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COVID-19 virtual patient cohort reveals immune mechanisms driving disease outcomes.

ABSTRACT: To understand the diversity of immune responses to SARS-CoV-2 and distinguish features that predispose individuals to severe COVID-19, we developed a mechanistic, within-host mathematical model and virtual patient cohort. Our results indicate that virtual patients with low production rates of infected cell derived IFN subsequently experienced highly inflammatory disease phenotypes, compared to those with early and robust IFN responses. In these in silico patients, the maximum concentration of IL-6 was also a major predictor of CD8 ⁺ T cell depletion. Our analyses predicted that individuals with severe COVID-19 also have accelerated monocyte-to-macrophage differentiation that was mediated by increased IL-6 and reduced type I IFN signalling. Together, these findings identify biomarkers driving the development of severe COVID-19 and support early interventions aimed at reducing inflammation.

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Understanding of how the immune system responds to SARS-CoV-2 infections is critical for improving diagnostic and treatment approaches. Identifying which immune mechanisms lead to divergent outcomes can be clinically difficult, and experimental models and longitudinal data are only beginning to emerge. In response, we developed a mechanistic, mathematical and computational model of the immunopathology of COVID-19 calibrated to and validated against a broad set of experimental and clinical immunological data. To study the drivers of severe COVID-19, we used our model to expand a cohort of virtual patients, each with realistic disease dynamics. Our results identify key processes that regulate the immune response to SARS-CoV-2 infection in virtual patients and suggest viable therapeutic targets, underlining the importance of a rational approach to studying novel pathogens using intra-host models.

SUBMITTER: Jenner AL

PROVIDER: S-EPMC7805446 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionThe onset of COVID-19 has caused an international upheaval of traditional in-person approaches to care delivery. Rapid system-level transitions to virtual care provision restrict the ability of healthcare professionals to evaluate care quality from the patient's perspective. This poses challenges to ensuring that patient-centered care is upheld within virtual environments. To address this, the study's objective was to review how virtual care has impacted patient experiences and outcomes during COVID-19, through the use of patient-reported experience and outcome measures (PREMs and PROMs), respectively.MethodsA systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines to evaluate patient responsiveness to virtual care during COVID-19. Using an exhaustive search strategy, relevant peer-reviewed articles published between January 2020 and 2022 were pulled from MEDLINE, CINAHL, EMBASE, and PsychInfo databases. Study quality was independently assessed by two reviewers using the Mixed Methods Appraisal Tool. A patient partner was consulted throughout the study to provide feedback and co-conduct the review.ResultsAfter removing duplicates, 6048 articles underwent title and abstract review, from which 644 studies were included in the full-text review stage. Following this, 102 articles were included in the study. Studies were published in 20 different countries, were predominantly cross-sectional, and reported on the delivery of virtual care in specialized adult outpatient settings. This review identified 29 validated PREMs and 43 PROMs. Several advantages to virtual care were identified, with patients citing greater convenience, (such as saving travel time and cost, less waiting experienced to see care providers) and increased protection from viral spread. Some studies also reported challenges patients and caregivers faced with virtual care, including feeling rushed during the virtual care appointment, lack of physical contact or examination presenting barriers, difficulty with communicating symptoms, and technology issues.ConclusionThis review provides supportive evidence of virtual care experiences during the COVID-19 pandemic from patient and caregiver perspectives. This research provides a comprehensive overview of what patient-reported measures can be used to record virtual care quality amid and following the pandemic. Further research into healthcare professionals' perspectives would offer a supportive lens toward a strong person-centered healthcare system.

Project description:Prior to the COVID-19 pandemic, patients attending ambulatory clinics at cancer centers in Ontario completed the Edmonton Symptom Assessment Scale (ESAS) at each visit. At our center, completion was via touchpad, with assistance from clinic volunteers. As of March 2020, clinic appointments were conducted virtually when possible and touch pads removed. We anticipated a negative impact on the collection of patient-reported outcomes (PROs) and the recognition of severe symptoms.MethodsWe performed a prospective cross-sectional cohort study to investigate remote ESAS completion by patients with appointments at a weekly surgical oncology clinic. Patients in the initial study cohort were asked to complete and return the ESAS virtually (V). Given low completion rates, the ensuing cohort was asked to complete a hard-copy (HC) ESAS. For the final cohort, we provided remote, personal mentorship by a member of the care team to support virtual electronic ESAS completion (virtual-mentored (VM) cohort).ResultsBetween May and July 2020, a total of 174 patient encounters were included in the study. For the V cohort, 20/46 patients (44%) successfully completed and returned the electronic ESAS, compared to 49/50 (98%) for the HC cohort. For the VM cohort, the overall completion rate was 74% (58/78); however, 12 of these 58 patients did not independently complete a virtual ESAS. Virtual questionnaire completion was not predicted by age, sex, or tumor site, although patients who completed the ESAS were more likely to be in active management rather than surveillance (p = 0.04). Of all completed forms, 42% revealed a depression score of ≥2, and 27% an anxiety score of ≥4.ConclusionsWe identified significant barriers to the virtual completion of ESAS forms, with a lack of predictive variables. The severe degree of psychological distress reported by ~50% of respondents demonstrates the need for ongoing regular collection/review of these data. Innovative solutions are required to overcome barriers to the virtual collection of PROs.

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COVID-19 virtual patient cohort reveals immune mechanisms driving disease outcomes.

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