Human leukocyte antigen alleles associate with COVID-19 vaccine immunogenicity and risk of breakthrough infection

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine immunogenicity varies between individuals, and immune responses correlate with vaccine efficacy. Using data from 1,076 participants enrolled in ChAdOx1 nCov-19 vaccine efficacy trials in the United Kingdom, we found that inter-individual variation in normalized antibody responses against SARS-CoV-2 spike and its receptor-binding domain (RBD) at 28 days after first vaccination shows genome-wide significant association with major histocompatibility complex (MHC) class II alleles. The most statistically significant association with higher levels of anti-RBD antibody was HLA-DQB1*06 (P = 3.2 × 10−9), which we replicated in 1,677 additional vaccinees. Individuals carrying HLA-DQB1*06 alleles were less likely to experience PCR-confirmed breakthrough infection during the ancestral SARS-CoV-2 virus and subsequent Alpha variant waves compared to non-carriers (hazard ratio = 0.63, 0.42–0.93, P = 0.02). We identified a distinct spike-derived peptide that is predicted to bind differentially to HLA-DQB1*06 compared to other similar alleles, and we found evidence of increased spike-specific memory B cell responses in HLA-DQB1*06 carriers at 84 days after first vaccination. Our results demonstrate association of HLA type with Coronavirus Disease 2019 (COVID-19) vaccine antibody response and risk of breakthrough infection, with implications for future vaccine design and implementation

"Epidemiology of Diphtheria in Yemen, 2017-2018: Surveillance Data Analysis" (Preprint)

BACKGROUND As a consequence of war and collapse of health system in Yemen, diphtheria fatal epidemic occurred at the end of 2017 OBJECTIVE This study aims to describe epidemiology of diphtheria in Yemen, determine its incidence and case fatality rate METHODS Data of patients with diphtheria was obtained from the Diphtheria program in a form of line list which were collected on daily basis by electronic Diseases Early Warning System (eDEWS). Probable case was defined as any person suffered from laryngitis or pharyngitis or tonsillitis and adherent membrane of the tonsils, pharynx and/or nose. Confirmed case was defined as probable case that is laboratory-confirmed or linked epidemiologically to laboratory-confirmed case RESULTS A total of 2,243 cases were reported during the period between July 2017 and August 2018. About 49% of cases were males and 51% of cases were females. About 44% of cases were 5 -15 years old. Respiratory tract infection was the predominant symptoms (91%) followed by psedumembrane (81%). Based on the vaccination status, the percentage of partial vaccinated patients, vaccinated, unvaccinated, and unknown were 7%, 31%, 48% and 14%, respectively. The overall incidence of diphtheria was 8 per 100,000 of population. The highest incidence was among age group &lt;15 years (11 per 100,000) and the lowest incidence was among age group of ≥ 15 years (5 per 100,000). The overall case fatality rate (CFR) among all age groups was 5%, being higher (10%) in the age group &lt; 5 years. . Five of difficult to access governorates had double CFR (22%) which were Raymah, Abyan , Sa'ada, Lahj, Al Jawf. CONCLUSIONS : Diphtheria in Yemen in 2017-2018 affected a significant number of people. The majority of patients were partially or not vaccinated. Children ≤ 15 years were more affected with higher fatality among children &lt; five years. Five of difficult to access governorates had double CFR of WHO estimate. To control diphthereia epidemic in Yemn, it is recommended to increase vaccination coverage through campaigns and boosters, increase public health awareness toward diphtheria and strengthen the surveillance system for early detection and immediate response and provide antitoxin for management of severe cases. </sec

Evaluation of Blood Transfusion Services in Public and Private Blood Bank Centers, Sana’a Capital, Yemen

The aim of this study was to evaluate blood transfusion services (BTS) at the main blood banks (BBs) of the Sana’a Capital. The 4 main BBs at Sana’a Capital were evaluated according to the safe World Health Organization BTS standards. Qualitative and quantitative data were collected using semi-structured questionnaires covering 6 components: activities, quality assurance system (QAS) and training, donation, grouping and compatibility testing, components, and screening for transfusion-transmitted infections (TTIs). An overall mean percent score for BTS was calculated where &lt;60% is considered unsatisfactory, 60% to 79.9% satisfactory, and ≥80% highly satisfactory. The 4 BBs screen for HIV, hepatitis B, and hepatitis C and perform all functions except therapeutic transfusion. While 75% of the staff in BBs had received training in biosafety and half of the staff had received training in Standard Operating Procedures (SOPs), no QAS in place at any of the 4 BBs. The 4 BBs depended on 71% of their transfusions on family donors. Two BBs do not perform reverse grouping and do not keep patient/donor samples for the required minimum 5 days. Only one BB achieved an overall high satisfactory score and one achieved a satisfactory score. Findings highlight the increasing challenges facing BTS in Sana’a Capital especially the lack of therapeutic transfusion, poor QAS, and predominant dependence on the family donors. Therefore, there is a need to develop and train staff on QAS and to increase awareness among public on importance of voluntary donation. A wider scale evaluation of BTS in Sana’a is recommended. </jats:p

