Investigation of bacterial and fungal population structure on environmental surfaces of three medical institutions during the COVID-19 pandemic.

Objectives: To evaluate the population structure of environmental bacteria and fungi in three different types of medical institutions and the potential risks due to antibiotic resistance during the coronavirus disease 2019 (COVID-19) pandemic. Methods: One hundred twenty-six environmental surface samples were collected from three medical institutions during the COVID-19 pandemic. A total of 6,093 and 13,514 representative sequences of 16S and ITS ribosomal RNA (rRNA) were obtained by amplicon sequencing analysis. The functional prediction was performed using the Phylogenetic Investigation of Communities by Reconstruction of Unobserved States tool based on the Greengenes database and the FAPROTAX database. Results: On environmental surfaces in three medical institutions during the COVID-19 pandemic, Firmicutes (51.6%) and Bacteroidetes (25%) were the dominant bacteria, while Ascomycota (39.4%) and Basidiomycota (14.2%) were the dominant fungi. A number of potential bacterial and fungal pathogens were successfully identified by the metagenomic approach. Furthermore, compared with the bacterial results, the fungi showed a generally closer Bray Curtis distance between samples. The overall ratio of Gram-negative bacteria to Gram-positive bacteria was about 3:7. The proportion of stress-tolerant bacteria in medical institutions A, B and C reached 88.9, 93.0 and 93.8%, respectively. Anaerobic bacteria accounted for 39.6% in outdoor environments, 77.7% in public areas, 87.9% in inpatient areas and 79.6% in restricted areas. Finally, the ß-Lactam resistance pathway and polymyxin resistance pathway were revealed through functional prediction. Conclusion: We described the microbial population structure changes in three different types of medical institutions using the metagenomic approach during the COVID-19 pandemic. We found that the disinfection measures performed by three healthcare facilities may be effective on the "ESKAPE" pathogens, but less effective on fungal pathogens. Moreover, emphasis should be given to the prevention and control of ß-lactam and polymyxin antibiotics resistance bacteria during the COVID-19 pandemic.

Pre-existing interstitial lung disease in patients with coronavirus disease 2019: A meta-analysis.

BACKGROUND: The impact of pre-existing interstitial lung disease (ILD) on the severity and mortality of COVID-19 remains largely unknown. The purpose of this meta-analysis was to investigate the prevalence of ILD among patients with COVID-19 and figure out the relationship between ILD and the poor clinical outcomes of COVID-19. METHODS: A systematic literature search was conducted in the PubMed, EMBASE, Web of Science and MedRxiv Database from 1 January 2020 to 26 May 2021. RESULTS: 15 studies with 135,263 COVID-19 patients were included for analysis of ILD prevalence. The pooled prevalence of comorbid ILD in patients with COVID-19 was 1.4% (95% CI, 1.1%-1.8%, I2 = 91%) with significant between-study heterogeneity. Moreover, the prevalence of ILD in non-survival patients with COVID-19 was 2.728-folds higher than that in corresponding survival patients (RR = 2.728, 95% CI 1.162-6.408, I2 = 54%, p = 0.021). Additionally, 2-3 studies were included for comparison analysis of clinical outcome between COVID-19 patients with and without ILD. The results showed that the mortality of COVID-19 patients with ILD was remarkably elevated compared with patients without ILD (RR = 2.454, 95% CI 1.111-5.421, I2 = 87%, p = 0.026). Meanwhile, the pooled RR of ICU admission for ILD vs. non-ILD cases with COVID-19 was 3.064 (95% CI 1.889-4.972, I2 = 0, p < 0.0001). No significant difference in utilizing rate of mechanical ventilation was observed between COVID-19 patients with and without ILD. CONCLUSIONS: There is great variability in ILD prevalence among patients with COVID-19 across the globe. Pre-existing ILD is associated with higher severity and mortality of COVID-19.

A Glimpse into the Diverse Cellular Immunity against SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific cellular immune response has been shown to play a critical role in preventing severe illness or death in patients infected with SARS-CoV-2 or its variants. Given the multiple T-cell epitopes shared by wild-type virus and its variants, we hypothesized that vaccines that target multiple T-cell epitopes of SARS-CoV-2 may provide a "universal protection" against the wild-type virus as well as its variants, even the heavily mutated ones. To test this, we assessed SARS-CoV-2-specific T-cell precursors in healthy individuals using overlapping peptide pools of SARS-CoV-2 structural and functional proteins, including spike (S), membrane (M), envelope (E), nucleocapsid (N), and protease (P) proteins as target antigens. Diverse T-cell precursor frequencies specific to these viral antigens were detected in healthy individuals, including high, medium, low, and no responders. This was further confirmed by efficient induction of anti-SARS-CoV-2 T-cell immune responses using ex vivo dendritic cell (DC)/T cell coculture. The results demonstrated T-cell responses consistent with the precursor frequencies of each of the individuals tested. Importantly, the combination of all five viral peptide pools induced the strongest cellular immune response, and further, after a DC-peptides re-stimulation, even the no responders developed an increased anti-viral T-cell response. These analyses recapitulate the presence of a broad anti-SARS-CoV-2 cellular immunity even in an immune naïve population, which could be enhanced by antigen presenting cells presenting the overlapping antigenic peptides. Given the critical role of cellular immunity in COVID-19 protection, these results have important implications for vaccine design and immunotherapy in fighting SARS-CoV-2 and its variants.

Respiratory supports of COVID-19 patients in intensive care unit: A systematic review.

