Viral RNA level, serum antibody responses, and transmission risk in recovered COVID-19 patients with recurrent positive SARS-CoV-2 RNA test results: a population-based observational cohort study

Yang, Chao; Jiang, Min; Wang, Xiaohui; Tang, Xiujuan; Fang, Shisong; Li, Hao; Zuo, Le; Jiang, Yixiang; Zhong, Yifan; Chen, Qiongcheng; Zheng, Chenli; Wang, Lei; Wu, Shuang; Wu, Weihua; Liu, Hui; Yuan, Jing; Liao, Xuejiao; Zhang, Zhen; Shi, Xiaolu; Yang, Geng; Zhang, Huan; Zheng, Huanying; Wan, Min; Lu, Linying; Ren, Xiaohu; Cui, Yu‐Jun; Zou, Xuan; Feng, Tiejian; Xia, Junjie; Liu, Yingxia; Mei, Shujiang; Li, Baisheng; Yang, Zhengrong; Hu, Qinghua

doi:10.1080/22221751.2020.1837018

Cited by 45 publications

(73 citation statements)

References 19 publications

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“…The second one reported 119 discharged patients and 111 close contacts up till 23 April 2020 [ 11 ]. The last one reported 479 recovered COVID-19 patients and 96 close contacts from February 1 to May 5, 2020 [ 10 ]. The above reports were limited to a small group of people; the observation and follow-up times were not long enough.…”

Section: Discussionmentioning

confidence: 99%

A follow-up study shows that recovered patients with re-positive PCR test in Wuhan may not be infectious

Wang

et al. 2021

BMC Med

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Background Previous studies showed that recovered coronavirus disease 2019 (COVID-19) patients can have a subsequent positive polymerase chain reaction (PCR) test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after they are discharged from the hospital. Understanding the epidemiological characteristics of recovered COVID-19 patients who have a re-positive test is vital for preventing a second wave of COVID-19. Methods This retrospective study analyzed the epidemiological and clinical features of 20,280 COVID-19 patients from multiple centers in Wuhan who had a positive PCR test between December 31, 2019, and August 4, 2020. The RT-PCR test results for 4079 individuals who had close contact with the re-positive cases were also obtained. Results In total, 2466 (12.16%) of the 20,280 patients had a re-positive SARS-CoV-2 PCR test after they were discharged from the hospital, and 4079 individuals had close contact with members of this patient group. All of these 4079 individuals had a negative SARS-CoV-2 PCR test. Conclusions This retrospective study in Wuhan analyzed the basic characteristics of recovered COVID-19 patients with re-positive PCR test and found that these cases may not be infectious.

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Section: Discussionmentioning

confidence: 99%

A follow-up study shows that recovered patients with re-positive PCR test in Wuhan may not be infectious

Wang

et al. 2021

BMC Med

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“…Second, as the study population contains only Chinese participants, it may be not generalizable to other ethnic groups. Third, all controls (nonrecurrent positive) were followed up for only two months, and it was not clear whether they will return to positive after that, but the current study showed that most recurrent occur within 1 month, rarely more than two months [5,19]. Because of the small number of cases in the Age and underlying disease (Diabetes, chronic pulmonary disease, coronary heart disease, chronic kidney disease, chronic liver disease, malignant tumor) subgroups, it is failed to calculate the effect value, confidence interval and interaction P value Because 1 patient is chronic lymphoblastic leukemia, there are abnormal values at the maximum of white blood cell count, lymphocyte count and lymphocyte percentage CI confidence interval, OR odd ratio…”

Section: Discussionmentioning

confidence: 64%

“…4 Department of Tuberculosis, Wuhan Pulmonary Hospital, Wuhan, China. 5 Department of Infectious Disease, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. 6 Administrative Office, Chengdu Public Health Clinical Center, Chengdu, China.…”

Section: Discussionmentioning

confidence: 99%

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The relationship between SARS-COV-2 RNA positive duration and the risk of recurrent positive

et al. 2021

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Background The management of discharge COVID-19 patients with recurrent positive SARS-CoV-2 RNA is challenging. However, there are fewer scientific dissertations about the risk of recurrent positive. The aim of this study was to explore the relationship between SARS-COV-2 RNA positive duration (SPD) and the risk of recurrent positive. Methods This case–control multi-center study enrolled participants from 8 Chinese hospital including 411 participants (recurrent positive 241). Using unadjusted and multivariate-adjusted logistic regression analyses, generalized additive model with a smooth curve fitting, we evaluated the associations between SPD and risk of recurrent positive. Besides, subgroup analyses were performed to explore the potential interactions. Results Among recurrent positive patients, there were 121 females (50.2%), median age was 50 years old [interquartile range (IQR): 38–63]. In non-adjusted model and adjusted model, SPD was associated with an increased risk of recurrent positive (fully-adjusted model: OR = 1.05, 95% CI: 1.02–1.08, P = 0.001); the curve fitting was not significant (P = 0.286). Comparing with SPD < 14 days, the risk of recurrent positive in SPD > 28 days was risen substantially (OR = 3.09, 95% CI: 1.44–6.63, P = 0.004). Interaction and stratified analyses showed greater effect estimates of SPD and risk of recurrent positive in the hypertension, low monocyte count and percentage patients (P for interaction = 0.008, 0.002, 0.036, respectively). Conclusion SPD was associated with a higher risk of recurrent positive and especially SPD > 28 day had a two-fold increase in the relative risk of re-positive as compared with SPD < 14 day. What’s more, the risk may be higher among those with hypertension and lower monocyte count or percentage.

