Clinical Course: Progression, Management, and Treatment

Mild or moderate illness

Most patients with COVID-19 experience asymptomatic, mild, or moderate illness that can be managed in an outpatient setting.

Management

Patients with no risk factors for severe COVID-19 may benefit from supportive care and symptomatic treatment including antipyretics, analgesics, and antitussives. Clinicians can also instruct patients on preventing SARS-CoV-2 transmission and COVID-19 symptoms that indicate additional medical attention.

For patients at increased risk for progression to severe COVID-19, clinicians should offer antivirals to significantly decrease the risk of hospitalization and death. Antivirals should be started within the first 5–7 days of symptom onset. ^{[1, 2, 3, 4, 5, 6, 7, 8, 9]}If declined, patients should be closely monitored.

Pulse oximetry has been used to monitor oxygenation in the ambulatory setting. However, pulse oximeters may not detect occult hypoxemia in all patients, especially in those who have darker skin. Smartphone-based pulse oximeters may not accurately detect hypoxia.  ^{[10, 11]}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).

Treatment

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

• Remdesivir (Veklury®) – This intravenous antiviral medication is approved by FDA for COVID-19 treatment in adults and pediatric patients.
• Nirmatrelvir with ritonavir (Paxlovid™) – This oral antiviral has been approved by FDA for the treatment of mild or moderate COVID-19 in adults who are at risk for progression to severe illness. Nirmatrelvir-ritonavir is available under the emergency use authorization (EUA) for eligible children ages 12–17 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 EUA for molnupiravir, an oral antiviral to treat patients with mild or moderate illness who are at risk for progression to severe illness.

Clinicians should refer to the IDSA Guidelines on the Treatment and Management of Patients with COVID-19 and the American College of Physician (ACP) Clinical Guidelines and Recommendations on COVID-19 for up-to-date recommendations regarding eligibility, effectiveness of therapeutics, rationale for treatment of sub-populations, specific drug classes, and therapeutic management.

FDA has issued an EUA for COVID-19 convalescent plasma (CP) with high titers of anti-SARS-CoV-2 antibodies. CP can be given to treat patients with immunosuppressive disease or patients receiving immunosuppressive treatment, in an in- or out-patient setting. For more information, please see the FDA Fact Sheet for Providers and IDSA Guidelines on the Treatment and Management of Patients with COVID-19.

Severe to critical illness

Progression

Severe illness from 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.

Older age (especially ages 65 and over) is the strongest risk factor for severe COVID-19 (hospitalization, ICU admission, and death). ^{[12, 13, 14, 15]} Certain and multiple underlying medical conditions can also increase a patient's risk of severe COVID-19. Clinicians should provide pharmacologic treatment consistent with a patient's clinical status and risk.

COVID-19 vaccination remains the best way to protect against COVID-19-associated critical illness and death. Vaccination also reduces the risk of Long COVID, which can develop following any acute infection.

Management

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

• Hypoxemic respiratory failure/ARDS
• Sepsis and septic shock
• Elevation in inflammatory cytokines
• Complications from prolonged hospitalization, including:
  • Thromboembolism
  • Hospital-acquired pneumonia
  • Hospital-acquired bacterial and fungal infections

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

Treatment

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 their care along with the rationale for the recommendations in the IDSA Guidelines on the Treatment and Management of Patients with COVID-19 and the ACP Clinical Guidelines and Recommendations on COVID-19.

More information

• COVID-19 Therapeutics Decision Aid
• Side-by-Side Overview of Therapeutics
• Outpatient COVID-19 Therapeutics Administration Guide for Healthcare Providers
• COVID-19 Drug Interactions
• Paxlovid: What Pharmacists and Prescribers Need to Know