The COVID-19 Textbook


CHAPTER 15 • Treatment of COVID-19 in Adults

speculation about the detrimental effects that NSAIDs may have on the course of COVID-19, this concern was subsequently not confirmed. 10,11 Hence, medications like NSAIDs and acetaminophen are regarded as safe options for symptom relief in people with COVID-19. For hospitalized patients with hypoxemia, therapy consists of pharmacologic agents along with respiratory and, at times, circulatory support and renal replacement therapy. Respiratory support may include provision of conventional oxygen, high-flow nasal cannula oxygen, noninvasive ventila tion, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO). COVID-19 Pathogenesis and Therapeutic Options Therapies for COVID-19 have advanced in line with our understanding of COVID-19 pathogenesis (Figure 15.1). 12,13 Initial symptoms and signs of COVID-19 are likely related to viral replication in the upper respiratory tract. Accordingly, patients with early COVID-19 usually have high levels of SARS-CoV-2 RNA in the nasopharynx; it is in this phase of the infection that antiviral therapies are thought to be most effective. By contrast, during the phase of severe COVID-19 when people are hospitalized, viral levels in the upper respiratory tract may be declining, but there is evidence for pneumonia and systemic inflammation, which may trigger hypercoagulability and dysfunction of multiple organs. During severe and critical COVID-19, anti-inflammatory/immunomodulatory medications and, in some individuals, anticoagulants are the mainstays of therapy. There is certainly overlap between phases, such that people who are early in their hospitalization course or who have high levels of circulating SARS-CoV-2 may still benefit from the use of specific antiviral agents, such as remdesivir. Pharmacologic Treatment Options for Nonhospitalized Patients With COVID-19 Specific antiviral therapies for mild-to-moderate COVID-19, typically in nonhospitalized patients, are in clinical use. As of January 2023, these include ritonavir-boosted nirmatrelvir (orally for 5 days), remdesivir (intravenously for 3 days) and, if those are not available or feasible to use, molnupiravir (orally for 5 days).

Treatment Across the COVID-19 Spectrum

Moderate illness

Severe illness

Critical illness

Asymptomatic/ Presymptomatic

Mild illness

Stage/ Severity:

+ SARS-CoV-2 test but no symptoms

Mild symptoms (eg, fever, cough, taste/smell changes); no dyspnea

O 2 saturation ≥94%, lower respiratory tract disease

O 2 saturation <94%, respiratory rate >30/min; lung infiltrates >50%

Respiratory failure, shock, multiorgan dysfunction/failure



Viral replication

Disease pathogenesis:




Potential treatment:


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FIGURE 15.1 Pathogenesis and treatment across the COVID-19 spectrum . COVID-19, coronavirus disease 2019; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2. (Adapted from Gandhi RT. The multidimensional challenge of treating coronavirus disease 2019 (COVID-19): remdesivir is a foot in the door. Clin Infect Dis . 2021;73:e4175-e4178; Gandhi RT, Lynch JB, Del Rio C. Mild or moderate Covid-19. N Engl J Med . 2020;383:1757-1766.)

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