Stress Resilience Program for Health Care Professionals During a Pandemic: A Pilot Program.

BACKGROUND: The COVID-19 pandemic has led to increased burnout and staff turnover for health care providers (HCPs). The purpose of this pilot study was to evaluate the safety and acceptability of a Stress Resilience Program (SRP) for reducing perceived stress and improving resilience among HCPs during a pandemic. METHOD: Of the 12 HCPs expressing interest in the study, 10 were enrolled in this study. Participants attended three in-person visits (consent/screen, baseline, and end-of-study). The SRP consisted of education related to resilience enhancement and a breathing device (BreatherFit®) for combined respiratory muscle training (cRMT). Participants completed 4 weeks of cRMT and applied situational breathing strategies as needed. Outcomes measured were changes in stress (PSS-10), resilience (BRS), depression (PRIME-MD), and sleep (PSQI and Oura Ring®). FINDINGS: The majority of participants were male (60%) and White (60%) with an average age of 39.7 years. Changes from baseline to end-of-treatment indicated a positive trend with significant stress reduction (-3.2 ± 3.9, p = .028) and nonsignificant depression reduction (-0.5 ± 0.7, p = .05). Resilience was high at baseline and continued to stay high during the study with a nonsignificant increase at end-of-study (+0.07 ± 0.7, p = .77). No changes in overall sleep scores were noted. All participants agreed the study was worthwhile, 80% indicated they would repeat the experience, while 90% indicated they would recommend the study to others. CONCLUSION/APPLICATION TO PRACTICE: Because of its size and portability, SRP is an easily applicable and promising option for reducing stress among HCPs during a high-stress period, such as a pandemic. Larger studies are needed.

Expanding repertoire of SARS-CoV-2 deletion mutations contributes to evolution of highly transmissible variants.

The emergence of highly transmissible SARS-CoV-2 variants and vaccine breakthrough infections globally mandated the characterization of the immuno-evasive features of SARS-CoV-2. Here, we systematically analyzed 2.13 million SARS-CoV-2 genomes from 188 countries/territories (up to June 2021) and performed whole-genome viral sequencing from 102 COVID-19 patients, including 43 vaccine breakthrough infections. We identified 92 Spike protein mutations that increased in prevalence during at least one surge in SARS-CoV-2 test positivity in any country over a 3-month window. Deletions in the Spike protein N-terminal domain were highly enriched for these 'surge-associated mutations' (Odds Ratio = 14.19, 95% CI 6.15-32.75, p value = 3.41 × 10-10). Based on a longitudinal analysis of mutational prevalence globally, we found an expanding repertoire of Spike protein deletions proximal to an antigenic supersite in the N-terminal domain that may be one of the key contributors to the evolution of highly transmissible variants. Finally, we generated clinically annotated SARS-CoV-2 whole genome sequences from 102 patients and identified 107 unique mutations, including 78 substitutions and 29 deletions. In five patients, we identified distinct deletions between residues 85-90, which reside within a linear B cell epitope. Deletions in this region arose contemporaneously on a diverse background of variants across the globe since December 2020. Overall, our findings based on genomic-epidemiology and clinical surveillance suggest that the genomic deletion of dispensable antigenic regions in SARS-CoV-2 may contribute to the evasion of immune responses and the evolution of highly transmissible variants.

Estradiol and Dihydrotestosterone Levels in COVID-19 Patients.

OBJECTIVE: To determine differences in plasma sex hormone levels in male and female coronavirus disease 2019 (COVID-19) patients and healthy volunteers (HVs) because cell entry of severe acute respiratory syndrome coronavirus 2 occurs via the angiotensin-converting enzyme 2 receptor which is downregulated by 17ß-estradiol. PATIENTS AND METHODS: Citrated plasma samples were collected from 101 patients with COVID-19 upon presentation to the emergency department and from 40 HVs between November 1, 2020, and May 30, 2021. Plasma 17ß-estradiol and 5α-dihydrotestosterone (DHT) levels were measured using enzyme-linked immunosorbent assay (pg/mL). Data are presented as median and quartiles (IQR). Wilcoxon rank sum test with a P value less than .05 was considered significant. RESULTS: Patients with COVID-19 (median age, 49 years) included 51 males and 50 females (25 postmenopausal). Hospital admission was required for 58.8% of male patients (n = 30) and 48.0% of female patients (n = 24) (66.7% postmenopausal, n = 16) Healthy volunteers (median age, 41 years) included 20 males and 20 females (9 postmenopausal). Female patients with COVID-19 were found to have decreased 17ß-estradiol levels (18.5 [IQR, 10.5-32.3] pg/mL; 41.4 [IQR, 15.5-111.0] pg/mL, P=.025), and lower 17ß-estradiol to DHT ratios (0.073 [IQR, 0.052-0.159] pg/mL; 0.207 [IQR, 0.104-0.538] pg/mL, P=.015) than female HVs. Male patients with COVID-19 were found to have decreased DHT levels (302.8 [IQR, 249.9-470.8] pg/mL; 457.2 [IQR, 368.7-844.3] pg/mL, P=.005), compared with male HVs. Levels of DHT did not differ between female patients with COVID-19 and female HVs, whereas 17ß-estradiol levels did not differ between male patients with COVID-19 and male HVs. CONCLUSION: Sex hormone levels differ between patients with COVID-19 and HVs, with sex-specific patterns of hypogonadism in males and females. These alterations may be associated with disease development and severity.

