Post-COVID Conditions and Burden of Disease.

Post-COVID condition (PCC), also known as long COVID, is a multi-systemic illness estimated to affect 10% to 20% of those infected, regardless of age, baseline health status, or initial symptom severity. PCC has affected millions of lives, with long-lasting debilitating effects, but unfortunately it remains an underrecognized and therefore poorly documented condition. Defining and disseminating the burden of PCC is essential for developing effective public health strategies to address this issue in the long term.

Long COVID: pathophysiological factors and abnormalities of coagulation.

Acute COVID-19 infection is followed by prolonged symptoms in approximately one in ten cases: known as Long COVID. The disease affects ~65 million individuals worldwide. Many pathophysiological processes appear to underlie Long COVID, including viral factors (persistence, reactivation, and bacteriophagic action of SARS CoV-2); host factors (chronic inflammation, metabolic and endocrine dysregulation, immune dysregulation, and autoimmunity); and downstream impacts (tissue damage from the initial infection, tissue hypoxia, host dysbiosis, and autonomic nervous system dysfunction). These mechanisms culminate in the long-term persistence of the disorder characterized by a thrombotic endothelialitis, endothelial inflammation, hyperactivated platelets, and fibrinaloid microclots. These abnormalities of blood vessels and coagulation affect every organ system and represent a unifying pathway for the various symptoms of Long COVID.

Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation.

COVID survivors frequently experience lingering neurological symptoms that resemble cancer-therapy-related cognitive impairment, a syndrome for which white matter microglial reactivity and consequent neural dysregulation is central. Here, we explored the neurobiological effects of respiratory SARS-CoV-2 infection and found white-matter-selective microglial reactivity in mice and humans. Following mild respiratory COVID in mice, persistently impaired hippocampal neurogenesis, decreased oligodendrocytes, and myelin loss were evident together with elevated CSF cytokines/chemokines including CCL11. Systemic CCL11 administration specifically caused hippocampal microglial reactivity and impaired neurogenesis. Concordantly, humans with lasting cognitive symptoms post-COVID exhibit elevated CCL11 levels. Compared with SARS-CoV-2, mild respiratory influenza in mice caused similar patterns of white-matter-selective microglial reactivity, oligodendrocyte loss, impaired neurogenesis, and elevated CCL11 at early time points, but after influenza, only elevated CCL11 and hippocampal pathology persisted. These findings illustrate similar neuropathophysiology after cancer therapy and respiratory SARS-CoV-2 infection which may contribute to cognitive impairment following even mild COVID.

Exploring team science, professional networks, and innovation success in the THRIVE COVID-19 fellowship program

IMPACT: Implement and evaluate a fellowship program to foster a new generation of entrepreneurial and collaboratively-minded team scientists, equipped with the knowledge and skills to innovate technology-based solutions for COVID-19 to advance human health OBJECTIVES/GOALS: Mount Sinai Targeted Healthcare Innovation Fellowship (THRIVE) is a 9-month program for participants from diverse professional backgrounds to develop HealthTech innovations related to COVID-19. The program is designed to provide an experiential team science platform for fellows to take an idea from concept to commercially viable innovation. METHODS/STUDY POPULATION: Following a competitive application process, 16 THRIVE fellows comprise four teams working collaboratively in an online forum with input from experts in the field. Success of the program will be evaluated by: assessing pre- and post- collaborative research orientation among THRIVE fellows using the ROI scale1 using social network analysis (SNA) to investigate the social networks of THRIVE fellows to capture patterns of communication and collaboration related to innovation development exploring participant experiences of group formation, teamwork and collaboration related to innovation development using one-to-one semi-structured interview determining team success in innovation development, measured by number of publications, funding awarded, provisional patents and viable products. RESULTS/ANTICIPATED RESULTS: Paired t-tests will determine whether collaborative orientation of THRIVE fellows changes pre- vs. post- program participation, indicating changes in attitude toward multidisciplinary team work. SNA will be used to describe structural patterns of communication that occur at individual and group levels. Network-level indices will provide insight into patterns of communication that exist in innovation development: degree centrality (number of connections per individual), betweenness centrality (number of bridges to others in a network), closeness centrality (closeness to others in a network). We will also test for associations between network characteristics and team success. DISCUSSION/SIGNIFICANCE OF FINDINGS: Understanding patterns of formal and informal relationships, interactions, and perceptions of the collaborative process among individuals in THRIVE teams will elucidate whether such a program can provide an effective forum for team science and innovation development related to COVID-19.

Post-acute COVID-19 Syndrome Negatively Impacts Physical Function, Cognitive Function, Health-Related Quality of Life, and Participation.

