Background: Mitochondria have been shown to play vital roles during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) development. Currently, it is unclear whether mitochondrial DNA (mtDNA) variants, which define mtDNA haplogroups and determine oxidative phosphorylation performance and reactive oxygen species production, are associated with COVID-19 risk. Methods: A population-based case–control study was conducted to compare the distribution of mtDNA variations defining mtDNA haplogroups between healthy controls ( n = 615) and COVID-19 patients ( n = 536). COVID-19 patients were diagnosed based on molecular diagnostics of the viral genome by qPCR and chest X-ray or computed tomography scanning. The exclusion criteria for the healthy controls were any history of disease in the month preceding the study assessment. MtDNA variants defining mtDNA haplogroups were identified by PCR-RFLPs and HVS-I sequencing and determined based on mtDNA phylogenetic analysis using Mitomap Phylogeny. Student’s t -test was used for continuous variables, and Pearson’s chi-squared test or Fisher’s exact test was used for categorical variables. To assess the independent effect of each mtDNA variant defining mtDNA haplogroups, multivariate logistic regression analyses were performed to calculate the odds ratios ( OR s) and 95% confidence intervals (CIs) with adjustments for possible confounding factors of age, sex, smoking and diseases (including cardiopulmonary diseases, diabetes, obesity and hypertension) as determined through clinical and radiographic examinations. Results: Multivariate logistic regression analyses revealed that the most common investigated mtDNA variations (> 10% in the control population) at C5178a (in NADH dehydrogenase subunit 2 gene, ND2 ) and A249d (in the displacement loop region, D-loop)/T6392C (in cytochrome c oxidase I gene, CO1 )/G10310A (in ND3 ) were associated with a reduced risk of severe COVID-19 ( OR = 0.590, 95% CI 0.428–0.814, P = 0.001; and OR = 0.654, 95% CI 0.457–0.936, P = 0.020, respectively), while A4833G ( ND2 ), A4715G ( ND2 ), T3394C ( ND1 ) and G5417A ( ND2 )/C16257a (D-loop)/C16261T (D-loop) were related to an increased risk of severe COVID-19 ( OR = 2.336, 95% CI 1.179–4.608, P = 0.015; OR = 2.033, 95% CI 1.242–3.322, P = 0.005; OR = 3.040, 95% CI 1.522–6.061, P = 0.002; and OR = 2.890, 95% CI 1.199–6.993, P = 0.018, respectively). Conclusions: This is the first study to explore the association of mtDNA variants with individual’s risk of developing severe COVID-19. Based on the case–control study, we concluded that the common mtDNA variants at C5178a and A249d/T6392C/G10310A might contribute to an individual’s resistance to developing severe COVID-19, whereas A4833G, A4715G, T3394C and G5417A/C16257a/C16261T might increase an individual’s risk of developing severe COVID-19.

Reliable diagnostics are necessary to identify influenza infections, and coronavirus disease 2019 (COVID-19) highlights the need to develop highly specific and sensitive viral detection methods to distinguish severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other respiratory pathogens to prevent their further spread. In this prospective study, 1070 clinical respiratory samples were collected from patients with acute respiratory infections from January 2019 to February 2021 to evaluate the diagnostic performance of a multiplex probe amplification (MPA) assay, designed to screen 18 pathogens, mainly those causing acute respiratory infections. Ninety-six positive samples and twenty negative samples for the 18 respiratory pathogens defined by the MPA assay and reverse transcription polymerase chain reaction (RT–PCR) were further confirmed by reference next-generation sequencing (NGS). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the MPA assay were 95.00%, 93.75%, 98.96% and 75.00%, respectively. Additionally, the co-infection rate for these positive samples were 25% (24/95). The MPA assay demonstrated a highly concordant diagnostic performance with NGS in the diagnosis of 18 respiratory pathogens and might play an important role in clinical respiratory pathogen diagnosis.

Background: High-mobility group box 1 (HMGB1) protein plays an important pathogenic role in various diseases such as pulmonary fibrosis. However, the relationship between variation of HMGB1 gene and susceptibility to coal worker's pneumoconiosis (CWP) remains unclear. The objective of the study was to determine the association between HMGB1 polymorphisms and CWP in Chinese Han population. Methods: The genotypes of HMGB1 gene rs1045411, rs2249825, rs1412125 and rs1360485 in 340 CWP patients and 312 healthy controls were determined and serum HMGB1 levels were detected. Results: Our finding showed that the HMGB1 rs1360485 G allele increased the risk of CWP in comparison with A allele (P = 0.005). HMGB1 rs1360485 GG genotype as well as AG+GG genotype increased the risk of CWP in comparison with AA genotype (P = 0.010, P = 0.025, respectively). Four haplotypes were identified and we found that the GCTA haplotype was associated with resistance to CWP (P = 0.005), while GCTG haplotype was associated with risk to CWP (P<0.001). Meanwhile, multifactor dimensionality reduction (MDR) analysis showed that the interaction between rs1360485 and exposure had the strongest, followed by rs2249825 and rs1412125. This study also found that the serum HMGB1 levels of the case group were significantly higher than that of the control group, and the serum HMGB1 levels of homozygous subjects with rs1360485 mutant were higher than that of the heterozygous wild type, respectively (P<0.001). Meanwhile, the levels of HMGB1 with GCTA haplotype was lower than with GCTG haplotype (P<0.001) Conclusion: Our findings indicated that HMGB1 gene rs1360485 polymorphism was associated with the susceptibility to CWP in Chinese Han population.