Immunological and Inflammatory Indicators of COVID-19 Patients With Returned-positive Nucleic Acid Tests During Hospitalization: a Retrospective Cohort Study (preprint)

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. 

Dynamic changes in peripheral blood lymphocyte subsets in adult patients with COVID-19.

INTRODUCTION: Coronavirus disease 2019 (COVID-19), caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread widely. The aim of this study was to investigate the dynamic changes in peripheral blood lymphocyte subsets in adult patients with COVID-19. METHODS: The electronic medical records were reviewed. Data including demographic characteristics, clinical manifestations, comorbidities, laboratory data, and radiological examinations of 435 hospitalized COVID-19 patients with a confirmed SARS-CoV-2 viral infection were extracted and analyzed retrospectively. Lymphocyte subset counts at each week after the onset of the illness were compared with those of the other weeks of illness and with those of control individuals. RESULTS: The various lymphocyte subsets (CD3+, CD4+, CD8+, CD19+, and CD16/56+) were below the normal ranges at 1 week after the onset of illness, reaching a nadir during the second week. They increased gradually during the third week and returned to normal levels in the fifth week, but were still lower than those of the healthy controls. The CD3+, CD4+, and CD8+ counts were significantly lower in patients with severe disease compared to those with non-severe disease, and in patients who died compared to those who recovered. DISCUSSION: This research indicates that the levels of peripheral blood lymphocyte subsets (CD3+, CD4+, and CD8+) are associated with disease progression and severity, and with the prognosis in patients with COVID-19. Dynamic monitoring of human immune function is one of the indicators for evaluating the severity of disease and the prognosis of COVID-19 patients, and is useful for formulating appropriate treatment strategies.

The comparative superiority of IgM-IgG antibody test to real-time reverse transcriptase PCR detection for SARS-CoV-2 infection diagnosis (preprint)

Background: As the increasing number of Corona Virus Disease 2019 (COVID-19) patients caused by the severe acute respiratory coronavirus 2 (SARS-CoV-2), which caused an outbreak initiated from Wuhan, China in December, 2019, the clinical features and treatment of COVID-19 patients have been understood. However, it is urgent to need the rapid and accurate detection for SARS-CoV-2 infection diagnosis. We aimed to evaluate the antibodies-based and nucleic acid-based tests (NAT) for SARS-CoV-2-infected patients. Method: We retrospectively and observationally studied 133 patients diagnosed with SARS-CoV-2 and admitted in Renmin Hospital of Wuhan University, China, from Feb 17 to Mar 1, 2020. Demographic data, symptoms, clinical examination, laboratory tests, and clinical outcomes were collected. Data were compared between IgM-IgG antibody test and real-time RT-PCR detection for COVID-19 patients. Results: Of 133 patients with SARS-CoV-2 infection, there were 44 moderate cases, 52 severe cases, and 37 critical cases with no significant difference of gender and age among three subgroups. Overall, the positive ratio in IgM antibody test was higher than in RT-PCR detection. In RT-PCR detection, the positive ratio was 65.91%, 71.15%, and 67.57% in moderate, severe, and critical cases, respectively. Whereas, the positive ratio of IgM/IgG antibody detection in patients was 79.55%/93.18%, 82.69%/100%, and 72.97%/97.30% in moderate, severe, and critical cases, respectively. Moreover, the concentrations of antibodies were also measured in three subgroups. Conclusion: The IgM-IgG antibodies-based test exhibited a comparative superiority to the NAT for COVID-19 diagnosis, which provides an effective complement to the false negative results from NAT for SARS-CoV-2 infection diagnosis.