A meta-analysis of comorbidities in COVID-19: Which diseases increase the susceptibility of SARS-CoV-2 infection?

Comput Biol Med. 2021 Mar;130:104219. doi: 10.1016/j.compbiomed.2021.104219. Epub 2021 Jan 16.


Comorbidities in COVID-19 patients often lead to more severe outcomes. The disease-specific molecular events, which may induce susceptibility to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, are being investigated. To assess this, we retrieved array-based gene expression datasets from patients of 30 frequently occurring acute, chronic, or infectious diseases. Comparative analyses of the datasets were performed after quantile normalization and log2 transformation. Among the 78 host genes prominently implicated in COVID-19 infection, ACE2 (receptor for SARS-CoV-2) was positively regulated in several cases, namely, leukemia, psoriasis, lung cancer, non-alcoholic fatty liver disease (NAFLD), breast cancer, and pulmonary arterial hypertension (PAH). FURIN was positively regulated in some cases, such as leukemia, psoriasis, NAFLD, lung cancer, and type II diabetes (T2D), while TMPRSS2 was positively regulated in only 3 cases, namely, leukemia, lung cancer, and T2D. Genes encoding various interferons, cytokines, chemokines, and mediators of JAK-STAT pathway were positively regulated in leukemia, NAFLD, and T2D cases. Among the 161 genes that are positively regulated in the lungs of COVID-19 patients, 99-111 genes in leukemia (including various studied subtypes), 77 genes in NAFLD, and 48 genes in psoriasis were also positively regulated. Because of the high similarity in gene expression patterns, the patients of leukemia, NAFLD, T2D, psoriasis, and PAH may need additional preventive care against acquiring SARS-CoV-2 infections. Further, two genes CARBONIC ANHYDRASE 11 (CA11) and CLUSTERIN (CLU) were positively regulated in the lungs of patients infected with either SARS-CoV-2, or SARS-CoV or Middle East Respiratory Syndrome Coronavirus (MERS-CoV).

Keywords: COVID-19; Cancer; Comorbidity; Leukemia; NAFLD; Psoriasis; SARS-CoV-2; Type II diabetes.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Angiotensin-Converting Enzyme 2 / biosynthesis*
  • COVID-19 / metabolism*
  • COVID-19 / mortality
  • Comorbidity
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetes Mellitus, Type 2 / mortality
  • Gene Expression Regulation, Neoplastic
  • Gene Expression Regulation, Viral
  • Humans
  • Neoplasm Proteins / metabolism*
  • Neoplasms / metabolism*
  • Neoplasms / mortality
  • Non-alcoholic Fatty Liver Disease / metabolism*
  • Non-alcoholic Fatty Liver Disease / mortality
  • Psoriasis / metabolism*
  • Psoriasis / mortality
  • Pulmonary Arterial Hypertension / metabolism*
  • Pulmonary Arterial Hypertension / mortality
  • SARS-CoV-2 / metabolism*
  • Signal Transduction


  • Neoplasm Proteins
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2