Maucourant, C., Filipovic, I., Ponzetta, A., Aleman, S., Cornillet, M., Hertwig, L., Björkström, N. K. (2020). Natural killer cell immunotypes related to COVID-19 disease severity. Science Immunology, 5(50). doi:10.1126/sciimmunol.abd6832

Smith College

- European Wide Cohort Study Examines Expression Levels of COVID-19 Susceptible Biomarkers in Patients with Severe Asthma
- Review Investigating the Immunopathogenesis of COVID-19
- Structures and distributions of SARS-CoV-2 spike proteins on intact virions
- Implications of sex differences in immunity for SARS-CoV-2 pathogenesis and design of therapeutic interventions
- Natural killer cell immunotypes related to COVID-19 disease severity

Studies Related to the Pathogenesis of COVID-19

A review study presented on the pathophysiology of the COVID-19 virus and found that entry and replication by the virus into cells expressing ACE 2 receptors triggers host cell pyroptosis, generating pro-inflammatory cytokines and chemokines which recruit monocytes, macrophages, and T-cells. This results in further inflammation and creation of a pro-inflammatory feedback loop, leading to overproduction of cytokines that accumulate in the lungs, causing a cytokine storm.

Review Investigating the Immunopathogenesis of COVID-19

A  European U-BIOPRED  (Unbiased BIOmarkers Predictive of REspiratory Disease outcomes) cohort study examined the mRNA expression level of ACE2, TMPRSS2, and Furin in the sputum, bronchial brush and bronchial biopsies of volunteer subjects.  These three biomarkers are heavily involved in the pathogenesis of COVID-19, and it was hypothesized that these expression levels would correlate with asthma severity or other molecular phenotypes.  These findings may help to explain why those with asthma and other respiratory diseases are more vulnerable to SARS-CoV-2 infection and symptoms of COVID-19.

Wide European Cohort Study That Examines Expression Levels of COVID-19 Susceptible Biomarkers in Patients with Severe Asthma

SARS-CoV-2 virions are surrounded by a lipid bilayer from which spike (S) protein trimers protrude. Heavily glycosylated S trimers bind the ACE2 receptor and mediate entry of virions into target cells. S exhibits extensive conformational flexibility: it modulates exposure of its receptor binding site and later undergoes complete structural rearrangement to drive fusion of viral and cellular membranes. 

The paper reports the application of cryo-electron microscopy and tomography to image intact SARS-CoV-2 virions, determining the high-resolution structure, conformational flexibility and distribution of S trimers in situ on the virion surface. These results reveal the conformations of S present on the virion, and provide a basis from which to understand interactions between S and neutralizing antibodies during infection or vaccination.

Structures and distributions of SARS-CoV-2 spike proteins on intact virions

Men present more frequently with severe manifestations of COVID-19 and are at higher risk for death, while studies from other viral infections have shown that females can mount stronger immune responses. The paper investigates the underlying mechanisms for these differences between female and male individuals infected with SARS-CoV-2.  

Emerging knowledge on the basic biological pathways that underlie differences in immune responses between women and men needs to be incorporated into research efforts on SARS-CoV-2 pathogenesis and pathology to identify targets for therapeutic interventions aimed at enhancing antiviral immune function and lung airway resilience while reducing pathogenic inflammation in COVID-19.

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