Covid continued…

In a follow on from my previous COVID blog, I wanted to present some interesting concepts relating to new findings on the virus. You will remember in my previous blog that I discussed the role of the immune system in the pathogenicity of the disease and how potential cytokine storms may present medical crisis in some patients. Emerging data may highlight that the severity of the disease may be affected by how the viral antigen is presented on the MHC scaffold and similarly by notably reduced expression of MHC class 1 in virally infected cells thus having an inhibitory effect on Cytotoxic T lymphocyte action as an evasive immune mechanism.

HLA antigens are proteins coded by MHC genes, which have up to 6 alleles. The distribution of these alleles are geographically variable. The affinity in which MHC can bind to antigens prior to T cell presentation based on the strength of interaction between the antigen and MHC binding grooves. A study by Nguyen et al (2020) was able to determine that HLA variation impacted the strength of this interaction and was correlated with poorer clinical outcomes. HLA B*46:01 has the lowest quantity of predicted binding sites in contrast to HLA B*15:03, which demonstrated better efficacy to present viral peptides on the MHC scaffold, leading to a successful Cell mediated response. An earlier study by Lin et al (2003) was able to determine the same outcome for HLA B*46.01 following exposure to the initial SARS virus using a fishers exact tests to compare interaction with other HLA types. studies into HLA B*46:01 have shown that this phenotype frequency is the result of a mutation probably conferred to offer protection against leprosy. the phenotype frequency is higher in south east Asians, which may be reflected in the poorer outcomes of those within BAME ethnic groups, in addition to the inequalities faced.

One study published in the Lancet looked at 1145 patients with confirmed sars-cov19 following viral load analysis and found that survival rates were significantly lower in those with a higher viral load. The mean log10 viral load was 5.6 copies/mL. The mean VL was significantly different in those who survived vs those who died (log 5.2 vs log 6.4), respectively. There are some similarities here with the clinical presentation of the HIV virus in terms of VL monitoring and clinical outcome. Both viruses differ, however in terms of the T cell response. A high VL in COVID 19 exacerbates T cell-mediated responses leading to mass inflammation of type 2 pneumocytes, whereas in HIV they are depleted over time. This understanding of the inflammatory response led to the used of immunosuppressive drugs to limit the inflammatory response through the use of dexamethasone as demonstrated in a study by professor peter Horby of Oxford University reducing fatalities in ventilated patients by 33% (p=0.0003)

Other avenues of interest include study if the compliment system. A Sars-Cov-2 study has shown the activation of C3 within the compliment pathway can exacerbate the inflammatory response using a mouse study of C3 deficient mice in spite of high viral load. The study noted a reduction of extravasation with neutrophils and other inflammatory white blood cells. This shows great promise in the application of C3 Blockades and IL-6 inhibitors as a route of treatment following successful results in vivo mouse studies.


Pujadas, Elisabet et al. SARS-CoV-2 viral load predicts COVID-19 mortality. The Lancet Respiratory Medicine, Volume 0, Issue 0

Human Leukocyte Antigen Susceptibility Map for Severe Acute Respiratory Syndrome Coronavirus 2Austin Nguyen, Julianne K. David, Sean K. Maden, Mary A. Wood, Benjamin R. Weeder, Abhinav Nellore, Reid F. ThompsonJournal of Virology Jun 2020, 94 (13) e00510-20; DOI: 10.1128/JVI.00510-20

Lin, M., Tseng, H., Trejaut, J.A. et al. Association of HLA class I with severe acute respiratory syndrome coronavirus infection. BMC Med Genet 4, 9 (2003).

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