Clinical features and predictive factors related to liver injury in SARS-CoV-2 Delta and Omicron variant-infected patients.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta and Omicron variants have become the dominant variants worldwide, and studies focused on liver injury in these patients are limited. MATERIALS AND METHODS: In this study, 157 SARS-CoV-2-infected patients were enrolled, including 77 Delta variant-infected patients and 80 Omicron variant-infected patients. Liver injury data and clinical data were summarized and compared between patients infected with the two variants, additionally, patients with or without liver injury were also compared and multivariate analysis was performed to explore the predictive factors related to liver injury in SARS-CoV-2-infected patients. RESULTS: Liver injury was found in 18 (23.4%)/15 (18.8%) in Delta/Omicron variant-infected patients on admission, and 4 (5.2%)/1 (1.3%) in Delta/Omicron variant-infected patients during hospitalization, respectively. The ratios of liver injury did not differ between the two groups ( χ2 = 1.571; P = 0.210). Among these patients, 17 (77.3%) and 12 (75.0%) Delta and Omicron variant-infected patients were considered to be related to SARS-CoV-2 infection, the biomarkers of liver function were mildly elevated, dominated by the parameter of cholangiocyte injury: 76.5% (13/17) and 83.3% (10/12) in Delta and Omicron variant-infected patients, and most of these patients recovered to normal during follow-up. Multivariate analysis showed that male sex [odds ratio (OR), 4.476; 95% confidence interval (CI), 1.235-16.222; P = 0.023] and high levels of peak viral load in the nasopharynx (OR, 3.022; 95% CI, 1.338-6.827; P = 0.008) were independent factors related to liver injury. CONCLUSION: Cholangiocyte injury biomarkers are dominated in Delta and Omicron variant-infected patients, male sex and high levels of peak viral load in the nasopharynx are predictive factors related to liver injury in SARS-CoV-2-infected patients.

Kinetics of Severity Biomarkers and Immunological Features of Methylprednisolone Therapy for Severe COVID-19 Patients

In contrast to dexamethasone, the clinical efficacy of methylprednisolone (MP) remains controversial, and a systems biology study on its mechanism is lacking. In this study, a total of 38 severe COVID-19 patients were included. The demographics, clinical characteristics, and severity biomarkers including C-reactive protein (CRP), d-dimer, albumin, and Krebs von den Lungen 6 of patients receiving MP (n=26, 40 mg or 80 mg daily for 3-5 days) and supportive therapy (n=12) were compared. Longitudinal measurements of 92 cytokines in MP group from admission to over six months after discharge were performed by multiplex Proximity Extension Assay. The results showed that demographics, baseline clinical characteristics were similar in MP and non-MP groups. No death occurred and the hospital stays between the two groups were similar. Kinetics studies showed that MP was not better than supportive therapy at improving the four severity biomarkers. Cytokines in MP group were characterized by five clusters according to their baseline levels and responses to MP. The immunological feature of severe COVID-19 could be defined by the “core signature” cytokines in cluster 2: MCP-3, IL-6, IFN-γ, and CXCL10, which strongly correlated with each other and CRP, and are involved in cytokine release storm. The “core signature” cytokines were significantly upregulated at baseline and remained markedly elevated after MP treatment. Our work showed a short course of MP therapy could not rapidly improve the immune disorders among severe COVID-19 patients or clinical outcomes, also confirmed “core signature” cytokines, as severity biomarkers similar to CRP, could be applied to evaluate clinical treatment effect.

Author Correction: Temporal dynamics in viral shedding and transmissibility of COVID-19.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Longitudinal clinical and radiographic evaluation reveals interleukin-6 as an indicator of persistent pulmonary injury in COVID-19.

Rationale: Previous studies of coronavirus disease 2019 (COVID-19) were mainly focused on cross-sectional analysis. In this study, we sought to evaluate the dynamic changes of immunological and radiographic features, and the association with the outcome of pulmonary lesions in COVID-19 patients. Methods: Peripheral blood samples and radiographic data were collected longitudinally for up to 8 weeks from 158 laboratory-confirmed COVID-19 patients. The chest computed tomography (CT) scans were scored based on a semi-quantification assessment according to the extent of pulmonary abnormalities; the temporal change of the immunological and radiographic features was analyzed. Results: Compared with mild and moderate patients, severe patients had significantly decreased counts of lymphocytes, CD4+ T cells, CD8+ T cells, and CD19+ B cells but dramatically elevated counts of neutrophils and levels of interleukin (IL)-6. Sequential monitoring showed a sustained increase in lymphocytes counts and significantly decreased levels of IL-6 in severe patients during the disease course. Notably, patients with persistent pulmonary lesions (CT score ≥ 5 in week 8) showed high levels of IL-6 during the follow-up period, compared with those with recovery lesions (CT score < 5 in week 8). More importantly, the peak expression of IL-6 prior to the aggravated lung injury was mainly found in patients with persistent lesions, and multivariate analysis showed that IL-6 level upon admission was an independent factor associated with the persistent pulmonary injury. Conclusion: Prolonged elevation of IL-6 is associated with persistent pulmonary lesions in COVID-19 patients. Sequential monitoring and timely intervention of IL-6 may favor the clinical management of COVID-19.

Temporal dynamics in viral shedding and transmissibility of COVID-19.

We report temporal patterns of viral shedding in 94 patients with laboratory-confirmed COVID-19 and modeled COVID-19 infectiousness profiles from a separate sample of 77 infector-infectee transmission pairs. We observed the highest viral load in throat swabs at the time of symptom onset, and inferred that infectiousness peaked on or before symptom onset. We estimated that 44% (95% confidence interval, 25-69%) of secondary cases were infected during the index cases' presymptomatic stage, in settings with substantial household clustering, active case finding and quarantine outside the home. Disease control measures should be adjusted to account for probable substantial presymptomatic transmission.

Detectable 2019-nCoV viral RNA in blood is a strong indicator for the further clinical severity.

The novel coronavirus (2019-nCoV) infection caused pneumonia. we retrospectively analyzed the virus presence in the pharyngeal swab, blood, and the anal swab detected by real-time PCR in the clinical lab. Unexpectedly, the 2109-nCoV RNA was readily detected in the blood (6 of 57 patients) and the anal swabs (11 of 28 patients). Importantly, all of the 6 patients with detectable viral RNA in the blood cohort progressed to severe symptom stage, indicating a strong correlation of serum viral RNA with the disease severity (p-value = 0.0001). Meanwhile, 8 of the 11 patients with annal swab virus-positive was in severe clinical stage. However, the concentration of viral RNA in the anal swab (Ct value = 24 + 39) was higher than in the blood (Ct value = 34 + 39) from patient 2, suggesting that the virus might replicate in the digestive tract. Altogether, our results confirmed the presence of virus RNA in extra-pulmonary sites.