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“…Sixteen (of 183 RT-PCR positive) study samples cultured for SARS-CoV-2 on VeroTMPRSS2 cells [16,25] from 14 participants were virus culture positive ( Figure 3A, red circles). In these 14 participants, the median time from symptom onset to last positive virus culture was 5 days (range [2][3][4][5][6][7][8][9][10][11]. No sample tested positive for virus culture beyond 11 days from symptom onset, even in the case of an immunocompromised participant who had positive RT-PCRs with low Ct values two months post-symptom onset ( Figure 3A).…”

Section: Resultsmentioning

confidence: 99%

Delayed rise of oral fluid antibodies, elevated BMI, and absence of early fever correlate with longer time to SARS-CoV-2 RNA clearance in an longitudinally sampled cohort of COVID-19 outpatients

Antar

Pisanic

et al. 2021

Preprint

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Background Viral and immune kinetics in mild to moderate COVID-19 are understudied because of challenges inherent in longitudinal sampling of people who are infectious to others, feeling ill, yet are not hospitalized. In particular, sustained molecular detection of SARS-CoV-2 RNA in the upper respiratory tract (URT) in mild to moderate COVID-19 is common and confounds surveillance efforts in the community. We sought to identify host and immune determinants of prolonged SARS-CoV-2 RNA detection via longitudinal viral RNA, virus culture, and plasma and oral fluid antibody sampling in a prospective observational cohort study of adult outpatients with COVID-19. Methods and Findings Samples from 95 non-hospitalized participants ≥ 30 years old with recent COVID-19 diagnosis and known symptom onset date were analyzed. Participants self-collected mid-turbinate nasal, oropharyngeal (OP), and gingival crevicular fluid (oral fluid) samples at home and in a research clinic a median of 6 times over 1-3 months. SARS-CoV-2 RT-PCR performed on 507 URT samples revealed a median time to viral RNA clearance of the URT of 33.5 days. Sixteen nasal-OP samples collected 2-11 days post-symptom onset were virus culture positive out of 183 RT-PCR positive samples tested. All participants but one with positive virus culture were negative for concomitant oral fluid anti-SARS-CoV-2 spike-receptor binding domain (S-RBD) antibodies. The kinetics of oral fluid anti-SARS-Cov-2 antibodies were measured using a multiplex immunoassay. The mean time to first detection of oral fluid anti-SARS-CoV-2 antibodies was 8-13 days post-symptom onset. Associations of symptoms, host demographics, comorbidities, and immune kinetics with time to SARS-CoV-2 RNA clearance were estimated using Cox proportional hazards models. A longer time to first detection of oral fluid anti-SARS-CoV-2 S antibodies was independently associated with a longer time to SARS-CoV-2 viral RNA clearance (aHR 0.96, 95% CI 0.92-0.99, p=0.020). BMI ≥ 25kg/m2 was also independently associated with a longer time to viral RNA clearance (aHR 0.37, 95% CI 0.18-0.78, p=0.009). Fever reported as one of first three COVID-19 symptoms was associated with shorter time to viral RNA clearance (aHR 2.06, 95% CI 1.02-4.18, p=0.044). Plasma titers of neutralizing antibodies, SARS-CoV-2 spike (S) antibodies, and S-receptor binding domain (S-RBD) antibodies were obtained at 1-4 months post-symptom onset. BMI was positively correlated with post-acute plasma SARS-CoV-2-specific neutralizing antibody titer and anti-S-RBD antibody titer. Conclusions In an intensively sampled cohort of 95 adult outpatients with COVID-19, we demonstrate that longer time to first detection of oral fluid SARS-CoV-2-specific antibodies, elevated BMI, and absence of early fever are independently associated with longer time to viral RNA clearance. This work provides insights into the host and immune factors most important for viral clearance in mild to moderate COVID-19.

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Viral RNA level, serum antibody responses, and transmission risk in recovered COVID-19 patients with recurrent positive SARS-CoV-2 RNA test results: a population-based observational cohort study

Abstract: (2020): Viral RNA level, serum antibody responses, and transmission risk in recovered COVID-19 patients with recurrent positive SARS-CoV-2 RNA test results: a population-based observational cohort study, Emerging Microbes & Infections,

Cited by 45 publications

References 19 publications

A follow-up study shows that recovered patients with re-positive PCR test in Wuhan may not be infectious

A follow-up study shows that recovered patients with re-positive PCR test in Wuhan may not be infectious

The relationship between SARS-COV-2 RNA positive duration and the risk of recurrent positive

Delayed rise of oral fluid antibodies, elevated BMI, and absence of early fever correlate with longer time to SARS-CoV-2 RNA clearance in an longitudinally sampled cohort of COVID-19 outpatients

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