Clinical Course: Progression, Management, and Treatment

Mild to Moderate Illness

Most patients with COVID-19 experience asymptomatic or mild illness that does not warrant medical intervention, or mild to moderate illness that can be managed in the outpatient setting. These patients can benefit from supportive care and symptomatic treatment, including antipyretics, analgesics, and antitussives. Patients can also be instructed on efforts they can take to reduce transmission and symptoms that indicate the need for additional medical attention.

Some patients with mild to moderate COVID-19 may be at increased risk for progression to severe COVID-19. For these patients, therapeutics, such as antivirals, have been shown to significantly decrease the risk of hospitalization and death, and outcomes are improved if therapeutics are started within the first days of illness.^(37,38) Test to treat strategies may allow for timely diagnosis and treatment of patients who are at risk for severe disease. Clinicians should consider offering therapeutics and monitoring closely patients with risk factors for severe illness.

The FDA has approved the intravenous antiviral medication remdesivir (Veklury) for the treatment of COVID-19 in adults and pediatric patients. The FDA has also approved the oral antiviral nirmatrelvir with ritonavir (Paxlovid) for the treatment of mild-to-moderate COVID-19 in adults who are at high risk for progression to severe disease. Paxlovid manufactured and packaged under the emergency use authorization (EUA) and distributed by the U.S. Department of Health and Human Services will continue to be available to ensure continued access for adults, as well as treatment of eligible children ages 12-18 who are not covered by the approval. For more information about nirmatrelvir and ritonavir (Paxlovid), please see the FDA Fact Sheet for Healthcare Providers and the approved label [5 MB, 51 pages]. In addition, the FDA has issued an emergency use authorization (EUA) for the oral antiviral molnupiravir (Lagevrio), which can be used for treatment of patients with mild to moderate illness who are at risk for severe illness. Clinicians should refer to the NIH COVID-19 Treatment Guidelines for up-to-date recommendations regarding eligibility, effectiveness of therapeutics, rationale for treatment of sub-populations, specific drug classes, general management, and therapeutic management.

Additionally, the FDA has issued an EUA to permit the emergency use of COVID-19 convalescent plasma with high titers of anti-SARS-CoV-2 antibodies for the treatment of COVID-19 in patients with immunosuppressive disease or receiving immunosuppressive treatment, in either the outpatient or inpatient setting. For more information, please see the FDA Fact Sheet for Providers. Please also see the NIH COVID-19 Treatment Guidelines, which provide recommendations on who should be considered for this treatment.

Pulse oximetry has been used to monitor oxygenation in the ambulatory setting, but pulse oximeters may not detect occult hypoxemia in all patients, especially in those who have darker skin, ⁽³⁹⁾ and smart phone-based pulse oximeters may not be able to accurately detect hypoxia.⁽⁴⁰⁾ Clinicians caring for patients with dyspnea should consider closely monitoring them because of the risk for progression to acute respiratory distress syndrome (ARDS).

Severe to Critical Illness

Most studies define severe illness related to COVID-19 as admission to the hospital or the ICU, placement on invasive mechanical ventilation, or death. Rates of death and other markers of severe illness may be associated with the variant that is in circulation, levels of vaccination coverage, treatment availability, and other factors. A study conducted during high levels of Omicron variant transmission in the U.S. found the ratio of peak ED visits, hospital admissions, and deaths, to cases during the Omicron period were lower than those observed during the winter of 2020–21 and the Delta period.⁽⁴¹⁾ The study also found that among hospitalized COVID-19 patients, the mean length of stay and percentages who were admitted to an ICU, received invasive mechanical ventilation (IMV), and died while in the hospital, were lower during the Omicron period than during previous periods.⁽⁴¹⁾

Available evidence suggests that the currently approved or authorized COVID-19 vaccines are highly effective against hospitalization and death for a variety of variants, and the risk of hospitalization and severe illness, regardless of variant, is higher in people who are unvaccinated than in those up to date with vaccination.^(42-44)

Clinical treatment recommendations for people with severe to critical COVID-19 are based on the severity of illness, and therapeutic management often includes care of common complications of severe illness, including hypoxemic respiratory failure/ARDS, sepsis and septic shock, elevation in inflammatory cytokines, and complications from prolonged hospitalization, including thromboembolism, pneumonia, and hospital-acquired bacterial and fungal infections.  Additionally, patients with COVID-19 may experience an exacerbation of underlying comorbidities or new onset cardiac, endocrine, hepatic, renal, gastrointestinal, or central nervous system disease.

The FDA has authorized the use of several medications for patients with severe or critical illness due to COVID-19. Clinicians can find general considerations and recommendations for the care of critically ill patients along with the rationale for the recommendations in the NIH COVID-19 Treatment Guidelines and the Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19. Research for effective treatments for COVID-19 is ongoing, and more information about clinical trials can be found at ClinicalTrials.gov.

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