COVID-19 caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has spread to 227 nations worldwide, causing the ongoing pandemic. Humans have suffered immensely as a result of this infection. When an individual develops an infection, the COVID-19 virus spreads predominantly through saliva droplets or nasal discharge.
Coronaviruses are known to be zoonotic, which means they are transmitted between animals and people. Respiratory symptoms, fever, cough, shortness of breath, and breathing difficulties are all common symptoms of infection. Infection can cause pneumonia, severe acute respiratory syndrome, renal failure, and, in the worst-case scenario, death.
Different countries appear to have different rates of infection and mortality. The subject’s genetic makeup could play a role in vulnerability to COVID-19 disease or a compromised immune system. In various European nations, the link of the angiotensin-converting enzyme 1 (ACE-1) genetic variation with vulnerability to SARS-CoV-2 infection and accompanying mortality was noted.ACE is the key component of the Renin Angiotensin System, which regulates blood pressure by controlling the volume of fluids in the body. It transforms angiotensin I, a hormone, into angiotensin II, an active vasoconstrictor.
As a result, the possibility that biochemical receptors play a role in susceptibility to SARS-CoV-2 infection and death cannot be dismissed. One such receptor was CCR5, whose role was examined in Covid-19.
What is CCR5?
CCR5 refers to Chemokine Receptor 5, found on the surface of immune cells and is constitutively expressed in the immune system. T cells, macrophages, dendritic cells, eosinophils, microglia, and a fraction of either breast or prostate cancer cells express CCR5. It belongs to the G protein-coupled receptor family.
CCR5 has been linked to the production of inflammation in a variety of infectious illnesses and the recruitment of leukocytes to inflammatory sites. CCR5 plays a vital role in a variety of viral diseases, including the Human Immunodeficiency Virus (HIV), Hepatitis C Virus (HCV) and Hepatitis B Virus (HBV), West Nile Virus (WNV), and Tick-Borne Encephalitis Virus (TBEV).
Association with Viral Illness
Differential CCR5 surface expression has been associated with viral illness susceptibility/resistance. The CCR5 gene is found on chromosome 3’s short arm (p.21). A common 32-bp deletion variant in the coding region results in the formation of a premature stop codon, resulting in a 215-amino-acid length rather than the full 352-amino-acid length. It was observed that the CCR5-Δ32(deletion of 32 bp) variant produced a truncated protein and also there was a dramatic reduction in receptor’s expression. The 32-bp deletion mutation in the CCR5 coding region (CCR5-Δ32) prevents receptor expression on the cell surface and leaves homozygous individuals without functional CCR5.
CCR5-Δ32 carriers show resistance to human immunodeficiency virus type-1 (HIV-1) infection due to CCR5 being one of two co-receptors for HIV-1. CCR5 Δ32 provides partial to full protection against HIV infection and therefore serves as a basis for gene deletion studies attempting to achieve a permanent HIV cure.
Covid-19 and CCR5-Δ32
The resistance to HIV infection in CCR5-Δ32 mutated individuals indicated a prospect of relation with Covid-19 infection. Chemokine receptors and their ligands, including CCR5 and CCL5, have been found to play important role in the inflammatory response, which most commonly involves the recruitment of leukocytes to eliminate infectious agents. Differential expression of chemokine receptor and ligand may contribute to variations in inflammatory pattern, which in turn may have distinct effects on the course or establishment of infections. The CCR5- Δ32 variant shows a significant reduction in the expression of a surface receptor, this results in an impact on resistance against viral diseases.
There exists a considerable difference in infection and mortality rate associated with Covid-19 worldwide. This arose the question of whether the CCR5-Δ32 mutation has any correlation with the distribution pattern or not.
A correlation test was performed using the available data of healthy controls and data of covid-19 infection rates and deaths. Also, the allelic frequency of CCR5-Δ32 was considered. The results indicated an association between CCR5- Δ32 and SARS CoV-2 infection and mortality.
In another case study, a patient from Brazil,59 years old who was homozygous for variant CCR5-Δ32 was tested positive for Covid-19. The genetic test performed was the analysis of polymorphisms which identified the presence of two Δ32 alleles in the CCR5 gene, supported by the rs333 polymorphism. This indicates no role of the mutation in protective function.
The CCR5- Δ32 mutated individuals otherwise resistant to HIV infection can still be infected with COVID-19. Thus the protective function of CCR5-Δ32 cannot be confirmed in this case.