Who is at high risk for COVID-19?
Now, at the peak of summer, worries about the rising risk of COVID-19 have returned. It may be useful at this time to look more closely at what causes serious conditions following coronavirus infection. The ability of the SARS-CoV-2 virus to evolve and evade human immune defenses is well known. However, it is not as well documented what kind of physical factors make a difference after infection.
The Japanese Ministry of Health, Labour, and Welfare announced measures against COVID-19 based on recommendations from the COVID-19 Advisory Board. According to such authorities, people with the following conditions have a higher risk of fatality. Those over age 65 with chronic kidney disease and/or immune deficiency have 2 or 3 times higher risk of fatality associated with COVID-19. In cases of cancer and obesity, the risk is 2 and 1.4 times higher, respectively. People between the ages of 40 and 49 with chronic kidney disease, diabetes or obesity show 20, 9, and 14 times higher risk of death. These risk calculations are widely accepted, though more information about what measures are being taken to protect such individuals would be useful. Unfortunately, details are as yet unclear.
A recent science paper shed light on some basic genetic differences which affect the probability of death associated with COVID-19 (“Whole-genome Sequencing Reveals Host Factors Underlying COVID-19”, A. Kousathanas et al. Nature (2022) 607, p97-103). Researchers determined the entire nucleotide sequences of genomes belonging to 7,491 people who experienced severe symptoms following infection. Those sequences were compared with 48,400 control samples from less symptomatic individuals. From this comparison, differences emerged in genetic sequences and the amount of protein synthesized within cells. Of particular interest are 23 separate genes where differences in genome-sequence were found related to protein production. Such differences led to changes in protein functions and affected the physiological role of the protein.
Among these 23 genes were 16 which had not been examined in detail to date. The functional roles of these proteins are divided into two categories. The first group consists of proteins that play a role in the suppression of viral propagation and lung inflammation. In the second group are proteins involved in blood coagulation.
The first group of genes are of specific proteins important for increasing white blood cell production involved in immune response. In such leukocytes are B-lymphocytes required for antibody production, and T-lymphocytes which along with dendrite cells are involved in killing viruses. Sufficient production of these cells is essential to remove the virus. In people at high risk of COVID-19, the function of these proteins is lower. Other proteins found in the first group also include interferon, a protein capable of killing cells carrying the virus. Mutations leading to decreases in interferon activity have been observed. For example, in order to kill infected cells, interferon requires a specific receptor protein. People with higher risk of COVID-19 have receptor proteins with a mutation that causes lower binding of interferon to the infected cells.
The second group contained genes of proteins related to blood coagulation like Coagulation Factor 8 in which genetic mutations led to cases of increased blood coagulation. For people with such changes in the function of blood coagulation factors, once infected with the virus, intravascular blood coagulation may occur with greater frequency, leading to pulmonary inflammation and lower oxygen levels contributing to hypoxaemic respiratory failure. This tends to support reported observations of high risk individuals in need of assistance from an ECMO (extracorporeal membrane oxygenation).
Some of the results reported in the paper from Nature are consistent with reported facts including that aged people with decreased immune activity suffer more acutely from COVID-19. Adding to this, these examples of proteins needed for activation of the immune system and regulation of blood coagulation suggest several measures to decrease the risks against CORONA virus propagation and the development of severe conditions.
In the paper, the authors propose that approaches taken in this study, including genome sequencing, may be applicable for other pandemics, whether viral and/or bacterial. These findings provide a clear example of how advancements in medicine based on molecular biology may contribute to a healthy life.