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Interim Clinical Guidance for Management of Patients with Confirmed 2019 Novel Coronavirus (2019-nCoV) Infection

https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-guidance-management-patients.html

Updated February 12, 2020

This interim guidance is for clinicians caring for patients with confirmed 2019 novel coronavirus (2019-nCoV) infection. This update includes additional information regarding time from illness onset to hospital admission, detection of 2019-nCoV in extrapulmonary specimens, clarifies the type of advanced support observed among hospitalized patients and provides interim guidance for discontinuation of transmission-based precautions and in-home isolation. CDC will update this interim guidance as more information becomes available.

Clinical Presentation

There are a limited number of reports that describe the clinical presentation of patients with confirmed 2019-nCoV infection, and most are limited to hospitalized patients with pneumonia. The incubation period is estimated at ~5 days (95% confidence interval, 4 to 7 days). [1] Some studies have estimated a wider range for the incubation period; data for human infection with other coronaviruses (e.g. MERS-CoV, SARS-CoV) suggest that the incubation period may range from 2-14 days. Frequently reported signs and symptoms include fever (83–98%), cough (46%–82%), myalgia or fatigue (11–44%), and shortness of breath (31%) at illness onset. [24] Sore throat has also been reported in some patients early in the clinical course. Less commonly reported symptoms include sputum production, headache, hemoptysis, and diarrhea. Some patients have experienced gastrointestinal symptoms such as diarrhea and nausea prior to developing fever and lower respiratory tract signs and symptoms. The fever course among patients with 2019-nCoV infection is not fully understood; it may be prolonged and intermittent. Asymptomatic infection has been described in one child with confirmed 2019-nCoV infection and chest computed tomography (CT) abnormalities. [5]

Risk factors for severe illness are not yet clear, although older patients and those with chronic medical conditions may be at higher risk for severe illness.  Most reported cases have occurred in adults (median age 59 years).[1]  In one study of 425 patients with pneumonia and confirmed 2019-nCoV infection, 57% were male. [1] Approximately one-third to one-half of reported patients had underlying medical comorbidities, including diabetes, hypertension, and cardiovascular disease. [23] In another study, compared to patients not admitted to an intensive care unit, critically ill patients were older (median age 66 years versus 51 years), and were more likely to have underlying co-morbid conditions (72% versus 37%). [3]

Clinical Course

Clinical presentation among reported cases of 2019-nCoV infection varies in severity from asymptomatic infection or mild illness to severe or fatal illness. Some reports suggest the potential for clinical deterioration during the second week of illness.[2] In one report, among patients with confirmed 2019-nCoV infection and pneumonia, just over half of patients developed dyspnea a median of 8 days after illness onset (range: 5–13 days). [2] In another report, the mean time from illness onset to hospital admission with pneumonia was 9 days.[1]

Acute respiratory distress syndrome (ARDS) developed in 17–29% of hospitalized patients, and secondary infection developed in 10%. [2,4] In one report, the median time from symptom onset to ARDS was 8 days.[3] Between 23–32% of hospitalized patients with 2019-nCoV infection and pneumonia have required intensive care for respiratory support.[23] In one study, among critically ill patients admitted to an intensive care unit, 11% received high-flow oxygen therapy, 42% received noninvasive ventilation, and 47% received mechanical ventilation. [3] Some hospitalized patients have required advanced organ support with endotracheal intubation and mechanical ventilation (4–10%), and a small proportion have also been supported with extracorporeal membrane oxygenation (ECMO, 3–5%).[34] Other reported complications include acute cardiac injury, arrhythmia, shock, and acute kidney injury. Among hospitalized patients with pneumonia, the case fatality proportion has been reported as 4–15%.[24] However, as this estimate includes only hospitalized patients it is biased upward. Nosocomial transmission among healthcare personnel and patients has been reported.

Diagnostic Testing

Information on specimen collection, handling, and storage is available at: Real-Time RT-PCR Panel for Detection 2019-Novel Coronavirus. After initial confirmation of 2019-nCoV infection, additional testing of clinical specimens can help inform clinical management, including discharge planning.

Laboratory and Radiographic Findings

The most common laboratory abnormalities reported among hospitalized patients with pneumonia on admission included leukopenia (9–25%), leukocytosis (24–30%), lymphopenia (63%), and elevated alanine aminotransferase and aspartate aminotransferase levels (37%). [2,4] Most patients had normal serum levels of procalcitonin on admission. Chest CT images have shown bilateral involvement in most patients. Multiple areas of consolidation and ground glass opacities are typical findings reported to date. [24, 69]

