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

BACKGROUND: T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains (TIGIT), an inhibitory receptor expressed on T cells, plays a dysfunctional role in antiviral infection and antitumor activity. However, it is unknown whether TIGIT expression on T cells influences the immunological effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inactivated vaccines. METHODS: Forty-five people living with HIV (PLWH) on antiretroviral therapy (ART) for more than two years and 31 healthy controls (HCs), all received a third dose of a SARS-CoV-2 inactivated vaccine, were enrolled in this study. The amounts, activation, proportion of cell subsets, and magnitude of the SARS-CoV-2-specific immune response of TIGIT + CD4 + and TIGIT + CD8 + T cells were investigated before the third dose but 6 months after the second vaccine dose (0W), 4 weeks (4W) and 12 weeks (12W) after the third dose. RESULTS: Compared to that in HCs, the frequency of TIGIT + CD8 + T cells in the peripheral blood of PLWH increased at 12W after the third dose of the inactivated vaccine, and the immune activation of TIGIT + CD8 + T cells also increased. A decrease in the ratio of both T naïve (T N ) and central memory (T CM ) cells among TIGIT + CD8 + T cells and an increase in the ratio of the effector memory (T EM ) subpopulation were observed at 12W in PLWH. Interestingly, particularly at 12W, a higher proportion of TIGIT + CD8 + T cells expressing CD137 and CD69 simultaneously was observed in HCs than in PLWH based on the activation-induced marker assay. Compared with 0W, SARS-CoV-2-specific TIGIT + CD8 + T-cell responses in PLWH were not enhanced at 12W but were enhanced in HCs. Additionally, at all time points, the SARS-CoV-2-specific responses of TIGIT + CD8 + T cells in PLWH were significantly weaker than those of TIGIT - CD8 + T cells. However, in HCs, the difference in the SARS-CoV-2-specific responses induced between TIGIT + CD8 + T cells and TIGIT - CD8 + T cells was insignificant at 4W and 12W, except at 0W. CONCLUSIONS TIGIT expression on CD8 + T cells may hinder the T-cell immune response to a booster dose of an inactivated SARS-CoV-2 vaccine, suggesting weakened resistance to SARS-CoV-2 infection, especially in PLWH. Furthermore, TIGIT may be used as a potential target to increase the production of SARS-CoV-2-specific CD8 + T cells, thereby enhancing the effectiveness of vaccination.
Humans ; Antibodies, Viral ; CD8-Positive T-Lymphocytes ; COVID-19/complications* ; COVID-19 Vaccines/immunology* ; HIV Infections/complications* ; Receptors, Immunologic ; SARS-CoV-2

Animals ; Antibodies, Neutralizing/biosynthesis* ; Antibodies, Viral/biosynthesis* ; Body Weight/immunology* ; COVID-19/virology* ; Disease Models, Animal ; Disease Progression ; Humans ; Immunohistochemistry ; Lung/virology* ; Male ; Mesocricetus ; Nasal Cavity/virology* ; RNA, Viral/immunology* ; SARS-CoV-2/pathogenicity* ; Severity of Illness Index ; 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

Objective: The coronavirus disease 2019 (COVID-19) pandemic continues to present a major challenge to public health. Vaccine development requires an understanding of the kinetics of neutralizing antibody (NAb) responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: In total, 605 serum samples from 125 COVID-19 patients (from January 1 to March 14, 2020) varying in age, sex, severity of symptoms, and presence of underlying diseases were collected, and antibody titers were measured using a micro-neutralization assay with wild-type SARS-CoV-2. Results: NAbs were detectable approximately 10 days post-onset (dpo) of symptoms and peaked at approximately 20 dpo. The NAb levels were slightly higher in young males and severe cases, while no significant difference was observed for the other classifications. In follow-up cases, the NAb titer had increased or stabilized in 18 cases, whereas it had decreased in 26 cases, and in one case NAbs were undetectable at the end of our observation. Although a decreasing trend in NAb titer was observed in many cases, the NAb level was generally still protective. Conclusion We demonstrated that NAb levels vary among all categories of COVID-19 patients. Long-term studies are needed to determine the longevity and protective efficiency of NAbs induced by SARS-CoV-2.
Adult ; Aged ; Aged, 80 and over ; Antibodies, Neutralizing/immunology* ; Antibodies, Viral/immunology* ; COVID-19/immunology* ; Female ; Humans ; Kinetics ; Male ; Middle Aged ; Neutralization Tests ; SARS-CoV-2

Antibodies, Neutralizing ; Antibodies, Viral/isolation & purification* ; B-Lymphocytes/virology* ; COVID-19/virology* ; Humans ; Immunity/genetics* ; RNA, Viral/immunology* ; SARS-CoV-2/pathogenicity* ; Single-Cell Analysis

Antibodies, Neutralizing/immunology* ; Antibodies, Viral/immunology* ; COVID-19/virology* ; COVID-19 Vaccines/immunology* ; Humans ; SARS-CoV-2/pathogenicity* ; Spike Glycoprotein, Coronavirus/immunology* ; Vaccines, Inactivated/immunology*

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

Antibodies, Viral/immunology* ; COVID-19/immunology* ; Humans ; Immunoglobulin G/immunology* ; Immunoglobulin M/immunology* ; SARS-CoV-2/immunology*

Dengue virus (DENV) is the most widely transmitted arbovirus in the world. Due to the lack of diagnostic technology to quickly identify the virus serotypes in patients, severe dengue hemorrhagic fever cases caused by repeated infections remain high. To realize the rapid differential diagnosis of different serotypes of DENV infection by immunological methods, in this study, four DENV serotype NS1 proteins were expressed and purified in mammalian cells. Monoclonal antibodies (MAbs) against NS1 protein were obtained by hybridoma technology after immunizing BALB/c mice. Enzyme-linked immunosorbent assay, indirect immunofluorescence assay, dot blotting, and Western blotting were used to confirm the reactivity of MAbs to viral native NS1 and recombinant NS1 protein. These MAbs include not only the universal antibodies that recognize all DENV 1-4 serotype NS1, but also serotype-specific antibodies against DENV-1, DENV-2 and DENV-4. Double antibody sandwich ELISA was established based on these antibodies, which can be used to achieve rapid differential diagnosis of serotypes of DENV infection. Preparation of DENV serotype-specific MAbs and establishment of an ELISA technology for identifying DENV serotypes has laid the foundation for the rapid diagnosis of DENV clinical infection.
Animals ; Antibodies, Monoclonal ; Antibodies, Viral/metabolism* ; Dengue/diagnosis* ; Dengue Virus/immunology* ; Enzyme-Linked Immunosorbent Assay ; Humans ; Mice ; Mice, Inbred BALB C ; Sensitivity and Specificity ; Serogroup ; Viral Nonstructural Proteins/immunology*