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Coronavirus infection causes endoplasmic reticulum stress inside the cells, which inhibits protein folding. Prolonged endoplasmic reticulum stress causes an apoptotic process of unfolded protein response-induced cell death. Endoplasmic reticulum stress rapidly induces the activation of mTORC1, responsible for the induction of the IRE1-JNK pathway. IRE1-JNK stands out for its dual nature: pro-apoptotic in the first stage of infection, anti-apoptotic in persistently infected cells. Once penetrated the cells, the virus can deflect the mitochondrial function by implementing both waterfalls pro-apoptotic and anti-apoptotic response. The virus prevents, through Open Reading Frame 9b (ORF-9b) interacting with mitochondria, the response of the type I interferon of the cells affected by the infection and is fundamental for generating an antiviral cellular state. ORF-9b has effects on mitochondrial dynamics, inducing fusion and autophagy and promoting cell survival. The recognition of ORF-9b has made it possible to identify it as a molecular target of some existing potentially effective drugs (Midostaurin and Ruxolitinib). Other drugs, with the same target, are currently being tested. Given the great importance of mitochondria in virus-host interaction, in-depth knowledge of the actors and pathways involved is essential to continue developing new therapeutic strategies against SARS CoV2.

Background: Pharmacists in ambulatory care can utilize population health approaches to identify patients needing disease management and improve outcomes. However, population health is only effective when identified patients are successfully outreached and show to appointments., Objective: Describe a population health approach utilized by pharmacists in primary care, report outcomes of outreach attempts and scheduled appointments, and determine whether patient and referral characteristics predict no-show appointments., Methods: Retrospective cohort study of patients referred for pharmacist management of hypertension or chronic pain through population health between 2013-2016. Outreach attempt and appointments outcomes were collected. Patient and referral characteristics were analyzed to determine whether predictive of no-show appointments using logistic regression., Results: Of 450 outreach attempts, 250 (56%) patients were not reached, 164 (36%) scheduled appointments, and 36 (8%) were reached but declined an appointment. Of 164 patients with appointments, 71 (43%) no-showed. Patients with higher systolic blood pressure were more likely to no-show (OR: 1.02, 95% CI: 1.00-1.04). Other characteristics were not predictive of no-show appointments., Conclusion: Successful outreach and showed appointments are essential components of successful population health programs. Using multiple outreach modalities and further identifying factors predictive of no-show appointments to refine the current approach may lead to increased efficiency.