Serum cortisol concentration and COVID-19 severity: a systematic review and meta-analysis.

The novel COVID-19 outbreak is a major health threat to human beings with multiorgan injuries. However, its endocrine system manifestations are much less studied. In this study, we aimed to reassess the available findings on the association between cortisol level and severity of COVID-19 infection. We conducted a systematic search on Medline/PubMed, Scopus, Web of Science, and Cochrane Library databases. To pool data, a random-effects model was performed depending on the heterogeneity among studies. Sensitivity analysis was also carried out by removing each study systematically. In addition, subgroup and meta-regression analyses were performed depending on the presence of the variables of sex and age. Subsequently, 11 studies (5 observational studies and 6 case reports) were included in the meta-analysis. Pooled analysis on the observational studies showed significantly higher levels of cortisol in patients with severe COVID-19 in comparison with those with mild-to-moderate COVID-19 (standardized mean difference: 1.48 µg/dL; 95% CI (0.51 to 2.46); p=0.003). Assessment of the results of case reports revealed that the patients with severe COVID-19 demonstrated higher cortisol levels than the patients with mild-to-moderate COVID-19. No publication bias was observed using the Begg's (p=0.08) and Egger's tests (p=0.09). Meta-regression illustrated a significant correlation between cortisol levels with sex. The serum cortisol level seems to be higher in patients with severe COVID-19 infection. This finding could be helpful to detect patients with poor prognosis at early stages of the disease, although age and sex may modify this level.

Molecular pathways involved in COVID-19 and potential pathway-based therapeutic targets.

Deciphering the molecular downstream consequences of severe acute respiratory syndrome coronavirus (SARS-CoV)- 2 infection is important for a greater understanding of the disease and treatment planning. Furthermore, greater understanding of the underlying mechanisms of diagnostic and therapeutic strategies can help in the development of vaccines and drugs against COVID-19. At present, the molecular mechanisms of SARS-CoV-2 in the host cells are not sufficiently comprehended. Some of the mechanisms are proposed considering the existing similarities between SARS-CoV-2 and the other members of the ß-CoVs, and others are explained based on studies advanced in the structure and function of SARS-CoV-2. In this review, we endeavored to map the possible mechanisms of the host response following SARS-CoV-2 infection and surveyed current research conducted by in vitro, in vivo and human observations, as well as existing suggestions. We addressed the specific signaling events that can cause cytokine storm and demonstrated three forms of cell death signaling following virus infection, including apoptosis, pyroptosis, and necroptosis. Given the elicited signaling pathways, we introduced possible pathway-based therapeutic targets; ADAM17 was especially highlighted as one of the most important elements of several signaling pathways involved in the immunopathogenesis of COVID-19. We also provided the possible drug candidates against these targets. Moreover, the cytokine-cytokine receptor interaction pathway was found as one of the important cross-talk pathways through a pathway-pathway interaction analysis for SARS-CoV-2 infection.

Positive association between severity of COVID-19 infection and liver damage: a systematic review and meta-analysis.

AIM: The current study aimed to report a pooled analysis of the association of the circulating levels of liver enzymes and total bilirubin with severe and non-severe COVID-19. BACKGROUND: The ongoing coronavirus outbreak is an important threat to health worldwide. Epidemiological data representing greater risk of liver failure in patients infected with Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). METHODS: Electronic databases were comprehensively searched using Medline, ISI Web of Science, EMBASE, and the Cochrane Library up to July 2020. Outcomes from each relevant study were pooled using a random-effects model. Heterogeneity was analyzed by Q test and I2 statistics. Sensitivity analysis was also evaluated. RESULTS: A total of 24 studies were included (4,246 patients) in this study. We found a significant association of COVID-19 severity with increased levels of ALT [SMD: 1.40 U/L; 95% CI (0.93, 1.88); P < 0.05, I2 = 96.5%, P Heterogenity = 0.000 ], AST [SMD: 2.11 U/L; 95% CI (1.40, 2.83); P < 0.05, I2 = 97.9%, P Heterogenity = 0.000], LDH [SMD: 3.88 U/L; 95% CI (2.70, 5); P < 0.05, I2 = 98.7%, P Heterogenity = 0.000] and TBil [SMD: 1.08 mol/L; 95% CI (0.44, 1.72); P = 0.001, I2 = 97.7, P Heterogenity = 0.000], whereas, ALP values [SMD: 0.31; 95% CI (-1.57, 2.20); P = 0.74] was not significant between severe and non-severe COVID-19 patients. Moreover, elevated liver enzymes were found more in males [OR: 1.52, (95% CI 1.26, 1.83), P < 0.05] with severe COVID-19 infection than in females. CONCLUSION: The alterations of liver function indexes caused by SARS-CoV-2 infection suggested a potential prognosis biomarker for screening of severe patients at early stages of the disease.

Increased inflammatory markers correlate with liver damage and predict severe COVID-19: a systematic review and meta-analysis.

AIM: This study aimed to determine whether patients with elevated CRP, TNFα, and IL-6 levels may be at increased risk for severe infection and liver damage of COVID-19. BACKGROUND: The COVID-19 outbreak is a serious health problem to human beings. The evidence suggests that inflammatory markers related to liver damage increase in severe forms of COVID-19 compared to mild cases. METHODS: The electronic databases ISI Web of Science, EMBASE, and Cochrane Library were comprehensively searched for articles published up to May, 2020. Data from each identified study was combined using the random effects model to estimate standardized mean difference (SMD) and 95% confidence intervals (95% CIs). Sensitivity and publication bias were also calculated. RESULTS: Totally, 23 studies were included in this meta-analysis comprising 4313 patients with COVID-19. The random effects results demonstrated that patients with severe COVID-19 had significantly higher levels of CRP [SMD = 3.26 mg/L; (95% CI 2.5, 3.9); p<0.05; I2 = 98.02%; PHeterogeneity = 0.00], TNFα [SMD = 1.78 ng/mL; (95% CI 0.39, 3.1); p=0.012; I2 = 98.2%; PHeterogeneity = 0.00], and IL-6 [ SMD = 3.67 ng/mL; (95% CI 2.4, 4.8); p<0.05; I2 = 97.8%; PHeterogeneity = 0.00] compared with those with the mild form of the disease. Significant heterogeneity was present. No significant publication bias was observed in the meta-analysis. Sensitivity analyses showed a similar effect size while reducing the heterogeneity. CONCLUSION: The data suggests that enhanced inflammation may be associated with COVID-19-related liver damage, possibly involving inflammatory marker-related mechanisms.