RESUMO
Long Covid - the disease encompassing the post-acute sequelae of SARS-CoV-2 (PASC) --affects millions of people around the world. Prevention of PASC is an urgent public health priority. In this work, we aimed to examine whether treatment with nirmatrelvir in the acute phase of COVID-19 is associated with reduced risk of post-acute sequelae. We used the healthcare databases of the US Department of Veterans Affairs to identify users of the health system who had a SARS-CoV-2 positive test between March 01, 2022 and June 30, 2022, were not hospitalized on the day of the positive test, had at least 1 risk factor for progression to severe COVID-19 illness and survived the first 30 days after SARS-CoV-2 diagnosis. We identify those who were treated with oral nirmatrelvir within 5 days after the positive test (n=9217) and those who received no COVID-19 antiviral or antibody treatment during the acute phase of SARS-CoV-2 infection (control group, n= 47,123). Inverse probability weighted survival models were used to estimate the effect of nirmatrelvir (versus control) on a prespecified panel of 12 post-acute COVID-19 outcomes and reported as hazard ratio (HR) and absolute risk reduction (ARR) in percentage at 90 days. Compared to the control group, treatment with nirmatrelvir was associated with reduced risk of PASC (HR 0.74 95% CI (0.69, 0.81), ARR 2.32 (1.73, 2.91)) including reduced risk of 10 of 12 post-acute sequelae in the cardiovascular system (dysrhythmia and ischemic heart disease), coagulation and hematologic disorders (deep vein thrombosis, and pulmonary embolism), fatigue, liver disease, acute kidney disease, muscle pain, neurocognitive impairment, and shortness of breath. Nirmatrelvir was also associated with reduced risk of post-acute death (HR 0.52 (0.35, 0.77), ARR 0.28 (0.14, 0.41)), and post-acute hospitalization (HR 0.70 (0.61, 0.80), ARR 1.09 (0.72, 1.46)). Nirmatrelvir was associated with reduced risk of PASC in people who were unvaccinated, vaccinated, and boosted, and in people with primary SARS-CoV-2 infection and reinfection. In sum, our results show that in people with SARS-CoV-2 infection who had at least 1 risk factor for progression to severe COVID-19 illness, treatment with nirmatrelvir within 5 days of a positive SARS-CoV-2 test was associated with reduced risk of PASC 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 reduces the risk of post-acute adverse health outcomes.
RESUMO
OBJECTIVE: Diurnal preference is an attribute reflecting whether people are alert and preferring to be active either early or late in the day. It also referred to as chronotype or morningness-eveningness trait. The PER3 genes have been known to influence diurnal preference. In this study, we have investigated the associations between the PER3 gene polymorphisms and diurnal preference in a healthy young population, controlling for the social and environmental confounding factors. METHODS: The participants in this experiment included 299 unrelated medical college students (M=191, F=108), with a mean age of 22.9 years. Diurnal preference was measured by a single administration of the 13-item Composite Scale for Morningness (CSM). Genotyping of the PER3 VNTR (rs57875989) was performed using polymerase chain reaction. A two-tailed alpha of 0.05 was chosen. RESULTS: The mean+/-SD score on the CSM scale for all subjects was 31.90+/-6.39. There was no significant difference in total CSM score between gender groups, although females showed a trend towards higher morningness score. Although PER3 5R/5R showed the tendency towards high CSM scores, there were no significant differences on CSM scores among genotypes and allele status of PER3 VNTR (rs57875989). CONCLUSIONS: We could not confirm that the PER3 VNTR is associated with diurnal preference in a Korean healthy young population. The future studies need to investigate the association between diurnal preference and other polymorphisms of PER3 gene in larger sample of Korean young healthy population.
