The novel SARS-CoV-2, that was first reported in Wuhan back in December 2019, has triggered an unprecedented human toll along with major global economic crisis. Earlier this year, researchers threw light on the mechanism of pathogenesis of the novel virus in human hosts, helping health experts to lay out the guidelines of precautions to reduce the chance of virus spread. Notably, an early observation made by health workers has been worth thinking about. Why do some patients develop severe symptoms whereas some pass simply as asymptomatic?
To find the answer to this puzzle, researchers turned to DNA to conduct genetic studies. DNA has been vital in deciding the severity of a disease in an individual. To put it simply, our DNA is a script which is read by the cellular machinery to synthesize meaningful proteins. Some of these proteins are involved in the mechanism of action of coronavirus in our body.
Since 0.1-0.5% variation in DNA is seen in between any two people, it is clear that proteins are expressed in different levels. Thus, different people respond differently to infectious pathogens. To find the mystery of this inter-individual variation in severity of COVID-19, a study was done to measure the genetic variations in people that make them more or less prone to COVID-19.
In March this year, a hospital-based case-control study was conducted in Wuhan that used chi-square analysis to test the frequency of the ABO blood group of patients getting severely affected by SARS-CoV-2. A total of 105 COVID-19 patients and 103 control cases (unaffected healthy individuals) were included. Note: only severely ill patients with respiratory failure needed hospitalization and were included in the analysis. The study was further sub-grouped based on the gender of the patients. Finally, considering lymphopenia as a characteristic of COVID-19, a relationship between the blood group frequencies and lymphocyte count was established.
More recently, a similar population study was taken up by multiple research groups in Italy and Spain. Genome-wide association study (GWAS) was used as the technique to scan for areas in DNA which gives information about the presence or absence of a disease. Scientists began with no idea about the genes involved in the disease and scanned the DNA to find regions that were associated with varying severity of infection. Again, 1980 hospitalized patients were included in the study along with 2318 healthy people who made the control set. The aim was to check for significant differences in the gene readouts of the infected and the control sets. Let’s see the process of GWAS in a step-wise fashion.
1. Genotyping- The entire DNA of each individual was read. This gave an obviously large output, unique to each human.
2. A series of wet lab experiments, including DNA microarray assay, were done to locate the genes that were over or under expressed in diseased condition.
3. Advanced statistical tools were employed to find out possibilities of variations associated with COVID-19 and jot down meaningful results of all experiments.
It was then concluded that two specific regions of the genome showed a significant difference in infected and uninfected individuals- genes on chromosome 9q, which determines blood group, and other genes possibly involved in the virus’s mode of infection.
Not surprising, the findings by the European research groups validated the previous statistical study conducted in Wuhan. Indeed blood type A patients were at a higher risk of respiratory failure compared to patients of other blood types. Additionally, it was found that people with blood group O were less likely to get hospitalized due to COVID-19 induced respiratory distress.
Should this study make people with blood group A panic?
Not at all!
Firstly, although the sample size of the population involved in these studies was a decent number, it is still not large enough to be extrapolated on a global scale. In short, more credible evidence is needed by means of replication studies on larger groups of people, before we can draw a firm conclusion.
Secondly, while blood groups are often associated with severity of diseases in cases of dengue hemorrhagic fever, hepatitis B and so on, this is a subtle factor in case of COVID-19. Other factors such as viral load, comorbidities, treatment, etc. play more important roles in deciding the severity of infection.
How is this study significant?
In case future experiments can establish a stronger association of blood group and COVID-19 infection severity, targeted drugs can be made depending on the blood group of patients. This customization will definitely help to create more effective therapeutics to combat the disease. But until then, preventive measures are all that we can take to survive this pandemic.
References:
1) Is your blood group making you more vulnerable to COVID-19?
2) Association Between ABO Blood Group System and COVID-19 Susceptibility in Wuhan
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