Postacute Sequelae of SARS-CoV-2 Infection-Lessons Learned From a Coordinated Health System Response.

Objective: To outline a consensus-designed process for triaging and managing patients with post-coronavirus disease (COVID-19) syndrome at Mayo Clinic. Patients and Methods: We convened a central multidisciplinary team including members from the departments of general internal medicine, occupational medicine, physical medicine and rehabilitation, psychology, allergy and immunology, infectious disease, pulmonology, neurology, cardiology, and pediatrics and otorhinolaryngology with membership from all Mayo Clinic sites in Arizona, Florida, Iowa, Minnesota, and Wisconsin. Results: Consensus recommendations were made for the best practice guidelines on triaging and managing patients. Several innovations were agreed upon, including a postacute sequelae of COVID-19-specific appointment request form for data collection, a bioregistry, a biorepository, and a postacute sequelae of COVID-19-specific treatment program. Conclusion: Given that each clinical site had individual clinical practices, these recommendations were implemented using different models, which may provide broad applicability to other clinical settings.

Post-COVID-19 syndrome: persistent neuroimaging changes and symptoms 9 months after initial infection.

A previously healthy and active middle-aged woman acquired COVID-19 as an occupational exposure with subsequent persistent post-COVID-19 symptoms including headache, dyspnoea on exertion, chest pressure, tachycardia, anosmia, parosmia, persistent myalgia, vertigo, cognitive decline and fatigue. She presented to a tertiary medical centre for further evaluation after 9 months of persistent symptoms and had a largely unremarkable workup with the exception of a persistently elevated monocyte chemoattractant protein 1, blunted cardiovagal response and non-specific scattered areas of low-level hypometabolism at the bilateral frontal, left precuneus, occipital and parietal regions on PET scan.

The Female-Predominant Persistent Immune Dysregulation of the Post-COVID Syndrome.

OBJECTIVE: To describe the clinical data from the first 108 patients seen in the Mayo Clinic post-COVID-19 care clinic (PCOCC). METHODS: After Institutional Review Board approval, we reviewed the charts of the first 108 patients seen between January 19, 2021, and April 29, 2021, in the PCOCC and abstracted from the electronic medical record into a standardized database to facilitate analysis. Patients were grouped into phenotypes by expert review. RESULTS: Most of the patients seen in our clinic were female (75%; 81/108), and the median age at presentation was 46 years (interquartile range, 37 to 55 years). All had post-acute sequelae of SARS-CoV-2 infection, with 6 clinical phenotypes being identified: fatigue predominant (n=69), dyspnea predominant (n=23), myalgia predominant (n=6), orthostasis predominant (n=6), chest pain predominant (n=3), and headache predominant (n=1). The fatigue-predominant phenotype was more common in women, and the dyspnea-predominant phenotype was more common in men. Interleukin 6 (IL-6) was elevated in 61% of patients (69% of women; P=.0046), which was more common than elevation in C-reactive protein and erythrocyte sedimentation rate, identified in 17% and 20% of cases, respectively. CONCLUSION: In our PCOCC, we observed several distinct clinical phenotypes. Fatigue predominance was the most common presentation and was associated with elevated IL-6 levels and female sex. Dyspnea predominance was more common in men and was not associated with elevated IL-6 levels. IL-6 levels were more likely than erythrocyte sedimentation rate and C-reactive protein to be elevated in patients with post-acute sequelae of SARS-CoV-2 infection.

Utilization of an Electronic Health Record Integrated Risk Score to Predict Hospitalization Among COVID-19 Patients.

