ABSTRACT
BACKGROUND: Previous studies have reported Blood type O to confer a lower risk of SARS-CoV-2 infection, while secretor status and other blood groups have been suspected to have a similar effect as well. STUDY DESIGN AND METHODS: To determine whether any other blood groups influence testing positive for SARS-CoV-2, COVID-19 severity, or prolonged COVID-19, we used a large cohort of 650,156 Danish blood donors with varying available data for secretor status and blood groups ABO, Rh, Colton, Duffy, Diego, Dombrock, Kell, Kidd, Knops, Lewis, Lutheran, MNS, P1PK, Vel, and Yt. Of these, 36,068 tested positive for SARS-CoV-2 whereas 614,088 tested negative between 2020-02-17 and 2021-08-04. Associations between infection and blood groups were assessed using logistic regression models with sex and age as covariates. RESULTS: The Lewis blood group antigen Lea displayed strongly reduced SARS-CoV-2 susceptibility OR 0.85 CI[0.79-0.93] p < .001. Compared to blood type O, the blood types B, A, and AB were found more susceptible toward infection with ORs 1.1 CI[1.06-1.14] p < .001, 1.17 CI[1.14-1.2] p < .001, and 1.2 CI[1.14-1.26] p < .001, respectively. No susceptibility associations were found for the other 13 blood groups investigated. There was no association between any blood groups and COVID-19 hospitalization or long COVID-19. No secretor status associations were found. DISCUSSION: This study uncovers a new association to reduced SARS-CoV-2 susceptibility for Lewis type Lea and confirms the previous link to blood group O. The new association to Lea could be explained by a link between mucosal microbiome and SARS-CoV-2.
ABSTRACT
Introduction: The pro-inflammatory immune response underlies severe cases of COVID-19. Antigens of the Duffy blood group systems are receptors for pro-inflammation chemokines. The ACKR1 c.-67T>C gene variation silences the expression of Duffy antigens on erythrocytes and individuals presenting this variant in homozygosity have impaired inflammatory response control. Our aim was to evaluate the association between the ACKR1 c.-67T>C and the severity of COVID-19. Methods: This was a retrospective single-center case-control study, enrolling 164 participants who were divided into four groups: 1) Death: COVID-19 patients who died during hospitalization; 2) Hospital Discharge: COVID-19 patients who were discharged for home after hospitalizations; 3) Convalescent Plasma Donors: COVID-19 patients who were not hospitalized, and; 4) Controls: patients with diagnosis other than COVID-19. Patients were genotyped for the ACKR1 c.-67T>C (FY*02 N.01 allele) and the frequency of individuals presenting the altered allele was compared between the groups. Results: The groups significantly differed in terms of the percentage of patients presenting at least one FY*02N.01 allele: 36.8% (Death group), 37% (Hospital Discharge group), 16.1% (Convalescent Plasma group) and 16.2% (Control group) (p = 0.027). The self-declared race (p < 0.001) and the occurrence of in hospital death (p = 0.058) were independently associated with the presence of the FY*02N.01 allele. Hypertension (p < 0.001), age (p < 0.001) and the presence of at least one FY*02N.01 allele (p = 0.009) were independently associated with the need for hospitalization. Conclusion: There is a suggestive association between the presence of the FY*02N.01 and the severity of COVID-19. This may be a mechanism underlying the worse prognosis for Afro-descendants infected with SARS-CoV-2.
ABSTRACT
The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has expanded into a global pandemic, with more than 220 million affected persons and almost 4.6 million deaths by 8 September 2021. In particular, Europe and the Americas have been heavily affected by high infection and death rates. In contrast, much lower infection rates and mortality have been reported generally in Africa, particularly in the sub-Saharan region (with the exception of the Southern Africa region). There are different hypotheses for this African paradox, including less testing, the young age of the population, genetic disposition, and behavioral and epidemiological factors. In the present review, we address different immunological factors and their correlation with genetic factors, pre-existing immune status, and differences in cytokine induction patterns. We also focus on epidemiological factors, such as specific medication coverage, helminth distribution, and malaria endemics in the sub-Saharan region. An analysis combining different factors is presented that highlights the central role of the NF-κB signaling pathway in the African paradox. Importantly, insights into the interplay of different factors with the underlying immune pathological mechanisms for COVID-19 can provide a better understanding of the disease and the development of new targets for more efficient treatment strategies.