The emerging of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused COVID-19 pandemic. The first case of COVID-19 was reported at early December in 2019 in Wuhan City, China. To examine specific antibodies against SARS-CoV-2 in biological samples before December 2019 would give clues when the epidemic of SARS-CoV-2 might start to circulate in populations. We obtained all 88,517 plasmas from 76,844 blood donors in Wuhan between 1 September and 31 December 2019. We first evaluated the pan-immunoglobin (pan-Ig) against SARS-CoV-2 in 43,850 samples from 32,484 blood donors with suitable sample quality and enough volume. Two hundred and sixty-four samples from 213 donors were pan-Ig reactive, then further tested IgG and IgM, and validated by neutralizing antibodies against SARS-CoV-2. Two hundred and thirteen samples (from 175 donors) were only pan-Ig reactive, 8 (from 4 donors) were pan-Ig and IgG reactive, and 43 (from 34 donors) were pan-Ig and IgM reactive. Microneutralization assay showed all negative results. In addition, 213 screened reactive donors were analyzed and did not show obviously temporal or regional tendency, but the distribution of age showed a difference compared with all tested donors. Then we reviewed SARS-CoV-2 antibody results from these donors who donated several times from September 2019 to June 2020, partly tested in a previous published study, no one was found a significant increase in S/CO of antibodies against SARS-CoV-2. Our findings showed no SARS-CoV-2-specific antibodies existing among blood donors in Wuhan, China before 2020, indicating no evidence of transmission of COVID-19 before December 2019 in Wuhan, China.
Humans ; Antibodies, Viral ; Blood Donors ; China/epidemiology* ; COVID-19/immunology* ; Immunoglobulin G ; Immunoglobulin M ; Pandemics ; SARS-CoV-2

With the number of cases of coronavirus disease-2019 (COVID-19) increasing rapidly, the World Health Organization (WHO) has recommended that patients with mild or moderate symptoms could be released from quarantine without nucleic acid retesting, and self-isolate in the community. This may pose a potential virus transmission risk. We aimed to develop a nomogram to predict the duration of viral shedding for individual COVID-19 patients. This retrospective multicentric study enrolled 135 patients as a training cohort and 102 patients as a validation cohort. Significant factors associated with the duration of viral shedding were identified by multivariate Cox modeling in the training cohort and combined to develop a nomogram to predict the probability of viral shedding at 9, 13, 17, and 21 d after admission. The nomogram was validated in the validation cohort and evaluated by concordance index (C-index), area under the curve (AUC), and calibration curve. A higher absolute lymphocyte count (
Aged ; Aged, 80 and over ; Antibodies, Viral/blood* ; Area Under Curve ; COVID-19/virology* ; Female ; Humans ; Lymphocyte Count ; Male ; Middle Aged ; Nomograms ; Proportional Hazards Models ; Retrospective Studies ; Viral Load ; Virus Shedding

Epidemiological evidence suggests that patients with hypertension infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are at increased risk of acute lung injury. However, it is still not clear whether this increased risk is related to the usage of renin-angiotensin system (RAS) blockers. We collected medical records of coronavirus disease 2019 (COVID-19) patients from the First Affiliated Hospital, Zhejiang University School of Medicine (Hangzhou, China), and evaluated the potential impact of an angiotensin II receptor blocker (ARB) on the clinical outcomes of COVID-19 patients with hypertension. A total of 30 hypertensive COVID-19 patients were enrolled, of which 17 were classified as non-ARB group and the remaining 13 as ARB group based on the antihypertensive therapies they received. Compared with the non-ARB group, patients in the ARB group had a lower proportion of severe cases and intensive care unit (ICU) admission as well as shortened length of hospital stay, and manifested favorable results in most of the laboratory testing. Viral loads in the ARB group were lower than those in the non-ARB group throughout the disease course. No significant difference in the time of seroconversion or antibody levels was observed between the two groups. The median levels of soluble angiotensin-converting enzyme 2 (sACE2) in serum and urine samples were similar in both groups, and there were no significant correlations between serum sACE2 and biomarkers of disease severity. Transcriptional analysis showed 125 differentially expressed genes which mainly were enriched in oxygen transport, bicarbonate transport, and blood coagulation. Our results suggest that ARB usage is not associated with aggravation of COVID-19. These findings support the maintenance of ARB treatment in hypertensive patients diagnosed with COVID-19.
Aged ; Aged, 80 and over ; Angiotensin Receptor Antagonists/therapeutic use* ; Angiotensin-Converting Enzyme 2/blood* ; Antibodies, Viral/blood* ; Antihypertensive Agents/therapeutic use* ; Biomarkers ; COVID-19/complications* ; China ; Female ; Humans ; Hypertension/drug therapy* ; Intensive Care Units ; Length of Stay ; Male ; Middle Aged ; Retrospective Studies ; Transcriptome ; Viral Load

