Liver test abnormalities in asymptomatic and mild COVID-19 patients and their association with viral shedding time

BACKGROUND Asymptomatic infections and mild symptoms are common in patients infected with the Omicron variant,and data on liver test abnormalities are rare.AIM To evaluated the clinical characteristics of asymptomatic and mild coronavirus disease 2019(COVID-19)patients with abnormal liver test results.METHODS This retrospective study included 661 laboratory-confirmed asymptomatic and mild COVID-19 patients who were treated in two makeshift hospitals in Ningbo from April 5,2022 to April 29,2022.Clinical information and viral shedding time were collected,and univariate and multivariate logistic regression models were performed in statistical analyses.RESULTS Of the 661 patients,83(12.6%)had liver test abnormalities,and 6(0.9%)had liver injuries.Abnormal liver tests revealed a reliable correlation with a history of liver disease(P<0.001)and a potential correlation with male sex and obesity(P<0.05).Elevated alanine aminotransferase was reliably associated with obesity(P<0.05)and a history of liver disease(P<0.001).Elevated aspartate transaminase(AST)was reliably correlated with a history of liver disease(P<0.001),and potentially correlated with age over 30 years(P<0.05).There was a reliable correlation between AST≥2×the upper limit of normal and a longer viral shedding time,especially in mild cases.CONCLUSION Obesity and a history of liver disease are risk factors for liver test abnormalities.Being male and an older age are potential risk factors.Attention should be given to liver tests in asymptomatic and mild COVID-19 patients,which has crucial clinical significance for evaluating the viral shedding time.

Viral load dynamics in asymptomatic and symptomatic patients during Omicron BA.2 outbreak in Shanghai,China,2022:A longitudinal cohort study

The SARS-CoV-2 virus,particularly the Omicron BA.2 variant,led to a significant surge in Shanghai,2022.However,the viral load dynamic in Omicron infections with varying clinical severities remain unclear.This prospective cohort included 48,830 hospitalized coronavirus disease 2019(COVID-19)patients across three hospitals in Shanghai,China,between 23 March and 15 May,2022.Systematic nucleic acid testing was performed using RT-PCR Cycle threshold(Ct)value as a proxy of viral load.We analyzed the kinetic characteristics of viral shedding by clinical severity and identified associated risk factors.The study comprised 31.06%asymptomatic cases,67.66%mild-moderate cases,1.00%severe cases,0.29%critical and fatal cases.Upon admission,57%of patients tested positive,with peak viral load observed at 4 days(median Ct value 27.5),followed by a decrease and an average viral shedding time(VST)of 6.1 days(Interquartile range,4.0–8.8 days).Although viral load exhibited variation by age and clinical severity,peak Ct values occurred at similar times.Unvaccinated status,age exceeding 60,and comorbidities including hypertension,renal issues kidney dialysis and kidney transplantation,neurological disorders,rheumatism,and psychotic conditions were found to correlate with elevated peak viral load and extended VST.Asymptomatic cases demonstrated a 40%likelihood of contagiousness within 6 days of detection,while mild-moderate and severe cases exhibited post-symptom resolution infectious probabilities of 27%and over 50%,respectively.These findings revealed that the initial Ct values serve as a predictive indicator of severe outcomes.Unvaccinated elderly individuals with particular comorbidities are at high-risk for elevated viral load and prolonged VST.

A Small-Scale Medication of Leflunomide as a Treatment of COVID-19 in an Open-Label Blank-Controlled Clinical Trial

We recently reported that inhibitors against human dihydroorotate dehydrogenase(DHODH)have broad-spectrum antiviral activities including their inhibitory efficacies on SARS-CoV-2 replication in infected cells.However,there are limited data from clinical studies to prove the application of DHODH inhibitors in Coronavirus disease 2019(COVID-19)patients.In the present study,we evaluated Leflunomide,an approved DHODH inhibitor widely used as a modest immune regulator to treat autoimmune diseases,in treating COVID-19 disease with a small-scale of patients.Cases of 10 laboratory-confirmed COVID-19 patients of moderate type with obvious opacity in the lung were included.Five of the patients were treated with Leflunomide,and another five were treated as blank controls without a placebo.All the patients accepted standard supportive treatment for COVID-19.The patients given Leflunomide had a shorter viral shedding time(median of5 days)than the controls(median of 11 days,P=0.046).The patients given Leflunomide also showed a significant reduction in C-reactive protein levels,indicating that immunopathological inflammation was well controlled.No obvious adverse effects were observed in Leflunomide-treated patients,and they all discharged from the hospital faster than controls.This preliminary study on a small-scale compassionate use of Leflunomide provides clues for further understanding of Leflunomide as a potential antiviral drug against COVID-19.

Development and validation of a nomogram to predict failure of 14-day negative nucleic acid conversion in adults with non-severe COVID-19 during the Omicron surge: a retrospective multicenter study

Background With the variability in emerging data,guidance on the isolation duration for patients with coronavirus disease 2019(COVID-19)due to the Omicron variant is controversial.This study aimed to determine the predictors of prolonged viral RNA shedding in patients with non-severe COVID-19 and construct a nomogram to predict patients at risk of 14-day PCR conversion failure.Methods Adult patients with non-severe COVID-19 were enrolled from three hospitals of eastern China in Spring 2022.Viral shedding time(VST)was defined as either the day of the first positive test or the day of symptom onset,whichever was earlier,to the date of the first of two consecutively negative PCR tests.Patients from one hospital(Cohort I,n=2033)were randomly grouped into training and internal validation sets.Predictors of 14-day PCR conversion failure were identified and a nomogram was developed by multivariable logistic regression using the training dataset.Two hospitals(Cohort II,n=1596)were used as an external validation set to measure the performance of this nomogram.Results Of the 2033 patients from Cohort I,the median VST was 13.0(interquartile range:10.0-16.0)days;716(35.2%)lasted>14 days.In the training set,increased age[per 10 years,odds ratio(OR)=1.29,95%confidence interval(CI):1.15-1.45,P<0.001]and high Charlson comorbidity index(OR=1.25,95%CI:1.08-1.46,P=0.004)were independent risk factors for VST>14 days,whereas full or boosted vaccination(OR=0.63,95%CI:0.42-0.95,P=0.028)and antiviral therapy(OR=0.56,95%CI:0.31-0.96,P=0.040)were protective factors.These predictors were used to develop a nomogram to predict VST>14 days,with an area under the ROC curve(AUC)of 0.73 in the training set(AUC,0.74 in internal validation set;0.76 in external validation set).Conclusions Older age,increasing comorbidities,incomplete vaccinations,and lack of antiviral therapy are risk factors for persistent infection with Omicron variant for>14 days.A nomogram based on these predictors could be used as a prediction tool to guide treatment and isolation strategies.