Characteristics of Viral Shedding in Respiratory Samples and Specific Antibodies Production in 564 COVID-19 Patients

Positive nucleic acid(NA)results have been found in recovered and discharged COVID-19 patients,but the proportion is unclear.This study was designed to analyze the recurrent positive rate of NA results after consecutively negative results,and the relationship between the specific antibody production and positive NA rate.According to Strengthening the Reporting of Observational Studies in Epidemiology guidelines,data of inpatients in Sino-French New City Branch of Tongji Hospital between Jan.28 and Mar.6,2020 were collected.A total of 564 COVID-19 patients over 14 years old who received the examinations of NA and antibodies against SARS-CoV-2 were included.Days of viral shedding and specific antibodies were recorded and assessed.Among NA tests in respiratory samples(throat swabs,nasopharyngeal swabs,sputum and flushing fluid in alveoli),the patients with all-negative NA results accounted for 17.20%,those with single-positive results for 46.63%,and those with multiple-positive results for 36.17%respectively.Besides,the recurrent positive NA results after consecutively negative results appeared in 66 patients(11.70%).For multiple-positive patients,median viral shedding duration was 20 days(range:1 to 57 days).Of the 205 patients who received 2 or more antibody tests,141(68.78%)had decreased IgG and IgM concentrations.IgM decreased to normal range in 24 patients,with a median of 44 days from symptom onset.Viral shedding duration was not significantly correlated with gender,age,disease severity,changes in pulmonary imaging,and antibody concentration.It is concluded that antibody level and antibody change had no significant correlation with the positive rate of NA tests and the conversion rate after continuous negative NA tests.In order to reduce the recurrent positive proportion after discharge,3 or more consecutive negative NA test results with test interval more than 24 h every time are suggested for the discharge or release from quarantine.

Prolonged SARS-CoV-2 Viral Shedding in Patients with COVID-19 was Associated with Delayed Initiation of Arbidol Treatment and Consulting Doctor Later: A Retrospective Cohort Study

Objective:To study data about SARS-CoV-2 virus shedding and clarify the risk factors for prolonged virus shedding.Methods:Data were retrospectively collected from adults hospitalized with laboratory-confirmed coronavirus disease-19(COVID-19)in Wuhan Union Hospital.We compared clinical features among patients with prolonged(a positive SARS-CoV-2 RNA on day 23 after illness onset)and short virus shedding and evaluated risk factors associated with prolonged virus shedding by multivariate regression analysis.Results:Among 238 patients,the median age was 55.5 years,57.1%were female,92.9%(221/238)were administered with arbidol,58.4%(139/238)were given arbidol in combination with interferon.The median duration of SARS-CoV-2 virus shedding was 23 days(IQR,17.8-30 days)with a longest one of 51 days.The patients with prolonged virus shedding had higher value of D-dimer(P=0.002),IL-6(P<0.001),CRP(P=0.005)and more lobes lung lesion(P=0.014)on admission,as well as older age(P=0.017)and more patients with hypertension(P=0.044)than in those the virus shedding less than 23 days.Multivariate regression analysis revealed that prolonged viral shedding was significantly associated with initiation arbidol≥8 days after symptom onset[OR:2.447,95%CI(1.351-4.431)],≥3 days from onset of symptoms to first medical visitation[OR:1.880,95%CI(1.035-3.416)],illness onset before Jan.31,2020[OR:3.289,95%CI(1.474-7.337)].Arbidol in combination with interferon was also significantly associated with shorter virus shedding[OR:0.363,95%CI(0.191-0.690)].Conclusion:Duration of SARS-CoV-2 virus shedding was long.Early initiation of arbidol and arbidol in combination with interferon as well as consulting doctor timely after illness onset were helpful for SARS-CoV-2 clearance.

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.

