Mass Testing and Proactiveness Affect Epidemic Spreading.

The detection and management of diseases become quite complicated when pathogens contain asymptomatic phenotypes amongst their ranks, as evident during the recent COVID-19 pandemic. Spreading of diseases has been studied extensively under the paradigm of susceptible-infected-recovered-deceased (SIRD) dynamics. Various game-theoretic approaches have also addressed disease spread, many of which consider S , I , R , and D as strategies rather than as states. Remarkably, most studies from the above approaches do not account for the distinction between the symptomatic or asymptomatic aspect of the disease. It is well-known that precautionary measures like washing hands, wearing masks and social distancing significantly mitigate the spread of many contagious diseases. Herein, we consider the adoption of such precautions as strategies and treat S , I , R , and D as states. We also attempt to capture the differences in epidemic spreading arising from symptomatic and asymptomatic diseases on various network topologies. Through extensive computer simulations, we examine that the cost of maintaining precautionary measures as well as the extent of mass testing in a population affects the final fraction of socially responsible individuals. We observe that the lack of mass testing could potentially lead to a pandemic in case of asymptomatic diseases. Network topology also seems to play an important role. We further observe that the final fraction of proactive individuals depends on the initial fraction of both infected as well as proactive individuals. Additionally, edge density can significantly influence the overall outcome. Our findings are in broad agreement with the lessons learnt from the ongoing COVID-19 pandemic.

COVID-19 lung disease shares driver AT2 cytopathic features with Idiopathic pulmonary fibrosis.

BACKGROUND: In the aftermath of Covid-19, some patients develop a fibrotic lung disease, i.e., post-COVID-19 lung disease (PCLD), for which we currently lack insights into pathogenesis, disease models, or treatment options. METHODS: Using an AI-guided approach, we analyzed > 1000 human lung transcriptomic datasets associated with various lung conditions using two viral pandemic signatures (ViP and sViP) and one covid lung-derived signature. Upon identifying similarities between COVID-19 and idiopathic pulmonary fibrosis (IPF), we subsequently dissected the basis for such similarity from molecular, cytopathic, and immunologic perspectives using a panel of IPF-specific gene signatures, alongside signatures of alveolar type II (AT2) cytopathies and of prognostic monocyte-driven processes that are known drivers of IPF. Transcriptome-derived findings were used to construct protein-protein interaction (PPI) network to identify the major triggers of AT2 dysfunction. Key findings were validated in hamster and human adult lung organoid (ALO) pre-clinical models of COVID-19 using immunohistochemistry and qPCR. FINDINGS: COVID-19 resembles IPF at a fundamental level; it recapitulates the gene expression patterns (ViP and IPF signatures), cytokine storm (IL15-centric), and the AT2 cytopathic changes, e.g., injury, DNA damage, arrest in a transient, damage-induced progenitor state, and senescence-associated secretory phenotype (SASP). These immunocytopathic features were induced in pre-clinical COVID models (ALO and hamster) and reversed with effective anti-CoV-2 therapeutics in hamsters. PPI-network analyses pinpointed ER stress as one of the shared early triggers of both diseases, and IHC studies validated the same in the lungs of deceased subjects with COVID-19 and SARS-CoV-2-challenged hamster lungs. Lungs from tg-mice, in which ER stress is induced specifically in the AT2 cells, faithfully recapitulate the host immune response and alveolar cytopathic changes that are induced by SARS-CoV-2. INTERPRETATION: Like IPF, COVID-19 may be driven by injury-induced ER stress that culminates into progenitor state arrest and SASP in AT2 cells. The ViP signatures in monocytes may be key determinants of prognosis. The insights, signatures, disease models identified here are likely to spur the development of therapies for patients with IPF and other fibrotic interstitial lung diseases. FUNDING: This work was supported by the National Institutes for Health grants R01- GM138385 and AI155696 and funding from the Tobacco-Related disease Research Program (R01RG3780).

Cancer and COVID-19: Why are cancer patients more susceptible to COVID-19?

The COVID-19 pandemic has engulfed the entire world and has claimed more than 3 million lives worldwide. This viral disease is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and mainly characterized by fever, dry cough, fatigue, anosmia, anorexia, and dyspnea. The severity of the disease increases with age and presence of comorbidities, including cancer. Multiple clinical studies have shown that the cancer patients are highly susceptible to the severe form of the viral disease. In this review article, we have summarized the available scientific literature regarding the molecular links between COVID-19 and cancer, which make the cancer patients highly susceptible to COVID-19. Few studies have shown that the angiotensin-converting enzyme 2 (ACE2) receptor, transmembrane protease serine 2 (TMPRSS2), and the immune response and inflammation establish the interconnection between the two diseases. Additionally, we have also discussed whether SARS-CoV-2 can contribute to cancer development in COVID-19 patients. A recent study has suggested that SARS-CoV-2 may create a microenvironment that may support cancer cell proliferation and induce the activation of dormant cancer cells (DCCs). In another study, the blood sera of COVID-19 patients were found to activate epithelial-to-mesenchymal transition (EMT) in cancer cells. Overall, this review article will surely help the scientific community to understand why the cancer patients are so much prone to COVID-19 and will also motivate the researchers to find new therapeutic strategies that may save the lives of many COVID-19-infected cancer patients.