Ganesh, Ravindra

Abstract Introduction/Objective: To assess the clinical utility of the FM/a® chemokine-cytokine assay in diagnosing fibromyalgia at an academic medical center. Methods: We performed a cross-sectional study on 50 patients diagnosed with fibromyalgia at a specialty fibromyalgia clinic between January 1, 2021 through July 31, 2021. Patients completed questionnaires and provided a venous blood sample sent to EpicGenetics, to complete the FM/a® test. Demographic, symptom, and historical data was obtained from chart review. Statistical analysis was performed. Results: Of 50 patients with a clinical diagnosis of fibromyalgia, the FM/a® test was positive in 45 (90%). Performance of the FM/a® test compared to the 2016 ACR criteria yielded an odds ratio of 3.5 with sensitivity of 0.91, specificity of 0.25. Univariate regression demonstrated an area under the curve (AUC) of 0.7337, which improved to 0.89 when adjusted for age, gender, and race. When compared to the 1990 ACR criteria, a positive FM/a® test had an odds ratio of 2.33 with sensitivity 0.92 and specificity 0.17. Univariate regression analysis demonstrated an AUC of 0.571, when adjusted for age, gender and race, AUC was similar at 0.585. Conclusion: The FM/a® test performed well overall, though inferiorly compared to the 1990 and 2016 ACR diagnostic criteria. When adjusted for age, gender, and race the test performed almost equivalently to the 2016 ACR criteria. The FM/a® test may be useful in general clinical practices to differentiate patients who are more likely to have FM.

ABSTRACT Although severe coronavirus disease 2019 (COVID-19) and hospitalization associated with COVID-19 are generally preventable among healthy vaccine recipients, patients with immunosuppression have poor immunogenic responses to COVID-19 vaccines and remain at high risk of infection with SARS-CoV-2 and hospitalization. In addition, monoclonal antibody therapy is limited by the emergence of novel SARS-CoV-2 variants that have serially escaped neutralization. In this context, there is interest in understanding the clinical benefit associated with COVID-19 convalescent plasma collected from persons who have been both naturally infected with SARS-CoV-2 and vaccinated against SARS-CoV-2 (“vax-plasma”). Thus, we report the clinical outcome of 386 immunocompromised outpatients who were diagnosed with COVID-19 and who received contemporary COVID-19-specific therapeutics (standard-of-care group) and a subgroup who also received concomitant treatment with very high titer COVID-19 convalescent plasma (vax-plasma group) with a specific focus on hospitalization rates. The overall hospitalization rate was 2.2% (5 of 225 patients) in the vax-plasma group and 6.2% (10 of 161 patients) in the standard-of-care group, which corresponded to a relative risk reduction of 65% ( P = 0.046). Evidence of efficacy in nonvaccinated patients cannot be inferred from these data because 94% (361 of 386 patients) of patients were vaccinated. In vaccinated patients with immunosuppression and COVID-19, the addition of vax-plasma or very high titer COVID-19 convalescent plasma to COVID-19-specific therapies reduced the risk of disease progression leading to hospitalization. IMPORTANCE As SARS-CoV-2 evolves, new variants of concern (VOCs) have emerged that evade available anti-spike monoclonal antibodies, particularly among immunosuppressed patients. However, high-titer COVID-19 convalescent plasma continues to be effective against VOCs because of its broad-spectrum immunomodulatory properties. Thus, we report clinical outcomes of 386 immunocompromised outpatients who were treated with COVID-19-specific therapeutics and a subgroup also treated with vaccine-boosted convalescent plasma. We found that the administration of vaccine-boosted convalescent plasma was associated with a significantly decreased incidence of hospitalization among immunocompromised COVID-19 outpatients. Our data add to the contemporary data providing evidence to support the clinical utility of high-titer convalescent plasma as antibody replacement therapy in immunocompromised patients.

