A Novel Prediction Model of COVID-19 Progression: A Retrospective Cohort Study.

INTRODUCTION: Estimating the risk of disease progression is of utmost importance for planning appropriate setting of care and treatment for patients with coronavirus disease 2019 (COVID-19). This study aimed to develop and validate a novel prediction model of COVID-19 progression. METHODS: In total, 814 patients in the training set were included to develop a novel scoring system; and 420 patients in the validation set were included to validate the model. RESULTS: A prediction score, called ACCCDL, was developed on the basis of six risk factors associated with COVID-19 progression: age, comorbidity, CD4+ T cell count, C-reactive protein (CRP), D-dimer, and lactate dehydrogenase (LDH). For predicting COVID-19 progression, the ACCCDL score yielded a significantly higher area under the receiver operating characteristic curve (AUROC) compared with the CALL score, CoLACD score, PH-COVID-19 score, neutrophil-lymphocyte ratio, and lymphocyte-monocyte ratio both in the training set (0.92, 0.84, 0.83, 0.83, 0.76, and 0.65, respectively) and in the validation set (0.97, 0.83, 0.83, 0.78, 0.74, and 0.60, respectively). Over 99% of patients with the ACCCDL score < 12 points will not progress to severe cases, and over 30% of patients with the ACCCDL score > 20 points will progress to severe cases. CONCLUSION: The ACCCDL score could stratify patients with at risk of COVID-19 progression, and was useful in regulating the large flow of patients with COVID-19 between primary health care and tertiary centers.

Efficacy Evaluation of Thymosin Alpha 1 in Non-severe Patients With COVID-19: A Retrospective Cohort Study Based on Propensity Score Matching.

Objective: Thymosin alpha 1 (Thymosin-α1) is a potential treatment for patients with COVID-19. We aimed to determine the effect of Thymosin-α1 in non-severe patients with COVID-19. Methods: We retrospectively enrolled 1,388 non-severe patients with COVID-19. The primary and secondary clinical outcomes were evaluated with comparisons between patients treated with or without Thymosin-α1 therapy. Results: Among 1,388 enrolled patients, 232 patients (16.7%) received both Thymosin-α1 therapy and standard therapy (Thymosin-α1 group), and 1,156 patients (83.3%) received standard therapy (control group). After propensity score matching (1:1 ratio), baseline characteristics were well-balanced between the Thymosin-α1 group and control group. The proportion of patients that progressed to severe COVID-19 is 2.17% for the Thymosin-α1 group and 2.71% for the control group (p = 0.736). The COVID-19-related mortality is 0.54% for the Thymosin-α1 group and 0 for the control group (p = 0.317). Compared with the control group, the Thymosin-α1 group had significantly shorter SARS-CoV-2 RNA shedding duration (13 vs. 16 days, p = 0.025) and hospital stay (14 vs. 18 days, p < 0.001). No statistically significant difference was found between the Thymosin-α1 group and control group in duration of symptoms (median, 4 vs. 3 days, p = 0.843) and antibiotic utilization rate (14.1% vs. 15.2%, p = 0.768). Conclusion: For non-severe patients with COVID-19, Thymosin-α1 can shorten viral RNA shedding duration and hospital stay but did not prevent COVID-19 progression and reduce COVID-19-related mortality rate.

Dynamic Changes in Liver Function Tests and Their Correlation with Illness Severity and Mortality in Patients with COVID-19: A Retrospective Cohort Study.

OBJECTIVE: To describe the longitudinal changes in liver function tests, and their association with illness severity and mortality in patients with COVID-19. METHODS: A retrospective cohort study of 1003 hospitalized patients with COVID-19 was conducted. Longitudinal liver function tests and clinical outcomes were analyzed. RESULTS: Abnormal liver function parameters were observed, both at admission (ALT 13.2%, AST 8.5%, ALP 2.0%, GGT 7.4%, LDH 37.6%, TBIL 4.0%, DBIL 7.8%, Albumin 10.1%) and peak hospitalization (ALT 29.4%, AST 17.5%, ALP 2.6%, GGT 13.4%, LDH 49.4%, TBIL 10.1%, DBIL 18.0%, Albumin 30.6%) in patients with COVID-19. Compared with non-severe patients, severe patients had markedly higher liver function parameters from baseline to 30 days after hospital admission. Abnormal ALT and LDH at hospital admission and some medications use (Hydroxychloroquine, Lopinavir/Ritonavir, and Traditional Chinese medicines) were associated with peak hospitalization ALT > 5× the upper limit unit of normal (ULN). On multivariate analysis, age >60 years, male, obesity, comorbidity, abnormal LDH and albumin at hospital admission and peak hospitalization were associated with progression to severe COVID-19 (OR > 1; p < 0.05). COX analysis revealed that ALT > 2 ULN (HR=7.0, p=0.011), AST > 2 ULN (HR=34.7, p < 0.001), and TBIL > 2 ULN (HR=54.6, p < 0.001) were associated with a higher mortality. CONCLUSION: Dynamic abnormalities of liver function parameters are common in hospitalized patients with COVID-19, and associated with illness severity and mortality.

