ABSTRACT
The inactivated vaccine CoronaVac is one of the most widely used COVID-19 vaccines globally. However, the longitudinal evolution of the immune response induced by CoronaVac remains elusive compared to other vaccine platforms. Here, we recruited 88 healthy individuals that received 3 doses of CoronaVac vaccine. We longitudinally evaluated their polyclonal and antigen-specific CD4+ T cells and neutralizing antibody response after receiving each dose of vaccine for over 300 days. Both the 2nd and 3rd dose of vaccination induced robust spike-specific neutralizing antibodies, with a 3rd vaccine further increased the overall magnitude of antibody response, and neutralization against Omicron sub-lineages B.1.1.529, BA.2, BA.4/BA.5 and BA.2.75.2. Spike-specific CD4+ T cell and circulating T follicular helper (cTFH) cells were markedly increased by the 2nd and 3rd dose of CoronaVac vaccine, accompanied with altered composition of functional cTFH cell subsets with distinct effector and memory potential. Additionally, cTFH cells are positively correlated with neutralizing antibody titers. Our results suggest that CoronaVac vaccine-induced spike-specific T cells are capable of supporting humoral immunity for long-term immune protection.
Subject(s)
COVID-19ABSTRACT
During the normalization phase of the COVID-19 epidemic, society has gradually reverted to using building space, especially for public buildings, e.g., offices. Prevention of airborne pollutants has emerged as a major challenge. Ventilation strategies can contribute to mitigating the spread of airborne disease in an indoor environment, including increasing supply air rate, modifying ventilation mode, etc. The larger ventilation rate can inevitably lead to high energy consumption, which may be also ineffective in reducing infection risk. As a critical factor affecting the spread of viral contaminant, the potential of ventilation modes for control of COVID-19 should be explored. This study compared several ventilation strategies in the office, including mixing ventilation (MV), zone ventilation (ZV), stratum ventilation (SV) and displacement ventilation (DV), through analyzing ventilation performance and infection risk for the optimal one. By using ANSYS Fluent, the distributions of airflow and pollutant were simulated under various ventilation modes and infected occupants. The SV showed greater performance in mitigating infection disease spread than MV, ZV and DV, with an air distribution performance index (ADPI) of 90.5% and minimum infection risk of 13%. This work can provide a reference for development of ventilation strategies in public space oriented the prevention of COVID-19.
ABSTRACT
Coronavirus disease 2019 (COVID-19), caused by coronavirus SARS-CoV-2, is known to disproportionately affect older individuals1,2. How aging processes affect the disease progression remains largely unknown. Here we found that DNA damage, one of the major causes of aging3, promoted susceptibility to SARS-CoV-2 infection in cells and intestinal organoids. SARS-CoV-2 entry was facilitated by DNA damage caused by telomere attrition or extrinsic genotoxic stress and hampered by inhibition of DNA damage response (DDR). Mechanistic analysis revealed that DDR increased expression of ACE2, the receptor of SARS-CoV-2, by activation of transcription factor c-Jun in vitro and in vivo. Expression of ACE2 was elevated in the older tissues and positively correlated with γH2Ax and phosphorylated c-Jun (p-c-Jun). Finally, targeting DNA damage by increasing the DNA repair capacity, alleviated cell susceptibility to SARS-CoV-2. Our data provide insights into the age-associated differences in SARS-CoV-2 infection and a novel target for anti-viral intervention.
Subject(s)
COVID-19ABSTRACT
Background Coronavirus infectious disease 2019 (COVID-19) has developed into a global pandemic. It is essential to investigate the clinical characteristics of COVID-19 and uncover potential risk factors for severe disease to reduce the overall mortality rate of COVID-19. Methods Sixty-one critical COVID-19 patients admitted to the intensive care unit (ICU) and 93 severe non-ICU patients at Huoshenshan Hospital (Wuhan, China) were included in this study. Medical records, including demographic, platelet counts, heparin-involved treatments, heparin-induced thrombocytopenia-(HIT) related laboratory tests, and fatal outcomes of COVID-19 patients were analyzed and compared between survivors and nonsurvivors. Findings Sixty-one critical COVID-19 patients treated in ICU included 15 survivors and 46 nonsurvivors. Forty-one percent of them (25/61) had severe thrombocytopenia, with a platelet count (PLT) less than 50x109/L, of whom 76% (19/25) had a platelet decrease of >50% compared to baseline; 96% of these patients (24/25) had a fatal outcome. Among the 46 nonsurvivors, 52.2% (24/46) had severe thrombocytopenia, compared to 6.7% (1/15) among survivors. Moreover, continuous renal replacement therapy (CRRT) could induce a significant decrease in PLT in 81.3% of critical CRRT patients (13/16), resulting in a fatal outcome. In addition, a high level of anti-heparin-PF4 antibodies, a marker of HIT, was observed in most ICU patients. Surprisingly, HIT occurred not only in patients with heparin exposure, such as CRRT, but also in heparin-naive patients, suggesting that spontaneous HIT may occur in COVID-19. Interpretation Anti-heparin-PF4 antibodies are induced in critical COVID-19 patients, resulting in a progressive platelet decrease. Exposure to a high dose of heparin may trigger further severe thrombocytopenia with a fatal outcome. An alternative anticoagulant other than heparin should be used to treat COVID-19 patients in critical condition.
Subject(s)
COVID-19 , Thrombocytopenia , Coronavirus InfectionsABSTRACT
In order to identify the clinical characteristics of patients with Corona Virus Disease 2019 (COVID-19) and find out the characteristic effects of 2019 New Coronavirus (SARS-CoV-2) infection on changes in clinical and laboratory data, we analyzed the medical records of 80 suspected cases who admitted in the national designated hospital due to the relevant clinical manifestations of SARS-CoV-2 infection from January 22 to February 13, 2020. 62 (77.5%) confirmed cases and 18 (22.5%) negative cases were confirmed by SARS-CoV-2 nucleic acid test. Epidemiological investigation and statistical analysis were carried out on the clinical and laboratory data of all suspected cases of COVID-19, the specific indicators were found, and the clinical characteristics of COVID-19 were described. Compared with the patients with negative nucleic acid test, the patients with positive nucleic acid test showed shorter time of onset of symptoms, higher plasma CO2 level, lower eosinophil ratio, lower platelet count and hematocrit, lower serum sodium level, higher serum creatinine, higher blood urea and plasma albumin levels (all P<0.05). Our results might provide some suggestions in diagnosis, clinical treatment and prevention for COVID-19.
Subject(s)
COVID-19 , Virus DiseasesABSTRACT
An excessive immune response contributes to SARS-CoV, MERS-CoV and SARS-CoV-2 pathogenesis and lethality, but the mechanism remains unclear. In this study, the N proteins of SARS-CoV, MERS-CoV and SARS-CoV-2 were found to bind to MASP-2, the key serine protease in the lectin pathway of complement activation, resulting in aberrant complement activation and aggravated inflammatory lung injury. Either blocking the N protein:MASP-2 interaction or suppressing complement activation can significantly alleviate N protein-induced complement hyper-activation and lung injury in vitro and in vivo. Complement hyper-activation was also observed in COVID-19 patients, and a promising suppressive effect was observed when the deteriorating patients were treated with anti-C5a monoclonal antibody. Complement suppression may represent a common therapeutic approach for pneumonia induced by these highly pathogenic coronaviruses.