The intersection of genetics and COVID-19 in 2021: preview of the 2021 Rodney Howell Symposium

Abstract

Coronavirus disease 2019 (COVID-19), caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first identified in late 2019 in China, has spread quickly throughout the world, resulting in significant morbidity and mortality. As of 21 January 2021, over 96 million cases and over 2 million deaths have occurred globally, with over 24 million cases and over 400,000 deaths in the United States alone (https://coronavirus.jhu.edu/). In addition to the direct effects of COVID-19 on illnesses and deaths, interventions to decrease transmission of SARS-CoV-2 have had devastating effects on preventive health services, education of children, economies of many countries, and biomedical research outside of COVID-19, among others. The recent availability of safe and effective COVID-19 vaccines is encouraging; however, it is expected that herd immunity and a return to normal life are several months away. Genetics in Medicine has organized the Rodney Howell Symposium for the upcoming 2021 American College of Medical Genetics and Genomics Meeting (April 2021), co-chaired by Drs. Robert Steiner and Michael Murray, to highlight some areas where the COVID-19 pandemic and the human genetics community have intersected. The pandemic year of 2020 has left a pervasive mark on all human communities, and the human genetics and genomics community is no different; this is made apparent by the breadth of topics covered by this expert group. The following are brief summaries of five presentations to be discussed at the Symposium on 16 April entitled "2021 COVID-19 State of the Science."

Innate immune suppression by SARS-CoV-2 mRNA vaccinations: The role of G-quadruplexes, exosomes, and MicroRNAs

“…Thus, the exceedingly important cancer regulatory genes BRCA1 and BRCA2 rely on IRF7 and IRF9, respectively, to carry out their protective effects. Rasmussen et al (2021) reviewed compelling evidence that deficiencies of either IRF7 or IRF9 lead to significantly greater risk of severe COVID-19 illness. Importantly, they also note that evidence suggests type I IFNs play a singularly important role in protective immunity against COVID-19 illness, a role that is shared by multiple cytokines in most other viral illnesses including influenza.…”

Innate Immune Suppression by SARS-CoV-2 mRNA Vaccinations: The role of G-quadruplexes, exosomes and microRNAs

“…In a preprint, Mamoor (2020) used gene expression analysis to determine that infection with either SARS-CoV-1 (in mice) or MERS-CoV (in vitro ) leads to increased production of IRF7 and IRF9, and the author speculates that "IRF7 and IRF9 may be important for SARS-CoV-2 immune defense in humans." [48] This speculation is somewhat confirmed by Rasmussen et al (2021), who reviewed the compelling evidence that deficiencies of either IRF7 or IRF9 lead to significantly greater risk of severe COVID-19 illness [49]. Importantly, they also note that evidence suggests type I IFNs play a singularly important role in protective immunity against COVID-19 illness, a role that is shared by multiple cytokines in most other viral illnesses including influenza.…”

Will Host Genetics Affect the Response to SARS-CoV-2 Vaccines? Historical Precedents

“…According to the reported data, SARS-CoV-2 can lead to extra-pulmonary diseases, including renal dysfunction, gastrointestinal complications, liver dysfunction, cardiac manifestations, mediastinal findings, neurological abnormalities, and hematological manifestations ( 59 ). Epidemiologists have identified age as the main factor for developing COVID-19 related complications, especially among patients over 65 years of age ( 60 ). On the other hand, younger individuals (<20 years) almost exclusively experienced another severe condition that has been linked to COVID-19, which is Multisystem Inflammatory Syndrome (MIS-C), that mimics Kawasaki disease (KD) ( 60 ).…”

“…Epidemiologists have identified age as the main factor for developing COVID-19 related complications, especially among patients over 65 years of age ( 60 ). On the other hand, younger individuals (<20 years) almost exclusively experienced another severe condition that has been linked to COVID-19, which is Multisystem Inflammatory Syndrome (MIS-C), that mimics Kawasaki disease (KD) ( 60 ). Importantly, this condition is believed to occur in genetically predisposed children following exposure to trigger such as viral infection ( 61 , 62 ).…”