Efficacy evaluation of intravenous immunoglobulin in non-severe patients with COVID-19: A retrospective cohort study based on propensity score matching.

OBJECTIVES: At the present time, there is an absence of any proven effective antiviral therapy for patients with coronavirus disease 2019 (COVID-19). The aim of this study was to assess the efficacy of intravenous immunoglobulin (IVIG) in non-severe patients with COVID-19. METHODS: A retrospective study based on propensity score matching (PSM) was designed. Primary outcomes included the severity and mortality rates. Secondary outcomes included the duration of fever, virus clearance time, length of hospital stay, and use of antibiotics. RESULTS: A total of 639 non-severe patients with COVID-19 were enrolled. Forty-five patients received IVIG therapy and 594 received non-IVIG therapy. After PSM (1:2 ratio), the baseline characteristics were well balanced between the IVIG group (n = 45) and control group (n = 90). No statistically significant difference was found between the IVIG group and control group in the duration of fever (median 3 vs 3 days, p = 0.667), virus clearance time (median 11 vs 10 days, p = 0.288), length of hospital stay (median 14 vs 13 days, p = 0.469), or use of antibiotics (40% vs 38.9%, p = 0.901). Meanwhile, compared to the IVIG group, no more patients in the control group progressed to severe disease (3.3% vs 6.6%, p = 0.376) or died (0 vs 2.2%, p = 0.156). CONCLUSIONS: In non-severe patients with COVID-19, no benefit was observed with IVIG therapy beyond standard therapy.

Molecular and cellular mechanisms of liver dysfunction in COVID-19.

Liver injury has been reported as a common complication in Coronavirus disease 2019 (COVID-19). Recently, more and more studies reported that the degree of liver damages was associated with the severity of COVID-19. Although the exact mechanism of liver injury in COVID-19 patients is unknown, recent studies have made some explorations and investigations. In this review, we summarized the potential mechanisms of liver dysfunction in COVID-19 patients gleaned from recently published research reports, which suggested that the progression of pre-existing liver diseases, direct damage of liver by SARS-CoV-2, systemic inflammation caused by SARS-CoV-2 infection, anti-viral drug toxicity, and hypoxia-reperfusion may be associated with liver injury in patients with COVID-19. Hypoxic liver injury due to ischemia and shock, cholestasis-related liver injury due to altered bile metabolism, and hepatocellular injury due to drug toxicity or overwhelming inflammation might occur in severe COVID-19 patients with sepsis. To understand the pathogenesis of liver dysfunction in COVID-19 patients, further research is needed to focus on liver-related comorbidities, the evidence of viral replication in hepatocytes and bile duct cells, histological features of liver injury, and the influence of hepatotoxic antiviral drugs. We also suggested that special attention should be paid to monitoring inflammatory cytokines and hypoxia for the prevention and treatment of liver injury in severe COVID-19 patients. A deep understanding of the mechanism of liver injury is helpful for the management and treatment of COVID-19 patients.

Efficacy Evaluation of Early, Low-Dose, Short-Term Corticosteroids in Adults Hospitalized with Non-Severe COVID-19 Pneumonia: A Retrospective Cohort Study.

OBJECTIVES: This study aimed to observe the efficacy of corticosteroids in non-severe COVID-19 pneumonia. METHODS: A retrospective study based on propensity score matching was designed to explore the effects of corticosteroids. Primary outcomes included the rate of patients who developed severe disease and mortality. Secondary outcomes included duration of fever, virus clearance time, length of hospital stay, and the use of antibiotics. RESULTS: A total of 475 patients with non-severe COVID-19 pneumonia were enrolled, 55 patients received early, low-dose, and short-term corticosteroids therapy, 420 patients received non-corticosteroids therapy. Compared to the non-corticosteroids group, there was a prolonged duration of fever (median 5 vs 3 days, p < 0.001), virus clearance time (median 18 vs 11 days, p < 0.001), and length of hospital stay (median 23 vs 15 days, p < 0.001) in the corticosteroids group. The percentages of antibiotics therapy (89.1% vs 23.6%, p < 0.001), use of at least two antibiotics (38.2% vs 12.7%, p = 0.002), and antifungal therapy (7.3% vs 0, p = 0.042) were higher in the corticosteroids group than those in the non-corticosteroids group. Compared to the non-corticosteroids group, more patients developed severe disease (12.7% vs 1.8%, p = 0.028) in the corticosteroids group. There was no significant difference between the two groups in mortality (1.8% vs 0, p = 0.315). CONCLUSION: In adult patients with non-severe COVID-19 pneumonia, early, low-dose, and short-term corticosteroids therapy was associated with worse clinical outcomes.