Symptoms and Management of Coronavirus Disease 2019 (COVID-19) FAQ 

Symptoms and Management of Coronavirus Disease 2019 (COVID-19) FAQ 

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Patients with a mild clinical presentation may not initially require hospitalization, but clinical signs and symptoms may worsen, with progression to lower respiratory tract disease in the second week of illness. Risk factors for progressing to severe illness may include, but are not limited to, older age and underlying chronic medical conditions (eg, lung disease, cancer, heart failure, cerebrovascular disease, renal disease, liver disease, diabetes, immunocompromising conditions, and pregnancy).

Most patients with confirmed COVID-19 have developed fever [1] and/or symptoms of acute respiratory illness (eg, cough, difficulty breathing).

Signs and symptoms of mild COVID-19

Severe pneumonia

Acute respiratory distress syndrome

Sepsis

Septic shock

Patient counseling

Home care

Home monitoring and resolution of symptoms

Exacerbation of symptoms

Patients should seek medical attention immediately if they begin to experience trouble breathing, have persistent chest pain or chest pressure, experience confusion or inability to arouse, or their lips or face turn blue.

Many factors can lead to immunocompromise, including cancer treatment, bone marrow or organ transplantation, immunodeficiencies, poorly controlled HIV or AIDS, and prolonged use of corticosteroids and other immune weakening medications. Patients known to be at risk include the following:

Not all patients with coronavirus disease 2019 (COVID-19) will require medical supportive care. Clinical management for hospitalized patients with COVID-19 is focused on supportive care of complications, including advanced organ support for respiratory failure, septic shock, and multiorgan failure. Empiric testing and treatment for other viral or bacterial etiologies may be warranted.

Supplemental oxygen therapy should immediately be administered to patients with severe COVID-19 who have severe acute respiratory infection (SARI) and respiratory distress, hypoxemia, or shock, with the peripheral oxygen saturation target being greater than 94%. [2]

Patients with severe COVID-19 should be closely monitored for signs of clinical deterioration (eg, rapidly progressive respiratory failure and sepsis), with supportive care interventions administered immediately. [2]

In a case of severe COVID-19, the patient’s comorbid condition(s) should be understood in order to tailor the management of critical illness. [2]

Fluid management: When shock is not evident, conservative fluid management should be used in patients with SARI. [2]

Empiric antimicrobial therapy should be administered as soon as possible to treat all likely pathogens causing SARI and sepsis, with such treatment provided within 1 hour of initial evaluation for patients with sepsis. [2]

Severe hypoxemic respiratory failure must be recognized when standard oxygen therapy is failing in a patient with respiratory distress; prepare for administration of advanced oxygen/ventilatory support. [2]

Corticosteroids are not routinely recommended for viral pneumonia or acute respiratory distress syndrome (ARDS) and should be avoided unless indicated for another reason (eg, COPD exacerbation, refractory septic shock).

Acute respiratory distress syndrome (ARDS)

Cardiovascular

Severe hypoxemic respiratory failure must be recognized when standard oxygen therapy is failing in a patient with respiratory distress; prepare for administration of advanced oxygen/ventilatory support. [2]

Prone ventilation for 12-16 hours per day is recommended in adult patients with severe acute respiratory distress syndrome (ARDS). [2]

Oxygenation for severe ARDS:

Corticosteroids are not routinely recommended for viral pneumonia or ARDS and should be avoided unless they are indicated for another reason (eg, COPD exacerbation, refractory septic shock).

Make plans to quickly identify and isolate cardiovascular patients with coronavirus disease 2019 (COVID-19) symptoms from other patients, including in the ambulatory setting. [3]

COVID-19–related cardiac complications include arrhythmia and acute cardiac injury. [3]

Conditions that can precipitate cardiac complications include acute-onset heart failure, myocardial infarction, myocarditis, and cardiac arrest, as well as any illness that places a higher cardiometabolic demand on patients. [3]

COVID-19 cardiac complications appear in line with severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and influenza analogs. [3]

Cardiologists should prepare to aid other specialists in managing cardiac complications in patients with severe COVID-19. [3]

Cardiology and critical-care teams should coordinate management of patients requiring extracorporeal circulatory support with veno-venous (V-V) versus veno-arterial (V-A) extracorporeal membrane oxygenation (ECMO). [3]

Obtain echocardiography in the setting of heart failure, arrhythmia, electrocardiographic (ECG) changes, or cardiomegaly. [3]

It is reasonable to triage patients with COVID-19 according to the presence of underlying cardiovascular, diabetic, respiratory, renal, oncologic, and other chronic diseases for prioritized treatment. [3]

Providers are cautioned that classic symptoms and presentation of acute myocardial infarction may be overshadowed in the context of COVID-19, resulting in underdiagnosis. [3]

No drugs or biologics have been proven to be effective for the prevention or treatment of COVID-19. Numerous antiviral agents, immunotherapies, and vaccines are being investigated and developed as potential therapies.

