High-resolution African HLA resource uncoversHLA-DRB1expression effects underlying vaccine response (preprint)

How human genetic variation contributes to vaccine immunogenicity and effectiveness is unclear, particularly in infants from Africa. We undertook genome-wide association analyses of eight vaccine antibody responses in 2,499 infants from three African countries and identified significant associations across the human leukocyte antigen (HLA) locus for five antigens spanning pertussis, diphtheria and hepatitis B vaccines. Using high-resolution HLA typing in 1,706 individuals from 11 African populations we constructed a continental imputation resource to fine-map signals of association across the class II HLA observing genetic variation explaining up to 10% of the observed variance in antibody responses. Using follicular helper T-cell assays, in silico binding, and immune cell eQTL datasets we find evidence of HLA-DRB1 expression correlating with serological response and inferred protection from pertussis following vaccination. This work improves our understanding of molecular mechanisms underlying HLA associations that should support vaccine design and development across Africa with wider global relevance. Teaser High-resolution typing of HLA diversity provides mechanistic insights into differential potency and inferred effectiveness of vaccines across Africa.

Clinical Outcomes and Independent Risk Factors for 90-day Mortality in Critically-ill Patients Infected with SARS CoV-2: A Multicenter Study in Turkish Intensive Care Units (preprint)

PurposeThere are limited data on long-term outcome of COVID-19 from different parts of the world. The aim of this study was to determine risk factors of 90-day mortality in critically-ill patients infected with SARS-CoV-2 in Turkish ICUs. MethodsPatients with COVID-19 from26 ICUs in Turkey were included in the study. Demographics, clinical characteristics, laboratory variables, treatment, and survival data were recorded. ResultsA total of 421 patients were included. The median age was 67 (IQR: 57-76) years, and 251 patients (59.6%) were men. 90-day mortality rate was 55.1%. Factors independently associated with 90-day mortality were invasive mechanical ventilation (HR 4.09 [95% CI: 2.20-7.63]), lactate level > 2 mmol/L (2.78 [1.93-4.01]), age ≥ 60 years (2.45 [1.48-4.06)]), cardiac arrhythmia during ICU stay (2.01 [1.27-3.20]), vasopressor treatment (1.94 [1.32-2.84]), positive fluid balance of ≥ 600 ml/per day (1.68 [1.21-2.34]), PaO2/FiO2 ratio of ≤ 150 mmHg (1.66 [1.18-2.32], and ECOG score ≥ 1 (1.42 [1.00-2.02]. ConclusionThis study has shown that long-term mortality was high in critically-ill COVID-19 patients in Turkish ICUs. Invasive mechanical ventilation, high lactate level, older age, presence of cardiac arrhythmia, need for vasopressor treatment, positive fluid balance, severe hypoxemia and not having fully-active performance were related with mortality.

Clinical Outcomes and Independent Risk Factors for 90-day Mortality in Critically-ill Patients Infected With SARS CoV-2: a Multicenter Study in Turkish Intensive Care Units (preprint)

Background: There are limited data on long-term outcome and mortality predictors of COVID-19 from different parts of the world. The aim of this study was to determine risk factors of 90-day mortality in critically-ill patients infected with SARS-CoV-2 in Turkish ICUs. Methods: This multicenter, retrospective study was performed in 26 ICUs in Turkey. All patients with confirmed SARS-CoV2 infection, requiring more than 24 hours of ICU follow-up were included in the study. Demographics, clinical characteristics, laboratory variables, respiratory support, treatment types, and survival data were recorded. Results: A total of 421 patients were included in the study. The median age was 67 (IQR: 57-76) years, and 251 patients (59.6%) were men. 90-day mortality rate was 55.1%. Factors independently associated with 90-day mortality were receiving invasive mechanical ventilation (HR 4.09 [95% CI: 2.20-7.63]), admission lactate level > 2 mmol/L (2.78 [1.93-4.01]), age ≥ 60 years (2.45 [1.48-4.06)]), having cardiac arrhythmia during ICU stay (2.01 [1.27-3.20]), receiving vasopressor treatment (1.94 [1.32-2.84]), positive fluid balance of ≥ 600 ml/per day during ICU follow-up (1.68 [1.21-2.34]), admission PaO2/FiO2 ratio of ≤ 150 mmHg (1.66 [1.18-2.32], and baseline ECOG score ≥ 1 (1.42 [1.00-2.02]. Conclusion: This study has shown that long-term mortality was high in critically-ill COVID-19 patients in Turkish ICUs. Invasive mechanical ventilation, high lactate level, older age, presence of cardiac arrhythmia, need for vasopressor treatment, positive fluid balance, severe hypoxemia and not having fully-active performance were related with mortality.