Does Covid 19 Change Your Gene Expression

Does Covid-19 change your gene expression?
In a modern world where information and misinformation are both overwhelmingly

abundant, especially one afflicted with a global pandemic, accurate and impactful
information is more important than ever before. Before humanity can overcome a
disease such as Covid-19, we must first better understand what it is and how it
functions.
SARS-CoV-2, or Covid-19, is a coronavirus of the Coronaviridae family. As such it is

an RNA virus with the means to interface with specific cellular processes. This could
involve anything from altering the structure of receptors on the cell’s surface,
changing the body’s immune response, or even evading most immunodetection
entirely. Understanding the interactions of Covid-19 with human cells and gene
expression, gives us a better understanding of how to treat symptoms and formulate
preventative measures against infection. In an article from WIREs RNA, it was
expressed that with the huge variety of interactions coronaviruses have with post-
transcriptional RNA mechanisms, further study of specific examples would be vital to
understanding their pathogenesis. It is our hope that this article will serve to highlight
and summarise the findings of several research groups focusing on different ways in
which Covid-19 alters human gene expression, sparking an interest in studies of this
nature to further research into Covid-19.
An article from the European Respiratory Journal(1), focusing on receptors for SARS-
CoV-2 in human airway epithelial cells and lung tissue expressed that SARS
coronavirus deaths were caused by the distress linked with damage of the alveolar
and diffuse bilateral pneumonia. Severe cases of COVID-19 are linked with infection
in the respiratory tracts. The SARS-Cov-2 has host molecules namely, angiotensin-
converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2)
that are needed for the entry of the virus into one's system. There are however more
hosts like ADAM17, cathepsin L, CD147 and GRP78 that can also allow this viral
entry. There is a mechanism found in the human lungs that regulates ACE2
expression that is also meant to promote infection of the host cell in the lung tissue.
ACE2, ADAM17, TMPRSS2, CTSL, CD147 and GRP78 are vital candidates for the
SARS-CoV-2 infection in the airway’s epithelial cells of humans. In the upper and
lower airways, low levels of ACE2 and high levels of GRP78 are expressed. ACE2
has the most variability also having the most expression in the trachea.
There is no relationship linked to age and sex of the individuals although smoking
does impact the gene expression levels. ACE2, TMPRSS2, CD147 and GRP78
expression is high in the cases of tobacco smoking individuals, specifically, smoking
tobacco is also associated with high levels of ACE2 expression in the bronchial
epithelial cells.
Various in situ protein profiling experiments were performed on samples from

patients that had tested positive for the SARS-CoV-2 infection. Data collected shows
how ACE2 expression in the airway’s in, in situ and in vitro is directly related to its
promoter activity in the bronchial area. ACE2 and SARS interact, and swap
mechanisms needed for ACE2 regulation in the mucosa.
In an article from Cell(2), focusing on how Covid-19 suppresses immune response by

disrupting integral cell processes it was said that cells have RNA sensors that detect
viral RNA’s which promote transcription, translation, and secretion of interferons
(IFN). IFN binds to cell-surface receptors leading to transcription and translation of
antiviral genes which ensures protection against viruses. Suppression of IFN
response causes increased severity of COVID-19. COVID-19 is surrounded by its
viral proteins (NSP1, NSP8, NSP9, NSP16 etc.), these interact with specific human
mRNAs to promote virus propagation. The NSP16 protein binds to pre-mRNA
synthesised during transcription in sites recognised by spliceosome (U1 and U2) to
splice introns and join exons producing mature mRNA, that is normally translated to
proteins in cytoplasm by ribosomes. Due to this, splicing of mRNA in SARS-CoV-2
infected human cells is inhibited, inhibition of splicing suppresses host IFN response
to viral infection.
In normal human cells (without NSP16) once the spliced mRNA is present in the
cytoplasm, translation begins with recognition of the 5’ cap by the small 40S subunit,
that scans mRNA to find the first start codon. NSP1 binds to the 18S ribosomal RNA,
the structural RNA component of the 40S ribosomal subunit. This association inhibits
host mRNA translation, suppressing protein production in SARS-CoV-2 infected
human cells. This results in the suppression of the cell’s innate immune response.
The Viral 5’ Leader sequence protects mRNA from NSP1-Mediated Translational
inhibition. It is crucial for mRNA to have a 5’ Leader sequence and for it to be
precisely positioned, relative to NSP1-bound 40S ribosome, to allow for translation
initiation.
SRP, (the complex that binds to 80S ribosome and co-translationally scans the
peptide to identify hydrophobic signal peptides in integral membrane proteins and
those secreted in the plasma membrane) is suppressed by NSP8 and NSP9 as they
alter translocation of secreted, and integral membrane proteins. As SARS-CoV-2
infected cells will have their SRP suppressed in addition to their IFN response,
Coronavirus disease results.
In an article from Blood, The Journal of The American Society of Hematology (3),
focused on the larger implications of interference with the haemostatic system of
critical Covid-19 patients it was shown that thrombotic complications seen in COVID-
19 patients that contribute to organ failure and mortality. It is known that severe
acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative pathogen
for the COVID-19 pandemic, which is associated with the development of acute
respiratory distress syndrome (ARDS). Almost half of COVID-19 patients ended up
in the ICU and half of those patients experienced respiratory failure and had to be
ventilated.
The above-mentioned thrombotic complications include pulmonary embolism,