For more information on investigational drugs and biologics being evaluated for COVID-19, see Investigational Drugs and Biologics.

The broad-spectrum antiviral agent remdesivir (GS-5734; Gilead Sciences, Inc) is a nucleotide analog prodrug. It was studied in clinical trials for Ebola virus infections but showed limited benefit. [4]

Remdesivir has been shown to inhibit replication of other human coronaviruses associated with high morbidity in tissue cultures, including severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003 and Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012. Efficacy in animal models has been demonstrated for SARS-CoV and MERS-CoV. [5]

Several phase 3 clinical trials are testing remdesivir for treatment of COVID-19 in the United States, South Korea, and China.

An adaptive randomized trial of remdesivir coordinated by the National Institute of Health (NCT04280705) was started first against placebo, but additional therapies can be added to the protocol as evidence emerges. The first experience with this study involved passengers of the Diamond Princess cruise ship in quarantine at the University of Nebraska Medical Center after returning to the United States from Japan following an on-board outbreak of COVID-19. [6]

Positive results were seen with remdesivir after use by the University of Washington in the first case of COVID-19 documented on US soil. [7] The drug was prescribed under an open-label Compassionate Use protocol, but the FDA has since moved to allow Expanded access to remdesivir, permitting approved sites to prescribe the investigational product for multiple patients under protocol without requesting permission for each. [8]

An in vitro study showed that the antiviral activity of remdesivir plus interferon beta (IFNb) was superior to that of lopinavir/ritonavir (LPV/RTV; Kaletra, Aluvia; AbbVie Corporation). Prophylactic and therapeutic remdesivir improved pulmonary function and reduced lung viral loads and severe lung pathology in mice, whereas LPV/RTV-IFNb slightly reduced viral loads without affecting other disease parameters. Therapeutic LPV/RTV-IFNb improved pulmonary function but did not reduce virus replication or severe lung pathology. [9]

In a randomized, controlled, open-label trial of hospitalized adults (n=199) with confirmed SARS-CoV-2 infection, patients were randomized to receive lopinavir/ritonavir 400 mg/100 mg PO BID for 14 days added to standard care or standard care alone.

The mortality rate at 28 days was numerically lower for lopinavir/ritonavir compared with standard care (19.2% vs 25%) but did not reach statistical significance. [10, 11]

Rintatolimod is a TLR-3 agonist (Poly I:Poly C12U; Ampligen; AIM ImmunoTech) (toll-like receptor 3 [TLR-3] agonist) that is being tested as a potential treatment for COVID-19 by the National Institute of Infectious Diseases (NIID) in Japan and the University of Tokyo. [12] It is a broad-spectrum antiviral agent. [13]

Plitidepsin (Aplidin; PharmaMar) is a member of the compound class known as didemnins. In vitro studies from Spain report plitidepsin potentially targets EF1A, which is key to multiplication and spread of the virus. [14]

Preliminary results of favipiravir’s (viral RNA polymerase inhibitor) moderate antiviral effect on COVID-19 have emerged from a study in China, although the parent company of the drug (Fujifilm Pharmaceuticals, Japan) has not confirmed the drug’s efficacy. [15] Favipiravir (Avigan) is approved in Japan and China for influenza and is investigational for use in COVID-19.

Interleukin-6 (IL-6) inhibitors may ameliorate severe damage to lung tissue caused by cytokine release in patients with serious COVID-19 infections. Several studies have indicated a “cytokine storm” with release of IL-6, IL-1, IL-12, and IL-18, along with tumor necrosis factor alpha (TNFα) and other inflammatory mediators. The increased pulmonary inflammatory response may result in increased alveolar-capillary gas exchange, making oxygenation difficult in patients with severe illness.

On March 16, 2020, Sanofi and Regeneron announced initiation of a phase 2/3 trial of the IL-6 inhibitor sarilumab (Kevzara). [16]

Genentech, maker of the IL-6 inhibitor tocilizumab (Actemra) is working with the FDA to initiate a randomized, double-blind, placebo-controlled phase III clinical trial in collaboration with BARDA to evaluate the safety and efficacy of tocilizumab plus standard of care in hospitalized adult patients with severe COVID-19 pneumonia. [17]

An open label, non-controlled, non–peer reviewed study was conducted in China in 21 patients with severe respiratory symptoms related to COVID-19. All patients received standard of care, including lopinavir and methylprednisolone. Patients received a single dose of 400 mg tocilizumab via intravenous infusion. In general, the patients improved with lower oxygen requirements, lymphocyte counts returned to normal, and 19 patients were discharged with a mean of 15.5 days after tocilizumab treatment. The authors concluded that tocilizumab was an effective treatment in patients with severe COVID-19. [18] All patients were receiving standard therapy for at least a week before tocilizumab was started.

