic respiratory failure despite conventional oxygen therapy 53 – For patients with persistent hypoxemia but without other indications for intubation, "awake prone positioning" can be attempted as a means to improve oxygenation40 – Mechanical ventilation may become necessary for patients in whom oxygenation targets cannot be met with less invasive measures or who cannot maintain the work of breathing (eg, PaO₂/FIO₂ ratio of less than 300 mm Hg) 3. Most published recommendations are based on the ARDSNet protocol 54 □ For patients with moderate to severe acute respiratory distress syndrome, prone positioning for 12 to 16 hours/day is recommended □ Lateral decubitus position for pregnant women □ Mechanical ventilation may be required for a prolonged period, necessitating tracheostomy ○ Fluid management – In patients with shock, administration of crystalloids (eg, lactated Ringer solution) is recommended; solutions such as hydroxyethyl starches, gelatins, dextrans, and albumin are not recommended  – Volume overload should be avoided as it may precipitate or exacerbate acute respiratory distress syndrome 55 – ○ Procedures – Extracorporeal membrane oxygenation □ General explanation □ Heart-lung bypass technique that allows transmembrane exchange of oxygen and carbon dioxide by circulation of the blood through a bypass machine; also supports arterial blood pressure 41, 37 □ Indication □ Refractory hypoxemia with or without hemodynamic compromise despite standard supportive measures

Complications and Prognosis


  • The most common ICU complications are: acute respiratory distress syndrome (60-70%), shock (30%), myocardial injury (20-30%), arrhythmias (44%), and acute kidney injury (10-30%) 3

  • Secondary bacterial and fungal infections and multiorgan failure are also commonly cited3

  • Thrombotic events, both venous and arterial, have become increasingly recognized3


  • Patients who require hospital admission often require prolonged inpatient stay (longer than 20 days) which may result in profound deconditioning26, 6

  • Laboratory markers associated with increased mortality include high D-dimer levels, high C-reactive protein levels, and low lymphocyte counts 3

  • Reported mortality rates in critically ill patients are high (40% or more) 3, 2



  • Patients with respiratory distress require prompt administration of supplemental oxygen; patients with respiratory failure require intubation and mechanical ventilation

  • Patients in shock require urgent fluid resuscitation and administration of empiric antimicrobial therapy to cover possible bacterial pathogens and/or influenza


Knowledge of this disease is incomplete and evolving; moreover, coronaviruses are known to mutate and recombine often, presenting an ongoing challenge to our understanding and to clinical management


  1. WHO: Coronavirus Disease 2019 (COVID-19): Situation Report--51. WHO website. Published March 11, 2020. Accessed April 29, 2021. https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200311-sitrep-51-covid-19.pdf

  2. CDC: COVID-19: Interim Clinical Guidance for Management of Patients with Confirmed Coronavirus Disease (COVID-19). CDC website. Updated February 16, 2021. Accessed April 29, 2021. https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-guidance-management-patients.html 2

  3. Phua J et al: Intensive care management of coronavirus disease 2019 (COVID-19): challenges and recommendations. Lancet Respir Med. ePub, April 6, 2020

  4. Tobin MJ et al: Why COVID-19 silent hypoxemia is baffling to physicians. Am J Respir Crit Care Med. ePub, June 15, 2020

  5. Bertran Recasens B et al: Lack of dyspnea in Covid-19 patients: another neurological conundrum? Eur J Neurol. ePub, April 17, 2020

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

  7. Atri D et al: COVID-19 for the cardiologist: a current review of the virology, clinical epidemiology, cardiac and other clinical manifestations and potential therapeutic strategies. JACC Basic Transl Sci. ePub, April 10, 2020

  8. Oxley TJ et al: Large-vessel stroke as a presenting feature of Covid-19 in the young. N Engl J Med. ePub, May 14, 2020

  9. Helms J et al: Neurologic features in severe SARS-CoV-2 infection. Letter to the editor. N Engl J Med. ePub, April 15, 2020

