Clinical Course: Progression, Management, and Treatment

Patients without risk factors for severe COVID-19 may benefit from supportive care and symptomatic treatment, including antipyretics, analgesics, and antitussives. Patients can also be instructed on preventing SARS-CoV-2 transmission and reducing COVID-19 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. The reductions in severe outcomes from antivirals are documented despite emergence of variants. Patient outcomes are improved if therapeutics are started within the first 5-7 days of illness. ^{(12, 14-21)} Test to treat may allow for timely diagnosis and treatment of patients who are at risk for severe illness. The Home Test to Treat program will end April 16, 2024, for all participants. Clinicians should consider offering therapeutics and closely monitoring patients with risk factors for severe illness.

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, and smart phone-based pulse oximeters may not be able to accurately detect hypoxia ^{(22, 23)}. Clinicians caring for patients with dyspnea should consider close monitoring with pulse oximeters because of the risk for progression to acute respiratory distress syndrome (ARDS).

The Infectious Disease Society of America (IDSA) recommend Nirmatrelvir with ritonavir (Paxlovid) and Remdesivir (Veklury) for treatment of mild-to-moderate COVID-19 in people at risk for severe illness.

• Remdesivir (Veklury) – The FDA has approved this intravenous antiviral medication for the treatment of COVID-19 in adults and pediatric patients.
• Nirmatrelvir with ritonavir (Paxlovid) – The FDA has approved this oral antiviral for the treatment of mild-to-moderate COVID-19 in adults who are at high risk for progression to severe illness. Nirmatrelvir-ritonavir (Paxlovid) is manufactured and packaged under the emergency use authorization (EUA) and distributed by the U.S. Department of Health and Human Services and will continue to be available to ensure continued access to treatment for adults, as well as treatment of eligible children ages 12-18 years, who are not covered by the approval. For more information about nirmatrelvir-ritonavir (Paxlovid), please see the FDA Fact Sheet for Healthcare Providers and the approved label [5 MB, 51 pages].

Molnupiravir is recommended as a second-line or alternative option for those unable to receive Remdesivir or Nirmatrelvir with ritonavir.

• Molnupiravir (Lagevrio) – FDA has issued an emergency use authorization (EUA) for molnupiravir, an oral antiviral which can be used for treatment of patients with mild to moderate illness who are at risk for progression to severe illness.

Clinicians should refer to the Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19 for up-to-date recommendations regarding eligibility, effectiveness of therapeutics, rationale for treatment of sub-populations, specific drug classes, general management, and therapeutic management.

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 Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19, which provide recommendations on who should be considered for this treatment.

Severe illness related to COVID-19 is defined as having oxygen saturation <94% on room air at sea level, a ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) <300 mm Hg, a respiratory rate >30 breaths/min, lung infiltrates >50%, or requiring invasive mechanical ventilation.

In adults, older age (especially ages 65 and over) is the strongest risk factor for severe COVID-19 illness and risk increases with increasing age.^(1–2) People aged 65 and older should receive 1 dose of an updated COVID-19 vaccine should receive 1 additional dose of an updated vaccine. Certain underlying medical conditions are also associated with increased risk of severe COVID-19, and the risk of hospitalization, ICU admission, and death increases as the number of high-risk underlying conditions increases.^(2–4) COVID-19 vaccination remains the best protection against COVID-19-associated hospitalization and death, including providing sustained protection against COVID-19-associated critical illness and death. Vaccination also reduces the chance of suffering the effects of Long COVID, which can develop during or following acute infection and last for an extended duration.

The COVID-19 pandemic highlighted racial, ethnic, and socioeconomic disparities in COVID-19 illnesses, hospitalizations, and deaths.^(4-6) Studies have identified racial and ethnic differences in at-home COVID-19 test use, vaccination coverage, and access to outpatient therapeutics.^(7-9) Studies also show that COVID-19 vaccination coverage is lower in rural counties than in urban counties, and from 2020 to 2022, the United States experienced higher COVID-19 incidence and mortality rates in rural than in urban areas.^(10,11)

Clinical treatment recommendations for people with severe to critical COVID-19 are based on the severity of illness. Management often includes care of complications of severe illness, including:

• hypoxemic respiratory failure/ARDS,
• sepsis and septic shock,
• elevation in inflammatory cytokines,
• and complications from prolonged hospitalization, including thromboembolism, hospital-acquired pneumonia, and hospital-acquired bacterial and fungal infections.

Additionally, patients with COVID-19 may experience an exacerbation of underlying comorbidities or new onset of cardiac, endocrine, hepatic, renal, gastrointestinal, or central nervous system disease.

The FDA has authorized or approved 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 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.