Impaired Humoral Immunity Identified in Inactivated SARS-CoV-2 Vaccine Recipients without Anti-Spike RBD Antibodies.

Inactivated SARS-CoV-2 vaccines have been deployed in a significant portion of the world population, who have widely varied responses to vaccination. Understanding this differential response would help the development of new vaccines for non-responders. Here, we conducted surveillance of anti-Spike receptor-binding domain (RBD) antibody levels in a large cohort of 534 healthy Chinese subjects vaccinated with two doses of inactivated SARS-CoV-2 vaccines. We show that the positive rate of antibodies among vaccinated subjects rapidly wanes as the interval between antibody testing and vaccination increases (14 to 119 days: 81.03%, 363 of 448 subjects; 120 to 149 days: 46.43%, 13 of 28 subjects; more than 150 days: 20%, 1 of 5 subjects). However, the antibodies were maintained at high levels in 16 convalescent COVID-19 patients at more than 150 days after recovery. We also found that increased age and body mass index are associated with decreased antibody levels. Vaccinated subjects who fail to produce antibodies display impaired B-cell activating humoral immunity, which was confirmed in COVID-19 patients without antibodies detected at 4 to 18 days after diagnosis. IMPORTANCE Our study illustrates the immune responses engaged by encountering antigen, highlighting the critical roles of B-cell activating humoral immunity in the body's antibody production.

Angiotensin-Converting Enzyme Genotype-Specific Immune Response Contributes to the Susceptibility of COVID-19: A Nested Case-Control Study.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19), which has resulted in a global pandemic. Methodology: We used a two-step polymerase chain reaction to detect the ACE genotype and ELISA kits to detect the cytokine factor. We also used proteomics to identify the immune pathway related to the ACE protein expression. Result: In this study, we found that the angiotensin-converting enzyme (ACE) deletion polymorphism was associated with the susceptibility to COVID-19 in a risk-dependent manner among the Chinese population. D/D genotype distributions were higher in the COVID-19 disease group than in the control group (D/D odds ratio is 3.87 for mild (p value < 0.0001), 2.59 for moderate (p value = 0.0002), and 4.05 for severe symptoms (p value < 0.0001), logic regression analysis. Moreover, genotype-specific cytokine storms and immune responses were found enriched in patients with the ACE deletion polymorphism, suggesting the contribution to the susceptibility to COVID-19. Finally, we identified the immune pathway such as the complement system related to the ACE protein expression of patients by lung and plasma proteomics. Conclusion: Our results demonstrated that it is very important to consider gene polymorphisms in the population to discover a host-based COVID-19 vaccine and drug design for preventive and precision medicine.

Drastic decline in sera neutralization against SARS-CoV-2 Omicron variant in Wuhan COVID-19 convalescents.

Global concern has been raised by the emergence and rapid transmission of the heavily mutated SARS-CoV-2 Omicron variant (B.1.1.529). So far, the infection features and immune escape ability of the Omicron variant have not been extensively studied. Here, we produced the Omicron pseudovirus and compared its entry, membrane fusion, and immune escape efficiency with the original strain and the dominating Delta variant. We found the Omicron variant showed slightly higher infectivity than the Delta variant and a similar ability to compete with the Delta variant in using Angiotensin-converting enzyme 2 (ACE2) in a BHK21-ACE2 cell line. However, the Omicron showed a significantly reduced fusogenicity than the original strain and the Delta variant in both BHK21-ACE2 and Vero-E6 cells. The neutralization assay testing the Wuhan convalescents' sera one-year post-infection showed a more dramatic reduction (10.15 fold) of neutralization against the Omicron variant than the Delta variant (1.79 fold) compared with the original strain with D614G. Notably, immune-boosting through three vaccine shots significantly improved the convalescents' immunity against the Omicron variants. Our results reveal a reduced fusogenicity and a striking immune escape ability of the Omicron variant, highlighting the importance of booster shots against the challenge of the SARS-CoV-2 antigenic drift.

Antibody neutralization to SARS-CoV-2 and variants after 1 year in Wuhan, China.

Most COVID-19 convalescents can build effective anti-SARS-CoV-2 humoral immunity, but it remains unclear how long it can maintain and how efficiently it can prevent the reinfection of the emerging SARS-CoV-2 variants. Here, we tested the sera from 248 COVID-19 convalescents around 1 year post-infection in Wuhan, the earliest known epicenter. SARS-CoV-2 immunoglobulin G (IgG) was well maintained in most patients and potently neutralizes the infection of the original strain and the B.1.1.7 variant. However, varying degrees of immune escape was observed on the other tested variants in a patient-specific manner, with individuals showing remarkably broad neutralization potency. The immune escape can be largely attributed to several critical spike mutations. These results suggest that SARS-CoV-2 can elicit long-lasting immunity but this is escaped by the emerging variants.

Serum nitrite and nitrate: A potential biomarker for post-covid-19 complications?

Nitric oxide (NO) plays an important role in cardiovascular and immune systems. Quantification of blood nitrite and nitrate, two relatively stable metabolites of NO (generally as NOx), has been acknowledged, in part, representing NO bioactivity. Dysregulation of NOx had been reported in SARS-CoV-2 infected populations, but whether patients recovered from COVID-19 disease present with restored NOx is unknown. In this study, serum NO2- and NO3- were quantified and analyzed among 109 recovered adults in comparison to a control group of 166 uninfected adults. Nitrite or nitrate levels were not significantly different among mild-, common-, severe- and critical-type patients. However, these recovered patients had dramatically lower NO2- and NO2-/NO3- than the uninfected group (p < 0.0001), with significantly higher NO3- levels (p = 0.0023) than the uninfected group. Nitrate and nitrite/nitrate were positively and negatively correlated with patient age, respectively, with age 65 being a turning point among recovered patients. These results indicate that low NO2-, low NO2-/NO3- and high NO3- may be potential biomarkers of long-term poor or irreversible outcomes after SARS-CoV-2 infection. It suggests that NO metabolites might serve as a predictor to track the health status of recovered COVID-19 patients, highlighting the need to elucidate the role of NO after SARS-CoV-2 infection.