OBJECTIVE: To evaluate the performance of an Electronic Health Record (EHR) integrated risk score for COVID-19 positive outpatients to predict 30-day risk of hospitalization. PATIENTS AND METHODS: A retrospective observational study of 67 470 patients with COVID-19 confirmed by polymerase chain reaction (PCR) test between March 12, 2020 and February 8, 2021. Risk scores were calculated based on data in the chart at the time of the incident infection. RESULTS: The Mayo Clinic COVID-19 risk score consisted of 13 components included age, sex, chronic lung disease, congenital heart disease, congestive heart failure, coronary artery disease, diabetes mellitus, end stage liver disease, end stage renal disease, hypertension, immune compromised, nursing home resident, and pregnant. Univariate analysis showed all components, except pregnancy, have significant (P < .001) association with admission. The Mayo Clinic COVID-19 risk score showed a Receiver Operating Characteristic Area Under Curve (AUC) of 0.837 for the prediction of admission for this large cohort of COVID-19 positive patients. CONCLUSION: The Mayo Clinic COVID-19 risk score is a simple score that is easily integrated into the EHR with excellent predictive performance for severe COVID-19. It can be leveraged to stratify risk for severe COVID-19 at initial contact, when considering therapeutics or in the allocation of vaccine supply.

Biomarkers of thromboinflammation correlate to COVID-19 infection and admission status in emergency department patients

Background COVID-19-associated coagulopathy is incompletely understood. Objectives To characterize thrombin generation, Von Willebrand Factor (VWF), neutrophil extracellular traps (NETs), and their role in COVID-19 risk stratification in the emergency department (ED). Patients/methods Plasma samples from 67 ED COVID-19 patients were compared to 38 healthy volunteers (HVs). Thrombin generation (calibrated automated thrombogram, CAT) was expressed as lag time (LT, min), peak height (PH, min), and time to peak (ttPeak, min). Citrullinated nucleosomes and histones were quantified with ELISA, VWF antigen and activity (IU/dL) through latex immunoassay, Factor VIII (IU/dL) through one-stage optical clot detection, and VWF multimers with western blot densitometry. Wilcoxon testing and multivariable logistic regression were performed. Results presented as median [Q1, Q3];p < 0.05 significant. Results COVID-19 patients had longer LT (4.00 [3.26, 4.67];2.95 [2.67, 3.10], p < 0.001) and ttPeak (7.33 [6.33, 8.04];6.45 [6.00, 7.50], p = 0.004), greater VWF antigen (212 [158, 275];110 [91, 128], p < 0.001) and Factor VIII levels (148 [106, 190];106 [86, 129], p < 0.001), with decreased high molecular weight multimers (Normalized multimer ratio 0.807 [0.759, 0.869];0.891 [0.858, 0.966], p < 0.001), than HVs. COVID-19 patients requiring admission from the ED had longer LT and ttPeak with greater VWF antigen and Factor VIII levels than those not admitted. Two and three variable models of CAT parameters and VWF correlated with COVID-19 and admission status (C-statistics 0.677 to 0.922). Conclusions Thrombin generation kinetics and VWF levels, independent of NETs, may have a role in predicting admission need for COVID-19 patients.

When Pandemics Collide: the Interplay of Obesity and COVID-19.

PURPOSE OF REVIEW: The COVID-19 pandemic has been associated with significant morbidity and mortality worldwide. In addition to those with advanced age and co-morbidities such as heart disease or cancer, obese individuals have also had very high rates of hospitalization, critical illness, need for ventilator support, as well as mortality. A number of factors associated with obesity have led to devastating consequences as these two pandemics have interacted. RECENT FINDINGS: Obese individuals through a combination of structural and cellular level changes have greater risk of ischemic heart disease, diabetes, cancer, and respiratory disease, which are themselves risk-factors for acquiring COVID-19 disease. These structural changes also result in increased intra-abdominal and intra-thoracic pressure as well as a restrictive lung physiology that leads to reduction in total lung capacity, functional residual capacity, and increase in airway hyper-reactivity. Adipose tissue is also impacted in obese individuals leading to local as well as systemic inflammation, which can contribute to increased release of free fatty acids and systemic insulin resistance. Additionally, angiotensin-converting enzyme 2 and dipeptidyl peptidase 4, which act as receptors for SARS-CoV-2 are also significantly increased in obese individuals. The present manuscript reviews these structural, immune, and molecular changes associated with obesity that make obese individuals more vulnerable to acquiring severe COVID-19 and more challenging to manage associated complications.

Role of senescence in the chronic health consequences of COVID-19.