Abstract Background Two independent placebo-controlled clinical trials conducted prior to SARS-CoV-2 Omicron demonstrated that sotrovimab and remdesivir reduced hospitalization among high-risk outpatients with mild to moderate COVID-19. However, their effectiveness have not been directly compared. Methods This retrospective study examined all high-risk outpatients with mild to moderate COVID-19 who received either remdesivir or sotrovimab at Mayo Clinic during the Omicron BA.1 surge from January to March 2022. COVID-19-related hospitalization or death within 28 days were compared between the two treatment groups. Results Among 3,257 patients, 2,158 received sotrovimab and 1,099 received remdesivir. Patients treated with sotrovimab were younger (median age, 60 vs. 69 years) and had lower comorbidity (Monoclonal Antibody Screening Score, 5 vs. 6; Charlson Comorbidity Index, 3 vs. 4), but were more likely to be immunocompromised (47.3% vs. 30.2%) than remdesivir-treated patients. The majority (89%) had received at least one dose of COVID-19 vaccine (median, 3 doses [IQR 2-3] for both groups). COVID-19-related hospitalization (1.5% and 1.0% in remdesivir and sotrovimab groups, respectively, p=.15) and mortality within 28 days (0.4% in both groups, p=.82) were similarly low. A propensity score weighted analysis demonstrated no significant difference in the rates of COVID-related hospitalization and death within 28 days between the two groups. Conclusion This study demonstrated favorable outcomes that were not significantly different between patients treated with remdesivir or sotrovimab. As sotrovimab is no longer authorized, these results support the continued use of remdesivir for treating high-risk patients with COVID-19 during the current Omicron-predominant epoch. Disclosures Christina G. Rivera (O'Connor), Pharm.D, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Board Member|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria Maria Gonzalez Suarez, M.D., Ph.D., Gilead: Grant/Research Support Ravindra Ganesh, M.B.B.S., M.D., Alpaca Health: Advisor/Consultant Raymund R. Razonable, MD, Allovir: Endpoint Adjudication Committee|American Society of Transplantation: Board Member|Gilead: Grant/Research Support|Novartis: DSMB|Regeneron: Grant/Research Support|Roche: Grant/Research Support

Abstract Background Remdesivir is FDA-approved for the treatment of hospitalized patients with severe COVID-19. Many patients improve clinically to allow for hospital dismissal before completing the 5-day course. In prior work, those who continued remdesivir in an outpatient setting had better outcomes. Here, we assessed patients’ perspectives and the economic impact of this outpatient practice. Methods During a one-year period, 3,029 patients received remdesivir for COVID-19 in the hospital; of them, 542 were dismissed to continue remdesivir in the outpatient setting and were surveyed. The cost of care was compared between those who remained in the hospital vs. those who were dismissed. Results 470 of 542 patients were surveyed, and 93 (19.8%) responded. Responders were older than non-responders (median, 63 vs. 58 years). The majority (70.5%) had symptoms resolved by the time of the survey. Ten patients (11.4%) had persistent symptoms attributed to long COVID-19, including fatigue (30.1%), brain fog (23.7%), and insomnia (18.3%). 73.8% were excited to learn about the outpatient remdesivir program. The majority (81.0%) felt that receiving therapy at home was the right decision; 79.5% had support and felt the benefits of completing treatment at home. The majority were satisfied with communication before (75.6%) and during (80.5%) the outpatient appointment, information on benefits (80.3%) and risks (58.5%), time spent at the infusion center (88.6%), quality of care (82.3%) and overall experience (76.0%). The benefits of treatment were high-value (82.6%), while the infusions' cost, inconvenience, and discomfort were unimportant for most responders. After adjusting for gender, comorbidity score, and WHO scale, the predicted costs for the groups were $16,544 (inpatient) and $9,097 (outpatient) per patient (difference of $7,447; p< .01). During this study, we estimated a total of 1,077 hospital room-days were made available to other patients. Conclusion An outpatient remdesivir program that allowed for early dismissal was perceived favorably by patients hospitalized for COVID-19. The program resulted in significant cost and resource savings, the latter in terms of the availability of hospital rooms for other patients needing critical services. Disclosures Christina G. Rivera (O'Connor), Pharm.D, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Board Member|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria Bijan J. Borah, Ph.D., Boehringer Ingelheim: Advisor/Consultant|Exact Sciences: Advisor/Consultant Ravindra Ganesh, M.B.B.S., M.D., Alpaca Health: Advisor/Consultant Raymund R. Razonable, MD, Allovir: Endpoint Adjudication Committee|American Society of Transplantation: Board Member|Gilead: Grant/Research Support|Novartis: DSMB|Regeneron: Grant/Research Support|Roche: Grant/Research Support

