viral rna level serum antibody responses and transmission risk in discharged covid 19 CORD-Papers-2021-10-25 (Version 1)

Title: Viral RNA level, serum antibody responses, and transmission risk in discharged COVID-19 patients with recurrent positive SARS-CoV-2 RNA test results: a population-based observational cohort study
Abstract: Background Managing discharged COVID-19 (DC) patients with recurrent positive (RP) SARS-CoV-2 RNA test results is challenging. We aimed to comprehensively characterize the viral RNA level and serum antibody responses in RP-DC patients and evaluate their viral transmission risk. Methods A population-based observational cohort study was performed on 479 DC patients discharged from February 1 to May 5, 2020 in Shenzhen, China. We conducted RT-qPCR, antibody assays, neutralisation assays, virus isolation, whole genome sequencing (WGS), and epidemiological investigation of close contacts. Findings Of 479 DC patients, the 93 (19%) RP individuals, including 36 with multiple RP results, were characterised by young age (median age: 34 years, 95% confidence interval [CI]: 29-38 years). The median discharge-to-RP length was 8 days (95% CI: 7-14 days; maximum: 90 days). After readmission, RP-DC patients exhibited mild (28%) or absent (72%) symptoms, with no disease progression. The viral RNA level in RP-DC patients ranged from 1.9-5.7 log10 copies/mL (median: 3.2, 95% CI: 3.1-3.5). At RP detection, the IgM, IgG, IgA, total antibody, and neutralising antibody (NAb) seropositivity rates in RP-DC patients were 38% (18/48), 98% (47/48), 63% (30/48), 100% (48/48), and 91% (39/43), respectively. Regarding antibody levels, there was no significant difference between RP-DC and non-RP-DC patients. The antibody level remained constant in RP-DC patients pre- and post-RP detection. Virus isolation of nine representative specimens returned negative results. WGS of six specimens yielded only genomic fragments. No clinical symptoms were exhibited by 96 close contacts of 23 RP-DC patients; their viral RNA (96/96) and antibody (20/20) test results were negative. After full recovery, 60% of patients (n=162, 78 no longer RP RP-DC and 84 non-RP-DC) had NAb titres of []1:32. Interpretation RP may occur in DC patients following intermittent and non-stable excretion of low viral RNA levels. RP-DC patients pose a low risk of transmitting SARS-CoV-2. An NAb titre of []1:32 may provide a reference indicator for evaluating humoral responses in COVID-19 vaccine clinical trials.
Published: 7/26/2020
DOI: 10.1101/2020.07.21.20125138
DOI_URL: http://doi.org/10.1101/2020.07.21.20125138
Author Name: Yang, C
Author link: https://covid19-data.nist.gov/pid/rest/local/author/yang_c
Author Name: Jiang, M
Author link: https://covid19-data.nist.gov/pid/rest/local/author/jiang_m
Author Name: Wang, X
Author link: https://covid19-data.nist.gov/pid/rest/local/author/wang_x
Author Name: Tang, X
Author link: https://covid19-data.nist.gov/pid/rest/local/author/tang_x
Author Name: Fang, S
Author link: https://covid19-data.nist.gov/pid/rest/local/author/fang_s
Author Name: Li, H
Author link: https://covid19-data.nist.gov/pid/rest/local/author/li_h
Author Name: Zuo, L
Author link: https://covid19-data.nist.gov/pid/rest/local/author/zuo_l
Author Name: Jiang, Y
Author link: https://covid19-data.nist.gov/pid/rest/local/author/jiang_y
Author Name: Zhong, Y
Author link: https://covid19-data.nist.gov/pid/rest/local/author/zhong_y
Author Name: Chen, Q
Author link: https://covid19-data.nist.gov/pid/rest/local/author/chen_q
Author Name: Zheng, C
Author link: https://covid19-data.nist.gov/pid/rest/local/author/zheng_c
Author Name: Wang, L
Author link: https://covid19-data.nist.gov/pid/rest/local/author/wang_l
