COVID-19 and ethnicity: A novel pathophysiological role for inflammation

Abstract

Introduction: There have been recent mounting concerns regarding multiple reports stating a significantly elevated relative-risk of COVID-19 mortality amongst the Black and Minority Ethnic (BAME) population. An urgent national enquiry investigating the possible reasons for this phenomenon has been issued in the UK. Inflammation is at the forefront of COVID-19 research as disease severity appears to correlate with pro-inflammatory cytokine dysregulation. This narrative review aims to shed light on the novel, pathophysiological role of inflammation in contributing towards the increased COVID-19 mortality risk amongst the BAME population.

Methods: Searches in PubMed, Medline, Scopus, medRxiv and Google Scholar were performed to identify articles published in English from inception to 18^th June 2020. These databases were searched using keywords including: 'COVID-19' or 'Black and Minority Ethnic' or 'Inflammation'. A narrative review was synthesized using these included articles.

Results: We suggest a novel pathophysiological mechanism by which acute inflammation from COVID-19 may augment existing chronic inflammation, in order to potentiate a 'cytokine storm' and thus the more severe disease phenotype observed in the BAME population. Obesity, insulin resistance, cardiovascular disease, psychological stress, chronic infections and genetic predispositions are all relevant factors which may be contributing to elevated chronic systemic inflammation amongst the BAME population.

Conclusion: Overall, this review provides early insights and directions for ongoing research regarding the pathophysiological mechanisms that may explain the severe COVID-19 disease phenotype observed amongst the BAME population. We suggest 'personalization' of chronic disease management, which can be used with other interventions, in order to tackle this.

Keywords: BAME; COVID-19; Cardiovascular risk; Cytokine storm; Ethnicity; Inflammation; Insulin resistance; Metabolic syndrome; Obesity; Psychological stress; SARS CoV-2; Type 2 diabetes mellitus; Visceral fat.

Fig. 1

Illustrating the complex, acute-on-chronic interplay between social determinants of health, acute COVID-19 pathophysiology and the chronic diseases discussed in this review, which are more prevalent in the Black and Minority Ethnic (BAME) population. Chronic diseases, and disease processes, that could be contributing to the more severe COVID-19 phenotype observed in the BAME population include Metabolic Syndrome (MetS), Type 2 Diabetes Mellitus (T2DM), Obesity, Hypertension (HTN), Dyslipidaemia, Visceral Fat, Non- Alcoholic Fatty Liver Disease (NAFLD), Obstructive Sleep Apnoea (OSA), Obesity Hypoventilation Syndrome (OHS), Psychological Stress (Psych Stress), Human Immunodeficiency Virus (HIV), Tuberculosis (TB), Hepatitis B and C, and Sickle Cell Disease (SCD). Of particular importance in potentiating the ‘cytokine storm’, we draw attention to 3 positive feedback loop mechanisms involving: (i) The Hypothalamic-Pituitary- Adrenal Axis (HPA), Sympathetic Nervous System (SNS) and Unhealthy Behaviours (UBs), (ii) Adipokine Dysregulation (Adipokine Dysreg) and (iii) COVID-19 acute infection. Subsequent Systemic Immune Response Syndrome (SIRS) and multi-organ failure secondary to COVID-19 can manifest as acute coronary syndrome (ACS), myocarditis, Venous Thrombo-Embolism (VTE), acute liver failure, respiratory failure, and acute renal injury, all of which can be directly potentiated by the aforementioned, pre-existing co-morbidities.