The COVID-19 Textbook

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CHAPTER 15 • Treatment of COVID-19 in Adults

COVID-19 research given the magnitude of the problem, with streamlining and acceleration of research to a pace that exceeded any previous era. The urgent need to address the COVID-19 crisis and public pressure on politicians, clinicians, researchers, health officials, and others also resulted in early or misguided therapeutic decisions that were based on preliminary and incomplete data or invalid extrapolation of data. For instance, many people, including patients and their relatives, caregivers, and public figures, were vocal about po tential benefits in COVID-19 of drugs that had been approved for other indications. Examples of medications that were recommended in the absence of sufficient evidence are the human immuno deficiency virus (HIV) medication lopinavir/ritonavir, the antiparasitic treatment ivermectin, and the antidepressant fluvoxamine. Other medications that temporarily became standard of care for the treatment of COVID-19 in some areas were azithromycin and hydroxychloroquine. All these medications were later found to be ineffective for COVID-19 in large randomized clinical trials. Use of drugs with insufficiently proven efficacy against COVID-19 not only exposes patients to the risk of adverse events but also has the potential to impede clinical research. Emergency use authorization (EUA) of hydroxychloroquine for the treatment of COVID-19, which was eventually withdrawn, may have dissuaded patients from participation in placebo-controlled trials. Moreover, supply short ages of hydroxychloroquine limited access for patients with rheumatologic illness and some in the public ingested high doses of ivermectin from supplies unintended for human consumption. It was only when well-conducted, randomized controlled trials started yielding results in May 2020 that progress was made. In the United States, the Adaptive COVID-19 Treatment Trial (ACTT) evaluated the use of remdesivir, an intravenous antiviral originally developed for Ebola, in hospitalized patients with COVID-19 pneumonia. Preliminary results demonstrated that rem desivir significantly shortened the time to recovery, which, in the absence of any other therapeutic options, led to swift EUA by the U.S. Food and Drug Administration (FDA), and recommen dations to use remdesivir to treat hospitalized patients with severe COVID-19 followed almost instantaneously. Soon thereafter, the RECOVERY trial in the United Kingdom demonstrated that dexamethasone, which decreases inflammation, reduced mortality in hospitalized patients requiring oxygen supplementation. These two early randomized studies set the stage for future trials of novel and repurposed agents. Ultimately, the lesson of COVID-19 therapeutics is a reminder of what we learned during the early days of HIV and, more recently, during Ebola. Not only can randomized clinical trials be performed during a pandemic, they must be done during a pandemic. 1,2 For in the face of a new infectious threat, we do not know what does and does not work, and randomized trials are the most definitive method for answering critical therapeutic questions. CLINICAL MANAGEMENT OF COVID-19 Management of COVID-19 has evolved considerably since the illness was first recognized in late 2019. 3 Various medical organizations have published guidelines for the management of individuals with COVID-19. Given the rapid changes in clinical management, it is important to consult the latest guidelines when caring for patients. 4 Most people with COVID-19 experience mild-to-moderate disease that does not require hos pitalization. However, moderate disease, defined as clinical or radiographic evidence of lower re spiratory tract infection in the absence of hypoxemia, requires close monitoring because of the risk of progression, as does severe disease, which is characterized by dyspnea, hypoxemia, or infiltrates involving more than 50% of the lungs. In severe COVID-19, hospitalization is typically indicated (Table 15.1). Initial Considerations Identifying patients who are at high risk for progression to severe COVID-19 is a priority, and research on predictors, including identifying biomarkers, is ongoing. Known risk factors for severe COVID-19 include older age, male sex, obesity, many forms of immunosuppression (including im munosuppressive medications), and chronic medical conditions like lung disease, cardiovascular dis ease, chronic kidney or liver disease, diabetes mellitus, and cancer. 5-9 Patients with these and other

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