Nirmatrelvir/Ritonavir for hemodialysis patients with COVID-19.

Background: Hemodialysis patients have a high risk of severe/critical COVID-19 and related high mortality, but nirmatrelvir/ritonavir is not recommended for hemodialysis patients with COVID-19 infection because of lack of evidence of safety. Objectives: Our study aims to evaluate the minimum plasma concentration (Cmin) of nirmatrelvir and its safety of different doses of nirmatrelvir/ritonavir in hemodialysis patients with mild COVID-19. Method: This was a prospective, two step, nonrandomized, open-label study. Participants were treated with nirmatrelvir 150 mg or 300 mg once a day (another 75 mg or 150 mg supplied after hemodialysis) and ritonavir 100 mg twice daily for 5 days, respectively. The primary outcome was the safety of nirmatrelvir/ritonavir, including the Cmin of nirmatrelvir and the number of adverse events (AE). The secondary outcome was the time of viral elimination in hemodialysis patients. Results: Adverse events were happened in 3 and 7 participants in the step 1 and step 2 group, respectively (p = 0.025). Among them, 2 and 6 participants were identified as drug-related adverse events (p = 0.054). No SAE or liver function damage happened. The Cmin of nirmatrelvir in step 1 and step 2 group were 5,294.65 ± 2,370.59 ng/mL and 7,675.67 ± 2,745.22 ng/mL (p = 0.125). The Cmin of the control group was 2,274.10 ± 1,347.25 ng/mL (p = 0.001 compared to step 2 and p = 0.059 compared to step 1). Compared to hemodialysis patients without nirmatrelvir/ritonavir, there were no statistical differences in overall viral elimination time (p = 0.232). Conclusion: In our study, two doses of nirmatrelvir/ritonavir appeared to be excessive for hemodialysis patients. Although all of the patients tolerated 5-day administration, nearly half of the patients experienced drug-related adverse events. In addition, the medication group did not show a significant advantage in the time of viral elimination.

Adaptive immune dysfunction in patients with COVID-19 and impaired kidney function during the omicron surge.

BACKGROUND: Little is known about the characteristics of lymphocyte subsets and the association with patient outcomes in COVID-19 with and without impaired kidney function. METHODS: Lymphocyte subsets were compared in COVID-19 patients with or without kidney dysfunction. The primary outcome was a composite of all-cause mortality or intensive care unit admission. Secondary outcomes included duration of viral shedding, length of hospital stay, and acute kidney injury. RESULTS: Lymphocyte subset cell counts demonstrated the lowest in patients with severe/critical COVID-19 and kidney dysfunction. Among all lymphocyte subset parameters, Th cell count was the most significant indicator for outcomes. ROC of the combined model of Th cell count and eGFR presented better predictive value than that of the other parameters. Th cell count <394.5 cells/µl and eGFR <87.5 ml/min/1·73m2 were independently associated with poor outcomes. The propensity score matching analysis revealed consistent results. CONCLUSIONS: Reduced Th cell count and eGFR may be applied as promising predictive indicators for identifying COVID-19 patients with high risk and poor outcomes.

Type 2 diabetes attributable to PM2.5: A global burden study from 1990 to 2019.

BACKGROUND: Long-term exposure to fine particulate matter (PM2.5) is associated with an increased risk of type 2 diabetes (T2D). However, limited data on trends in the global burden of T2D attributed to PM2.5, particularly in different regions by social-economic levels. We evaluated the spatio-temporal changes in the disease burden of T2D attributed to PM2.5 from 1990 to 2019 in 204 countries and regions with different socio-demographic indexes (SDI). METHODS: This is a retrospective analysis with data from the Global Burden of Disease Study 2019 (GBD2019) database. The burden of T2D attributed to PM2.5, age-standardized mortality rate (ASMR) and age-standardized disability-adjusted life year rate (ASDR) were estimated according to sex, age, nationality and SDI. The annual percentage change (APCs) and the average annual percentage change (AAPCs) were calculated by using the Joinpoint model to evaluate the changing trend of ASMR and ASDR attributed to PM2.5 from 1990 to 2019. The Gaussian process regression model was used to estimate the relationship of SDI with ASMR and ASDR. RESULTS: Overall, the global burden of T2D attributable to PM2.5 increased significantly since 1990, particularly in the elderly, men, Africa, Asia and low-middle SDI regions. The ASMR and ASDR of T2D attributable to PM2.5 in 2019 were 2.47 (95% CI: 1.71, 3.24) per 100,000 population and 108.98 (95% CI: 74.06, 147.23) per 100,000 population, respectively. From 1990 to 2019, the global ASMR and ASDR of T2D attributed to T2D increased by 57.32% and 86.75%, respectively. The global AAPCs of ASMR and ASDR were 1.57 (95% CI: 1.46, 1.68) and 2.17 (95% CI: 2.02, 2.32), respectively. Declining trends were observed in North America, South America, Europe, Australia, and other regions with high SDI. CONCLUSIONS: Over this 30-years study, the global T2D burden attributable to PM2.5 has increased particularly in regions with low-middle SDI. PM2.5 remains a great concern on the global burden of diabetes.

Coronavirus disease 2019 (COVID-19): current status and future perspectives.

Coronavirus disease 2019 (COVID-19) originated in the city of Wuhan, Hubei Province, Central China, and has spread quickly to 72 countries to date. COVID-19 is caused by a novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [previously provisionally known as 2019 novel coronavirus (2019-nCoV)]. At present, the newly identified SARS-CoV-2 has caused a large number of deaths with tens of thousands of confirmed cases worldwide, posing a serious threat to public health. However, there are no clinically approved vaccines or specific therapeutic drugs available for COVID-19. Intensive research on the newly emerged SARS-CoV-2 is urgently needed to elucidate the pathogenic mechanisms and epidemiological characteristics and to identify potential drug targets, which will contribute to the development of effective prevention and treatment strategies. Hence, this review will focus on recent progress regarding the structure of SARS-CoV-2 and the characteristics of COVID-19, such as the aetiology, pathogenesis and epidemiological characteristics.