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Nirmatrelvir & Risk of Post-COVID-19 Condition

In a cohort study of people with 1 or more risk factors for progression to severe COVID-19, post-COVID-19 condition (PCC) occurred less often among those treated with nirmatrelvir within 5 days of a positive SARS-CoV-2 test. The relationship was present among the mostly male participants in this VA study regardless of vaccination status and history of prior infection. “The totality of findings suggests that treatment with nirmatrelvir during the acute phase of COVID-19 may reduce the risk of post–acute adverse health outcomes,” the investigators conclude.

Participants were patients in VA health care databases who had a SARS-CoV-2 positive test result between Jan. 3, 2022, and Dec. 31, 2022, who were not hospitalized on the day of the positive test result, who had at least 1 risk factor for progression to severe COVID-19 illness, and who had survived the first 30 days after SARS-CoV-2 diagnosis. The cohort group comprised 35,717 patients treated with oral nirmatrelvir within 5 days after the positive test; the control group was 246,076 patients who received no COVID-19 antiviral or antibody treatment during the acute phase of SARS-CoV-2 infection.

Using inverse probability-weighted survival models to estimate the association of nirmatrelvir (vs control) with post–acute death, post–acute hospitalization, and a prespecified panel of 13 post–acute COVID-19 sequelae (components of PCC), the researchers found these relative risks (RRs), hazard ratios (HRs), and absolute scale as absolute risk reduction in percentage at 180 days (ARR): “A total of 281,793 patients (mean [SD] age, 61.99 [14.96]; 242,383 [86.01%] male) who had a positive SARS-CoV-2 test result and had at least 1 risk factor for progression to severe COVID-19 illness were studied.… Compared with the control group, nirmatrelvir was associated with reduced risk of PCC (RR, 0.74; 95% CI, 0.72-0.77; ARR, 4.51%; 95% CI, 4.01-4.99), including reduced risk of 10 of 13 post–acute sequelae (components of PCC) in the cardiovascular system (dysrhythmia and ischemic heart disease), coagulation and hematologic disorders (pulmonary embolism and deep vein thrombosis), fatigue and malaise, acute kidney disease, muscle pain, neurologic system (neurocognitive impairment and dysautonomia), and shortness of breath. Nirmatrelvir was also associated with reduced risk of post–acute death (HR, 0.53; 95% CI, 0.46-0.61); ARR, 0.65%; 95% CI, 0.54-0.77), and post–acute hospitalization (HR, 0.76; 95% CI, 0.73-0.80; ARR, 1.72%; 95% CI, 1.42-2.01). Nirmatrelvir was associated with reduced risk of PCC in people who were unvaccinated, vaccinated, and boosted, and in people with primary SARS-CoV-2 infection and reinfection.”

Source: JAMA Internal Medicine