Nomogram for Predicting Viral Shedding Time of SARS-CoV-2 Delta Variant in Patients with COVID-19:A Retrospective Study

Background The coronavirus disease 2019(COVID-19)cases continue to rise,and the demand for medical treatment and resources in healthcare systems surges.Assessing the viral shedding time(VST)of patients with COVID-19 can facilitate clinical decision making.Although some studies have been conducted on the factors affecting the VST of severe acute respiratory syndrome coronavirus 2(SARS-COV-2),few prediction models are currently available.Methods This retrospective study included the consecutive patients with COVID-19 admitted to Xi’an Chest Hospital in Shaanxi,China,for treatment between December 19,2021 and February 5,2022.The clinical data of the patients were extracted from their electronic medical records.Combining significant factors affecting the VST,a nomogram was developed to predict the VST of the SARS-CoV-2 Delta variant in patients with COVID-19.Results We included 332 patients in this study.The average VST was 21 d.VST was significantly prolonged in patients with severe clinical symptoms,sore throat,old age,long time from onset to diagnosis,and an abnormal white blood cell count.Consequently,we developed a nomogram prediction model using these 5 variables.The concordance index(C-index)of this nomogram was 0.762,and after internal validation using bootstrapping(1000 resamples),the adjusted C-index was 0.762.The area under the nomogram’s receiver operator characteristic curve showed good discriminative ability(0.965).The calibration curve showed high consistency.The VST was prolonged in the group with lower model fitting scores according to the Kaplan-Meier curve(χ2=286,log-rank P<0.001).Conclusions We developed a nomogram for predicting VST based on 5 easily accessible factors.It can effectively estimate the appropriate isolation period,control viral transmission,and optimize clinical strategies.

Risk of extended viral shedding of Omicron BA.2 in Shanghai:Implications for vaccination strategy optimization

Background:In late March 2022,an outbreak of coronavirus disease 2019(COVID-19)caused by the Omicron BA.2 strain occurred in Shanghai,China.This retrospective study aimed to investigate the clinical characteristics,laboratory parameters,and vaccine protectiveness related to this disease in China.Methods:We conducted a single-center retrospective study on 735 patients with COVID-19 hospitalized from March 17 to May 14,2022.Clinical characteristics were analyzed based on vaccination status and viral shedding time(VST).The least absolute shrinkage and selection operator(LASSO)regression and 5-fold cross-validation were applied to screen factors linked to the rate of the VST.Generalized linear models were further applied to estimate the odds ratios for factors influencing the VST.Results:The median VST of unvaccinated patients was 13(11-16)days,which was longer than that of patients vaccinated with one or two doses(11[9-13]days)and with completed booster doses(11[8-12]days).A LASSO regression model and 5-fold cross-validation showed that age of≥60 years(β=0.01),pneumonia(β=0.53),and higher number of comorbidities(β=0.69)were positively associated with the VST,whereas the platelet count(β=-8.0×10-5)was inversely associated with the VST.Subgroup analysis revealed that the number of vaccinations was significantly associated with a decreased VST among patients with renal dysfunction(odds ratio[OR],0.65;95%confidence interval[CI],0.44-0.97;P=0.034)and patients with two or more comorbidities(OR,0.09;95%CI,0.03-0.28;P<0.001).The lymphocyte count was significantly associated with a decreased VST among patients aged<60 years(OR,0.51;95%CI,0.30-0.85;P=0.011),patients with normal renal function(OR,0.41;95%CI,0.21-0.80;P=0.009),and patients with fewer than two comorbidities(OR,0.49;95%CI,0.30-0.80;P=0.005).Conclusion:Our preliminary results suggest that the complete and booster vaccination contributes to the viral clearance of Omicron BA.2 variants,while the protectiveness of vaccination is most imperative in patients with impaired renal function and more comorbidities.

Comparable outcomes but higher risks of prolonged viral RNA shedding duration and secondary infection in cancer survivors with COVID-19: A multi-center, matched retrospective cohort study

