Association of genetic variants with the progression of COVID-19 symptoms in diabetic patients: a systematic review and in silico protein interaction analysis

Diabetes mellitus is a global public health issue and, at the onset of the COVID-19 pandemic, was identified as a risk factor associated with high morbidity and mortality in cases of acute respiratory infection caused by the SARS-CoV-2 coronavirus. This study investigated genetic variants in diabetic patients with COVID-19 through a systematic analysis of the PubMed/NCBI, EMBASE, Web of Science, SCOPUS, and Virtual Health Library databases, with the protocol registered on the PROSPERO platform (registration number CRD42020181311). Fifteen genetic variants were associated with five specific genes in symptomatic diabetic patients with COVID-19. Inheritance models, diabetic individuals carrying the heterozygous genotype TC (VDR rs4516035) showed ~10-15-fold higher odds of symptomatic COVID-19. Protein-protein interaction (PPI) analysis showed that the proteins ACE, ACE2, IL-6, and IL-17 exhibited strong predicted interactions with each other, as well as with insulin and the TMPRSS2 protease. Limitations include small number of eligible studies, heterogeneity in populations and outcome definitions. These preliminary findings highlight the need for further studies to understand better the relationship between the identified genetic variants and the progression of COVID-19 in diabetic patients.