Hydroxychloroquine and chloroquine are widely used antimalarial drugs that elicit immunomodulatory effects and are therefore also used to treat autoimmune conditions (eg, systemic lupus erythematosus, rheumatoid arthritis). [19] The pharmacological activity of chloroquine and hydroxychloroquine was tested using SARS-CoV-2–infected Vero cells. Hydroxychloroquine was found to be more potent than chloroquine in vitro. Based on PBPK models, the authors recommend a loading dose of hydroxychloroquine 400 mg PO BID, followed by 200 mg BID for 4 days. [20] Published reports stemming from the worldwide outbreak of COVID-19 have evaluated the potential usefulness of these drugs in controlling cytokine release syndrome in critically ill patients. [20, 21]

According to a consensus statement from a multicenter collaboration group in China, chloroquine phosphate 500 mg (300 mg base) twice daily in tablet form for 10 days may be considered in patients with COVID-19 pneumonia. [22]

Gao and colleagues noted that 100 patients demonstrated significant improvement with this regimen without documented toxicity. [21]

A study of hydroxychloroquine for postexposure prophylaxis in healthcare workers or household contacts is underway. [23]

One study in France recently evaluated patients treated with hydroxychloroquine against a control group who received standard of care. [24]

Cardiac toxicity has been reported.

The small open-label study of hydroxychloroquine in France included azithromycin in 6 patients for potential bacterial superinfection. These patients were reported to have 100% clearance of SARS-CoV-2. While intriguing, these results warrant further analysis.

The patients receiving combination therapy had lower viral loads, and, when compared with patients receiving hydroxychloroquine alone with similar viral burden, the results are fairly similar (6/6 vs 7/9). [24] Hydroxychloroquine and azithromycin each carry the warning of QT prolongation and can be associated with an increased risk of cardiac death when used in a broader population. [25]

Early guidelines for management of critically ill adults with COVID-19 specify when to use low-dose corticosteroids and when to refrain from using corticosteroids. The recommendations depend on the precise clinical situation (eg, refractory shock, mechanically ventilated patients with ARDS); however, these particular recommendations are based on evidence listed as weak. [26]

A study describing clinical outcomes of patients diagnosed with COVID-19 was conducted in Wuhan China (N = 201). Eighty-four patients (41.8%) developed ARDS, and of those, 44 (52.4%) died. Among patients with ARDS, treatment with methylprednisolone decreased the risk of death (HR, 0.38; 95% CI, 0.20-0.72). [27]

An open-label prospective trial is planned to study clinical improvement in patients treated with methylprednisolone IV. [28]

The FDA is facilitating convalescent plasma, antibody-rich products that are collected from eligible donors who have recovered from the COVID-19 virus. Use of this product in patients with serious or immediately life-threatening COIVD-19 infections may shorten duration or severity of illness. [29]

The FDA has posted information for investigators wishing to study convalescent plasma for use in patients with serious or immediately life-threatening COVID-19 infections through the process of single patient emergency Investigational New Drug (IND) applications for individual patients.

Published findings from the 2004 SARS-CoV infection suggest the potential role of inhaled nitric oxide (iNO; Mallinckrodt Pharmaceuticals, plc) as a supportive measure for treating infection in patients with pulmonary complications. Treatment with iNO reversed pulmonary hypertension, improved severe hypoxia, and shortened the length of ventilatory support compared with matched control patients with SARS. [30]

A phase 2 study of iNO is underway in patients with COVID-19 with the goal of preventing disease progression in those with severe ARDS. [31]

The Society of Critical Care Medicine recommends against the routine use of iNO in patients with COVID-19 pneumonia. Instead, they suggest a trial only in mechanically ventilated patients with severe ARDS and hypoxemia despite other rescue strategies. [18]

Overview

What are the signs and symptoms of mild coronavirus disease 2019 (COVID-19)?

What are the signs and symptoms of severe or critical coronavirus disease 2019 (COVID-19)?

How is mild coronavirus disease 2019 (COVID-19) managed?

Who is at risk for severe coronavirus disease 2019 (COVID-19)?

How is severe or critical coronavirus disease 2019 (COVID-19) managed?