Results Sixty-one cancer survivors and 183 matched non-cancer patients were screened from 2,828 COVID-19 infected patients admitted to 4 hospitals in Wuhan,China.The median ages of the cancer survivor cohort and non-cancer patient cohort were 64.0(55.0–73.0)and 64.0(54.0–73.5),respectively(P=0.909).Cancer survivors reported a higher incidence of symptom onset than non-cancer patients.Fever(80.3%vs.65.0%;P=0.026)was the most prevalent symptom,followed by cough(65.6%vs.37.7%;P<0.001),myalgia,and fatigue(45.9%vs.13.6%;P<0.001).The risks of the development of severe events(adjusted hazard ratio[AHR]=1.25;95%confidence interval[CI]:0.76–2.06;P=0.378)and mortality(relative risk[RR]=0.90,95%CI:0.79–1.04;P=0.416)in the cancer survivor cohort were comparable to those of the matched non-cancer patient cohort.However,the cancer survivor cohort showed a higher incidence of secondary infection(52.5%vs.30.1%;RR=1.47,95%CI:1.11–1.95;P=0.002)and a prolonged viral RNA shedding duration(32 days[IQR 26.0–46.0]vs.24.0 days[IQR 18.0–33.0];AHR=0.54;95%CI:0.38–0.80;P<0.05).Conclusion Compared to non-cancer patients,cancer survivors with COVID-19 exhibited a higher incidence of secondary infection,a prolonged period of viral shedding,but comparable risks of the development of severe events and mortality.It is helpful for clinicians to take tailored measures to treat cancer survivors with COVID-19.

Laboratory Diagnosis and Monitoring the Viral Shedding of SARS-CoV-2 Infection

The worldwide epidemic of coronavirus disease 2019(COVID-19)is ongoing.Rapid and accurate detection of the causative virus SARSCoV-2 is vital for the treatment and control of COVID-19.In this study,the comparative sensitivity of different respiratory specimen types were retrospectively analyzed using 3,552 clinical samples from 410 COVID-19 patients confirmed by Guangdong CDC(Center for Disease Control and Prevention).Except for bronchoalveolar lavage fluid(BALF),the sputum possessed the highest positive rate(73.4%–87.5%),followed by nasal swabs(53.1%–85.3%)for both severe and mild cases during the first 14 days after illness onset(d.a.o.).Viral RNA could be detected in all BALF samples collected from the severe group within 14 d.a.o.and lasted up to 46 d.a.o.Moreover,although viral RNA was negative in the upper respiratory samples,it was also positive in BALF samples in most cases from the severe group during treatment.Notably,no viral RNA was detected in BALF samples from the mild group.Despite typical ground-glass opacity observed via computed tomographic scans,no viral RNA was detected in the first three or all upper respiratory tract specimens from some COVID-19 patients.In conclusion,sputum is most sensitive for routine laboratory diagnosis of COVID-19,followed by nasal swabs.Detection of viral RNA in BALF improves diagnostic accuracy in severe COVID-19 patients.

Viral shedding in Chinese young adults with mild 2009 H1N： influenza

Background The duration of viral shedding and the transmission of 2009 H1N1 influenza among individuals, especially among the younger population with mild illness, are not well understood now. The aim of this study was to determine the viral shedding of the young adult patients with mild 2009 H1N1 influenza in China.Methods From September 2009 to January 2010, the clinical data and serial nasopharyngeal swabs of 67 patients with 2009 H1N1 influenza and 37 patients with seasonal influenza aged from 18 years to 35 years were collected. The nasopharyngeal swab samples were detected by real time RT-PCR to determine the viral shedding. All the patients did not receive the antiviral therapy but Chinese medicine for detoxicating.Results Among the patients with H1N1 virus infection, 82.1% （55/67） patients presented with fever symptom, while more patients with high fever （≥39℃） were found in seasonal influenza patients （P〈0.05）. For the H1N1 patients, the median interval between the symptom onset and the undetectable RNA was six days （4-10 days）. But viral shedding was still found in 31.3% patients after 7 days following illness onset. The median interval between disappearance of fever and an undetectable viral RNA level was three days （2-8 days）, and 17.9% patients were found to be viral shedding 6 days later after normalization of body temperature. For the seasonal influenza patients, 94.6% patients were detected out viral RNA within 7 days. The median interval of seasonal influenza between the symptom onset and the undetectable RNA was four days （3-8 days）. The median interval between disappearance of fever and an undetectable viral RNA level was three days （2-6 days）.Conclusion It suggests that 7 days isolation period from the illness onset or 24 hours after the resolution of fever and respiratory symptoms are not long enough to cut off the transmission among Chinese young adults with mild illness

Gastrointestinal viral shedding in children with SARS‑CoV‑2:a systematic review and meta‑analysis