While the full impact of COVID-19 is not yet clear, early studies have indicated that upwards of 10% of patients experience COVID-19 symptoms longer than 3 weeks, known as Long-Hauler's Syndrome or PACS (postacute sequelae of SARS-CoV-2 infection). There is little known about risk factors or predictors of susceptibility for Long-Hauler's Syndrome, but older adults are at greater risk for severe outcomes and mortality from COVID-19. The pillars of aging (including cellular senescence, telomere dysfunction, impaired proteostasis, mitochondrial dysfunction, deregulated nutrient sensing, genomic instability, progenitor cell exhaustion, altered intercellular communication, and epigenetic alterations) that contribute to age-related dysfunction and chronic diseases (the "Geroscience Hypothesis") may interfere with defenses against viral infection and consequences of these infections. Heightening of the low-grade inflammation that is associated with aging may generate an exaggerated response to an acute COVID-19 infection. Innate immune system dysfunction that leads to decreased senescent cell removal and/or increased senescent cell formation could contribute to accumulation of senescent cells with both aging and viral infections. These processes may contribute to increased risk for long-term COVID-19 sequelae in older or chronically ill patients. Hence, senolytics and other geroscience interventions that may prolong healthspan and alleviate chronic diseases and multimorbidity linked to fundamental aging processes might be an option for delaying, preventing, or alleviating Long-Hauler's Syndrome.

Use of telehealth in home nutrition support: Challenges and advantages.

Coronavirus disease 2019 (COVID-19), after initially being detected in Wuhan, China in late 2019, quickly spread to most regions of the world, meeting World Health Organization criteria for a pandemic. Social distancing along with other measures implemented to control spread had a drastic impact on the provision of healthcare including deferred elective procedures and surgeries as well as delayed care and evaluation for emergent diagnoses such as heart attacks and strokes. In the home nutrition practice, patients began to delay routine laboratory tests and were canceling or deferring annual visits. Our group soon began to rapidly deploy telehealth to meet the needs of the home nutrition patients. Telehealth is not a new concept with descriptions of healthcare being provided at a distance with the use of telephone in the 1870s. However, widespread adoption has been limited because of regulation (licensure, prescriptions, credentialing, and privileges), lack of reimbursement, as well as adoption and availability of technology needed to carry out telehealth visits. As regulations and limits on reimbursements were waived during COVID-19 pandemic, our home nutrition practice began to evaluate core components of the care we provide for our patients and assess which could be successfully transitioned to telehealth. In addition to the history and regulation of telehealth, the current manuscript provides details regarding successful implementation of telehealth visits such as change management, selection of telehealth platform, scheduling and logistics, as well as carrying out the virtual visit including history and physical exam.

Central Sensitization Phenotypes in Post Acute Sequelae of SARS-CoV-2 Infection (PASC): Defining the Post COVID Syndrome.

OBJECTIVE: To develop and implement criteria for description of post COVID syndrome based on analysis of patients presenting for evaluation at Mayo Clinic Rochester between November 2019 and August 2020. METHODS: A total of 465 patients with a history of testing positive for COVID-19 were identified and their medical records reviewed. After a thorough review, utilizing the DELPHI methods by an expert panel, 42 (9%) cases were identified with persistent central sensitization (CS) symptoms persisting after the resolution of acute COVID-19, herein referred to as Post COVID syndrome (PoCoS). In this report we describe the baseline characteristics of these PoCoS patients. RESULTS: Among these 42 PoCoS patients, the mean age was 46.2 years (median age was 46.5 years). Pain (90%), fatigue (74%), dyspnea (43%), and orthostatic intolerance (38%) were the most common symptoms. The characteristics of an initial 14 patients were utilized for the development of clinical criteria via a modified Delphi Method by a panel of experts in central sensitization disorders. These criteria were subsequently applied in the identification of 28 additional cases of suspected PoCoS. A 2-reviewer system was used to analyze agreement with using the criteria, with all 28 cases determined to be either probable or possible cases by the reviewers. Inter-reviewer agreement using these proposed defining criteria was high with a Cohen's alpha of .88. CONCLUSIONS: Here we present what we believe to be the first definitional criteria for Post COVID syndrome. These may be useful in clinical phenotyping of these patients for targeted treatment and future research.

PROMIS Scales for Assessment of Persistent Post-COVID Symptoms: A Cross Sectional Study.