Background: Complementary and alternative medicine (CAM) interventions are growing in popularity as possible treatments for long COVID symptoms. However, comprehensive analysis of current evidence in this setting is still lacking. Objective: This study aims to review existing published studies on the use of CAM interventions for patients experiencing long COVID through a systematic review. Design: Systematic review of randomized controlled trials (RCTs). Methods: A comprehensive electronic literature search was performed in multiple databases and clinical trial registries from September 2019 to January 2023. RCTs evaluating efficacy and safety of CAM for long COVID were included. Methodological quality of each included trial was appraised with the Cochrane ‘risk of bias’ tool. A qualitative analysis was conducted due to heterogeneity of included studies. Results: A total of 14 RCTs with 1195 participants were included in this review. Study findings demonstrated that CAM interventions could benefit patients with long COVID, especially those suffering from neuropsychiatric disorders, olfactory dysfunction, cognitive impairment, fatigue, breathlessness, and mild-to-moderate lung fibrosis. The main interventions reported were self-administered transcutaneous auricular vagus nerve stimulation, neuro-meditation, dietary supplements, olfactory training, aromatherapy, inspiratory muscle training, concurrent training, and an online breathing and well-being program. Conclusion: CAM interventions may be effective, safe, and acceptable to patients with symptoms of long COVID. However, the findings from this systematic review should be interpreted with caution due to various methodological limitations. More rigorous trials focused on CAM for long COVID are warranted in the future.

The objective of this observational study is to determine whether vaccination for SARS-CoV-2 alters the clinical presentation of post-COVID conditions (PCC). Self-reported data provided by patients requesting care for PCC at the Mayo Clinic were analyzed to assess for a relationship between vaccination status prior to COVID infection and PCC symptoms. In all, 477 subjects were included in this study. In total, 245 (51.4%) were vaccinated. Vaccinated subjects with PCC reported less abdominal pain, anosmia, parosmia, chest pain/tightness, dizziness, numbness/tingling, dyspnea, spells/tremors, and weakness. For hospitalized patients who developed PCC, vaccinated patients reported less chest pain, cough, dizziness, and dyspnea. After applying Bonferroni correction for multiple comparisons, decreased abdominal pain remained significant. We conclude that vaccination against SARS-CoV-2 may reduce the symptoms of PCC, leading to improved morbidity and function. Further studies on the impact of vaccination on PCC and recovery are needed.