Early short course of neuromuscular blocking agents in patients with COVID-19 ARDS: a propensity score analysis

Background: The role of neuromuscular blocking agents (NMBAs) in coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS) is not fully elucidated. Therefore, we aimed to investigate in COVID-19 patients with moderate-to-severe ARDS the impact of early use of NMBAs on 90-day mortality, through propensity score (PS) matching analysis. Methods: We analyzed a convenience sample of patients with COVID-19 and moderate-to-severe ARDS, admitted to 244 intensive care units within the COVID-19 Critical Care Consortium, from February 1, 2020, through October 31, 2021. Patients undergoing at least 2&nbsp;days and up to 3 consecutive days of NMBAs (NMBA treatment), within 48&nbsp;h from commencement of IMV were compared with subjects who did not receive NMBAs or only upon commencement of IMV (control). The primary objective in the PS-matched cohort was comparison between groups in 90-day in-hospital mortality, assessed through Cox proportional hazard modeling. Secondary objectives were comparisons in the numbers of ventilator-free days (VFD) between day 1 and day 28 and between day 1 and 90 through competing risk regression. Results: Data from 1953 patients were included. After propensity score matching, 210 cases from each group were well matched. In the PS-matched cohort, mean (± SD) age was 60.3 ± 13.2&nbsp;years and 296 (70.5%) were male and the most common comorbidities were hypertension (56.9%), obesity (41.1%), and diabetes (30.0%). The unadjusted hazard ratio (HR) for death at 90&nbsp;days in the NMBA treatment vs control group was 1.12 (95% CI 0.79, 1.59, p = 0.534). After adjustment for smoking habit and critical therapeutic covariates, the HR was 1.07 (95% CI 0.72, 1.61, p = 0.729). At 28&nbsp;days, VFD were 16 (IQR 0-25) and 25 (IQR 7-26) in the NMBA treatment and control groups, respectively (sub-hazard ratio 0.82, 95% CI 0.67, 1.00, p = 0.055). At 90 days, VFD were 77 (IQR 0-87) and 87 (IQR 0-88) (sub-hazard ratio 0.86 (95% CI 0.69, 1.07; p = 0.177). Conclusions: In patients with COVID-19 and moderate-to-severe ARDS, short course of NMBA treatment, applied early, did not significantly improve 90-day mortality and VFD. In the absence of definitive data from clinical trials, NMBAs should be indicated cautiously in this setting

Stroke in critically ill patients with respiratory failure due to COVID-19: Disparities between low-middle and high-income countries

Purpose: We aimed to compare the incidence of stroke in low-and middle-income countries (LMICs) versus high-income countries (HICs) in critically ill patients with COVID-19 and its impact on in-hospital mortality. Methods: International observational study conducted in 43 countries. Stroke and mortality incidence rates and rate ratios (IRR) were calculated per admitted days using Poisson regression. Inverse probability weighting (IPW) was used to address the HICs vs. LMICs imbalance for confounders. Results: 23,738 patients [20,511(86.4 %) HICs vs. 3,227(13.6 %) LMICs] were included. The incidence stroke/1000 admitted-days was 35.7 (95 %CI = 28.4–44.9) LMICs and 17.6 (95 %CI = 15.8–19.7) HICs; ischemic 9.47 (95 %CI = 6.57–13.7) LMICs, 1.97 (95 %CI = 1.53, 2.55) HICs; hemorrhagic, 7.18 (95 %CI = 4.73–10.9) LMICs, and 2.52 (95 %CI = 2.00–3.16) HICs; unspecified stroke type 11.6 (95 %CI = 7.75–17.3) LMICs, 8.99 (95 %CI = 7.70–10.5) HICs. In regression with IPW, LMICs vs. HICs had IRR = 1.78 (95 %CI = 1.31–2.42, p &lt; 0.001). Patients from LMICs were more likely to die than those from HICs [43.6% vs 29.2 %; Relative Risk (RR) = 2.59 (95 %CI = 2.29–2.93), p &lt; 0.001)]. Patients with stroke were more likely to die than those without stroke [RR = 1.43 (95 %CI = 1.19–1.72), p &lt; 0.001)]. Conclusions: Stroke incidence was low in HICs and LMICs although the stroke risk was higher in LMICs. Both LMIC status and stroke increased the risk of death. Improving early diagnosis of stroke and redistribution of healthcare resources should be a priority. Trial registration: ACTRN12620000421932 registered on 30/03/2020