Soluble uric acid inhibits ß2 integrin-mediated neutrophil recruitment in innate immunity.

Neutrophils are key players during host defense and sterile inflammation. Neutrophil dysfunction is a characteristic feature of the acquired immunodeficiency during kidney disease. We speculated that the impaired renal clearance of the intrinsic purine metabolite soluble uric acid (sUA) may account for neutrophil dysfunction. Indeed, hyperuricemia (HU, serum UA of 9-12 mg/dL) related or unrelated to kidney dysfunction significantly diminished neutrophil adhesion and extravasation in mice with crystal- and coronavirus-related sterile inflammation using intravital microscopy and an air pouch model. This impaired neutrophil recruitment was partially reversible by depleting UA with rasburicase. We validated these findings in vitro using either neutrophils or serum from patients with kidney dysfunction-related HU with or without UA depletion, which partially normalized the defective migration of neutrophils. Mechanistically, sUA impaired ß2 integrin activity and internalization/recycling by regulating intracellular pH and cytoskeletal dynamics, physiological processes that are known to alter the migratory and phagocytic capability of neutrophils. This effect was fully reversible by blocking intracellular uptake of sUA via urate transporters. In contrast, sUA had no effect on neutrophil extracellular trap formation in neutrophils from healthy subjects or patients with kidney dysfunction. Our results identify an unexpected immunoregulatory role of the intrinsic purine metabolite sUA, which contrasts the well-known immunostimulatory effects of crystalline UA. Specifically targeting UA may help to overcome certain forms of immunodeficiency, for example in kidney dysfunction, but may enhance sterile forms of inflammation.

Global Percentage of Asymptomatic SARS-CoV-2 Infections Among the Tested Population and Individuals With Confirmed COVID-19 Diagnosis: A Systematic Review and Meta-analysis.

Importance: Asymptomatic infections are potential sources of transmission for COVID-19. Objective: To evaluate the percentage of asymptomatic infections among individuals undergoing testing (tested population) and those with confirmed COVID-19 (confirmed population). Data Sources: PubMed, EMBASE, and ScienceDirect were searched on February 4, 2021. Study Selection: Cross-sectional studies, cohort studies, case series studies, and case series on transmission reporting the number of asymptomatic infections among the tested and confirmed COVID-19 populations that were published in Chinese or English were included. Data Extraction and Synthesis: This meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Random-effects models were used to estimate the pooled percentage and its 95% CI. Three researchers performed the data extraction independently. Main Outcomes and Measures: The percentage of asymptomatic infections among the tested and confirmed populations. Results: Ninety-five unique eligible studies were included, covering 29 776 306 individuals undergoing testing. The pooled percentage of asymptomatic infections among the tested population was 0.25% (95% CI, 0.23%-0.27%), which was higher in nursing home residents or staff (4.52% [95% CI, 4.15%-4.89%]), air or cruise travelers (2.02% [95% CI, 1.66%-2.38%]), and pregnant women (2.34% [95% CI, 1.89%-2.78%]). The pooled percentage of asymptomatic infections among the confirmed population was 40.50% (95% CI, 33.50%-47.50%), which was higher in pregnant women (54.11% [95% CI, 39.16%-69.05%]), air or cruise travelers (52.91% [95% CI, 36.08%-69.73%]), and nursing home residents or staff (47.53% [95% CI, 36.36%-58.70%]). Conclusions and Relevance: In this meta-analysis of the percentage of asymptomatic SARS-CoV-2 infections among populations tested for and with confirmed COVID-19, the pooled percentage of asymptomatic infections was 0.25% among the tested population and 40.50% among the confirmed population. The high percentage of asymptomatic infections highlights the potential transmission risk of asymptomatic infections in communities.

Effects of temperature and humidity on the daily new cases and new deaths of COVID-19 in 166 countries.

The coronavirus disease 2019 (COVID-19) pandemic is the defining global health crisis of our time and the greatest challenge facing the world. Meteorological parameters are reportedly crucial factors affecting respiratory infectious disease epidemics; however, the effect of meteorological parameters on COVID-19 remains controversial. This study investigated the effects of temperature and relative humidity on daily new cases and daily new deaths of COVID-19, which has useful implications for policymakers and the public. Daily data on meteorological conditions, new cases and new deaths of COVID-19 were collected for 166 countries (excluding China) as of March 27, 2020. Log-linear generalized additive model was used to analyze the effects of temperature and relative humidity on daily new cases and daily new deaths of COVID-19, with potential confounders controlled for, including wind speed, median age of the national population, Global Health Security Index, Human Development Index and population density. Our findings revealed that temperature and relative humidity were both negatively related to daily new cases and deaths. A 1 °C increase in temperature was associated with a 3.08% (95% CI: 1.53%, 4.63%) reduction in daily new cases and a 1.19% (95% CI: 0.44%, 1.95%) reduction in daily new deaths, whereas a 1% increase in relative humidity was associated with a 0.85% (95% CI: 0.51%, 1.19%) reduction in daily new cases and a 0.51% (95% CI: 0.34%, 0.67%) reduction in daily new deaths. The results remained robust when different lag structures and the sensitivity analysis were used. These findings provide preliminary evidence that the COVID-19 pandemic may be partially suppressed with temperature and humidity increases. However, active measures must be taken to control the source of infection, block transmission and prevent further spread of COVID-19.