ABSTRACT
BNT162b2, an mRNA-based SARS-CoV-2 vaccine (Pfizer- BioNTech), is one of the most effective COVID-19 vaccines and has been approved by more than 130 countries worldwide. However, several studies have reported that the COVID-19 vaccine shows high interpersonal variability in terms of humoral and cellular responses, such as those with respect to SARS-CoV-2 spike protein immunoglobulin (Ig)G, IgA, IgM, neutralizing antibodies, and CD4+ & CD8+ T cells. The objective of this study is to investigate the kinetic changes in anti-SARS-CoV-2 spike IgG (IgG-S) profiles and adverse reactions and their associations with HLA profiles among 100 hospital workers from the Center Hospital of the National Center for Global Health and Medicine (NCGM), Tokyo, Japan. DQA1*03:03:01 (p = 0.017;OR 2.80, 95% CI 1.05-7.25) was significantly associated with higher IgG-S production after two doses of BNT162b2 while DQB1*06:01:01:01 (p = 0.028, OR 0.27, 95% CI 0.05-0.94) was significantly associated with IgG-S declines after two doses of BNT162b2. No HLA alleles were significantly associated with either local symptoms or fever. However, C*12:02:02 (p = 0.058;OR 0.42, 95% CI 0.15-1.16), B*52:01:01 (p = 0.031;OR 0.38, 95% CI 0.14-1.03), DQA1*03:02:01 (p = 0.028;OR 0.39, 95% CI 0.15-1.00) and DPB1*02:01:02 (p = 0.024;OR 0.45, 95% CI 0.21-0.97) appeared significantly associated with protection against systemic symptoms after two doses of BNT162b2 vaccination. Further studies with larger sample sizes are clearly warranted to determine HLA allele associations with the production and long-term sustainability of IgG-S after COVID-19 vaccination.
ABSTRACT
Coronavirus disease 2019 (COVID-19) was announced as an outbreak by the World Health Organization (WHO) in January 2020 and as a pandemic in March 2020. The majority of infected individuals have experienced no or only mild symptoms, ranging from fully asymptomatic cases to mild pneumonic disease. However, a minority of infected individuals develop severe respiratory symptoms. The objective of this study was to identify susceptible HLA alleles and clinical markers that can be used in risk prediction models for the early identification of severe COVID-19 among hospitalized COVID-19 patients. A total of 137 patients with mild COVID-19 (mCOVID-19) and 53 patients with severe COVID-19 (sCOVID-19) were recruited from the Center Hospital of the National Center for Global Health and Medicine (NCGM), Tokyo, Japan for the period of February-August 2020. High-resolution sequencing-based typing for eight HLA genes was performed using next-generation sequencing. In the HLA association studies, HLA-A∗11:01:01:01 [Pc = 0.013, OR = 2.26 (1.27-3.91)] and HLA-C∗12:02:02:01∼HLAB∗ 52:01:01:02 [Pc = 0.020, OR = 2.25 (1.24-3.92)] were found to be significantly associated with the severity of COVID-19. After multivariate analysis controlling for other confounding factors and comorbidities, HLAA∗ 11:01:01:01 [P = 3.34E-03, OR = 3.41 (1.50-7.73)], age at diagnosis [P = 1.29E-02, OR= 1.04 (1.01-1.07)] and sex at birth [P = 8.88E-03, OR= 2.92 (1.31-6.54)] remained significant. The area under the curve of the risk prediction model utilizing HLA-A∗11:01:01:01, age at diagnosis, and sex at birth was 0.772, with sensitivity of 0.715 and specificity of 0.717. To the best of our knowledge, this is the first article which describes associations of HLA alleles with COVID-19 at the 4-field (highest) resolution level. Early identification of potential COVID-19 could help clinicians prioritize medical utility and significantly decrease mortality from COVID-19.
ABSTRACT
The COVID-19 outbreak continues to evolve with the number of cases increasing in Malaysia, placing a significant burden on general practitioners (GPs) to assess and manage suspected cases. GPs must be well equipped with knowledge to set up their clinics, use Personal Protective Equipment (PPE) appropriately, adopt standard protocols on triaging and referrals, as well as educate patients about PPE. The correct use of PPE will help GPs balance between personal safety and appropriate levels of public concern.