Author Name: Wu, S
Author link: https://covid19-data.nist.gov/pid/rest/local/author/wu_s
Author Name: Wu, W
Author link: https://covid19-data.nist.gov/pid/rest/local/author/wu_w
Author Name: Liu, H
Author link: https://covid19-data.nist.gov/pid/rest/local/author/liu_h
Author Name: Yuan, J
Author link: https://covid19-data.nist.gov/pid/rest/local/author/yuan_j
Author Name: Liao, X
Author link: https://covid19-data.nist.gov/pid/rest/local/author/liao_x
Author Name: Zhang, Z
Author link: https://covid19-data.nist.gov/pid/rest/local/author/zhang_z
Author Name: Lin, Y
Author link: https://covid19-data.nist.gov/pid/rest/local/author/lin_y
Author Name: Geng, Y
Author link: https://covid19-data.nist.gov/pid/rest/local/author/geng_y
Author Name: Zhang, H
Author link: https://covid19-data.nist.gov/pid/rest/local/author/zhang_h
Author Name: Zheng, H
Author link: https://covid19-data.nist.gov/pid/rest/local/author/zheng_h
Author Name: Wan, M
Author link: https://covid19-data.nist.gov/pid/rest/local/author/wan_m
Author Name: Lu, L
Author link: https://covid19-data.nist.gov/pid/rest/local/author/lu_l
Author Name: Ren, X
Author link: https://covid19-data.nist.gov/pid/rest/local/author/ren_x
Author Name: Cui, Y
Author link: https://covid19-data.nist.gov/pid/rest/local/author/cui_y
Author Name: Zou, X
Author link: https://covid19-data.nist.gov/pid/rest/local/author/zou_x
Author Name: Feng, T
Author link: https://covid19-data.nist.gov/pid/rest/local/author/feng_t
Author Name: Xia, J
Author link: https://covid19-data.nist.gov/pid/rest/local/author/xia_j
Author Name: Yang, R
Author link: https://covid19-data.nist.gov/pid/rest/local/author/yang_r
Author Name: Liu, Y
Author link: https://covid19-data.nist.gov/pid/rest/local/author/liu_y
Author Name: Mei, S
Author link: https://covid19-data.nist.gov/pid/rest/local/author/mei_s
Author Name: Li, B
Author link: https://covid19-data.nist.gov/pid/rest/local/author/li_b
Author Name: Yang, Z
Author link: https://covid19-data.nist.gov/pid/rest/local/author/yang_z
Author Name: Hu, Q
Author link: https://covid19-data.nist.gov/pid/rest/local/author/hu_q
sha: 36f9a09ff8f4fa3376933cca672fb25c2d1657d0
license: medrxiv
source_x: MedRxiv; WHO
source_x_url: https://www.who.int/
url: http://medrxiv.org/cgi/content/short/2020.07.21.20125138v1?rss=1 https://doi.org/10.1101/2020.07.21.20125138
has_full_text: TRUE
Keywords Extracted from Text Content: patients IgM Shenzhen, China IgA RP-44 serum COVID-19 NAb IgG specimens post-RP NRP-DC patient antibody Wölfel medRxiv RP-RC Figure 3b steroid SARS-CoV-2-specific anti-RBD 230 antibody specimens R=0·77 CRP NAb titre 234 appendix Figure S4 57/93 patient medRxiv preprint NAb 232 people R>0·40 methylprednisolone SARS-CoV-2 RNA tests cellular R=0·73 Figure 114 1b dexamethasone QS2020060007 IgG patients IgM SARS-CoV-2 300 SARS-CoV-2 317 steroids 171 C-reactive NRP-DC patients p<0.05 p=0·03 COVID-19 patients p>0·05 CoV-2 appendix Figure S1 NAb [3/94]j medRxiv preprint 11 patients mid-study nasopharyngeal swab medRxiv medRxiv preprint anal serum specimens SARS-CoV-2 374 serum 376 sputum specimens
Extracted Text Content in Record: First 5000 Characters:26 Background Managing discharged COVID-19 (DC) patients with recurrent positive (RP) SARS-27 CoV-2 RNA test results is challenging. We aimed to comprehensively characterize the viral RNA 28 level and serum antibody responses in RP-DC patients and evaluate their viral transmission risk. 29 30 Methods A population-based observational cohort study was performed on 479 DC patients 31 discharged from February 1 to May 5, 2020 in Shenzhen, China. We conducted RT-qPCR, antibody 32 assays, neutralisation assays, virus isolation, whole genome sequencing (WGS), and 33 epidemiological investigation of close contacts. 