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Immunological and Inflammatory Indicators of COVID-19 Patients With Returned-positive Nucleic Acid Tests During Hospitalization: a Retrospective Cohort Study
Weili Yan
Children hospital of Fudan University
Corresponding Author
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Background: COVID-19 cases with suspected returned-positive SRAS-CoV-2 tests following consecutive negative tests have been reported, but evidence-based explanations for this phenomenon is still lacking. We aimed to describe the clinical and laboratory characteristics of returned-positive COVID-19 patients during treatment in comparison with other patients.
Methods: From January 20 to April 10, 2020, all COVID-19 inpatient with at least three RT-PCR SARS-CoV-2 tests in Renmin Hospital in Wuhan, China were enrolled. Patients with 2 consecutively negative RT-PCR results followed by a positive result were classified as returned-positive patients, and their characteristics and repeatedly measured laboratory results were compared with the rest of the patients. Linear mixed effects models were performed.
Results: A total of 789 COVID-19 patients were included and 22.8% patients returned positive in RT-PCR SARS-CoV-2 test. No significant differences were found for general characteristics between the returned-positive and the control groups. The trends of inflammatory and immune factors including the third component of complement (C3), C-reactive protein, procalcitonin (PCT), IL-4, IL-6, the counts of lymphocyte, CD3+, CD8+, white blood cell and immunoglobulin levels during hospitalization were significantly different between the two groups. During the returned-positive period, C3, PCT, serum IgM, anti-SARS-CoV-2 IgM and anti-SARS-CoV-2 IgG were significantly higher in the returned-positive patients at certain time points.
Conclusions: Returned-positive COVID-19 patients appeared to be more sever at admission, and had periodically higher levels in C3, PCT, serum IgM and two specific antibodies during hospitalization. This suggests that positive return of SARS-COV-2 could not be completely explained by false-negative testing and longer observation of these patients is warranted.
Keywords
COVID-19, SARS-CoV-2, returned-positive, the third component of complement, procalcitonin, anti-SARS-CoV-2 IgM, anti-SARS-CoV-2 IgG
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Appendix Table 1 Characteristics of included and excluded COVID-19 patients. Appendix Fig. 1 The estimated results of lab-results by mixed models, numbers of patients at each phase, and p value of each phase between two groups of COVID-19 patients with significant different trends during the hospitalization Returned-positive was defined as patients with two consecutive negative RT-PCR results of SARS-CoV-2 tests followed by a positive result (a certain sequence of results: negative, negative, positive), with an interval of over 24 hours between RT-PCR tests. The rest of the enrolled COVID-19 patients were defined as the control group. From the date of confirmed diagnosis of SARS-CoV-2 infection, the course of disease (days) was ordinally categorized into phases by an interval of 5 days. Linear mixed effect models were used to analyze the difference in trends of laboratory markers over time (by phase) between returned-positive patients and their counterparts. Returned-positive period stands for the inter-quartile range (IQR) of the time of COVID-19 patients appeared with returned-positive phenomenon. Appendix Fig. 2 The estimated results of lab-results by mixed models, numbers of patients at each phase, and p value of each phase between two groups of COVID-19 patients during the hospitalization. Returned-positive was defined as patients with two consecutive negative RT-PCR results of SARS-CoV-2 tests followed by a positive result (a certain sequence of results: negative, negative, positive), with an interval of over 24 hours between RT-PCR tests. The rest of the enrolled COVID-19 patients were defined as the control group. From the date of confirmed diagnosis of SARS-CoV-2 infection, the course of disease (days) was ordinally categorized into phases by an interval of 5 days. Linear mixed effect models were used to analyze the difference in trends of laboratory markers over time (by phase) between returned-positive patients and their counterparts. Returned-positive period stands for the inter-quartile range (IQR) of the time of COVID-19 patients appeared with returned-positive phenomenon. Appendix Fig. 3 The estimated results of lab-results by mixed models, numbers of patients at each phase, and p value of each phase between two groups of COVID-19 patients during the hospitalization. Returned-positive was defined as patients with two consecutive negative RT-PCR results of SARS-CoV-2 tests followed by a positive result (a certain sequence of results: negative, negative, positive), with an interval of over 24 hours between RT-PCR tests. The rest of the enrolled COVID-19 patients were defined as the control group. From the date of confirmed diagnosis of SARS-CoV-2 infection, the course of disease (days) was ordinally categorized into phases by an interval of 5 days. Linear mixed effect models were used to analyze the difference in trends of laboratory markers over time (by phase) between returned-positive patients and their counterparts. Returned-positive period stands for the inter-quartile range (IQR) of the time of COVID-19 patients appeared with returned-positive phenomenon. Appendix Fig. 4 The estimated results of specific antibodies against SARS-CoV-2 by mixed models in different groups, numbers of patients at each phase, and p value of each phase between two groups of COVID-19 patients during the hospitalization. From the date of confirmed diagnosis of SARS-CoV-2 infection, the course of disease (days) was ordinally categorized into phases by an interval of 5 days. Linear mixed effect models were used to analyze the difference in trends of specific antibodies between groups. Group A stands for the patients discharged within 45 days from the date of confirmed diagnosis of SARS-CoV-2 infection (all the patients in this group were cured and discharged). Group B stands for the patients hospitalized longer than 45 days from the date of confirmed infection (6 patients were died during hospitalization). Group C stands for the patients died within 45 days from the date of confirmed infection.
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This preprint is under consideration at BMC Infectious Diseases. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Immunological and Inflammatory Indicators of COVID-19 Patients With Returned-positive Nucleic Acid Tests During Hospitalization: a Retrospective Cohort Study
Weili Yan
Children hospital of Fudan University
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 13 Jan, 2021
No community comments so far
Editor assigned
On 12 Jan, 2021
Submission checks complete
On 07 Jan, 2021
Editor invited
On 05 Jan, 2021
First submitted
On 28 Oct, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Infectious Diseases
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: COVID-19 cases with suspected returned-positive SRAS-CoV-2 tests following consecutive negative tests have been reported, but evidence-based explanations for this phenomenon is still lacking. We aimed to describe the clinical and laboratory characteristics of returned-positive COVID-19 patients during treatment in comparison with other patients.
Methods: From January 20 to April 10, 2020, all COVID-19 inpatient with at least three RT-PCR SARS-CoV-2 tests in Renmin Hospital in Wuhan, China were enrolled. Patients with 2 consecutively negative RT-PCR results followed by a positive result were classified as returned-positive patients, and their characteristics and repeatedly measured laboratory results were compared with the rest of the patients. Linear mixed effects models were performed.
Results: A total of 789 COVID-19 patients were included and 22.8% patients returned positive in RT-PCR SARS-CoV-2 test. No significant differences were found for general characteristics between the returned-positive and the control groups. The trends of inflammatory and immune factors including the third component of complement (C3), C-reactive protein, procalcitonin (PCT), IL-4, IL-6, the counts of lymphocyte, CD3+, CD8+, white blood cell and immunoglobulin levels during hospitalization were significantly different between the two groups. During the returned-positive period, C3, PCT, serum IgM, anti-SARS-CoV-2 IgM and anti-SARS-CoV-2 IgG were significantly higher in the returned-positive patients at certain time points.
Conclusions: Returned-positive COVID-19 patients appeared to be more sever at admission, and had periodically higher levels in C3, PCT, serum IgM and two specific antibodies during hospitalization. This suggests that positive return of SARS-COV-2 could not be completely explained by false-negative testing and longer observation of these patients is warranted.
Figure 1
Figure 2
Figure 3