Limited data are available about the detection of 2019-nCoV and infectious virus in clinical specimens. 2019-nCoV RNA has been detected from upper and lower respiratory tract specimens, and the virus has been isolated from upper respiratory tract specimens and bronchoalveolar lavage fluid. 2019-nCoV RNA has been detected in blood and stool specimens, but whether infectious virus is present in extrapulmonary specimens is currently unknown. The duration of 2019-nCoV RNA detection in the upper and lower respiratory tracts and in extrapulmonary specimens is not yet known. It is possible that RNA could detected for weeks, which has occurred in some cases of MERS-CoV or SARS-CoV infection.[918] Viable SARS-CoV has been isolated from respiratory, blood, urine, and stool specimens. In contrast, viable MERS-CoV has only been isolated from respiratory tract specimens. [1820]

Clinical Management and Treatment

Healthcare personnel should care for patients in an Airborne Infection Isolation Room (AIIR). Standard Precautions, Contact Precautions, and Airborne Precautions with eye protection should be used when caring for the patient. See Interim Health Care Infection Prevention and Control Recommendations for Patients Under Investigation for 2019 Novel Coronavirus.

Patients with a mild clinical presentation may not initially require hospitalization. However, clinical signs and symptoms may worsen with progression to lower respiratory tract disease in the second week of illness; all patients should be monitored closely. Possible risk factors for progressing to severe illness may include, but are not limited to, older age, and underlying chronic medical conditions such as lung disease, cancer, heart failure, cerebrovascular disease, renal disease, liver disease, diabetes, immunocompromising conditions, and pregnancy.

The decision to monitor a patient in the inpatient or outpatient setting should be made on a case-by-case basis. This decision will depend not only on the clinical presentation, but also on the patient’s ability to engage in monitoring, home isolation, and the risk of transmission in the patient’s home environment. For more information, see Criteria to Guide Evaluation of Patients Under Investigation (PUI) for 2019-nCoV.

No specific treatment for 2019-nCoV infection is currently available. Clinical management includes prompt implementation of recommended infection prevention and control measures and supportive management of complications, including advanced organ support if indicated.

Corticosteroids should be avoided unless indicated for other reasons (for example, chronic obstructive pulmonary disease exacerbation or septic shock per Surviving Sepsis guidelinesexternal icon), because of the potential for prolonging viral replication as observed in MERS-CoV patients. [12, 2123]

For more information, see: WHO interim guidance on clinical management of severe acute respiratory infection when novel coronavirus (nCoV) infection is suspectedpdf iconexternal icon and Diagnosis and Treatment of Adults with Community-acquired Pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of Americaexternal icon.

Investigational Therapeutics

There are currently no antiviral drugs licensed by the U.S. Food and Drug Administration (FDA) to treat patients with 2019-nCoV infection. Some in-vitro or in-vivo studies suggest potential therapeutic activity of compounds against related coronaviruses, but there are no available data from observational studies or randomized controlled trials in humans to support recommending any investigational therapeutics for patients with confirmed or suspected 2019-nCoV infection at this time. Remdesivir, an investigational antiviral drug, was reported to have in-vitro activity against 2019-nCoV. [24] A small number of patients with 2019-nCoV infection have received intravenous remdesivir for compassionate use outside of a clinical trial setting. A randomized placebo-controlled clinical trial of remdesivir for treatment of hospitalized patients with pneumonia and 2019-nCoV infection has been implemented in China. A randomized open label trial of combination lopinavir-ritonavir treatment has been also been conducted in hospitalized patients with pneumonia and 2019-nCoV infection in China, but no results are available to date. Clinical trials of other potential therapeutics for 2019-nCoV infection are being planned. For information on specific clinical trials underway for treatment of patients with 2019-nCoV infection, see clinicaltrials.govexternal icon.

Interim Guidance for Discontinuing Transmission-based Precautions or In-Home Isolation for Persons with Laboratory-confirmed 2019-nCoV Infection*

Standard and Transmission-based precautions (i.e., Contact and Airborne precautions with eye protection) should be used for persons with laboratory-confirmed 2019-nCoV infection. This guidance applies to patients being managed in a hospital in an airborne infection isolation room (AIIR) and to patients being cared for in-home isolation.

Decisions to discontinue transmission-based precautions or in-home isolation can be made on a case-by-case basis in consultation with clinicians, infection prevention and control specialists, and public health based upon multiple factors, including disease severity, illness signs and symptoms, and results of laboratory testing for 2019-nCoV in respiratory specimens.

