The effect of nirmatrelvir‐ritonavir on the long‐term risk of neuropsychiatric sequelae following COVID‐19

Abstract

The retrospective cohort was conducted to assess the effect of nirmatrelvir-ritonavir (NMV-r) on the long-term risk of neuropsychiatric sequela following COVID-19.TriNetX research network was used to identify nonhospitalized adult patients who tested positive for severe acute respiratory syndrome coronavirus 2 infection or were diagnosed with COVID-19 between March 1, 2020 and July 1, 2022. Further propensity score matching method was used to create two matched cohorts with and without receiving NMV-r. The primary outcome was the incidence of neuropsychiatric sequela within a 90-day to 1-year period following a diagnosis of COVID-19. After screening 119 494 527 electronic health records, two matched cohorts of each 27 194 patients were identified. During the follow-up period, the NMV-r group demonstrated a reduced risk of any neuropsychiatric sequelae compared to the control group (odds ratio [OR], 0.634; 95% confidence interval [CI], 0.604−0.667). In comparison with the control group, the patient treated with NMV-r exhibited a markedly diminished risk of developing neurocognitive sequela (OR, 0.377; 95% CI, 0.325−0.439) and psychiatric sequela (OR, 0.629; 95% CI, 0.593−0.666). In addition, patients treated with NMV-r had a significantly reduced risk of developing dementia (OR, 0.365; 95% CI, 0.255−0.522), depression (OR, 0.555; 95% CI, 0.503−0.612), insomnia (OR, 0.582; 95% CI, 0.508−0.668) and anxiety disorder (OR, 0.645 95% CI, 0.600−0.692). Moreover, the beneficial effect of NMV-r on the neuropsychiatric sequelae was observed across further subgroup analyses. Among nonhospitalized COVID-19 patients, who at risk of disease progression, the use of NMV-r is associated with a reduction in the long-term risk of neuropsychiatric sequela, including dementia, depression, insomnia and anxiety disorder. It may be necessary to re-evaluate the use of NMV-r, as a preventive measure to reduce the risk of severe acute disease and post-acute adverse mental health outcomes.

Effectiveness of Antiviral Therapy on Long COVID: A Systematic Review and Meta-Analysis

“…In total, these studies included a sample size of 3,352,235. Three studies were retrospective cohort studies, and two large-scale studies used 1:1 propensity score matching [18,19]. The number of participants ranged from 649 to 2,361,239, and the mean age ranged from 55.9 (±16.7) to 69.8 (±11.7) years [17][18][19]21].…”

“…The specific details of each study are presented in Table 1 [9,[17][18][19][20][21]. The studies were conducted in four countries (the Netherlands, Italy, Taiwan, and the United States), with two studies investigating a global health collaborative clinical research platform called TriNetX [18,19] and the other two investigating the US Department of Veterans Affairs healthcare database [20,21]. In total, these studies included a sample size of 3,352,235 Three studies were retrospective cohort studies, and two large-scale studies used 1:1 pro pensity score matching [18,19].…”

“…In total, these studies included a sample size of 3,352,235 Three studies were retrospective cohort studies, and two large-scale studies used 1:1 pro pensity score matching [18,19]. The number of participants ranged from 649 to 2,361,239 and the mean age ranged from 55.9 (±16.7) to 69.8 (±11.7) years [17][18][19]21]. Most studies involved individuals 18 years of age or older who tested positive for SARS-CoV-2.…”

“…All six studies compared patients receiving antiviral treatment with those withou antiviral treatment: two studies with nirmatrelvir/ritonavir [18][19][20], one with remdesivir [9], one with molnupiravir [21], and one with any antiviral agent, including nirma trelvir/ritonavir, molnupiravir, or remdesivir [17]. All six studies compared patients receiving antiviral treatment with those without antiviral treatment: two studies with nirmatrelvir/ritonavir [18][19][20], one with remdesivir [9], one with molnupiravir [21], and one with any antiviral agent, including nirmatrelvir/ritonavir, molnupiravir, or remdesivir [17].…”

“…The follow-up period in the six studies ranged from 1 to 12 months [17,19]. The definition of PASC varied considerably among studies but was mostly consistent with the inclusion of any systemic symptoms (cardiovascular, coagulation and hematological, fatigue and malaise, gastrointestinal, kidney, musculoskeletal, metabolic, neurologic, and pulmonary).…”