Identifying risk factors for post-acute sequelae of COVID-19 (PASC) is important. We conducted a multicenter cross-sectional survey study to define and characterize risk factors for severe COVID-19 in adults (≥18 years) treated at our virtual COVID-19 clinic from March 1, 2020, through March 31, 2021. We assessed patient demographics, symptom types, and persistence, incidence of PASC, and COVID-19–caused hospitalizations. Surveyed patients were also asked to rate their perception of the severity of their acute COVID-19 symptoms. Continuous variables were summarized descriptively. Differences among groups categorized by acute COVID-19 symptom severity level (mild/very mild, moderate, and severe/very severe) were evaluated with the Kruskal–Wallis rank sum test for continuous measures and the Pearson χ 2 test for categorical measures. A total of 3094 adults completed the survey. More respondents with severe/very severe acute COVID-19 symptoms reported having PASC than did those with mild/very mild and moderate acute symptoms. A significantly greater proportion of respondents with PASC were women (68.4% vs 56.7%, p < 0.001), had been hospitalized (12.2% vs 4.4%, p < 0.001), reported having negative psychological COVID-19–related repercussions (39.9% vs 15.3%, p < 0.001), and required more than 1 month to resume normal activities (38.8% vs 12.9%, p < 0.001) than did those without PASC. These findings may improve our understanding of PASC and provide a framework for early recognition of and intervention for patients at higher risk for PASC. Further research is needed to understand the predictors of persistent symptoms after acute SARS-CoV-2 infection and the risk of PASC.

Objective: The purpose of this feasibility pilot study was to evaluate safety and adherence of a wearable brain sensing wellness device designed to reduce stress among healthcare professionals (HCP). Methods: A total of 40 HCP were invited to participate in an open-label pilot study. Participants were asked to use a brain sensing wearable device (MUSE-S™) on a daily basis to reduce their stress, for a total of 90 days. Total study participation duration was 180 days. Study enrollment began in August 2021 and ended December 2021. The exploratory outcomes included stress, depression, sleep, burn-out, resilience, quality of life, and cognition. Results: Among the 40 HCP in study, the majority were female (85%), white (87.5%) and with an average age of 41.3 ± 11.0 years (SD). Participants used the wearable device an average of 23.8 times over a 30-day period with a mean duration of 5.8 min with each use. Study results demonstrate the positive impact of guided mindfulness using the wearable device MUSE-S™ and its accompanying application (APP). A statistically significant improvement was found for a reduction in stress ( P < .001) and improvement in resilience ( P = .02), quality of life ( P = .003), and cognition ( P < .001). The majority (91.9%) of the participants indicated they felt more relaxed after using the device, and 73% indicated they would continue to use this device at end-of-study. No adverse effects were reported. Conclusion: Study results show that 3 to 10 min of guided meditation during work hours through the use of a brain sensing wearable device is safe and acceptable, with associated health benefits for HCP.

AbstractObjectivesDysfunction in smell or taste is well recognized phenomenon in patients infected with SARS‐CoV‐2. This study aimed to quantify the incidence and associated co‐morbidities of reported olfactory or gustatory dysfunction in patients who tested positive for SARS‐CoV‐2.MethodsFrom March 23, 2020 through July 31, 2020, 192,683 patients were tested for SARS‐CoV‐2 at Mayo Clinic. These patients with a positive test were contacted via telephone by physicians at Mayo Clinic and information gathered on patient demographics, comorbidities, symptoms and clinical risk stratification based on these factors.ResultsTwo thousand two hundred and fifty patients tested positive for SARS‐CoV‐2 (1.2%). Six hundred and sixty‐seven (29.6%) of these patients reported loss of smell or taste. Factors found to be correlated with reporting loss of smell or taste on multivariate analysis were: younger age, female sex, or symptoms of chest pain or tightness, cough, or headache and lower clinical risk category. Coronary artery disease (CAD) was associated with not reporting loss of taste or smell.ConclusionOf 2250 patients testing positive for SARS‐CoV‐2 at Mayo Clinic, 667 reported loss of taste and smell. Patients who reported loss of smell or taste were younger, female and more likely to report cough, chest pain, headache, or history of chronic obstructive pulmonary disease (COPD), but overall had fewer high‐risk comorbidities. Those who were older, male, and a reported history of CAD were less likely to report chemosensory dysfunction. Our data are the largest single institution data reporting COVID‐19 associated loss of smell or taste, and the first to associate COPD and CAD as factors that affect rates of reported chemosensory dysfunction.Level of evidenceIIB.