How is acute respiratory distress syndrome (ARDS) managed in patients with critical coronavirus disease 2019 (COVID-19)?

How are acute cardiac complications managed in patients with coronavirus disease 2019 (COVID-19)?

Which drugs are effective for the treatment of coronavirus disease 2019 (COVID-19)?

What is the status of the antiviral drug remdesivir in the treatment of coronavirus disease 2019 (COVID-19)?

What is the status of the antivirals lopinavir/ritonavir in the treatment of coronavirus disease 2019 (COVID-19)?

What is the status of the antiviral drug rintatolimod in the treatment of coronavirus disease 2019 (COVID-19)?

What is the status of the antiviral drug plitidepsin in the treatment of coronavirus disease 2019 (COVID-19)?

What is the status of the antiviral drug favipiravir in the treatment of coronavirus disease 2019 (COVID-19)?

What is the status of interleukin-6 (IL-6) inhibitors in the treatment of coronavirus disease 2019 (COVID-19)?

What is the status of hydroxychloroquine and chloroquine in the treatment of coronavirus disease 2019 (COVID-19)?

What is the status of azithromycin in the treatment of coronavirus disease 2019 (COVID-19)?

What is the status of corticosteroids (such as methylprednisolone) in the treatment of coronavirus disease 2019 (COVID-19)?

What is the status of convalescent plasma in the treatment of coronavirus disease 2019 (COVID-19)?

What is the status of nitric oxide in the treatment of coronavirus disease 2019 (COVID-19)?

CDC. Coronavirus Disease 2019 (COVID-19): Evaluating and Testing PUI. Centers for Disease Control and Prevention. Available at https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-criteria.html. March 24, 2020; Accessed: March 31, 2020.

World Health Organization. Severe Acute Respiratory Infections Treatment Centre. Practical manual to set up and manage a SARI treatment centre and a SARI screening facility in health care facilities. WHO. Available at https://www.who.int/publications-detail/severe-acute-respiratory-infections-treatment-centre. March 2020; Accessed: March 31, 2020.

American College of Cardiology. ACC clinical bulletin: COVID-19 clinical guidance for the cardiovascular care team. ACC. Available at https://www.acc.org/~/media/665AFA1E710B4B3293138D14BE8D1213.pdf. March 6, 2020; Accessed: March 23, 2020.

Mulangu S, Dodd LE, Davey RT Jr, et al. A Randomized, Controlled Trial of Ebola Virus Disease Therapeutics. N Engl J Med. 2019 Dec 12. 381 (24):2293-2303. [Medline].

Martinez MA. Compounds with therapeutic potential against novel respiratory 2019 coronavirus. Antimicrob Agents Chemother. 2020 Mar 9. [Medline].

National Institutes of Health. NIH clinical trial of remdesivir to treat COVID-19 begins. Department of Health and Human Services. Available at https://www.nih.gov/news-events/news-releases/nih-clinical-trial-remdesivir-treat-covid-19-begins. February 25, 2020; Accessed: March 24, 2020.

Holshue ML, DeBolt C, Lindquist S, et al. First Case of 2019 Novel Coronavirus in the United States. N Engl J Med. 2020 Mar 5. 382 (10):929-936. [Medline].

Remdesivir access program. Gilead Sciences. Available at https://rdvcu.gilead.com/.

Sheahan TP, Sims AC, Leist SR, Schäfer A, Won J, Brown AJ, et al. Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV. Nat Commun. 2020 Jan 10. 11 (1):222. [Medline].

Cao B, Wang Y, Wen D, et al. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. N Engl J Med. 2020 Mar 18. [Medline].

Baden LR, Rubin EJ. Covid-19 – The Search for Effective Therapy. N Engl J Med. 2020 Mar 18. [Medline].

Ampligen as an antiviral. AIM ImmunoTech. Available at https://b2icontent.irpass.com/2265/180859.pdf. February 2020; Accessed: March 13, 2020.

AIM ImmunoTech’s Drug Ampligen to Be Tested by Japan’s National Institute of Infectious Diseases as a Potential Treatment for the New SARS Coronavirus (SARS-CoV-2) Responsible for the New Human Infectious Disease COVID-19. AIM ImmunoTech. Available at https://aimimmuno.irpass.com/AIM-ImmunoTechs-Drug-Ampligen-to-Be-Tested-by-Japans-National-Institute-of-Infectious-Diseases-as-a-Potential-Treatment-for-the-New-SARS-Coronavirus-SARS-CoV-2-Responsible-for-the-New-Human-Infectious. March 9, 2020;

PharmaMar reports positive results for Aplidin against coronavirus HCoV-229E. PharmaMar. Available at http://pharmamar.com/wp-content/uploads/2020/03/PR_Results_Aplidin_coronavirus.pdf. March 13, 2020;

Dong L, Hu S, Gao J. Discovering drugs to treat coronavirus disease 2019 (COVID-19). Drug Discov Ther. 2020. 14 (1):58-60. [Medline].

