To the Editor,
In a recent paper [1], social interactions, as shaped by religious denomination, have been related to COVID-19 incidence and associated mortality in Western Germany. The number of infections and deaths during the early pandemic phase (spring 2020) was found to be higher in predominantly Catholic countries with stronger family and social ties. The relationship was confirmed at the county level and the individual level. Catholics, relative to non-Catholics, had tighter and more frequent interactions with their family and friends. The intensity of social interaction was able to partially explain the relationship between COVID-19 incidence and the share of Catholics at the country level. To test this hypothesis, we carefully analyzed this statement and compared the relationship between the COVID-19 religious denomination with several genetic confounders.
Because religious geography is explained in part by historical political facts, which are associated with genographics, the pronounced geographical variation in prevalence and mortality during the COVID-19 pandemic has also been linked to genetic variability [2], [3], [4], [5], [6]. As a result, the question arises if the relationship between religion and COVID-19 is independent from an underlying genetic variation of the host. We previously showed that the variability in genotype distribution of a number of immune-related human polymorphisms [2], [3], [4], [5], [6] also partly explains the variable geographical prevalence of the COVID-19 infection.
Mortality data (per 1,000,000 inhabitants) of the COVID-19 infection from several European countries were included in the study: Austria, Belgium, Cyprus, Croatia, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Italy, Ireland, Latvia, Lithuania, Luxemburg, Moldova, the Netherlands, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland, and the United Kingdom were included in the analysis. Data reported on April 30, 2020 by Johns Hopkins were analyzed [7].
Concurrently, data on the geographical variation of some immune system-related human plasma protein polymorphisms were collected from the literature, including the deletion/insertion (D/I) polymorphism of the angiotensin-converting enzyme 1 (ACE1) gene, human homeostatic iron regulator protein (HFE), complement factor C3, haptoglobin, and vitamin D binding protein [2, 6].
In a first analysis, the various COVID-19 mortality data of the 11 Dutch provinces were plotted against COVID-19 mortality [8]. Using regression analysis, a striking relationship between COVID-19 mortality and the percentage of Catholics in the population was found: y (COVID-19 mortality per 100.000 inhabitants) = 0.891 (% Catholics) +3.120; r2 = 0.907. This relationship was confirmed in a multiple regression model, including the S-116 haplotype.
However, when investigating the European COVID-19 prevalence in a multiple regression analysis model (including the religious denomination [9]), the prevalence of COVID-19 significantly correlated with ACE1 polymorphism. The log-transformed mortality of COVID-19 in Europe (on April 30, 2020) negatively correlated with the ACE D allele frequency: log(COVID-19 mortality; no. of cases/106 inhabitants) = 5.567–0.05 (D-allele frequency, %) + 0.0156 (% catholics), r2 = 0.623; p = 0.0001. In this equation, the p value for the D-allele frequency was 0.02 (vs. only 0.668 for the religious denomination).
Although the local data in the Netherlands seem to support the thesis that religious denomination can be related to COVID-19 associated mortality as in neighbouring Western Germany, this observation could not be expanded to a larger European context. The 1555 Peace of Augsburg dramatically changed the scenery for the coexistence of Lutheranism and Catholicism in the Holy Roman Empire along the principle of “Cuius regio, eius religio” (The ruler dictates the religion of those ruled). The rule initially did not hold for Calvinism but the 1648 Peace of Westphalia prohibited converting rulers to force-convert their subjects and by determining the official religion of imperial territories to the status of 1624 as a normative year. Thus the regional distribution between Catholicism, Lutheranism and Calvinism remained essentially stable over time. Our data are pleading for a role of genetics rather than of religious denomination in COVID-19 associated mortality.
-
Research funding: None declared.
-
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
-
Competing interests: Authors state no conflict of interest.
-
Informed consent: Not applicable.
-
Ethical approval: Not applicable.
References
1. Laliotis, I, Minos, D. Religion, social interactions, and COVID-19 incidence in Western Germany. Eur Econ Rev 2022;141:103992. https://doi.org/10.1016/j.euroecorev.2021.103992.Search in Google Scholar PubMed PubMed Central
2. Delanghe, JR, Speeckaert, MM, De Buyzere, ML. COVID-19 infections are also affected by human ACE1 D/I polymorphism. Clin Chem Lab Med 2020;58:1125–6. https://doi.org/10.1515/cclm-2020-0425.Search in Google Scholar PubMed
3. Delanghe, JR, De Buyzere, ML, De Bruyne, S, Van Criekinge, W, Speeckaert, MM. The potential influence of human Y-chromosome haplogroup on COVID-19 prevalence and mortality. Ann Oncol 2020;31:1582–4. https://doi.org/10.1016/j.annonc.2020.08.2096.Search in Google Scholar PubMed PubMed Central
4. Jacobs, M, Lahousse, L, Van Eeckhoutte, HP, Wijnant, SRA, Delanghe, JR, Brusselle, GG, et al.. Effect of ACE1 polymorphism rs1799752 on protein levels of ACE2, the SARS-CoV-2 entry receptor, in alveolar lung epithelium. ERJ Open Res 2021;7:00940–2020. https://doi.org/10.1183/23120541.00940-2020.Search in Google Scholar PubMed PubMed Central
5. Delanghe, J, Speeckaert, MM, De Buyzere, ML. ACE polymorphism is a determinant for COVID-19 mortality in the post-vaccination era. Clin Chem Lab Med 2022;60:e32–3. https://doi.org/10.1515/cclm-2021-1001.Search in Google Scholar PubMed
6. Delanghe, JR, Speeckaert, MM. Host polymorphisms and COVID-19 infection. Adv Clin Chem 2022;107:41–77. ISSN 0065-2423. https://doi.org/10.1016/bs.acc.2021.07.002.Search in Google Scholar PubMed PubMed Central
7. www.worldometers.info/coronavirus/countries. Search in Google Scholar. [Assessed Apr 30 2020].Search in Google Scholar
8. Schmeets, H. De religieuze kaart van Nederland. CBS 2016. Centraal Bureau voor de statistiek, Den Haag; 2016.Search in Google Scholar
9. www.Wikipedia. Catholic Church by country. [Assessed Apr 3 2022].Search in Google Scholar
© 2022 Walter de Gruyter GmbH, Berlin/Boston
