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.

Small-molecule anti-COVID-19 drugs and a focus on China's homegrown mindeudesivir(WV116)

The coronavirus disease 2019(COVID-19)pandemic has stimulated tremendous efforts to develop therapeutic agents that target severe acute respiratory syndrome coronavirus 2 to control viral infection.So far,a few small-molecule antiviral drugs,including nirmatrelvir-ritonavir(Paxlovid),remdesivir,and molnupiravir have been marketed for the treatment of COVID-19.Nirmatrelvir-ritonavir has been recommended by the World Health Organization as an early treatment for outpatients with mild-to-moderate COVID-19.However,the existing treatment options have limitations,and effective treatment strategies that are cost-effective and convenient for tackling COVID-19 are still needed.To date,four domestically developed oral anti-COVID-19 drugs have been granted conditional market approval in China.These drugs include azvudine,simnotrelvir-ritonavir(Xiannuoxin),leritrelvir,and mindeudesivir(VV11).Preclinical and clinical studies have explored the efficacy and tolerability of mindeudesivir and supported its early use in mild-to-moderate COVID-19 cases at high risk for progression.In this review,we discuss the most recent findings regarding the pharmacological mechanism and therapeutic effects focusing on mindeudesivir and other small-molecule antiviral agents for COVID-19.These findings will expand our understanding and highlight the potential widespread application of China's homegrown anti-COVID-19 drugs.