Regeneron and Sanofi Begin Global Kevzara (Sarilumab) Clinical Trial Program in Patients with Severe COVID-19. Regeneron/Sanofi. Available at https://investor.regeneron.com/news-releases/news-release-details/regeneron-and-sanofi-begin-global-kevzarar-sarilumab-clinical. March 16, 2020;

Genentech Initiates Phase III Clinical Trial of Actemra in Hospitalized Patients with Severe COVID-19 Pneumonia. Genentech. Available at https://www.gene.com/media/press-releases/14841/2020-03-18/genentech-initiates-phase-iii-clinical-t. March 18, 2020;

National Health Commission (NHC) of the People’s Republic of China. The diagnosis and treatment guide of COVID-19 pneumonia caused by new coronavirus infection 7th Edition, published March 3rd, 2020.

Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020 Mar. 30 (3):269-271. [Medline].

Yao X, Ye F, Zhang M, Cui C, Huang B, Niu P, et al. In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis. 2020 Mar 9. [Medline].

Gao J, Tian Z, Yang X. Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends. 2020 Mar 16. 14 (1):72-73. [Medline].

multicenter collaboration group of Department of Science and Technology of Guangdong Province and Health Commission of Guangdong Province for chloroquine in the treatment of novel coronavirus pneumonia. [Expert consensus on chloroquine phosphate for the treatment of novel coronavirus pneumonia]. Zhonghua Jie He He Hu Xi Za Zhi. 2020 Mar 12. 43 (3):185-188. [Medline].

Post-exposure Prophylaxis for SARS-Coronavirus-2. ClinicalTrials.gov. Available at https://clinicaltrials.gov/ct2/show/NCT0430866. March 23, 2020; Accessed: March 24, 2020.

Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Mailhe M, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020 Mar 20. 105949. [Medline].

Ray WA, Murray KT, Hall K, Arbogast PG, Stein CM. Azithromycin and the risk of cardiovascular death. N Engl J Med. 2012 May 17. 366 (20):1881-90. [Medline].

[Guideline] Alhazzani W, Møller MH, Arabi YM, et al. Surviving Sepsis Campaign: Guidelines on the Management of Critically Ill Adults with Coronavirus Disease 2019 (COVID-19). Crit Care Med. 2020 Mar 27. [Medline].

Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, et al. Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern Med. 2020 Mar 13. [Medline].

Zhou YH, Qin YY, Lu YQ, Sun F, Yang S, Harypursat V, et al. Effectiveness of glucocorticoid therapy in patients with severe novel coronavirus pneumonia: protocol of a randomized controlled trial. Chin Med J (Engl). 2020 Mar 5. [Medline].

FDA News Release. Coronavirus (COVID-19) Update: Daily Roundup, March 24 2020. US Food and Drug Administration. Available at https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-daily-roundup-march-24-2020. March 24, 2020; Accessed: March 26, 2020.

Chen L, Liu P, Gao H, Sun B, Chao D, Wang F, et al. Inhalation of nitric oxide in the treatment of severe acute respiratory syndrome: a rescue trial in Beijing. Clin Infect Dis. 2004 Nov 15. 39 (10):1531-5. [Medline].

Nitric Oxide Gas Inhalation for Severe Acute Respiratory Syndrome in COVID-19. ClinicalTrials.gov. Available at https://clinicaltrials.gov/ct2/show/NCT04290871. March 6, 2020; Accessed: March 13, 2020.

CDC. Interim guidelines for collecting, handling, and testing clinical specimens from persons for coronavirus disease 2019 (COVID-19). Centers for Disease Control and Prevention. Available at https://www.cdc.gov/coronavirus/2019-nCoV/lab/guidelines-clinical-specimens.html. March 17, 2020; Accessed: March 31, 2020.

Medscape Novel Coronavirus (COVID-19) Resource Center. WebMD Inc. Available at https://www.medscape.com/resource/coronavirus. March 2020; Accessed: March 31, 2020.

Colson P, Rolain JM, Raoult D. Chloroquine for the 2019 novel coronavirus SARS-CoV-2. Int J Antimicrob Agents. 2020 Mar. 55 (3):105923. [Medline].

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Symptoms and Management of Coronavirus Disease 2019 (COVID-19) FAQ 

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