Got Covid and Never Knew it? Let’s find out Why…
How might this understanding have changed the course of the pandemic?
Dr Been’s Video:
https://www.youtube.com/live/lJjxiZIPFwg?feature=share
The Mystery
Why during the pandemic were there people who tested positive for SARS-CoV-2 but were asymptomatic, or never got sick and never got tested but were discovered to have antibodies later? We all know of cases of people deathly ill at home but the rest of the family never got it.
The study.
Basic terms you need to know before we start:
Allele - a variation of the same sequence of nucleotides at the same place on a long DNA molecule
gene - a sequence of nucleotides in DNA that is transcribed to produce a functional RNA
T Cell - one of the important types of white blood cells of the immune system that play a central role in the adaptive immune response
Major histocompatibility complex(MHC) - a large locus on vertebrate DNA containing a set of closely linked polymorphic genes that code for cell surface proteins essential for the adaptive immune system.
HLA or human leukocyte antigens - a complex of genes on chromosome 6 in humans which encode cell-surface proteins responsible for regulation of the immune system.
TC 4:29
About 86% of the population have human coronaviruses in their throats from exposure to the common cold.
14 to 16 percent of seasonal cold infections are caused by coronaviruses.
Some people with this prior exposure are showing that they can handle exposure to Covid-19 so efficiently that they don’t develop any symptoms at all.
How does this work?
Summary
When a nucleated cell gets infected with a virus, the virus starts replicating. Before it has multiplied enough to disable the cell’s defence machinery, the cell will defend itself by picking up the small pieces of virus that are being formed, and loading it onto an MHC molecule then pushing it out on an arm called MHC-1 to be presented to any defenders in the neighborhood. Professional antigen presenting cells (macrophages, dendritic cells, B cells) are cruising the neighborhood looking for pathogens (bacteria, viruses, dead cells, fungi) to clear out in the process of Phagocytosis.
The antigen presenting cell (Defender) shreds the pathogen into smaller pieces and in turn, loads those pieces onto an arm called MHC-2 and expresses that molecule on its surface to signal other warrior cells to recruit reinforcements.
Antigen presenting cells have both MHC-1 and MHC-2. So if they get infected with a virus, they will shred and present on both arms, one to announce its health status and sound the alarm, the other to recruit more troops to aid in fighting the infection. This is how the acquired immune system gets activated. The binding regions of those various arms all have slight variations from person to person, depending on their genetic makeup.
A cytotoxic T Cell also has perforins and granzymes to attack the infected cells and kill them, but what is important is this T cell is presenting a piece of a coronavirus Spike protein on its surface .
TC 14:45
On the petite arm of chromosome #6 location number 21.31 there is a set of genes called human leukocyte antigen genes or HLA genes.
Chromosomes have two arms: the petite arm or small arm and a big arm or Q arm
These genes encode MHC-1, MHC-2 and MHC-3, aka HLA Class 1, HLA Class 2, HLA Class 3.
Class 1 or MHC-1, is further divided into types A, B and C.
Here’s the key: Some people have a gene called HLA-B*15-01, aka human leukocyte antigen in their chromosomes . The Allele in question is Class 1, B, subcategory 15-01 or HLA-B*15-01. This unique gene allele makes an MHC-1 molecule (announcing the presence of a virus infection) which has a special affinity to a distinct part of the spike protein. That part is similar or “conserved” across human viruses and SARS-CoV-2. In SARS-CoV-2 the part is called NQKLIANQF. In human coronaviruses this piece is called NQKLIANAF with one amino acid difference.
When someone carrying the HLA-B*15-01 gene reacts to HUMAN coronavirus, perhaps sometime in the past, pre-pandemic, they develop T-Cells that attack a conserved part of the spike protein, a part that is conserved in SARS-CoV-2 as well. When these people are subsequently exposed to SARS-CoV-2, their memory T-cells leap into action and quickly attack the conserved part of the spike protein and kill the virus even before symptoms can develop.
Food for thought: How could this knowledge have made a difference in the approach of public health to the pandemic? How could it influence the actions of regulators going forward?
Method
TC 23:15
The study enrolled 29,947 unvaccinated individuals who may have given bone marrow in the past and so the genetic makeup of their cells was known.
They were tracked on a weekly basis. 1428 reported they had tested positive and some of those didn’t have symptoms. An examination of the genetics of those without symptoms found that they had a strong association with HLA-B*15-01.
The survey was repeated in Europe and other cohorts.
It was confirmed again when they built a peptide copying the piece of spike protein and handed that piece of spike protein over to the T cells from the asymptomatic individuals Some (but not all) of those reacted as well.
We show that, among participants reporting a positive test result for SARS-CoV-2, HLA-B*15:01 is significantly associated with asymptomatic infection. We observed that individuals carrying this common allele (approximately 10% in individuals with European ancestry) are more than twice as likely to remain asymptomatic after SARS-CoV-2 infection compared with those who do not, and a notable effect of HLA-B*15:01 homozygosity increasing the chance of remaining asymptomatic by more than eight times. This suggests important features of early infection with SARS-CoV-2. Supporting the role of HLA-B*15:01 in mediating asymptomatic infection, we found a highly similar frequency distribution of this allele in asymptomatic versus symptomatic patients in two independent cohorts.
Questions:
Could Vitamin D levels play a part in in association with this genetic makeup?
How far back did they become infected with human coronavirus to indicate how long the memory T-cells remain active?
Useful Links:
A common allele of HLA is associated with asymptomatic SARS-CoV-2 infection | Nature https://www.nature.com/articles/s4158...
SARS-CoV-2 antigen exposure history shapes phenotypes and specificity of memory CD8+ T cells | Nature Immunology https://www.nature.com/articles/s4159...
CD4+ T cells support polyfunctionality of cytotoxic CD8+ T cells with memory potential in immunological control of tumor - PMC https://www.ncbi.nlm.nih.gov/pmc/arti....
Biochemistry, HLA Antigens - StatPearls - NCBI Bookshelf https://www.ncbi.nlm.nih.gov/books/NB....
Gene Mutation May Explain Why Some Don’t Get Sick from COVID-19 | UC San Francisco https://www.ucsf.edu/news/2023/06/425...
Did you get COVID but never feel sick? New study hints at why https://news.yahoo.com/did-covid-neve...