  10. Recalcati S et al: Acral cutaneous lesions in the time of COVID-19. J Eur Acad Dermatol Venereol. ePub, April 24, 2020

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

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

  15. CDC COVID-19 Response Team: Severe outcomes among patients with coronavirus disease 2019 (COVID-19)--United States, February 12-March 16, 2020. MMWR Morb Mortal Wkly Rep. 69(12):343-6, 2020

  16. Richardson S et al: Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area. JAMA. ePub, April 22, 2020

  17. CDC: COVID-19: People With Certain Medical Conditions. CDC website. Updated February 22, 2021. Accessed April 29, 2021. https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-medical-conditions.html

  18. CDC: Coronavirus Disease 2019 (COVID-19): People Who Are at Higher Risk for Severe Illness. CDC website. Updated May 14, 2020. Accessed May 20, 2020. https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-at-higher-risk.html

  19. CDC: COVID-19: Frequently Asked Questions: People at Higher Risk for Severe Illness. CDC website. Updated February 25, 2021. Accessed February 28, 2021. https://www.cdc.gov/coronavirus/2019-ncov/faq.html#People-at-Higher-Risk-for-Severe-Illness

  20. CDC: COVID-19: Interim Guidelines for Collecting, Handling, and Testing Clinical Specimens for COVID-19. CDC website. Updated February 17, 2021. Accessed April 29, 2021.

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

  22. Hanson KE et al: Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19:Serologic Testing. Clin Infect Dis. ePub, 2020

  23. 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

  24. CDC: COVID-19: Overview of Testing for SARS-CoV-2 (COVID-19). Updated October 21, 2020. Accessed February 24, 2021. https://www.cdc.gov/coronavirus/2019-ncov/hcp/testing-overview.html

  25. CDC: Interim Guidance for Antigen Testing for SARS-CoV-2. CDC website. Updated December 16, 2020. Accessed February 25, 2021. https://www.cdc.gov/coronavirus/2019-ncov/lab/resources/antigen-tests-guidelines.html

  26. 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

  27. 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

  28. Januzzi JL Jr: Troponin and BNP use in COVID-19. Cardiology Magazine. ePub, March 18, 2020

  29. Shi H et al: Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study. Lancet. ePub, February 24, 2020

  30. Zhu N et al: A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. ePub, January 24, 2020

  31. Kanne JP: Chest CT findings in 2019 novel coronavirus (2019-nCoV) infections from Wuhan, China: key points for the radiologist. Radiology. ePub, February 4, 2020

  32. Rubin GD et al: The role of chest imaging in patient management during the COVID-19 pandemic: a multinational consensus statement from the Fleischner Society. Chest. ePub, April 7, 2020

  33. Yoon SH et al: Chest radiographic and CT findings of the 2019 novel coronavirus disease (COVID-19): analysis of nine patients treated in Korea. Korean J Radiol. 21(4):494-500, 2020

  34. Peng QY et al: Using echocardiography to guide the treatment of novel coronavirus pneumonia. Crit Care. 24(1):143, 2020

  35. WHO: Clinical Care of Severe Acute Respiratory Infections--Tool Kit: Interim Guidance. WHO website. Updated April 11, 2020. Accessed February 28, 2021. https://www.who.int/publications/i/item/clinical-care-of-severe-acute-respiratory-infections-tool-kit

  36. CDC: COVID-19: Interim Infection Prevention and Control Recommendations for Healthcare Personnel During the Coronavirus Disease 2019 (COVID-19) Pandemic. CDC website. Updated February 10, 2021. Accessed February 21, 2021. https://www.cdc.gov/coronavirus/2019-ncov/hcp/infection-controlrecommendations.htmL

  37. Alhazzani W et al: Surviving Sepsis Campaign guidelines on the management of adults with coronavirus disease 2019 (COVID-19) in the ICU: first update. Crit Care Med. ePub, February 2021