Background Coronavirus disease 2019(COVID-19)has diferent manifestations in pediatric cases.It is assumed that they might present more gastrointestinal symptoms with a diferent viral shedding pattern in gastrointestinal samples.In this systematic review and meta-analysis,we aimed to evaluate the viral shedding pattern in gastrointestinal specimens of children with COVID-19.Methods We searched all published studies in English language in PubMed,Web of Science,and Scopus,up to date as of October 2021.Our search included the term"severe acute respiratory syndrome coronavirus 2,COVID-19,SARS-CoV-2,novel coronavirus,or coronavirus;and shed,excrete,secret,or carriage;and stool or rectal;and children or pediatrics".We included studies evaluating SARS-CoV-2 shedding in gastrointestinal specimens,including rectal swabs and stool samples of children with COVID-19 infection.We excluded duplicated data,case reports,and studies without original data.Results Twelve studies met the eligibility criteria for the qualitative synthesis,10 of which were included in the meta-analysis.The pooled prevalence of gastrointestinal severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)RNA in children with COVID-19 was 86%(95%confdence interval 73%–96%,I 2=62.28%).After respiratory specimen had become negative,72%(43/60)had persistent shedding in gastrointestinal specimens.The gastrointestinal RNA had a positive test result for more than 70 days after symptoms onset.Conclusions Gastrointestinal shedding of SARS-CoV-2 might occur in a substantial portion of children and might persist long after negative respiratory testing.Further research is recommended to fnd the role of SARS-CoV-2 gastrointestinal shedding in transmission in children.

Prolonged Viral Shedding in Three Young Adult Cases of COVID-19

Severe acute respiratory syndrome coronavirus-2 infection is usually self-limited,with a short duration for viral shedding within several weeks.However,prolonged viral shedding has been observed in severe or immune-compromised coronavirus disease 2019(COVID-19)cases.Here,we reported that three young adult cases of COVID-19 patients,who were either immunosuppressed nor severe,showed prolonged viral RNA shedding from the upper respiratory tract for 58,81,and 137 days since initial diagnosis.To our knowledge,this is the longest duration of viral shedding reported to date in young adult patients.Further studies on factors relevant to prolonged viral positivity,as well as the correlation between viral positivity and transmission risk are needed for the optimal management of COVID-19 patients with prolonged nucleic acid positive.

High fecal calprotectin levels are associated with SARS-CoV-2 intestinal shedding in COVID-19 patients:A proof-of-concept study

BACKGROUND One third of coronavirus disease 2019(COVID-19)patients have gastrointestinal symptoms.Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)RNA has been detected in stool samples of approximately 50%of COVID-19 individuals.Fecal calprotectin is a marker of gastrointestinal inflammation in the general population.AIM To investigate if fecal calprotectin correlates with SARS-CoV-2 intestinal shedding in COVID-19 patients with pneumonia.METHODS Patients with SARS-CoV-2 pneumonia admitted to the Infectious Disease Unit(University Hospital of Trieste,Italy)from September to November 2020 were consecutively enrolled in the study.Fecal samples were collected and analyzed for quantification of fecal calprotectin(normal value<50 mg/kg)and SARS-CoV-2 RNA presence by polymerase chain reaction(PCR).Inter-group differences were determined between patients with and without diarrhea and patients with and without detection of fecal SARS-CoV-2.RESULTS We enrolled 51 adults(40 males)with SARS-CoV-2 pneumonia.Ten patients(20%)presented with diarrhea.Real-time-PCR of SARS-CoV-2 in stools was positive in 39 patients(76%),in all patients with diarrhea(100%)and in more than two thirds(29/41,71%)of patients without diarrhea.Obesity was one of the most common comorbidities(13 patients,25%);all obese patients(100%)(P=0.021)tested positive for fecal SARS-CoV-2.Median fecal calprotectin levels were 60 mg/kg[interquartile range(IQR)21;108];higher fecal calprotectin levels were found in the group with SARS-CoV-2 in stools(74 mg/kg,IQR 29;132.5)compared to the group without SARS-CoV-2(39 mg/kg,IQR 14;71)(P<0.001).CONCLUSION High fecal calprotectin levels among COVID-19 patients correlate with SARSCoV-2 detection in stools supporting the hypothesis that this virus can lead to bowel inflammation and potentially to the‘leaky gut’syndrome.