34 35 Findings Of 479 DC patients, the 93 (19%) RP individuals, including 36 with multiple RP results, 36 were characterised by young age (median age: 34 years, 95% confidence interval [CI]: 29-38 years). 37 The median discharge-to-RP length was 8 days (95% CI: 7-14 days; maximum: 90 days). After 38 readmission, RP-DC patients exhibited mild (28%) or absent (72%) symptoms, with no disease 39 progression. The viral RNA level in RP-DC patients ranged from 1·9-5·7 log10 copies/mL (median: 40 3·2, 95% CI: 3·1-3·5). At RP detection, the IgM, IgG, IgA, total antibody, and neutralising antibody 41 (NAb) seropositivity rates in RP-DC patients were 38% (18/48), 98% (47/48), 63% (30/48), 100% 42 (48/48), and 91% (39/43), respectively. Regarding antibody levels, there was no significant 43 difference between RP-DC and non-RP-DC patients. The antibody level remained constant in RP-44 DC patients pre-and post-RP detection. Virus isolation of nine representative specimens returned 45 negative results. WGS of six specimens yielded only genomic fragments. No clinical symptoms 46 were exhibited by 96 close contacts of 23 RP-DC patients; their viral RNA (96/96) and antibody 47 CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted July 26, 2020. . https://doi.org/10.1101/2020.07.21.20125138 doi: medRxiv preprint qPCR. After quarantine, DC patients were regularly followed-up on the 7 th , 14 th , 30 th , and 60 th days 102 post-discharge. Demographic and clinical severity information was extracted from electronic 103 hospital medical records. Clinical severity on first admission was classified as asymptomatic, mild, 104 moderate, or critical based on Chinese Guidelines for Diagnosis and Treatment for Novel 105 Coronavirus Pneumonia 12 . 106 The study was approved by the Ethics Committee of Shenzhen CDC (QS2020060007). As data 108 collection is part of the public health investigation of an emerging outbreak, individual informed 109 consent was waived. 110 111 Because negative results from two consecutive SARS-CoV-2 RNA tests were part of the discharge 113 criteria, a DC patient with recurrent positive test results was defined as an RP-DC patient ( Figure 114 1b and appendix Figure S1 ). These patients were readmitted to hospital for further medical 115 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted July 26, 2020. We performed statistical analyses using R version 3.6.1. Categorical and continuous variables were 144 compared using Chi-squared and Mann-Whitney U tests, respectively. Correlations were assessed 145 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted July 26, 2020. The funders had no role in study design; data collection, analysis, or interpretation; or report writing. 149 The corresponding authors had full access to all study data and had final responsibility for the 150 decision to submit for publication. 151 Figure S1 ). 164 165 There were more female (57/93, 61%) than male RP-DC patients (36/93, 39%, underlying immunodeficiency diseases, and 14 RP-DC patients (15%) were treated with steroids 171 (methylprednisolone and/or dexamethasone) during hospitalization. There were no significant 172 differences between RP-DC and NRP-DC patients in terms of hospitalization period, clinical 173 severity on first admission, or steroid use (p>0·05). The C-reactive protein (CRP) level of RP-DC 174 patients on first admission was significantly higher than that of NRP-DC patients (p=0·03), but there 175 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted July 26, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version
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