Single cell sequencing unraveling genetic basis of severe COVID19 in obesity

• Published in: Obesity medicine Vol. 20; p. 100303
• Main Authors: AbdelMassih, Antoine Fakhry, Fouda, Raghda, Kamel, Aya, Mishriky, Fady, Ismail, Habiba-Allah, El Qadi, Layla, Malak, Lauris, Mohamed, Maram, Arsanyous, Mariem, Hazem, Maysa, El-Husseiny, Miral, Ashraf, Mirette, Hafez, Nada, AlShehry, Nada, El-Husseiny, Nadine, AbdelRaouf, Nora, Shebl, Noura, Hafez, Nouran, Youssef, Nourhan, Afdal, Peter, Hozaien, Rafeef, Menshawey, Rahma, Saeed, Rana, Yasser, Reem, Hesham, Shereen, Zakarriah, Wesam, Khattab, Shahenda, Elammary, Yasmine, Ye, Jianping
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.12.2020
• Subjects: Beneficial inflammation; COVID-19; Deleterious inflammation; Immunologic switch; Obesity; Review; Shared immunogenetics; Single cell sequencing; COVID-19; Obesity; Single cell sequencing; Shared immunogenetics; Deleterious inflammation; Beneficial inflammation; Immunologic switch
• ISSN: 2451-8476; 2451-8476
• DOI: 10.1016/j.obmed.2020.100303

COVID-19 has shown a substantial variation in the rate and severity by which it impacts different demographic groups. Specifically, it has shown a predilection towards obese patients as well as well as other vulnerable groups including predilection of males over females, old age over young age and black races over Caucasian ones. Single cell sequencing studies have highlighted the role of cell polarity and the co-expression of proteases, such as Furin, along with ACE2 in the genesis of coronavirus disease rather than exclusively link tissue involvement with ACE2 levels thought previously. It has also forged a connection between the genetic and immune cellular mechanisms underlying COVID infection and the inflammatory state of obese patients, offering a more accurate explanation as to why obese patients are at increased risk of poor COVID outcomes. These commonalities encompass macrophage phenotype switching, genetic expression switching, and overexpression of the pro-inflammatory cytokines, depletion of the regulatory cytokines, in situ T cell proliferation, and T cell exhaustion. These findings demonstrate the necessity of single cell sequencing as a rapid means to identify and treat those who are most likely to need hospital admission and intensive care, in the hopes of precision medicine. Furthermore, this study underlines the use of immune modulators such as Leptin sensitizers, rather than immune suppressors as anti-inflammation therapies to switch the inflammatory response from a drastic immunological type 1 response to a beneficial type 2 effective one. •Sc Sequencing identified two types of inflammation in COVID-19: type 1, linked to worse clinical outcome and type 2 which is rather beneficial.•Type 1 is characterized by lack of memory B cells, defective antigen presentation, predominance of M1 macrophages, and T cell depletion.•Intriguingly, vulnerable groups, such as the obese, the old aged, male gender, African Americans show the same landscape as COVID-19 immunotype 1.•Sc Sequencing was also able to determine, that tissue tropism of COVID-19 is not solely related to ACE2 but rather to tissue proteases as Furin.•Sc sequencing, was also able to identify that milder strains of SARS-CoV-2 have less affinity to Furin.