Project description:Dysregulated immune responses contribute to the excessive and uncontrolled inflammation observed in severe COVID-19. However, how immunity to SARS-CoV-2 is induced and regulated remains unclear. Here we uncover a role of the complement system in the induction of innate and adaptive immunity to SARS-CoV-2. Complement rapidly opsonizes SARS-CoV-2 particles via the lectin pathway. Complement-opsonized SARS-CoV-2 efficiently induces type-I interferon and pro-inflammatory cytokine responses via activation of dendritic cells, which are inhibited by antibodies against the complement receptors (CR) 3 and 4. Serum from COVID-19 patients, or monoclonal antibodies against SARS-CoV-2, attenuate innate and adaptive immunity induced by complement-opsonized SARS-CoV-2. Blocking of CD32, the FcγRII antibody receptor of dendritic cells, restores complement-induced immunity. These results suggest that opsonization of SARS-CoV-2 by complement is involved in the induction of innate and adaptive immunity to SARS-CoV-2 in the acute phase of infection. Subsequent antibody responses limit inflammation and restore immune homeostasis. These findings suggest that dysregulation of the complement system and FcγRII signaling may contribute to severe COVID-19.
Project description:BackgroundCOVID-19 has raised special concern for patients with β-thalassemia major (β-TM) due to frequent comorbidities, regular blood transfusions, and iron overload. However, the exact implications of COVID-19 for patients with β-TM remain uncertain. We aimed to explore the COVID-19 incidence and severity, and the serological response to SARS-CoV-2 infection and vaccination in patients with β-TM.MethodsPatients with β-TM (n = 105) and age-matched healthy controls, all individuals of all control groups were health care workers of the hospital, were prospectively enrolled at the haematology department of Al-Shifa hospital in the Gaza Strip from January 1st, 2021 to December 31st, 2021. Data on COVID-19 incidence and severity were analysed, with Alpha, Beta, and Delta SARS-CoV-2 variants dominating at that time. Anti-SARS-CoV-2 IgG antibody levels were measured and compared between study groups.FindingsPatients with β-TM showed a higher incidence of SARS-CoV-2 infection than the general population (61.9% vs. 7.1%, p < 0.0001). Most patients with β-TM had asymptomatic (70.8%) or mild disease (26.1%), with no fatalities recorded. COVID-19 illness was more severe among female than male patients with β-TM. Anti-SARS-CoV-2 IgG antibodies were significantly higher in symptomatic patients with β-TM than controls post-infection (geometric mean ÷ geometric standard deviation 1299.0 ÷ 3.3 vs. 555.7 ÷ 2.4 AU/mL, p = 0.009) and post-vaccination (8404.0 ÷ 3.9 vs. 2785.6 ÷ 5.0 AU/mL, p = 0.015). Similar responses were observed when comparing splenectomised to non-splenectomised (both asymptomatic and symptomatic) patients with β-TM post-infection (595.4 ÷ 3.9 vs. 280.7 ÷ 3.5 AU/mL, p = 0.005) and post-vaccination (13,778.2 ÷ 3.2 vs. 4961.8 ÷ 4.1 AU/mL, p = 0.045).InterpretationThis distinctive β-TM cohort exhibited a high susceptibility to SARS-CoV-2 infection but mild disease course. Our findings support favourable serological responses to SARS-CoV-2 infection and to vaccination in patients with β-TM, indicating a potential interplay between iron availability and COVID-19-related immunity.FundingThis study was funded by Mr. Hosam and Wasim s. El Helou.
Project description:To explore the relationship between SARS-CoV-2 infection in different time before operation and postoperative main complications (mortality, main pulmonary and cardiovascular complications) 30 days after operation; To determine the best timing of surgery after SARS-CoV-2 infection.
