| BackgroundSARS-CoV-2,or new coronavirus,has cause a continued outbreak of new coronavirus pneumonia(COVID-19)caused,posing a serious threat to global public health.Since the outbreak of new coronavirus pneumonia,a large number of patients Who meet the discharge criteria have been discharged from the hospital.Due to the special needs of epidemic prevention and control,China has established regulations for continued isolation management and health status monitoring for 14 days after discharge from hospitals,some of the recovered patients have re-tested positive for the nucleic acid of SARS-CoV-2(referred to as re-positive)on samples such as nasopharyngeal or anal swabs or sputum during observation at isolation sites or during later home isolation.Since the infectiousness of the re-positive patients is unknown,they should be isolated and observed in a designated hospital.These patients staying in the hospital for long periods of time or coming back repeatedly due to repositive viral nucleic acid increase the medical burden,seriously affects the normal life of patients and complicate the management of COVID-19 patients.In this study,we comprehensively analyzed the characteristics and explored the pathogenesis of local and imported positive retest cases admitted to Guangzhou Eighth People’s Hospital,Guangzhou Medical University,which is of crucial importance for the prevention and control management of SARS-CoV-2,population transmission and understanding the natural history of the disease.Part Ⅰ Clinical characteristics and infectiousness analysis of nucleic acid re-positive in SARS-CoV-2 Delta variant infected patients.ObjectiveTo summarize the characteristics of Delta variant infected patients with positive retest viral RNA after discharge,explore whether this population poses a risk to public health and assess their own recovery.Methods1.Cross-sectional survey of the rate of re-positive patients infected with Delta variant and its influence by age,sex,symptoms and history of underlying disease,and comparative analysis of the differences in laboratory test indexes between the repositive group and the recovered group at admission.2.To assess the risk of transmission of re-positive patients by collecting nasopharyngeal swabs from re-positive patients for live virus culture experiments and conducting epidemiological surveys of close contacts with re-positive patients in the community.3.We statistically analyzed the clinical symptoms of the patients in the repositive stage and quantitatively analyzed the degree of lung inflammation and the speed of improvement of inflammation using the AI score to assess whether further treatment was needed in the re-positive stage.Results1.After infection with SARS-CoV-2 Delta variant,77 out of 158(48.73%)local patients and 437 out of 679(64.36%)imported patients were re-positive.There was no statistical difference in age,sex,symptoms and history of underlying disease between the re-positive group and the recovered group(P>0.05).The re-positive group of the imported tended to have lower lymphocytes,eosinophils and basophils,and higher serum lactate dehydrogenase(LDH)and serum amyloid A(SAA)levels than the recovered group at the time of admission(P<0.05,but still within normal ranges).Additionly,the peak viral nucleic acid levels in the hospitalization phase of the repositive group were comparable to those of the recovered group,with no statistical difference(Ct: 18.7 vs 19,P=0.675 for local re-positive vs recovered;Ct: 17 vs 18,P=0.092 for imported re-positive vs recovered).The viral load in the re-positive phase was generally lower(the mean peak nucleic acid Ct was 34.7 for local repositives and36.3 for imported repositives).2.Twenty-five nasopharyngeal swabs(two of which had Ct values of 29 and 25)were not cultured for live virus.Futhermore,epidemiological viral RNA detection among 259 close contact cases with 23 cases with positive retest viral RNA in the community failed to find any community transmission events.3.The vast majority of the re-positive patients showed further absorption of viral pneumonia and no obvious clinical symptoms.In a smaller number of cases(19/289,6.57%),mild symptoms such as cough(18/19,94.74%),expectoration(10/19,52.63%),throat discomfort(4/19,21.05%),tiredness(2/19,10.53%),hyposmia(1/19,5.26%),chest distress and shortness of breath(1/19,5.26%)were reported,but no special drug treatment was required.ConclusionsThe re-positive phenomenon after infection with SARS-CoV-2 Delta variant is common,and laboratory tests cannot predict the occurrence of re-positives.The peak viral nucleic acid level of re-positive patients in the hospitalization phase is comparable to that of recovered patients,and the viral RNA load in the re-positive viral nucleic acid phase is low.No virus was isolated,no community transmission events occurred,and the risk of infectiousness is low.The vast majority of patients in the re-positive phase showed further absorption of viral pneumonia and no obvious clinical symptoms,while a few patients had mild clinical symptoms that did not require further extended hospitalization.Part Ⅱ Study on the potential mechanism of nucleic acid re-positive in SARS-CoV-2 Delta variant infected patients ObjectiveTo further investigate the potential mechanism of SARS-CoV-2 RNA repositivity,we compared the re-positivity rates of different SARS-CoV-2 variant strains,the tissue sites where re-positivity occurred,and analyzed the effects of vaccination and treatment with neutralizing antibodies(BRII-196/198)on the repositivity rates.Methods1.Cross-sectional study of the re-positive rate of different SARS-CoV-2 variant strains and the tissue sites where re-positive occurred.2.Statistical analysis of the effect of vaccination on the rate of re-positive and analysis of the effect of vaccination on individual immune profiles by transcriptome sequencing using PBMC.3.Statistical analysis of the effect of neutralizing antibody use on the rate of repositive.Results1.The re-positive rate was 61.41%(514/837)for Delta variant,39.53%(119/301)for Omicron variant and 7.27%(21/289)for WT variant.In contrast to the WT variant,which was mainly found mainly in the gastrointestinal tract(71%),the Delta variant was mainly found in the upper respiratory tract(90%).2.The level of RBD-Ig G antibodies was significantly higher in Delta breakthrough infected patients than in unvaccinated patients after vaccination,but the rate of re-positives did not decrease in vaccine breakthrough infected patients(65.52%,266/406).The dynamic levels of RBD-Ig G were similar in the re-positive and recovered groups among those with breakthrough infection with two doses of inactivated vaccine.There was no statistical difference in the number of days of hospitalization between those who re-tested positive and those who recovered(the repositives Vs.recovered group : 7.7 VS 8.5,P=0.069).The immune profile of the repositive group was similar to that of the recovered group.3.After the use of neutralizing antibodies,the patients’ RBD-Ig G levels increased significantly,but did not reduce the rate of re-positives(67.27%,37/55).The dynamic levels of antibodies in the re-positive group were similar to those in the recovered group.There was no statistical difference in the number of days of hospitalization between those who re-tested positive and those who recovered(the re-positive Vs.recovered group: 22.1 VS 21.4,P=0.637).ConclusionsThe percentage of positive retests was different for different SARS-CoV-2variants.The rate of positive retests in patients infected with Delta and Omicron variants was significantly higher than that of ancestral virus.The tissue sites where positive retest viral RNA appeared varied among different variants,with Delta variant RNA mainly appearing in the upper respiratory tract(90%),while WT variant RNA mainly appeared in the gastrointestinal tract.Vaccination did not reduce the rate of repositives,and there were no significant differences in RBD-Ig G levels,hospitalization days,or PBMCs transcriptome levels between the re-positive and recovered groups in those with breakthrough infection from two doses of inactivated vaccine.The use of neutralizing antibodies did not reduce the re-positive rate despite high concentrations of virus-neutralizing antibodies in the blood.There were no significant differences in antibody dynamic levels and days of hospitalization between the re-positive and recovered groups. |
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