  38. Bhimraj A et al: Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19. Clin Infect Dis. ePub, 2020

  39. FDA: FDA Approves First Treatment for COVID-19. FDA News Release. FDA website. Published October 22, 2020. Accessed February 28, 2021. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-covid-19

  40. NIH: COVID-19 Treatment Guidelines. NIH website. Updated February 23, 2021. Accessed February 28, 2021. https://covid19treatmentguidelines.nih.gov/

  41. Alhazzani W et al: Surviving Sepsis Campaign: guidelines on the management of critically ill adults with coronavirus disease 2019 (COVID-19). Crit Care Med. ePub, March 27, 2020

  42. WHO: Clinical Management of COVID-19: Interim Guidance. WHO website. Updated May 27, 2020. Accessed April 29, 2021. https://apps.who.int/iris/rest/bitstreams/1278777/retrieve

  43. Chief Investigators of the RECOVERY trial (Randomised Evaluation of COVID-19 Therapy): Low-Cost Dexamethasone Reduces Death by up to One Third in Hospitalised Patients With Severe Respiratory Complications of COVID-19. RECOVERY trial website. Updated June 16, 2020. Accessed February 25, 2021. https://www.recoverytrial.net/news/low-cost-dexamethasone-reduces-death-by-up-to-one-third-in-hospitalised-patients-with-severe-respiratorycomplications-of-covid-19

  44. FDA: Fact Sheet for Health Care Providers: Emergency Use Authorization (EUA) of COVID-19 Convalescent Plasma for Treatment of COVID-19 in Hospitalized Patients. FDA website. Published August 23, 2020. Updated February 4, 2021. Accessed February 25, 2021. https://www.fda.gov/media/141478/download

  45. Eli Lilly and Company: Fact Sheet for Healthcare Providers: Emergency Use Authorization (EUA) of Baricitinib. FDA website. Published November 2020. Accessed February 25, 2021. https://www.fda.gov/media/143823/download

  46. Clinical Pharmacology powered by ClinicalKey: Sarilumab. ClinicalKey website. Accessed December 3, 2020. https://www.clinicalkey.com/#!/content/drug_monograph/6-s2.0-4949

  47. Lan SH et al: Tocilizumab for severe COVID-19: a systematic review and meta-analysis. Int J Antimicrob Agents. 106103, 2020

  48. FDA: FDA News Release: Coronavirus (COVID-19) Update: FDA Revokes Emergency Use Authorization for Chloroquine and Hydroxychloroquine. FDA website. Published June 15, 2020. Accessed February 28, 2021. https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-updatefda-revokes-emergency-use-authorization-chloroquine-and

  49. Clinical Pharmacology powered by ClinicalKey: Azithromycin. ClinicalKey website. Accessed December 3, 2020. https://www.clinicalkey.com/#!/content/drug_monograph/6-s2.0-53

  50. Thachil J et al: ISTH interim guidance on recognition and management of coagulopathy in COVID-19. J Thromb Haemost. 18(5):1023-1026, 2020

  51. American Society of Hematology: COVID-19 and VTE/Anticoagulation: Frequently Asked Questions. Version 8.0. ASH website. Updated January 29, 2021. Accessed February 25, 2021. https://www.hematology.org/covid-19/covid-19-and-vte-anticoagulation

  52. Moores LK et al: Prevention, diagnosis, and treatment of VTE in patients with COVID-19: CHEST guideline and expert panel report. Chest. ePub, June 2, 2020

  53. Murthy S et al: Care for critically ill patients with COVID-19. JAMA. ePub, March 11, 2020

  54. National Heart, Lung, and Blood Institute: NIH NHLBI ARDS Clinical Network: Mechanical Ventilation Protocol Summary. ARDSNet website. Accessed February 28, 2021. http://www.ardsnet.org/files/ventilator_protocol_2008-07.pdf

  55. Bentzer P et al: Will This Hemodynamically Unstable Patient Respond to a Bolus of Intravenous Fluids? JAMA. 316(12):1298-309, 2016