Comprehensive humoral and cellular immune responses to SARS-CoV-2 variants in diverse Chinese populations: A benefit perspective of national vaccination (preprint)

The emerging SARS-CoV-2 variants have made great challenges to current vaccine and pandemic control strategies. B.1.1.529 (Omicron), which was classified as a variant of concern (VOC) by the World Health Organization on November 26th, 2021, has quickly become the dominant circulating variant and causing waves of infections. It is urgent to understand the current immune status of the general population given that pre-existing immunity has been established by national vaccination or exposure to past variants. Using sera from 85 individuals (including 21 convalescents of natural infection, 15 cases suffered a breakthrough infection after vaccination, and 49 vaccinated participants without infection history), we showed that the cross-neutralizing activity against VOCs such as Omicron can be detected in 53 (62.4%) cases, although less potent than against the Wuhan-1 strain (WT), with a 3.9-fold reduction in geometric mean neutralizing titer (GMT) (130.7, 95% CI 88.4-193.3 vs 506, 355.8-719.7, respectively). Subgroup analysis revealed significantly enhanced neutralizing activity against WT and VOCs in Delta convalescent sera. The neutralizing antibodies against Omicron were detectable in 75% of convalescents and 44.9% of healthy donors (p = 0.006), with a GMT of 289.5, 180.9-463.3 and 42.6, 31.3-59, respectively. However, the protective effect against VOCs was weaker in young convalescents (aged < 18y), with a detectable rate of 50% and a GMT of 46.4 against Omicron, similar to vaccinees. The pan-sarbecovirus neutralizing activities were not observed in vaccinated SARS-CoV-1 survivors. A booster dose significantly increased the breadth and magnitude of neutralization against WT and VOCs to different degrees than full vaccination. In addition, we showed that COVID-19 inactivated vaccines can elicit Omicron-specific T cell responses. The positive rates of ELISpot reactions were 26.7% (4/15) and 43.8% (7/16) in the full vaccination group and the booster vaccination group, respectively. The neutralizing antibody titers declined while T-cell responses remain robust over 6 months. These findings will inform the optimization of public health vaccination and intervention strategies to protect diverse populations against SARS-CoV-2 variants.

Investigation of the Impact of SARS-CoV-1 Infection on the Immunologic Status and Lung Function After 15 Years (preprint)

Background: To investigate the long-term effects of SARS-CoV-1 on patients’ lung and immune systems 15 years post-infection. Methods: We enrolled 58 health care workers with confirmed SARS in Peking University People’s Hospital in 2003. We evaluated lung damage by mMRC score, pulmonary function tests, and chest CT. Immune function was assessed by their serum levels of globin, complete components, and peripheral T cell subsets. ELISA was used to detect SARS-CoV-specific IgG antibodies in sera. Results: After 15 years of disease onset, 19 (36.5%), 8 (34.6%), and 19 (36.5%) subjects had impaired DL(CO), RV, and FEF25-75, respectively. 17 (30.4%) subjects had an mMRC score ≥ 2. Fourteen (25.5%) cases had residual CT abnormalities. T regulatory cells were a bit higher in the SARS survivors. IgG antibodies against SARS S-RBD protein and N protein were detected in 11 (18.97%) and 12 (20.69%) subjects, respectively. Subgroup analysis revealed that small airway dysfunction and CT abnormalities were more common in the severe group than in the non-severe group (57.1% vs 22.6%, 54.5% vs 6.1%, respectively, p < 0.05). Conclusions: SARS-CoV-1 could cause permanent damage to the lung, which requires early pulmonary rehabilitation. The long-lived immune memory response against coronavirus requires further studies to assess the potential benefit.Trail registration: ClinicalTrials.gov, NCT03443102. Registered prospectively on 22/02/2018.