OBJECTIVE: Persistent post-COVID symptoms are estimated to occur in up to 10% of patients who have had COVID-19. These lingering symptoms may persist for weeks to months after resolution of the acute illness. This study aimed to add insight into our understanding of certain post-acute conditions and clinical findings. The primary purpose was to determine the persistent post COVID impairments prevalence and characteristics by collecting post COVID illness data utilizing Patient-Reported Outcomes Measurement Information System (PROMIS®). The resulting measures were used to assess surveyed patients physical, mental, and social health status. METHODS: A cross-sectional study and 6-months Mayo Clinic COVID recovered registry data were used to evaluate continuing symptoms severity among the 817 positive tested patients surveyed between March and September 2020. The resulting PROMIS® data set was used to analyze patients post 30 days health status. The e-mailed questionnaires focused on fatigue, sleep, ability to participate in social roles, physical function, and pain. RESULTS: The large sample size (n = 817) represented post hospitalized and other managed outpatients. Persistent post COVID impairments prevalence and characteristics were determined to be demographically young (44 years), white (87%), and female (61%). Dysfunction as measured by the PROMIS® scales in patients recovered from acute COVID-19 was reported as significant in the following domains: ability to participate in social roles (43.2%), pain (17.8%), and fatigue (16.2%). CONCLUSION: Patient response on the PROMIS® scales was similar to that seen in multiple other studies which used patient reported symptoms. As a result of this experience, we recommend utilizing standardized scales such as the PROMIS® to obtain comparable data across the patients' clinical course and define the disease trajectory. This would further allow for effective comparison of data across studies to better define the disease process, risk factors, and assess the impact of future treatments.

Managing Patients in the COVID-19 Pandemic: A Virtual Multidisciplinary Approach.

OBJECTIVE: To study the impact of a 60-day pilot of an innovative virtual-care model using general internal medicine physicians and nurses to respond rapidly to more than 1200 coronavirus disease-2019 (COVID-19)-positive nasopharyngeal polymerase chain reaction tests. PATIENTS AND METHODS: The current study was approved by the Mayo Clinic COVID-19 Research Committee and the Mayo Clinic Institutional Review Board. The data for all SARS-CoV-2-positive patients treated by our team were entered into a prospectively maintained internal research electronic data capture database. We searched this database retrospectively for the first 60 days of our program (March 23, 2020 to May 22, 2020). The data included basic deidentified demographics; symptoms at intake into the program; date of symptom onset; risk factors; location; and outcomes including hospitalization, admission to intensive care unit, and death. RESULTS: Patients were contacted, on average, 6.3 hours after their results became available. There was a total of 138 ED visits. Of these, 40% were admitted to the hospital, with 36% of those admitted requiring intensive care unit level of care. Of the 849 patients in this sample, there were only 2 deaths (0.23%) at 60 days. CONCLUSION: Our innovative multidisciplinary COVID team provided excellent clinical care for patients with COVID, with a very low mortality rate compared with the national average. Although data are not available on a national scale for time to contact patient, our team was able to contact patients within the established recommendation for contact within 48 hours of testing, which is optimal.

Clinical Nutrition Research and the COVID-19 Pandemic: A Scoping Review of the ASPEN COVID-19 Task Force on Nutrition Research.

The purpose of this scoping review by the American Society for Parenteral and Enteral Nutrition (ASPEN) Coronavirus Disease 2019 (COVID-19) Nutrition Task Force was to examine nutrition research applicable to the COVID-19 pandemic. The rapid pace of emerging scientific information has prompted this activity to discover research/knowledge gaps. This methodology adhered with recommendations from the Joanna Briggs Institute. There were 2301 citations imported. Of these, there were 439 articles fully abstracted, with 23 main topic areas identified across 24 article types and sourced across 61 countries and 51 specialties in 8 settings and among 14 populations. Epidemiological/mechanistic relationships between nutrition and COVID-19 were reviewed and results mapped to the Population, Intervention, Comparator, Outcome, and Time (PICO-T) questions. The aggregated data were analyzed by clinical stage: pre-COVID-19, acute COVID-19, and chronic/post-COVID-19. Research gaps were discovered for all PICO-T questions. Nutrition topics meriting urgent research included food insecurity/societal infrastructure and transcultural factors (pre-COVID-19); cardiometabolic-based chronic disease, pediatrics, nutrition support, and hospital infrastructure (acute COVID-19); registered dietitian nutritionist counseling (chronic/post-COVID-19); and malnutrition and management (all stages). The paucity of randomized controlled trials (RCTs) was particularly glaring. Knowledge gaps were discovered for PICO-T questions on pediatrics, micronutrients, bariatric surgery, and transcultural factors (pre-COVID-19); enteral nutrition, protein-energy requirements, and glycemic control with nutrition (acute COVID-19); and home enteral and parenteral nutrition support (chronic/post-COVID-19). In conclusion, multiple critical areas for urgent nutrition research were identified, particularly using RCT design, to improve nutrition care for patients before, during, and after COVID-19.