Emergence of SARS-CoV-2 Variants of Concern Induced by Dengue Viral Coinfections

Abstract

Background: SARS-CoV-2 emerged in late 2019 has accumulated a series of point mutations and evolved into several variants of concern (VOC), some of which are more transmissible and potentially more severe than the original strain. The most notable VOCs are Alpha, Beta, Gamma, Delta and Omicron, which have spread to various parts of the world. The study conducted in Jashore, Bangladesh aimed to investigate the effect of coinfection with Dengue virus on SARS-CoV-2 evolution and the emergence of VOC.

Methods: A hospital-based COVID-19 surveillance from June to August, 2021 identified 9,453 positive patients in the surveillance area. The study enrolled 572 randomly selected COVID-19 positive patients, of which 11 (2%) had Dengue viral coinfection. Whole genome sequences of SARS-CoV-2 were analyzed and compared between coinfection positive and negative group. Additionally, we extracted 185 genome sequences from GISAID to investigate the cross-correlation function between SARS-CoV-2 mutations and VOC; multiple ARIMAX (p,d,q) models were developed to estimate the average number of amino acid (aa) substitution among different SARS-CoV-2 VOCs.

Results: The results of the study showed that the coinfection group had an average of 30.6(±1.7) aa substitutions in SARS-CoV-2, whereas the dengue negative COVID-19 group had that average of 25.6(±1.8) (p<0.01). The coinfection group showed a significant difference of aa substitutions in ORF and N-protein when compared to Dengue negative group (p≤0.01). Our ARIMAX models estimated that the emergence of SARS-CoV-2 variants Delta required additional 9 to 12 aa substitutions than Alpha, Beta or Gamma variant. The emergence of Omicron accumulated additional 19 (95% CI: 15.74, 21.95) aa substitution than Delta.

Conclusions: The study suggests that coinfection with Dengue virus may have influenced the emergence of SARS-CoV-2 variants of concern by compromising the immune function of the host and inducing the adaptation of the virus with higher frequency of amino acid substitution.

Funding: The study was funded (JUST/Research Cell/Research Project/2020-21/FOET11) by Jashore University of Science and Technology, Jashore-7408, Bangladesh.

Declaration of Interest: All authors have no competing interest to declare.

Ethical Approval: The study has gone through the Ethical Review Board of Jashore University of Science and Technology (ERC no: ERC/FBST/JUST/2021-62) and approved the study. The participants have been informed about the purpose and the objectives of this study. Verbal consent obtained from optimistic respondents before they were enrolled in this study, written informed consent has been taken before the processing of the samples. We ensured that all ethical considerations have been taken into account while conducting the research involved human participants. This includes obtaining the informed consent, protecting participants privacy and confidentiality, and ensuring that the study was conducted in an ethical and responsible manner. The research was conducted in accordance with the applicable laws and regulation, and that any potential risks or ethical concerns were addressed and managed appropriately.

Keywords: SARS-CoV-2, COVID-19, Dengue, Coinfection, non-synonymous mutation, amino acid substitution, ARIMAX