The aim of this study was to estimate the seroprevalence of immunoglobulin M (IgM) and G (IgG) antibodies against SARS-CoV-2 in asymptomatic people in Wuhan. This was a cross-sectional study, which enrolled 18,712 asymptomatic participants from 154 work units in Wuhan. Pearson Chi-square test,
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antibodies, Viral/blood* ; COVID-19/immunology* ; Carrier State/immunology* ; Child ; Child, Preschool ; China/epidemiology* ; Coronavirus Nucleocapsid Proteins/immunology* ; Cross-Sectional Studies ; Female ; Humans ; Immunoglobulin G/blood* ; Immunoglobulin M/blood* ; Male ; Middle Aged ; Occupations/classification* ; Phosphoproteins/immunology* ; SARS-CoV-2/immunology* ; Seroepidemiologic Studies ; Spike Glycoprotein, Coronavirus/immunology* ; Young Adult

To screen the best genotypeⅠJapanese encephalitis virus subunit vaccine candidate antigens, the prMEIII gene, the polytope gene and the prMEIII-polytope fusion gene of the GenotypeⅠJapanese encephalitis virus GS strain were cloned into prokaryotic expression vector pET-30a. The recombinant proteins were obtained after the induction and purification. The prepared recombinant proteins were immunized to mice, and the immunogenicity of the subunit vaccine candidate antigens was evaluated through monitoring the humoral immune response by ELISA, detecting the neutralizing antibody titer by plaque reduction neutralization test, and testing the cell-mediated immune response by lymphocyte proliferation assay and cytokine profiling. The recombinant proteins with the molecular weights of 35 (prMEIII), 28 (polytope antigen) and 57 kDa (prMEIII-polytope) induced strong humoral and cellular immune responses in mice. Compared with prMEIII-polytope and polytope proteins, the prMEIII protein induced a significant expression of IL-2 and IFN-γ (P<0.05) and the significant lymphoproliferation of splenocytes (P<0.05). The neutralizing antibody titer induced by the prMEIII protein was close to that induced by the commercial attenuated vaccine SA14-14-2 (P>0.05). The study suggests that the prMEIII protein can be used for the development of the Japanese encephalitis virus subunit vaccine.
Animals ; Antibodies, Viral ; blood ; Antigens, Viral ; immunology ; Encephalitis Virus, Japanese ; immunology ; Encephalitis, Japanese ; immunology ; prevention & control ; Immunogenicity, Vaccine ; Mice ; Mice, Inbred BALB C ; Vaccines, Subunit ; immunology ; Viral Vaccines ; immunology

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which first affected humans in China on December 31, 2019 (Shi et al., 2020). Coronaviruses generally cause mild, self-limiting upper respiratory tract infections in humans, such as the common cold, pneumonia, and gastroenteritis (To et al., 2013; Berry et al., 2015; Chan et al., 2015). According to the Report of the World Health Organization (WHO)-China Joint Mission on COVID-19 (WHO, 2020), the case fatality rate of COVID-19 increases with age, while the rate among males is higher than that among females (4.7% and 2.8%, respectively). Since an effective vaccine and specific anti-viral drugs are still under development, passive immunization using the convalescent plasma (CP) of recovered COVID-19 donors may offer a suitable therapeutic strategy for severely ill patients in the meantime. So far, several studies have shown therapeutic efficacy of CP transfusion in treating COVID-19 cases. A pilot study first reported that transfusion of CP with neutralizing antibody titers above 1:640 was well tolerated and could potentially improve clinical outcomes through neutralizing viremia in severe COVID-19 cases (Chen et al., 2020). Immunoglobulin G (IgG) and IgM are the most abundant and important antibodies in protecting the human body from viral attack (Arabi et al., 2015; Marano et al., 2016). Our study aimed to understand the aspects of plasma antibody titer levels in convalescent patients, as well as assessing the clinical characteristics of normal, severely ill, and critically ill patients, and thus provide a basis for guiding CP therapy. We also hoped to find indicators which could serve as a reference in predicting the progression of the disease.
Adult ; Aged ; Antibodies, Neutralizing/blood* ; Antibodies, Viral/blood* ; COVID-19/therapy* ; China ; Female ; Humans ; Immunization, Passive ; Immunoglobulin G/blood* ; Immunoglobulin M/blood* ; Male ; Middle Aged