OBJECTIVE: This report describes persistent symptoms associated with post-acute COVID-19 syndrome (PACS) and the impact of these symptoms on physical function, cognitive function, health-related quality of life, and participation. DESIGN: This study used a cross-sectional observational study design. Patients attending Mount Sinai's post-acute COVID-19 syndrome clinic completed surveys containing patient-reported outcomes. RESULTS: A total of 156 patients completed the survey, at a median (range) time of 351 days (82-457 days) after COVID-19 infection. All patients were prevaccination. The most common persistent symptoms reported were fatigue (n = 128, 82%), brain fog (n = 105, 67%), and headache (n = 94, 60%). The most common triggers of symptom exacerbation were physical exertion (n = 134, 86%), stress (n = 107, 69%), and dehydration (n = 77, 49%). Increased levels of fatigue (Fatigue Severity Scale) and dyspnea (Medical Research Council) were reported, alongside reductions in levels of regularly completed physical activity. Ninety-eight patients (63%) scored for at least mild cognitive impairment (Neuro-Qol), and the domain of the EuroQol: 5 dimension, 5 level most impacted was Self-care, Anxiety/Depression and Usual Activities. CONCLUSIONS: Persistent symptoms associated with post-acute COVID-19 syndrome seem to impact physical and cognitive function, health-related quality of life, and participation in society. More research is needed to further clarify the relationship between COVID-19 infection and post-acute COVID-19 syndrome symptoms, the underlying mechanisms, and treatment options.

Remote Patient Monitoring Identifies the Need for Triage in Patients with Acute COVID-19 Infection.

Introduction: Telehealth was frequently used in the provision of care and remote patient monitoring (RPM) during the COVID-19 pandemic. The Precision Recovery Program (PRP) remotely monitored and supported patients with COVID-19 in their home environment. Materials and Methods: This was a single-center retrospective cohort study reviewing data acquired from the PRP clinical initiative. Results: Of the 679 patients enrolled in the PRP, 156 patients were screened by a clinician following a deterioration in symptoms and vital signs on a total of 240 occasions, and included in the analyses. Of these 240 occasions, 162 (67%) were escalated to the PRP physician. Thirty-six patients were referred to emergency department, with 12 (7%) admitted to the hospital. The most common risk factors coinciding with hospital admissions were cardiac (67%), age >65 (42%), obesity (25%), and pulmonary (17%). The most common symptoms reported that triggered a screening event were dyspnea/tachypnea (27%), chest pain (14%), and gastrointestinal issues (8%). Vital signs that commonly triggered a screening event were pulse oximetry (15%), heart rate (11%), and temperature (9%). Discussion: Common factors (risk factors, vital signs, and symptoms) among patients requiring screening, triage, and hospitalization were identified, providing clinicians with further information to support decision making when utilizing RPM in this cohort. Conclusion: A clinician-led RPM program for patients with acute COVID-19 infection provided supportive care and screening for deterioration. Similar models should be considered for implementation in COVID-19 cohorts and other conditions at risk of rapid clinical deterioration in the home setting.

Multisensory, Nature-Inspired Recharge Rooms Yield Short-Term Reductions in Perceived Stress Among Frontline Healthcare Workers.

We are currently facing global healthcare crisis that has placed unprecedented stress on healthcare workers as a result of the coronavirus disease 2019 (COVID-19). It is imperative that we develop novel tools to assist healthcare workers in dealing with the significant additional stress and trauma that has arisen as a result of the pandemic. Based in research on the effects of immersive environments on mood, a neuroscience research laboratory was rapidly repurposed using commercially available technologies and materials to create a nature-inspired relaxation space. Frontline healthcare workers were invited to book 15-min experiences in the Recharge Room before, during or after their shifts, where they were exposed to the immersive, multisensory experience 496 Recharge Room users (out of a total of 562) completed a short survey about their experience during an unselected, consecutive 14-day period. Average self-reported stress levels prior to entering the Recharge Room were 4.58/6 (±1.1). After a single 15-min experience in the Recharge Room, the average user-reported stress level was significantly reduced 1.85/6 (±1.2; p < 0.001; paired t-test). Net Promoter Score for the experience was 99.3%. Recharge Rooms such as those described here produce significant short-term reductions in perceived stress, and users find them highly enjoyable. These rooms may be of general utility in high-stress healthcare environments.

Remote Patient Monitoring for Home Management of Coronavirus Disease 2019 in New York: A Cross-Sectional Observational Study.

Background: Coronavirus disease 2019 (COVID-19) poses a global public health emergency, overwhelming health systems worldwide and forcing rapid adoption of telemedicine strategies. Introduction: The COVID-19 Precision Recovery Program (PRP) is a remote patient monitoring (RPM) clinical program that was deployed by a New York health system to perform physiologic and symptomatic monitoring for patients with confirmed or suspected COVID-19 diagnoses. Methods: The present cross-sectional descriptive study reports retrospective data collected from the PRP during the COVID-19 crisis in New York. Results: One hundred twelve patients were included; mean (standard deviation) age was 49 (17.6) years and 60.7% were female. Most prevalent reported comorbidities were hypertension (36.3%), hypercholesterolemia (26.5%), and diabetes (17.7%). Less than half (44.6%) had a positive polymerase chain reaction COVID test (PCR-test), 33% had an unknown COVID status, and 17.9% had a negative test result. The most commonly reported symptoms included dyspnea (55.4%) and anxiety (55.4%). Anxiety was ranked as the most severe symptom (9.8%), followed by difficulty concentrating (4.5%). Symptom presentation did not significantly differ based on PCR-test status. Discussion: RPM can be a valuable tool for delivering care to patients with confirmed or suspected COVID-19 diagnoses. Considering similarities in symptom presentation between PCR-test statuses, access to COVID-related clinical care should not be based on PCR-test results. Conclusions: RPM has strong potential to assist in the effective management of suspected COVID-19 patients.