venous thrombosis, and ischemic stroke. Platelets have a major role in the
development of these thrombotic complications. The haemostatic system and
immune defence are linked through platelets, this includes viral illness. When
invading pathogens are detected, platelets directly and indirectly mediate an immune
response.
Several methods have been used to prove the importance platelets have on the
gene expression of patients with COVID-19. RNA-sequencing and analysis, flow
cytometry for platelet activation and aggregation measured using a lumi-
aggregometer, etc.
RNA sequencing showed significant changes in the human platelet transcriptome of

COVID-19 patients. Although platelet counts and the mean platelet volume were
within normal ranges, RNA sequencing revealed that c-MPL, the gene encoding for
the plasma thrombopoietin (TPO) was decreased while TPO levels were elevated in
all COVID-19 patients. Platelet aggregation during SARS-CoV-2 infection is
increased, showing platelet hyperactivity. SARS-CoV-2 changes platelet gene
expression and causes platelet hyperreactivity which may contribute to COVID-19
pathophysiology by elevated platelet-leukocyte and platelet-platelet interactions.
ADP has been identified as a key player during the development of microvascular
thrombosis in patients with COVID-19. Aspirin was shown to reduce platelet
hyperactivity during SARS-CoV-2 infection. This suggests that antiplatelet therapies
may be useful in treating COVID-19 patients.
These results correlate with findings from previous reports which suggest that
platelet hyperreactivity during SARS-CoV-2 infection can contribute to thrombotic
complications during COVID-19. To conclude, COVID-19 is linked to major changes
in the platelet transcriptome as well as platelet hyperreactivity.
In conclusion, research has shown that coronaviruses interact with RNA expression
in many ways. Virus cells interact with and change membrane proteins in cells in
order to attach to and infect them. The host molecules linked with Covid-19 are
expressed significantly more in the lungs of tobacco smokers, placing them at
additional risk of infection. Once cells are infected, the virus’s structural changes as it
matures allow it to bypass host immunoreceptors, in addition it modifies mechanisms
required by the cell for immune response and prevents the cell from targeting it.
Infected individuals that are in critical condition are at increased risk of thrombosis
induced failures of certain organs due to the virus induced platelet
hyperactivity. These factors shed some light on why some people react so
aggressively to the disease and symptoms vary so much in their intensity. They also
serve to inform research into preventing infection by determining the target proteins
and how the virus interacts with them. These are but a few of the interactions
between Covid-19 and a host’s RNA but they give significant insight into infection,
response and symptoms of an organism that has been infected.
References
(1) Aguiar, J., Tremblay, B., Mansfield, M., Woody, O., Lobb, B., Banerjee, A.,
Chandiramohan, A., Tiessen, N., Cao, Q., Dvorkin-Gheva, A., Revill, S.,
Miller, M., Carlsten, C., Organ, L., Joseph, C., John, A., Hanson, P., Austin,
R., McManus, B., Jenkins, G., Mossman, K., Ask, K., Doxey, A. and Hirota, J.,
2020. Gene expression and in situ protein profiling of candidate SARS-CoV-2
receptors in human airway epithelial cells and lung tissue. European
Respiratory Journal, 56(3), p.2001123.
(2) Banerjee, A., Blanco, M., Bruce, E., Honson, D., Chen, L., Chow, A., Bhat, P.,
Ollikainen, N., Quinodoz, S., Loney, C., Thai, J., Miller, Z., Lin, A., Schmidt,
M., Stewart, D., Goldfarb, D., De Lorenzo, G., Rihn, S., Voorhees, R., Botten,
J., Majumdar, D. and Guttman, M., 2020. SARS-CoV-2 Disrupts Splicing,
Translation, and Protein Trafficking to Suppress Host Defenses. Cell, 183(5),
pp.1325-1339.e21.
(3) Manne, B., Denorme, F., Middleton, E., Portier, I., Rowley, J., Stubben, C.,
Petrey, A., Tolley, N., Guo, L., Cody, M., Weyrich, A., Yost, C., Rondina, M.
and Campbell, R., 2020. Platelet gene expression and function in patients
with COVID-19. Blood, 136(11), pp.1317-1329.

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Does Covid-19 change your gene expression?

In a modern world where information and misinformation are both overwhelmingly

SARS-CoV-2, or Covid-19, is a coronavirus of the Coronaviridae family. As such it is

Various in situ protein profiling experiments were performed on samples from

In an article from Cell(2), focusing on how Covid-19 suppresses immune response by

The above-mentioned thrombotic complications include pulmonary embolism,

RNA sequencing showed significant changes in the human platelet transcriptome of

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