The ongoing pandemic of Coronavirus disease 19 (COVID-19) is caused by a newly discovered β Coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). How long the adaptive immunity triggered by SARS-CoV-2 can last is of critical clinical relevance in assessing the probability of second infection and efficacy of vaccination. Here we examined, using ELISA, the IgG antibodies in serum specimens collected from 17 COVID-19 patients at 6-7 months after diagnosis and the results were compared to those from cases investigated 2 weeks to 2 months post-infection. All samples were positive for IgGs against the S- and N-proteins of SARS-CoV-2. Notably, 14 samples available at 6-7 months post-infection all showed significant neutralizing activities in a pseudovirus assay, with no difference in blocking the cell-entry of the 614D and 614G variants of SARS-CoV-2. Furthermore, in 10 blood samples from cases at 6-7 months post-infection used for memory T-cell tests, we found that interferon γ-producing CD4
Adaptive Immunity/physiology* ; Adult ; Aged ; Antibodies, Neutralizing/blood* ; COVID-19/immunology* ; Cohort Studies ; Female ; Humans ; Immunoglobulin G/blood* ; Male ; Middle Aged ; SARS-CoV-2/immunology* ; T-Lymphocytes/physiology* ; Time Factors ; Viral Proteins/immunology*

Antibodies, Viral ; blood ; Betacoronavirus ; Coronavirus ; immunology ; Coronavirus Infections ; immunology ; Humans ; Immunoglobulin G ; blood ; Pandemics ; Pneumonia, Viral ; immunology

Antibodies, Viral ; blood ; Betacoronavirus ; immunology ; Coronavirus Infections ; diagnosis ; Gold Colloid ; chemistry ; Humans ; Immunoassay ; methods ; Immunoglobulin G ; blood ; Immunoglobulin M ; blood ; Pandemics ; Pneumonia, Viral ; diagnosis ; Reagent Kits, Diagnostic

BACKGROUND: The coronavirus disease 2019 (COVID-19) outbreak occurred during the flu season around the world. This study aimed to analyze the impact of influenza A virus (IAV) exposure on COVID-19. METHODS: Seventy COVID-19 patients admitted to the hospital during January and February 2020 in Wuhan, China were included in this retrospective study. Serum tests including respiratory pathogen immunoglobulin M (IgM) and inflammation biomarkers were performed upon admission. Patients were divided into common, severe, and critical types according to disease severity. Symptoms, inflammation indices, disease severity, and fatality rate were compared between anti-IAV IgM-positive and anti-IAV IgM-negative groups. The effects of the empirical use of oseltamivir were also analyzed in both groups. For comparison between groups, t tests and the Mann-Whitney U test were used according to data distribution. The Chi-squared test was used to compare disease severity and fatality between groups. RESULTS: Thirty-two (45.71%) of the 70 patients had positive anti-IAV IgM. Compared with the IAV-negative group, the positive group showed significantly higher proportions of female patients (59.38% vs. 34.21%, χ = 4.43, P = 0.035) and patients with fatigue (59.38% vs. 34.21%, χ = 4.43, P = 0.035). The levels of soluble interleukin 2 receptor (median 791.00 vs. 1075.50 IU/mL, Z = -2.70, P = 0.007) and tumor necrosis factor α (median 10.75 vs. 11.50 pg/mL, Z = -2.18, P = 0.029) were significantly lower in the IAV-positive group. Furthermore, this group tended to have a higher proportion of critical patients (31.25% vs. 15.79%, P = 0.066) and a higher fatality rate (21.88% vs. 7.89%, P = 0.169). Notably, in the IAV-positive group, patients who received oseltamivir had a significantly lower fatality rate (0 vs. 36.84%, P = 0.025) compared with those not receiving oseltamivir. CONCLUSIONS The study suggests that during the flu season, close attention should be paid to the probability of IAV exposure in COVID-19 patients. Prospective studies with larger sample sizes are needed to clarify whether IAV increases the fatality rate of COVID-19 and to elucidate any benefits of empirical usage of oseltamivir.
Adult ; Aged ; Antibodies, Viral/blood* ; Betacoronavirus ; COVID-19 ; Coronavirus Infections/mortality* ; Female ; Humans ; Immunoglobulin M/blood* ; Influenza A virus/immunology* ; Influenza, Human/complications* ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral/mortality* ; Retrospective Studies ; SARS-CoV-2 ; Severity of Illness Index