See: Interim Considerations for Disposition of Hospitalized Patients with 2019-nCoV Infection

See: Interim Considerations for Disposition of Non-Hospitalized Patients with 2019-nCoV Infection Under In-Home Isolation

Additional resources:

References

  1. Li Q, Guan X, Wu P, Wang X, Zhou L, et al. Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia. N Engl J Med. 2020 Jan 29.
  2. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet. 2020 Jan 24.
  3. Wang D, Hu B, Hu C, Zhu F, Liu X et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan. Published online February 7, 2020.
  4. Chen N, Zhou M, Dong X, Qu J, Gong F. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020 Jan 30. [Epub ahead of print]
  5. Chan JF, Yuan S, Kok K, To KK, Chu H, 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. 2020 Jan 24. [Epub ahead of print]
  6. Chang D, Minggui L, Wei L, Lixin X, Guangfa Z et al. Epidemiologic and Clinical Characteristics of Novel Coronavirus Infections Involving 13 Patients Outside Wuhan China. Published online February 7, 2020.
  7. Zhu N, Zhang D, Wang W, Li X, Yang B, et al; China Novel Coronavirus Investigating and Research Team. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020 Jan 24. [Epub ahead of print]
  8. Phan LT, Nguyen TV, Luong QC, Nguyen TV, Nguyen HT et al. Importation and Human-to-Human Transmission of a Novel Coronavirus in Vietnam. N Engl J Med. 2020 Jan 28. doi: 10.1056/NEJMc2001272. [Epub ahead of print]
  9. Holshue ML, DeBolt C, Lindquist S, Lofy KH, Wiesman J et al. First Case of 2019 Novel Coronavirus in the United States. N Engl J Med. 2020 Jan 31. doi: 10.1056/NEJMoa2001191. [Epub ahead of print]Huang C, Wang Y, Li X, Ren L, Zhao J, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Jan 24. [Epub ahead of print]
  10. Lei J, Li J, Li X, Qi X. CT Imaging of the 2019 Novel Coronavirus (2019-nCoV) Pneumonia. Radiology. 2020 Jan 31:200236. doi: 10.1148/radiol.2020200236. [Epub ahead of print]
  11. Memish ZA, Assiri AM, Al-Tawfiq JA. Middle East respiratory syndrome coronavirus (MERS-CoV) viral shedding in the respiratory tract: an observational analysis with infection control implications. Int J Infect Dis. 2014 Dec;29:307-8.
  12. Zumla A, Hui DS, Perlman S. Middle East respiratory syndrome. Lancet. 2015 Sep 5;386(9997):995-1007. doi: 10.1016/S0140-6736(15)60454-8. Epub 2015 Jun 3. Review.
  13. Chan KH, Poon LL, Cheng VC, Guan Y, Hung IF et al. Detection of SARS coronavirus in patients with suspected SARS. Emerg Infect Dis. 2004 Feb;10(2):294-9.
  14. Cheng PK, Wong DA, Tong LK, Ip SM, Lo AC et al. Viral shedding patterns of coronavirus in patients with probable severe acute respiratory syndrome. Lancet. 2004 May 22;363(9422):1699-700.
  15. Hung IF, Cheng VC, Wu AK, Tang BS, Chan KH et al. Viral loads in clinical specimens and SARS manifestations. Emerg Infect Dis. 2004 Sep;10(9):1550-7.
  16. Peiris JS, Chu CM, Cheng VC, Chan KS, Hung IF, et al; HKU/UCH SARS Study Group. Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study. Lancet. 2003 May 24;361(9371):1767-72.
  17. Liu W, Tang F, Fontanet A, Zhan L, Zhao QM et al. Long-term SARS coronavirus excretion from patient cohort, China. Emerg Infect Dis. 2004 Oct;10(10):1841-3.
  18. Corman VM, Albarrak AM, Omrani AS, Albarrak MM, Farah ME, et al. Viral Shedding and Antibody Response in 37 Patients With Middle East Respiratory Syndrome Coronavirus Infection. Clin Infect Dis. 2016 Feb 15;62(4):477-483.
  19. Al-Abdely HM, Midgley CM, Alkhamis AM, Abedi GR, Lu X, et al. Middle East respiratory syndrome coronavirus infection dynamics and antibody responses among clinically diverse patients, Saudi Arabia. Emerg Infect Dis. 2019 Apr;25(4):753-766.
  20. Al-Abdely HM, Midgley CM, Alkhamis AM, Abedi GR, Tamin A et al. Infectious MERS-CoV Isolated From a Mildly Ill Patient, Saudi Arabia. Open Forum Infect Dis. 2018 May 15;5(6):ofy111.
  21. Arabi YM, Mandourah Y, Al-Hameed F, Sindi AA, Almekhlafi GA, et al; Saudi Critical Care Trial Group. Corticosteroid Therapy for Critically Ill Patients with Middle East Respiratory Syndrome. Am J Respir Crit Care Med. 2018 Mar 15;197(6):757-767.
  22. Russell CD, Millar JE, Baillie JK. Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury.  Lancet. 2020 Feb 6; S0140-6736(20)30305-6.
  23. Metlay JP, Waterer GW, Long AC, Anzueto A, Brozek J, et al. Diagnosis and treatment of adults with community-acquired pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-e67.
  24. Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, Shi Z, Hu Z, Zhong W, Xiao G. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020 Feb 4. doi: 1038/s41422-020-0282-0. [Epub ahead of print] PubMed PMID: 32020029.

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