INTRODUCTION: We aimed to describe the respiratory supports and determine their association with clinical outcomes of COVID-19 patients in intensive care unit (ICU). METHODS: A systemic literature search was conducted in PubMed, EMBASE, MedRxiv and BioRxiv database from December 2019 to 2 July 2020. Studies reporting the application of respiratory supports in COVID-19 patients admitted to ICU were included. RESULTS: Forty studies with 15320 COVID-19 patients were included in this systematic review. The proportion of invasive mechanical ventilation (IMV) application in ICU patients with COVID-19 was 73.8%. Further analysis elucidated that the use rate of IMV in Asia, Europe and North America was 47%, 76.2% and 80.2%, respectively. The proportion of patients treated with prone positioning and IMV was 29.4%. 25.5% of COVID-19 patients requiring IMV developed ventilator-associated pneumonia. The mortality of patients treated with IMV was 51.1%, while only 17.5% of critically ill COVID-19 patients treated with non-IMV respiratory support died. Additionally, the utilization rate of IMV in non-survival patients was shown 17.26-folds (95%CI 2.89-103.24, p = 0.002) higher than that in survival patients, while the use rate of ECMO was no significant difference. CONCLUSIONS: Our findings highlight respiratory supports of COVID-19 patients admitted to ICU in different continents. IMV is a life-saving strategy for critically ill COVID-19 patients with ARDS, yet the mortality remains very high.

Case Report: Identification of SARS-CoV-2 in Cerebrospinal Fluid by Ultrahigh-Depth Sequencing in a Patient With Coronavirus Disease 2019 and Neurological Dysfunction.

We reported that the complete genome sequence of SARS-Coronavirus-2 (SARS-CoV-2) was obtained from a cerebrospinal fluid (CSF) sample by ultrahigh-depth sequencing. Fourteen days after onset, seizures, maxillofacial convulsions, intractable hiccups and a significant increase in intracranial pressure developed in an adult coronavirus disease 2019 patient. The complete genome sequence of SARS-CoV-2 obtained from the cerebrospinal fluid indicates that SARS-CoV-2 can invade the central nervous system. In future, along with nervous system assessment, the pathogen genome detection and other indicators are needed for studying possible nervous system infection of SARS-CoV-2.

The impact of coronavirus disease 2019 (COVID-19) on liver injury in China: A systematic review and meta-analysis.

INTRODUCTION: The evidence for the incidence and severity of liver injury in Chinese patients with coronavirus disease 2019 (COVID-19) is still controversial. The purpose of this study was to summarize the incidence of liver injury and the differences between liver injury markers among different patients with COVID-19 in China. METHODS: Computer searches of PubMed, Embase, China National Knowledge Infrastructure (CNKI) and medRxiv were used to obtain reports on the incidence and markers of liver injury in Chinese patients with COVID-19, from January 1, 2020 to April 10, 2020. (No. CRD42020181350). RESULTS: A total of 57 reports from China were included, including 9889 confirmed cases of COVID-19 infection. The results of the meta-analysis showed that among the patients with early COVID-19 infection in China, the incidence of liver injury events was 24.7% (95% CI, 23.4%-26.4%). Liver injury in severe patients was more common than that in non-severe patients, with a risk ratio of 2.07 (95% CI, 1.77-2.43). Quantitative analysis showed that the severe the coronavirus infection, the higher the level of alanine aminotransferase (ALT), aspertate aminotransferase (AST), total bilirubin (TB), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT), and the lower the level of albumin (ALB). CONCLUSION: There is a certain risk of liver injury in Chinese patients with COVID-19, and the risk and degree of liver injury are related to the severity of COVID-19.

Post-lockdown SARS-CoV-2 nucleic acid screening in nearly ten million residents of Wuhan, China.

Stringent COVID-19 control measures were imposed in Wuhan between January 23 and April 8, 2020. Estimates of the prevalence of infection following the release of restrictions could inform post-lockdown pandemic management. Here, we describe a city-wide SARS-CoV-2 nucleic acid screening programme between May 14 and June 1, 2020 in Wuhan. All city residents aged six years or older were eligible and 9,899,828 (92.9%) participated. No new symptomatic cases and 300 asymptomatic cases (detection rate 0.303/10,000, 95% CI 0.270-0.339/10,000) were identified. There were no positive tests amongst 1,174 close contacts of asymptomatic cases. 107 of 34,424 previously recovered COVID-19 patients tested positive again (re-positive rate 0.31%, 95% CI 0.423-0.574%). The prevalence of SARS-CoV-2 infection in Wuhan was therefore very low five to eight weeks after the end of lockdown.

Mitochondrial-targeted ubiquinone: A potential treatment for COVID-19.

Immune dysregulation characterized by T cell exhaustion and high level of inflammatory cytokines is associated with severe COVID-19. Figuring out the early event of immune dysregulation would provide a potential treatment for COVID-19. Recent evidence indicate that mitochondrial dysfunction participates in the development of COVID-19 and may be responsible for the dysregulated immune response. Mitochondrial-targeted ubiquinone (MitoQ), a mitochondrial-targeted antioxidant, shows beneficial effects on various diseases through improving mitochondrial dysfunction. We hypothesize that MitoQ could act as a potential treatment in COVID-19. MitoQ may alleviate cytokine storm and restore the function of exhausted T cells in COVID-19 patients through improving mitochondrial dysfunction. In this article, we provide evidence to support the use of MitoQ as a potential treatment or adjunct therapy in the context of COVID-19.