Project description:HAE cultures were infected with SARS-CoV, SARS-dORF6 or SARS-BatSRBD and were directly compared to A/CA/04/2009 H1N1 influenza-infected cultures. Cell samples were collected at various hours post-infection for analysis. Time Points = 0, 12, 24, 36, 48, 60, 72, 84 and 96 hrs post-infection for SARS-CoV, SARS-dORF6 and SARS-BatSRBD. Time Points = 0, 6, 12, 18, 24, 36 and 48 hrs post-infection for H1N1. Done in triplicate or quadruplicate for RNA Triplicates/quadruplicates are defined as 3/4 different wells, plated at the same time and using the same cell stock for all replicates. Time matched mocks done in triplicate from same cell stock as rest of samples. Culture medium (the same as what the virus stock is in) will be used for the mock infections. Infection was done at an MOI of 2.
Project description:HAE cultures were infected with SARS-CoV, SARS-ddORF6 or SARS-BatSRBD and were directly compared to A/CA/04/2009 H1N1 influenza-infected cultures. Cell samples were collected at various hours post-infection for analysis. Time Points = 0, 12, 24, 36, 48, 60, 72, 84 and 96 hrs post-infection for SARS-CoV. Time Points = 0, 24, 48, 60, 72, 84 and 96 hrs post-infection forSARS-ddORF6 and SARS-BatSRBD. Time Points = 0, 6, 12, 18, 24, 36 and 48 hrs post-infection for H1N1. Done in triplicate/quadruplicate for RNA Triplicates/quadruplicates are defined as 3/4 different wells, plated at the same time and using the same cell stock for all replicates. Time matched mocks done in triplicate from same cell stock as rest of samples. Culture medium (the same as what the virus stock is in) will be used for the mock infections. Infection was done at an MOI of 2.
Project description:HAE cultures were infected with SARS-CoV, SARS-dORF6 or SARS-BatSRBD and were directly compared to A/CA/04/2009 H1N1 influenza-infected cultures. Cell samples were collected at various hours post-infection for analysis. Time Points = 0, 12, 24, 36, 48, 60, 72, 84 and 96 hrs post-infection for SARS-CoV, SARS-dORF6 and SARS-BatSRBD. Time Points = 0, 6, 12, 18, 24, 36 and 48 hrs post-infection for H1N1. Done in triplicate for RNA Triplicates are defined as 3 different wells, plated at the same time and using the same cell stock for all replicates. Time matched mocks done in triplicate from same cell stock as rest of samples. Culture medium (the same as what the virus stock is in) will be used for the mock infections. Infection was done at an MOI of 2 for SARS viruses and an MOI of 1 for H1N1.
Project description:Recent clinical data have suggested a correlation between coronavirus disease 2019 (COVID-19) and diabetes. Here, we describe the detection of SARS-CoV-2 viral antigen in pancreatic beta cells in autopsy samples from individuals with COVID-19. Single-cell RNA sequencing and immunostaining from ex vivo infections confirmed that multiple types of pancreatic islet cells were susceptible to SARS-CoV-2, eliciting a cellular stress response and the induction of chemokines. Upon SARS-CoV-2 infection, beta cells showed a lower expression of insulin and a higher expression of alpha and acinar cell markers, including glucagon and trypsin1, respectively, suggesting cellular transdifferentiation. Trajectory analysis indicated that SARS-CoV-2 induced eIF2-pathway-mediated beta cell transdifferentiation, a phenotype that could be reversed with trans-integrated stress response inhibitor (trans-ISRIB). Altogether, this study demonstrates an example of SARS-CoV-2 infection causing cell fate change, which provides further insight into the pathomechanisms of COVID-19.
Project description:The aim of the study was to investigate the real-life experience of persons infected with SARS-CoV-2 in Slovenia in the first pandemic wave and how the buffering effect of social and informational support affected negative feelings. We used a self-administrated questionnaire. There were 1182 eligible notified cases with the response rate 64.9%. At least 62% of responders were able to follow the isolation rules, while 21.1% did not or could not organize their living separately from other household members. The main providers during the isolation period were close family members. The most prevalent emotion in our study was worry (70.3%) and fear (37.6%). Worry and fear during the illness were less probable for men than women, but more probable for older patients. Participants with strong emotional support had lower odds of being sad. Those who were exposed to a larger number of sources of information had higher odds of being worried. Those patients who used a higher number of more credible sources of information had higher odds of being afraid during illness. Pets did not play a special role in psychological well-being. The role of the media and public health communications should be explored further to achieve an improved response.