The COVID-19 Textbook


SECTION 5 • Medical Response

scientists have expressed concern that, based on its mechanism of action, molnupiravir may accel erate the development of mutations that lead to new variants; this concern is heightened in patients who are immunosuppressed and have persistent SARS-CoV-2 replication. Anti-SARS-CoV-2 Monoclonal Antibodies Besides the small-molecule drugs described earlier, monoclonal antibodies against the SARS-CoV-2 spike protein have been used for the treatment of COVID-19 in high-risk nonhospitalized patients. These antibodies are highly specific, which comes at the cost of a relatively low threshold for re sistance. Initial hopes that the low mutation rate of coronaviruses in comparison to other viruses (like influenza virus, hepatitis C virus, HIV) would largely prevent development of drug resistance were dashed by the rapid appearance of mutations in spike that led to loss of neutralization by the monoclonal antibodies. The anticipated resistance of circulating variants led the FDA to withdraw authorizations for the treatment of COVID-19 with bamlanivimab, bamlanivimab plus etesevimab, casirivimab plus imdevimab, sotrovimab, and bebtelovimab. COVID-19 Prophylaxis Prophylaxis of COVID-19 with antiviral medications has been studied. The anti-SARS-CoV-2 monoclonal antibody combination tixagevimab plus cilgavimab was found to prevent symptomatic COVID-19 when given as pre-exposure prophylaxis and was authorized for use in people who could not be vaccinated (eg, because of reactions to the vaccine) or were expected to have an impaired response to vaccination because of being immunosuppressed or taking immunosuppressive medi cations. The circulating Omicron subvariants that emerged in late 2022 are not anticipated to be susceptible to tixagevimab plus cilgavimab and it is therefore no longer authorized for use in the United States. Pharmacologic Treatment Options for Hospitalized Patients With COVID-19 Hospitalized patients are more likely to be advanced in the course of the disease, are often beyond the phase of peak viral replication, and have a higher degree of immune activation and inflammation. This recognition was the basis for evaluating anti-inflammatory and immunomodulatory strategies in ad dition to or instead of antiviral therapies. Inflammation may also trigger thrombosis, which has led to recommendations that all patients hospitalized with COVID-19 receive prophylactic doses of anticoagu lation and that some receive therapeutic anticoagulation if there are no contraindications. 4 Treatment op tions for hospitalized patients are further stratified by severity of respiratory insufficiency (Table 15.2). 4 Dexamethasone was shown in the RECOVERY trial to reduce the risk of death in hospitalized patients who require oxygen supplementation but is potentially harmful in those not requiring ox ygen. 20 Other immunomodulatory medications that have been evaluated and demonstrated clinical benefit in hospitalized patients include baricitinib, 21 a janus kinase (JAK) inhibitor used to treat rheu matoid arthritis, and tocilizumab, a monoclonal antibody against the interleukin 6 (IL-6) receptor. IL-6 is an important proinflammatory cytokine and was found to be significantly elevated in patients hospitalized with COVID-19. Of note, immunosuppression caused by these agents can potentially lead to complications like reactivation of latent infections (eg, Strongyloides ); patients with known latent infection or who are from endemic areas may benefit from preemptive anti-infective therapy. Direct-acting antivirals for hospitalized patients include intravenous remdesivir. In 2020, only a few months into the COVID-19 pandemic, the ACTT-1 study demonstrated remdesivir hastened clinical recovery in hospitalized patients with COVID-19 pneumonia (median 10 days with rem desivir and 15 days with placebo) with a trend toward lower mortality. 18 The initial results of the World Health Organization (WHO)-sponsored Solidarity study suggested remdesivir did not lower mortality but in the final analysis, remdesivir use was associated with a reduction in mortality in patients who were not yet ventilated (albeit with no effect on mortality in those who were already ventilated). 22 Remdesivir should be given as early as possible to maximize the therapeutic benefit. Hospitalized Patient With No Supplemental Oxygen Requirement Patients who do not require supplemental oxygen may be hospitalized because of reasons other than respiratory insufficiency from COVID-19. For example, given the high incidence of COVID-19 over the course of the pandemic, many people test positive for SARS-CoV-2 incidentally when

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