Targeted capture enrichment and sequencing identifies HLA variants associated with the severity of COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is currently a global pandemic. The pathogenesis of severe COVID-19 has been widely investigated, but it is still unclear. Human leukocyte antigen (HLA) plays a central role in immune response, and its variants might be related to COVID-19 progression and severity. OBJECTIVE: To investigate the hypothesis that individual HLA variations could alter the course of COVID-19 and might be associated with the severity of COVID-19. METHODS: In this study, we conducted an HLA targeted capture enrichment and sequencing of severe COVID-19 patients matched to mild cases. A total of 16 COVID-19 patients, confirmed by SARS-CoV-2 viral RNA polymerase-chain-reaction (PCR) test and chest computed tomography (CT) scan, were enrolled in this study. The HLA targeted capture enrichment and sequencing were conducted. HLA typing was performed by comparing contigs with IPD-IMGT/HLA Database. RESULTS: In this study, 139 four-digit resolution HLA alleles were acquired. The results showed that HLA-DRB3*01:01 allele was significantly associated with the severity of COVID-19 (odds ratio [OR] = 27.64, 95% confidence interval [CI] = 1.35-560.50, P = 0.0064). And HLA-K*01:01 might be a potential risk factor for COVID-19 severity (OR = 0.11, 95% CI = 0.017-0.66, P = 0.019), but HLA-K*01:02 might be a protective factor (OR = 7.50, 95% CI = 1.48-37.92, P = 0.019). CONCLUSION: Three non-classical HLA alleles, including HLA-DRB3*01:01, HLA-K*01:01, HLA-K*01:02 were identified to be associated with the severity of COVID-19 by comparing mild and severe patients. The current findings would be helpful for exploring the influence of HLA gene polymorphisms on the development and severity of COVID-19.

Neutralizing activity of BBIBP-CorV vaccine-elicited sera against Beta, Delta and other SARS-CoV-2 variants of concern.

The global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the generation of variants that may diminish host immune responses to vaccine formulations. Here we show a registered observational clinical trial (NCT04795414), we assess the safety and immunogenicity of the inactivated SARS-CoV-2 vaccine BBIBP-CorV in a cohort of 1006 vaccine recipients. No serious adverse events are observed during the term of the study. Detectable virus-specific antibody is measured and determined to be neutralizing in 698/760 (91.84%) vaccine recipients on day 28 post second vaccine dose and in 220/581 (37.87%) vaccine recipients on day 180 post second vaccine dose, whereas vaccine-elicited sera show varying degrees of reduction in neutralization against a range of key SARS-CoV-2 variants, including variant Alpha, Beta, Gamma, Iota, and Delta. Our work show diminished neutralization potency against multiple variants in vaccine-elicited sera, which indicates the potential need for additional boost vaccinations.

Characterization of antibody responses to SARS-CoV-2 in convalescent COVID-19 patients.

The coronavirus disease 2019 (COVID-19) is a pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, little is known about the durability of the antibody response during COVID-19 convalescent phase. We investigated the prevalence of anti-SARS-CoV-2 specific antibodies including immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies and the dynamic changes in antibody levels in convalescent COVID-19 patients. A total of 159 blood samples were collected from 52 recovered COVID-19 patients up to six months after symptom onset for longitudinal serological tests. The positive rate of IgG and IgM antibodies was 92.3% and 90.4% in the first month after symptom onset, and the seropositivity of IgG antibody remained high at all follow-up time points, whereas the seropositivity of IgM antibody decreased to 22.73% by the sixth months after symptom onset. The level of IgG antibody was stable, the level of IgM antibody decreased slightly in the early convalescent phase and was detected in only five patients in the sixth month after symptom onset. The level of IgG antibody was higher in the severe and critical group than in the moderate group. The anti-SARS-CoV-2 specific antibodies have a long-term persistence in convalescent COVID-19 patients, whether they have long-term protection need to be further investigated.

Analysis of Risk Factors for 24 Patients With COVID-19 Developing From Moderate to Severe Condition.

Objective: The present study aimed at investigating the clinical risk factors for COVID-19 patients developing from moderate condition to severe condition, and providing reference for early intervention and prognosis. Methods: We collected the clinical data of 24 patients with moderate-to-severe COVID-19 who were admitted to the isolation ward of the First Affiliated Hospital of Bengbu Medical College from January, 2020 to February 20, 2020, and evaluated the data of clinical characteristics, blood test results, inflammatory index, chest CT imaging characteristics, and antiviral treatment, comparing this with the clinical data of 41 patients with moderate condition in the same period. From this comparison we thus summarized the current knowledge of potential risk factors for COVID-19 patients developing from moderate to severe condition. Results: (1) Clinical characteristics: The moderate-to-severe group and the moderate group in terms of combined common underlying diseases and respiratory frequency showed significant difference statistically (t-value were 13.32, 6.17, respectively, P < 0.05), while no significant difference between the two groups in gender, age, or clinical symptoms was statistically observed(P > 0.05). (2) Analysis of blood test results: The lymphocyte count and plasma albumin of the moderate-to-severe group were significantly lower than those of the moderate group (t-values were 4.16, 4.11, respectively, P < 0.05), and the blood glucose and urea of the moderate-to-severe group were significantly higher than those of the moderate group (t-value were 3.27, 4.19, respectively, P < 0.05). However, there was no significant difference in terms of white blood cell count (WBC), platelet count (PLT), and glutamic-pyruvic transaminase (GPT) (P > 0.05). (3) Comparison of inflammatory indicators: The level of IL-6 and CRP of the moderate-to-severe group were significantly higher than those of the moderate group (t-values were 2.84, 4.88, respectively, P < 0.05). (4) Imaging comparison: As for patients with moderate COVID-19, the imaging manifestations were the concurrence of ground-glass opacity, patchy shadow, and consolidation shadow in both lungs, diffuse ground-glass opacity in both lungs accompanied by air bronchogram, and large area consolidation of both lungs with pulmonary interstitial changes. The possibility for these patients to develop into severe condition increased, and the differences were statistically significant (t = 10.92, P < 0.05). (5) Clinical antiviral treatment: There was no statistically significant difference in the combination of two or three antiviral drugs between the two groups (χ2 = 0.05, P > 0.05). Conclusion: Current evidence suggested that the combination of common underlying diseases, respiratory frequency, lymphocyte count, blood glucose, albumin, urea level, inflammatory factors (CRP, IL-6), and imaging manifestations collectively contributed to the potential risk factors for the development of COVID-19 from moderate condition to severe condition. Particular attention should be paid to early detection and intervention during clinical work, which will be of vital significance to the ascent of the recovery rate as well as the reduction of mortality.