Commit 14f7045e authored by Marek Ostaszewski's avatar Marek Ostaszewski
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Curation roadmap added

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# COVID-19 Disease Map biocuration roadmap
COVID-19 Disease Map pathways span a range of currently known host-cell virus interactions and mechanisms. Nevertheless, certain aspects of the disease are not represented in detail, particularly cell-type-specific immune response, and susceptibility features. Their mechanistic description is of great importance, as suggested by clinical reports on the involvement of these pathways in the molecular pathophysiology of the disease. The mechanisms outlined below will be the next targets in our curation roadmap.
## Cell type-specific immune response
COVID-19 causes serious disbalance in multiple populations of immune cells, including peripheral CD4+ and CD8+ cytotoxic T lymphocytes, B cells and NK cells [1–6]. This may be the result of functional exhaustion due to SARS-CoV-2 S protein and excessive pro-inflammatory cytokine response [2,7], promoted by an abnormal increase of the Th17:Treg cell ratio [8]. Moreover, the ratio of naive-to-memory helper T-cells increases while the level of T regulatory cells decreases in severe cases [9]. Pulmonary recruitment of lymphocytes into the airways, including Th17 and cytotoxic CD8+ T-cells [10], may explain this imbalance and the increased neutrophil‐lymphocyte ratio in peripheral blood [1,11,12]. To address this aspect of the disease we plan to implement cell type representations of different populations, and encode their cell surface receptors and transition mechanisms. With the help of single-cell omics profiling, we plan to adapt these to reflect COVID-19 specificity.
## Susceptibility features of the host
SARS-CoV-2 infection is associated with increased morbidity and mortality in individuals with underlying medical conditions, chronic diseases or a compromised immune system [13–16]. Groups at risk are men, pregnant and postpartum women, and individuals with high occupational viral exposure [17–19]. Other susceptibility factors include the ABO blood groups [20–27] and respiratory conditions [28–33].
Importantly, age is one of the key aspects contributing to the severity of the disease [15,34]. Age-related elevated levels of inflammation [34–37], immunosenescence and cellular stress of ageing cells [15,34,38–40] may contribute to the risk. In contrast, children are generally less likely to develop severe disease [41,42], with the exception of infants [38,43–45]. However, some previously healthy children and adolescents can develop a multisystem inflammatory syndrome following SARS-CoV-2 infection [46–50].
Finally, several genetic factors have been proposed and identified to influence susceptibility and severity, including the ACE2 gene, HLA locus, errors influencing type I IFN production, TLR pathways, myeloid compartments, as well as cytokine polymorphisms [23,51–58].
Connecting the susceptibility features to specific molecular mechanisms will allow us to better understand the contributing factors. These features can be directly incorporated as elements of relevant diagrams. Another possibility is connecting the diagrams of the Map to clinical and phenotypic data following big data workflows as demonstrated in other settings [59,60]. This can lead to a series of testable hypotheses, including the role of lipidomic reprogramming [61,62] or of vitamin D [63–65] in modifying the severity of the disease. Another testable hypothesis is that the immune phenotype associated with asthma inhibits pro-inflammatory cytokine production and modifies gene expression in the airway epithelium, protecting against severe COVID-19 [32,33,66].
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