Probability Distribution of SARS-Cov-2 (COVID) Infectivity Following Onset of Symptoms: Analysis from First Principles

The phasing out of protective measures by governments and public health agencies, despite continued seriousness of the coronavirus pandemic, leaves individuals who are concerned for their health with two basic options over which they have control: 1) minimize risk of infection by being vaccinated and by wearing a face mask when appropriate, and 2) minimize risk of transmission upon infection by self-isolating. For the latter to be effective, it is essential to have an accurate sense of the probability of infectivity as a function of time following the onset of symptoms. Epidemiological considerations suggest that the period of infectivity follows a lognormal distribution. This proposition is tested empirically by construction of the lognormal probability density function and cumulative distribution function based on quantiles of infectivity reported by several independent investigations. A comprehensive examination of a prototypical ideal clinical study, based on general statistical principles (the Principle of Maximum Entropy and the Central Limit Theorem) reveals that the probability of infectivity is a lognormal random variable. Subsequent evolution of new variants may change the parameters of the distribution, which can be updated by the methods in this paper, but the form of the probability function is expected to remain lognormal as this is the most probable distribution consistent with mathematical requirements and available information.

Corticosteroids Treatment of Patients with Coronavirus Disease 2019:A Propensity Score Matching Study

The role of corticosteroids in the treatment of coronavirus disease 2019(COVID-19)is controversial.In the present study,we evaluated the effects of adjuvant corticosteroids treatment on the outcome of patients with COVID-19(n=966),using Propensity Score Matching to adjust for potential differences between the corticosteroids group(n=289)and the non-corticosteroids group(n=677).Analysis of data without adjusting differences in baseline characteristics indicated that the proportion of mechanical ventilation and the mortality was higher in the corticosteroids treatment group in total or severe/critical patients.The duration of viral shedding was longer in the non-corticosteroids treatment group in total or general/mild patients.After adjusting the difference between the corticosteroids and non-corticosteroids treatment group,the analysis revealed that the use of corticosteroids had no effect on the duration of viral shedding,in-hospital mortality or 28-day mortality.

Efficacy of physiological seawater nasal irrigation for the treatment of children with SARS-CoV-2 Omicron BA.2 variant infection:a randomized controlled trial

Background Saline nasal irrigation is an effective therapy for relieving common cold symptoms.This study aimed to investigate and explore the efficacy of physiological seawater nasal irrigation(PSNI)on children with mild and asymptomatic infection with Omicron.Methods This randomized controlled trial was conducted in Shanghai,China,and 403 children with mild and asymptomatic infection with Omicron were included.These children were allocated into the PSNI group and the control group.The primary outcome was the duration of viral shedding(DVS),and the secondary outcome was the change in clinical symptoms.Results The median age of all participants was 5.59(6.26)years old.The DVS was significantly shorter in the PSNI group[2.40(1.13)]than in the control group[3.09(2.14)](P=0.014).The multivariable Cox regression model also showed that patients in the PSNI group had an increased probability of shorter DVS compared with patients in the control group[hazard ratio(HR),1.27;95%confidence interval(CI),1.04–1.55;P=0.017].Subgroup analysis suggested that the DVS of patients without full vaccination was significantly reduced in the PSNI group.The proportions of runny nose and stuffy nose were apparently reduced in the first three days in the PSNI group or the control group,but there was no evidence showing that PSNI contributes to the benefit compared with the control group.Conclusion PSNI can reduce the DVS of patients with mild and asymptomatic infection with SARS-CoV-2 Omicron BA.2 variant.

Viral and Antibody Kinetics of COVID-19 Patients with Different Disease Severities in Acute and Convalescent Phases:A 6-Month Follow-Up Study

Coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has spread rapidly around the world,posing a major threat to human health and the economy.Currently,long-term data on viral shedding and the serum antibody responses in COVID-19 patients are still limited.Herein,we report the clinical features,viral RNA loads,and serum antibody levels in a cohort of 112 COVID-19 patients admitted to the Honghu People’s Hospital,Hubei Province,China.Overall,5.36%(6/112)of patients showed persistent viral RNA shedding(>45 days).The peak viral load was higher in the severe disease group than in the mild group(median cycle threshold value,36.4 versus 31.5;P=0.002).For most patients the disappearance of IgM antibodies occurred approximately 4–6 weeks after symptoms onset,while IgG persisted for over 194 days after the onset of symptoms,although patients showed a 46%reduction in antibodies titres against SARS-CoV-2 nucleocapsid protein compared with the acute phase.We also studied18 asymptomatic individuals with RT-qPCR confirmed SARS-CoV-2 infection together with 17 symptomatic patients,and the asymptomatic individuals were the close contacts of these symptomatic cases.Delayed IgG seroconversion and lower IgM seropositive rates were observed in asymptomatic individuals.These data indicate that higher viral loads and stronger antibody responses are related to more severe disease status in patients with SARS-CoV-2 infection,and the antibodies persisted in the recovered patient for more than 6 months so that the vaccine may provide protection against SARS-CoV-2 infection.

Development and validation of an individualized nomogram for early prediction of the duration of SARS-CoV-2 shedding in COVID-19 patients with non-severe disease

With the number of cases of coronavirus disease-2019(COVID-19)increasing rapidly,the World Health Organization(WHO)has recommended that patients with mild or moderate symptoms could be released from quarantine without nucleic acid retesting,and self-isolate in the community.This may pose a potential virus transmission risk.We aimed to develop a nomogram to predict the duration of viral shedding for individual COVID-19 patients.This retrospective multicentric study enrolled 135 patients as a training cohort and 102 patients as a validation cohort.Significant factors associated with the duration of viral shedding were identified by multivariate Cox modeling in the training cohort and combined to develop a nomogram to predict the probability of viral shedding at 9,13,17,and 21 d after admission.The nomogram was validated in the validation cohort and evaluated by concordance index(C-index),area under the curve(AUC),and calibration curve.A higher absolute lymphocyte count(P=0.001)and lymphocyte-to-monocyte ratio(P=0.013)were correlated with a shorter duration of viral shedding,while a longer activated partial thromboplastin time(P=0.007)prolonged the viral shedding duration.The C-indices of the nomogram were 0.732(95%confidence interval(CI):0.685-0.777)in the training cohort and 0.703(95%CI:0.642-0.764)in the validation cohort.The AUC showed a good discriminative ability(training cohort:0.879,0.762,0.738,and 0.715 for 9,13,17,and 21 d;validation cohort:0.855,0.758,0.728,and 0.706 for 9,13,17,and 21 d),and calibration curves were consistent between outcomes and predictions in both cohorts.A predictive nomogram for viral shedding duration based on three easily accessible factors was developed to help estimate appropriate self-isolation time for patients with mild or moderate symptoms,and to control virus transmission.

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.

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.

Comparison of Clinical and Epidemiological Characteristics of Asymptomatic and Symptomatic SARS-CoV-2 Infection in Children

To understand the epidemiological and clinical features of the symptomatic and asymptomatic pediatric cases of COVID-19,we carried out a prospective study in Shanghai during the period of January 19 to April 30,2020.A total of 49 children(mean age 11.5±5.12 years)confirmed with SARS-CoV-2 infection were enrolled in the study,including 11(22.4%)domestic cases and 38(77.6%)imported cases.Nine(81.8%)local cases and 12(31.6%)imported cases had a definitive epidemiological exposure.Twenty-eight(57.1%)were symptomatic and 21(42.9%)were asymptomatic.Neither asymptomatic nor symptomatic cases progressed to severe diseases.The mean duration of viral shedding for SARS-CoV-2 in upper respiratory tract was 14.1±6.4 days in asymptomatic cases and 14.8±8.4 days in symptomatic cases(P>0.05).Forty-five(91.8%)cases had viral RNA detected in stool.The mean duration of viral shedding in stool was 28.1±13.3 days in asymptomatic cases and 30.8±18.6 days in symptomatic participants(P>0.05).Children<7 years shed viral RNA in stool for a longer duration than school-aged children(P<0.05).Forty-three(87.8%)cases had seropositivity for antibodies against SARS-CoV-2 within 1–3 weeks after confirmation with infection.In conclusion,asymptomatic SARS-CoV-2 infection may be common in children in the community during the COVID-19 pandemic wave.Asymptomatic cases shed viral RNA in a similar pattern as symptomatic cases do.It is of particular concern that asymptomatic individuals are potentially seed transmission of SARS-CoV-2 and pose a challenge to disease control.