Application of weighted gene co-expression network and immune infiltration for explorations of key genes in the brain of elderly COVID-19 patients.

Introduction: Although many studies have demonstrated the existing neurological symptoms in COVID-19 patients, the mechanisms are not clear until now. This study aimed to figure out the critical molecular and immune infiltration situations in the brain of elderly COVID-19 patients. Methods: GSE188847 was used for the differential analysis, WGCNA, and immune infiltration analysis. We also performed GO, KEGG, GSEA, and GSVA for the enrich analysis. Results: 266 DEGs, obtained from the brain samples of COVID-19 and non-COVID-19 patients whose ages were over 70 years old, were identified. GO and KEGG analysis revealed the enrichment in synapse and neuroactive ligand-receptor interaction in COVID-19 patients. Further analysis found that asthma and immune system signal pathways were significant changes based on GSEA and GSVA. Immune infiltration analysis demonstrated the imbalance of CD8+ T cells, neutrophils, and HLA. The MEpurple module genes were the most significantly different relative to COVID-19. Finally, RPS29, S100A10, and TIMP1 were the critical genes attributed to the progress of brain damage. Conclusion: RPS29, S100A10, and TIMP1 were the critical genes in the brain pathology of COVID-19 in elderly patients. Our research has revealed a new mechanism and a potential therapeutic target.

Duration of viable virus shedding and polymerase chain reaction positivity of the SARS-CoV-2 Omicron variant in the upper respiratory tract: a systematic review and meta-analysis.

OBJECTIVES: To assess the duration of viable virus shedding and polymerase chain reaction (PCR) positivity of the SARS-CoV-2 Omicron variant in the upper respiratory tract. METHODS: We systematically searched PubMed, Cochrane, and Web of Science for original articles reporting the duration of viable virus shedding and PCR positivity of the SARS-CoV-2 Omicron variant in the upper respiratory tract from November 11, 2021 to December 11, 2022. This meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was registered with PROSPERO (CRD42022357349). We used the DerSimonian-Laird random-effects meta-analyses to obtain the pooled value and the 95% confidence intervals. RESULTS: We included 29 studies and 230,227 patients. The pooled duration of viable virus shedding of the SARS-CoV-2 Omicron variant in the upper respiratory tract was 5.16 days (95% CI: 4.18-6.14), and the average duration of PCR positivity was 10.82 days (95% CI: 10.23-11.42). The duration of viable virus shedding and PCR positivity of the SARS-CoV-2 Omicron variant in symptomatic patients was slightly higher than that in asymptomatic patients, but the difference was not significant (P >0.05). CONCLUSION: The current study improves our understanding of the status of the literature on the duration of viable virus shedding and PCR positivity of Omicron in the upper respiratory tract. Our findings have implications for pandemic control strategies and infection control measures.

Global Excess Mortality during COVID-19 Pandemic: A Systematic Review and Meta-Analysis.

BACKGROUND: Currently, reported COVID-19 deaths are inadequate to assess the impact of the pandemic on global excess mortality. All-cause excess mortality is a WHO-recommended index for assessing the death burden of COVID-19. However, the global excess mortality assessed by this index remains unclear. We aimed to assess the global excess mortality during the COVID-19 pandemic. METHODS: We searched PubMed, EMBASE, and Web of Science for studies published in English between 1 January 2020, and 21 May 2022. Cross-sectional and cohort studies that reported data about excess mortality during the pandemic were included. Two researchers independently searched the published studies, extracted data, and assessed quality. The Mantel-Haenszel random-effects method was adopted to estimate pooled risk difference (RD) and their 95% confidence intervals (CIs). RESULTS: A total of 79 countries from twenty studies were included. During the COVID-19 pandemic, of 2,228,109,318 individuals, 17,974,051 all-cause deaths were reported, and 15,498,145 deaths were expected. The pooled global excess mortality was 104.84 (95% CI 85.56-124.13) per 100,000. South America had the highest pooled excess mortality [134.02 (95% CI: 68.24-199.80) per 100,000], while Oceania had the lowest [-32.15 (95% CI: -60.53--3.77) per 100,000]. Developing countries had higher excess mortality [135.80 (95% CI: 107.83-163.76) per 100,000] than developed countries [68.08 (95% CI: 42.61-93.55) per 100,000]. Lower middle-income countries [133.45 (95% CI: 75.10-191.81) per 100,000] and upper-middle-income countries [149.88 (110.35-189.38) per 100,000] had higher excess mortality than high-income countries [75.54 (95% CI: 53.44-97.64) per 100,000]. Males had higher excess mortality [130.10 (95% CI: 94.15-166.05) per 100,000] than females [102.16 (95% CI: 85.76-118.56) per 100,000]. The population aged ≥ 60 years had the highest excess mortality [781.74 (95% CI: 626.24-937.24) per 100,000]. CONCLUSIONS: The pooled global excess mortality was 104.84 deaths per 100,000, and the number of reported all-cause deaths was higher than expected deaths during the global COVID-19 pandemic. In South America, developing and middle-income countries, male populations, and individuals aged ≥ 60 years had a heavier excess mortality burden.

Incubation Period of COVID-19 Caused by Unique SARS-CoV-2 Strains: A Systematic Review and Meta-analysis.

Importance: Several studies were conducted to estimate the average incubation period of COVID-19; however, the incubation period of COVID-19 caused by different SARS-CoV-2 variants is not well described. Objective: To systematically assess the incubation period of COVID-19 and the incubation periods of COVID-19 caused by different SARS-CoV-2 variants in published studies. Data Sources: PubMed, EMBASE, and ScienceDirect were searched between December 1, 2019, and February 10, 2022. Study Selection: Original studies of the incubation period of COVID-19, defined as the time from infection to the onset of signs and symptoms. Data Extraction and Synthesis: Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline, 3 reviewers independently extracted the data from the eligible studies in March 2022. The parameters, or sufficient information to facilitate calculation of those values, were derived from random-effects meta-analysis. Main Outcomes and Measures: The mean estimate of the incubation period and different SARS-CoV-2 strains. Results: A total of 142 studies with 8112 patients were included. The pooled incubation period was 6.57 days (95% CI, 6.26-6.88) and ranged from 1.80 to 18.87 days. The incubation period of COVID-19 caused by the Alpha, Beta, Delta, and Omicron variants were reported in 1 study (with 6374 patients), 1 study (10 patients), 6 studies (2368 patients) and 5 studies (829 patients), respectively. The mean incubation period of COVID-19 was 5.00 days (95% CI, 4.94-5.06 days) for cases caused by the Alpha variant, 4.50 days (95% CI, 1.83-7.17 days) for the Beta variant, 4.41 days (95% CI, 3.76-5.05 days) for the Delta variant, and 3.42 days (95% CI, 2.88-3.96 days) for the Omicron variant. The mean incubation was 7.43 days (95% CI, 5.75-9.11 days) among older patients (ie, aged over 60 years old), 8.82 days (95% CI, 8.19-9.45 days) among infected children (ages 18 years or younger), 6.99 days (95% CI, 6.07-7.92 days) among patients with nonsevere illness, and 6.69 days (95% CI, 4.53-8.85 days) among patients with severe illness. Conclusions and Relevance: The findings of this study suggest that SARS-CoV-2 has evolved and mutated continuously throughout the COVID-19 pandemic, producing variants with different enhanced transmission and virulence. Identifying the incubation period of different variants is a key factor in determining the isolation period.