The pathogenesis of COVID-19 is driven by two main processes: replication of SARS-CoV-2 and a dysregulated immune/inflammatory response. Therapies that target SARS-CoV-2 (ritonavir-boosted nirmatrelvir, remdesivir, bebtelovimab and molnupiravir) are most effective early in the disease, while immunosuppressive/anti-inflammatory therapies (dexamethasone, baricitinib, or tocilizumab) are more beneficial later on. More evidence is being gathered for the use of anticoagulation in different stages of the disease. The clinical spectrum of SARS-CoV-2 infection ranges from asymptomatic to critical illness, and treatment varies accordingly. According to the National Institute of Health COVID-19 Treatment Guidelines, treatment options are categorized based on the disposition of the patient and the risk factors for progression into a severe case.
In patients who are not hospitalized and have no risk of progressing to severe disease, no specific treatment is warranted other than supportive and symptomatic treatment including steps to reduce the risk of SARS-CoV-2 transmission (including isolating the patient), and advising patients on when to contact a health care provider and seek an in-person evaluation. Treatment of symptoms includes using over-the-counter antipyretics, analgesics, or antitussives for fever, headache myalgias, and cough; patients should be advised to drink fluids regularly to avoid dehydration; rest is recommended as needed during acute phase ambulation and other forms of activity should be increased according to patient’s tolerance; education about variability time resolution and complete recovery are important, and when possible telehealth visits determine whether they require COVID specific therapy and in-person care.
For adults who are at high risk of progression to severe disease (i.e., age ≥65 years, asthma, cancer, cardiovascular disease, chronic kidney disease, chronic liver disease, chronic lung disease, diabetes, advanced or untreated HIV infection, obesity, pregnancy, cigarette smoking, and being a recipient of immunosuppressive therapy or a transplant), several antiviral therapeutic options are available to reduce the risk of hospitalization or death. NIH guidelines recommend ritonavir-boosted nirmatrelvir (Paxlovid) and remdesivir as preferred therapeutic options as phase 3, randomized, placebo-controlled trials have reported high clinical efficacies for these agents in high-risk patients with COVID-19 who are unvaccinated. If ritonavir-boosted nirmatrelvir is not available or clinically appropriate because of drug-drug interactions, the Panel recommends using remdesivir as the second option. Bebtelovimab and molnupiravir are recommended as alternative therapeutic options and should ONLY be used when neither of the preferred treatment options is available, feasible to use, or clinically appropriate.
In patients with moderate to severe disease who are hospitalized but not requiring supplemental oxygen therapy, Remdesivir is recommended and should be administered for 5 days or until hospital discharge, whichever comes first. The use of dexamethasone or other systemic corticosteroids is not recommended for the treatment of COVID-19 in these patients and may be associated with harm. Routine prophylactic measures should be administered for deep venous thrombosis and thromboembolic disease.
Patients with COVID-19 who are hospitalized and need conventional oxygen therapy (i.e., no need for HFNC or NIV), remdesivir alone should be given if oxygen supplementation is minimal (i.e., 1-3/min). For those patients with higher oxygen requirements, dexamethasone plus remdesivir should be given. If remdesivir is not available, NIH guidelines recommend using dexamethasone alone in patients who require conventional oxygen. A second immunomodulatory drug to dexamethasone should be added (tocilizumab or baricitinib) in patients who have rapidly increasing oxygen needs and systemic inflammation. In addition, a therapeutic dose of heparin for nonpregnant patients with D-dimer levels above the upper limit of normal should be given to all patients who require conventional oxygen and who do not have an increased bleeding risk.
For patients requiring high-flow nasal cannula oxygen or noninvasive ventilation, the available evidence suggests that the benefits of adding baricitinib or tocilizumab to dexamethasone treatment outweigh the potential risks of these agents. NIH guidelines recommend using 1 of the following combinations of immunomodulators: dexamethasone plus oral (PO) baricitinib; or dexamethasone plus intravenous (IV) tocilizumab. If PO baricitinib and IV tocilizumab are not available or not feasible to use, PO tofacitinib can be used instead of PO baricitinib, and IV sarilumab can be used instead of IV tocilizumab. The use of remdesivir is not recommended in these patients. Remdesivir can be added to one of the immunomodulating agents in these patients but it should not be given alone.
Finally, in patients who are mechanically ventilated or on ECMO, the clinicians should promptly start 1 of the following, if not already initiated: dexamethasone plus PO baricitinib, or dexamethasone plus IV tocilizumab. If baricitinib, tofacitinib, tocilizumab, or sarilumab cannot be obtained, then dexamethasone alone.
At this point, therapeutic (or intermediate) dose heparin is not recommended for ICU patients who are on HFNC, NIV, mechanically ventilated, or ECMO if there is no proven indication. NIH guidelines recommend switching to prophylactic dose heparin if the patient was already started on a therapeutic dose prior to ICU admission. However, the recent COVID-PACT trial showed a decreased rate of venous and arterial thrombosis without a mortality benefit in ICU patients and NIH guidelines may change based on this study.
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Reference
NIH Guidelines: https://www.covid19treatmentguidelines.nih.gov/tables/therapeutic-management-of-hospitalized-adults/