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Various medical treatments for COVID-19 are attempted. After patients are discharged, SARS-CoV-2 recurring cases are reported and the recurrence could profoundly impact patient healthcare and social economics. To date, no data on the effects of medical treatments on recurrence has been published. We analyzed the treatment data of combinations of ten different drugs for the recurring cases in a single medical center, Shenzhen, China. A total of 417 patients were considered and 414 of them were included in this study (3 deaths) with mild-to-critical COVID-19. Patients were treated by 10 different drug combinations and followed up for recurrence for 28 days quarantine after being discharged from the medical center between February and May, 2020. We applied the Synthetic Minority Oversampling Technique (SMOTE) to overcome the rare recurring events in certain age groups and performed Virtual Twins (VT) analysis facilitated by random forest regression for medical treatment-recurrence classification. Among those drug combinations, Methylprednisolone/Interferon/Lopinavir/Ritonavir/Arbidol led to the lowest recurring rate (0.133) as compared to the average recurring rate (0.203). For the younger group (age 20-27) or the older group (age 60-70), the optimal drug combinations are different, but the above combination is still the second best. For obese patients, the combination of Ribavirin/Interferon/Lopinavir/Ritonavir/Arbidol led to the lowest recurring rate for age group of 20-50, whereas the combination of Interferon/Lopinavir/Ritonavir/Arbidol led to lowest recurring rate for age group of 50-70. The insights into combinatorial therapy we provided here shed lights on the use of a combination of (biological and chemical) anti-virus therapy and/or anti-cytokine storm as a potentially effective therapeutic treatment for COVID-19.
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IMPORTANCEHow to appropriately care for patients who become PCR-negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still not known. Patients who have recovered from coronavirus disease 2019 (COVID-19) could profoundly impact the health care system if a subset were to be PCR-positive again with reactivated SARS-CoV-2. OBJECTIVETo characterize a single center COVID-19 cohort with and without recurrence of PCR positivity, and develop an algorithm to identify patients at high risk of retest positivity after discharge to inform health care policy and case management decision-making. DESIGN, SETTING, AND PARTICIPANTSA cohort of 414 patients with confirmed SARS-CoV-2 infection, at The Second Affiliated Hospital of Southern University of Science and Technology in Shenzhen, China from January 11 to April 23, 2020. EXPOSURESPolymerase chain reaction (PCR) and IgM-IgG antibody confirmed SARS-CoV-2 infection. MAIN OUTCOMES AND MEASURESUnivariable and multivariable statistical analysis of the clinical, laboratory, radiologic image, medical treatment, and clinical course of admission/quarantine/readmission data to develop an algorithm to predict patients at risk of recurrence of PCR positivity. RESULTS16.7% (95CI: 13.0%-20.3%) patients retest PCR positive 1 to 3 times after discharge, despite being in strict quarantine. The driving factors in the recurrence prediction model included: age, BMI; lowest levels of the blood laboratory tests during hospitalization for cholinesterase, fibrinogen, albumin, prealbumin, calcium, eGFR, creatinine; highest levels of the blood laboratory tests during hospitalization for total bilirubin, lactate dehydrogenase, alkaline phosphatase; the first test results during hospitalization for partial pressure of oxygen, white blood cell and lymphocyte counts, blood procalcitonin; and the first test episodic Ct value and the lowest Ct value of the nasopharyngeal swab RT PCR results. Area under the ROC curve is 0.786. CONCLUSIONS AND RELEVANCEThis case series provides clinical characteristics of COVID-19 patients with recurrent PCR positivity, despite strict quarantine, at a 16.7% rate. Use of a recurrence prediction algorithm may identify patients at high risk of PCR retest positivity of SARS-CoV-2 and help modify COVID-19 case management and health policy approaches. Key PointsO_ST_ABSQuestionC_ST_ABSWhat are the characteristics, clinical presentations, and outcomes of COVID-19 patients with PCR retest positivity after resolution of the initial infection and consecutive negative tests? Can we identify recovered patients, prior to discharge, at risk of the recurrence of SARS-CoV-2 PCR positivity? FindingsIn this series of 414 COVID-19 inpatients discharged to a designated quarantine center, 69 retest positive (13 with 2 readmissions, and 3 with 3 readmissions). A multivariable model was developed to predict the risk of the recurrence of SARS-CoV-2 PCR positivity. MeaningRate and timing of the recurrence of PCR positivity following strict quarantine were characterized. Our prediction algorithm may have implications for COVID-19 clinical treatment, patient management, and health policy.
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OBJECTIVE@#To determine the composition and distribution of beta-thalassemia-associated genotypes in Liuzhou area of Guangxi, China.@*METHODS@#From January to December 2017, 13 847 individuals who came for premarital examination, maternity examination or health check were recruited with informed consent. The subjects were analyzed by reverse dot blotting (RDB) for 17 common beta-thalassemia-associated variants among the Chinese population. Individuals with inconsistent results by blood test, electrophoresis, and RDB were subjected to Sanger sequencing to detect rare variants of the beta globin gene.@*RESULTS@#In total 2098 individuals were found to harbor beta-thalassemia-associated variants, which included 2075 heterozygotes (98.90%), 12 compound heterozygotes (0.57%) and 11 homozygotes (0.52%). CD41-42 (48.43%) and CD17 (31.45%) were the most common variants. Three hundred and thirty eight-individuals were found to also carry heterozygous variants of the alpha globin gene, with the most common types being --SEA/aa, -a3.7/aa, aCSa/aa, -a4.2/aa. Through Sanger sequencing, rare genotypes such as beta-32/betaN, betaCD41-42/betaIVS-II-5 and betaCD30/betaN were detected.@*CONCLUSION@#Liuzhou area has a high incidence of beta-thalassemia, but with a complex variant spectrum and clinical phenotypes different from other regions. Genetic counseling and prenatal diagnosis for the carrier population is crucial for the reduction of the related birth defects. Our result may provide valuable information for the prevention and control of beta-thalassemia in this area.