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Clinical Management Summary

Last Updated: April 8, 2022

Two main processes are thought to drive the pathogenesis of COVID-19. Early in the clinical course, the disease is primarily driven by the replication of SARS-CoV-2. Later in the clinical course, the disease appears to be driven by a dysregulated immune/inflammatory response to SARS-CoV-2 that leads to tissue damage. Based on this understanding, it is anticipated that therapies that directly target SARS-CoV-2 would have the greatest effect early in the course of the disease, while immunosuppressive/anti-inflammatory therapies are likely to be more beneficial in the later stages of COVID-19.

The clinical spectrum of SARS-CoV-2 infection includes asymptomatic or presymptomatic infection and mild, moderate, severe, and critical illness. Figure 1 provides guidance for clinicians on the therapeutic management of nonhospitalized adult patients. This includes patients who do not require hospitalization or supplemental oxygen and those who have been discharged from an emergency department or a hospital. Figure 2 provides guidance on the therapeutic management of hospitalized adult patients according to their disease severity and oxygen requirements. Figure 3 provides guidance on the therapeutic management of pediatric patients with multisystem inflammatory syndrome in children (MIS-C).

Therapeutic Management for Nonhospitalized Adults With COVID-19
a For a list of risk factors, see the CDC webpage Underlying Medical Conditions Associated With Higher Risk for Severe COVID-19 and the Patient Prioritization for Treatment section in Therapeutic Management of Nonhospitalized Adults With COVID-19.
b Ritonavir-boosted nirmatrelvir has significant drug-drug interactions. Clinicians should carefully review a patient’s concomitant medications and evaluate potential drug-drug interactions.
c If a patient requires hospitalization after starting treatment, the full treatment course can be completed at the health care provider’s discretion.
d Administration of remdesivir requires 3 consecutive days of IV infusion.
e Bebtelovimab is active in vitro against all circulating Omicron subvariants, but there are no clinical efficacy data from placebo-controlled trials that evaluated the use of bebtelovimab in patients who are at high risk of progressing to severe COVID-19. Therefore, bebtelovimab should be used only when the preferred treatment options are not available, feasible to use, or clinically appropriate.
f Molnupiravir has lower efficacy than the preferred treatment options. Therefore, it should be used only when the preferred options are not available, feasible to use, or clinically appropriate.
g There is currently a lack of safety and efficacy data on the use of this agent in outpatients with COVID-19; using systemic glucocorticoids in this setting may cause harm.
h These individuals should receive oximetry monitoring and close follow-up through telehealth, visiting nurse services, or in-person visits.
i Provide an advanced level of home care, including supplemental oxygen (whether patients are receiving oxygen for the first time or are increasing their baseline oxygen requirements), pulse oximetry, laboratory monitoring, and close follow-up through telehealth, visiting nurse services, or in-person visits.

j See Therapeutic Management of Hospitalized Adults With COVID-19.

Key: AE = adverse event; CDC = Centers for Disease Control and Prevention; ED = emergency department; IV = intravenous; the Panel = the COVID-19 Treatment Guidelines Panel; PO = orally

Figure 2. Therapeutic Management of Adults Hospitalized for COVID-19 Based on Disease Severity


Therapeutic Management of Hospitalized Pediatric Patients With Multisystem Inflammatory Syndrome in Children (MIS-C) (With Discussion on Multisystem Inflammatory Syndrome in Adults [MIS-A])
b In certain patients with severe illness, intensification therapy may include dual therapy with higher-dose glucocorticoids and infliximab or anakinra. Anakinra and infliximab should not be given in combination.

c Infliximab should not be used in patients with macrophage activation syndrome.

Key: CAA = coronary artery aneurysm; IBW = ideal body weight; IV = intravenous; IVIG = intravenous immunoglobulin; LV = left ventricular; MIS-C = multisystem inflammatory syndrome in children; PO = oral; SUBQ = subcutaneously