The COVID-19 Textbook


SECTION 5 • Medical Response

TABLE 15.2 Tiers and risk groups in the National Institutes of Health COVID-19 treatment guidelines as of January 2023 Tier Risk Group 1 • Immunocompromised and not expected to mount an adequate response to COVID-19 vaccination or infection (regardless of vaccination status) • Unvaccinated individuals at the highest risk of severe COVID-19 ( ≥ 75 or ≥ 65 yr with additional risk factors) 2 • Unvaccinated at risk not included in tier 1 and at risk of severe disease (anyone ≥ 65 yr and anyone < 65 yr but with clinical risk factors) 3 • Vaccinated at risk for severe disease ( ≥ 65 or < 65 yr with clinical risk factors) COVID-19, coronavirus disease 2019. Adapted from the National Institutes of Health. COVID-19 Treatment Guidelines . Accessed January 27, 2023. https://www​; Panel C-TG. Coronavirus 2019 (COVID-19) Treatment Guidelines . National Institutes of Health. Several anti-SARS-CoV-2 monoclonal antibody therapeutics were shown to reduce the risk for progression to severe COVID-19. However, these monoclonal antibodies were found to have reduced activity against newer SARS-CoV-2 variants, leading to reconsideration of their use. The anti-SARS-CoV-2 monoclonal antibodies target the viral spike protein responsible for angiotensin-­ converting enzyme 2 (ACE2) binding, and spike appears to have the strongest evolutionary pressure to acquire immune-evasive mutations. By contrast, ritonavir-boosted nirmatrelvir (targeting protease), These medications are currently reserved for patients at high risk for progression to severe dis ease who have recently developed signs and symptoms of COVID-19. 14 However, the criteria for treatment are likely to evolve as additional research informs use of these and other medications. Not all patients qualify for the same medications (depending on regulatory agency authorization), and some individuals have contraindications to certain therapies, for example, those who must re ceive concomitant medications that have significant interactions with the ritonavir component of ritonavir-boosted nirmatrelvir. The National Institutes of Health (NIH) COVID-19 Treatment Guideline Panel has priori tized different risk groups to facilitate allocation of treatments to patients who are most likely to benefit and to inform triage decisions when drug supplies or ability to administer agents is limited (Table 15.2). The tiers and risk factors may be revised with changing virology and epidemiology of COVID-19 and further understanding of risk factors. For example, underlying medical conditions that are considered to be associated with higher risk for severe COVID-19 have changed over time, hence it is recommended to refer to up-to-date, current information like the one provided by the Centers for Disease Control and Prevention in the United States. 14 SARS-CoV-2 Antivirals Antiviral drugs inhibit SARS-CoV-2 replication at various stages of the virus life cycle and mecha nisms differ among antiviral agents. Several drugs that were initially proposed to be antivirals against SARS-CoV-2 did not show efficacy when studied in large, well-conducted, and randomized con trolled trials, including lopinavir/ritonavir, hydroxychloroquine, azithromycin, ivermectin, fluvox amine, and others. Of the many drugs that have been evaluated, several agents demonstrated efficacy in phase III randomized clinical trials and have now been approved or authorized for use in the United States. Of note, the trials that led to approval or authorizations were performed in unvacci nated individuals who were at high risk for progression and the initial studies precede the Omicron era. In the EPIC-HR 16 , PINETREE 17 and MOVe OUT 15 trials, treatment with ritonavir-boosted nirmatrelvir, remdesivir, and molnupiravir was associated with relative risk reduction of developing severe COVID-19 of 88%, 87% and 30%, respectively. This translated into a number needed to treat of 18, 22, and 35, respectively 18 . Although ritonavir-boosted nirmatrelvir and remdesivir appear to be similarly efficacious (reduction of hospitalization or death by almost 90% in their study popu lations), the efficacy of molnupiravir appears to be substantially lower.

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