Mueller, Michael

Objectives Long-term symptoms following infection with acute respiratory syndrome coronavirus-2 (SARS-CoV-2), termed post-acute sequelae of SARS-CoV-2 infection (PASC) or Long COVID (LC), persist beyond 90 days and may impact at least 10% of patients with acute infection. The exact cause of LC remains unknown, but several theories include persistent viral particles, immune dysfunction, and autonomic nervous system (ANS) imbalance, particularly involving the vagus nerve. Given the role of the vagus nerve in inflammation regulation, vagal nerve stimulation (VNS) is being explored as a treatment option. The present study aimed to evaluate the feasibility, safety, and exploratory effects of a handheld external transcutaneous cervical non-invasive VNS (tcVNS) on the primary endpoint of Post-COVID Functional Status (PCFS) grade, alongside secondary outcomes such as LC-related fatigue and other symptoms. Methods Participants from our Post COVID Care Clinic were randomized into treatment (tcVNS treatments two minutes, three times a day) and control (no VNS) groups for a study period of 12 weeks. Participants completed validated questionnaires, PET-CT scans, and inflammatory cytokines at baseline and 12 weeks. Results All randomized patients (8 tcVNS, 10 control) completed the 12-week study. Participants randomized to tcVNS were observed to have improvements in PHQ-9, PROMIS-F, and COMPASS-31 when compared to controls, but these differences were not statistically significant. Cortisol and DHEA were also observed to increase less in the tcVNS group when compared to the control group, but these changes were also not statistically significant. Conclusions tcVNS was well tolerated and may be a promising therapeutic approach for LC, a chronic disease with no approved treatments and very low rates of complete recovery.

Objective Long COVID (LC) refers to the long-term symptoms occurring after SARS-CoV-2 infection and resolution of the initial disease prodrome. While LC is increasingly recognized, knowledge about its biomarkers is still limited. This study examines imaging findings in 18 F-FDG PET-CT scans in 40 patients with LC from an academic LC Clinic, for potential imaging biomarkers. Methods This study included patients aged 18 and older with confirmed positive SARS-CoV-2 PCR test and at least 28 days post-symptom onset. 18 F-FDG PET-CT scans were performed, and brain metabolic activity was compared to a control database to generate Z-scores. Participants were grouped based on their clinical phenotype and Z-scores of different brain regions were analyzed using t-tests. Results The study group was mainly female (70%), with a median age of 53 years, and predominantly non-Hispanic White (90%). Most had pre-existing conditions such as gastrointestinal, cardiovascular, endocrine, and psychiatric disorders. The findings showed significant cerebral hypometabolism in 29 patients with fatigue and post-exertional malaise (PEM), particularly in the left sensorimotor cortex (p=0.0253) and bilateral primary visual cortex (right: p=0.0096, left: p=0.0016), which persisted up to two years after infection. Conclusions In summary, this study identified persistent cerebral hypometabolism in LC patients, especially those with fatigue with PEM, up to two years post-infection. These results suggest that 18 F-FDG PET-CT could be a valuable tool for diagnosing and managing LC. Further research is essential to confirm these findings and improve treatment strategies for patients with LC.

Ramadan is the Islamic holy month when Muslims around the world fast from dawn to sunset. This 30-day pattern of intermittent diurnal fasting can have a significant physiologic impact on the body. Importantly, oral intake is forbidden during this time, and many patients do not wish to take medications. From a clinical perspective, this potentially impacts healthcare delivery and chronic disease states. Despite these important changes, awareness of individual patient practices remains limited among healthcare providers in North America, which may worsen health disparities in Muslim patients. A fundamental understanding of the cultural and physiological implications of fasting during Ramadan can improve cultural competence and patient outcomes. In this paper, we review the physiologic changes during fasting, medical exemptions to fasting, and special considerations for the care of Muslim patients with chronic conditions who may fast during Ramadan.

Background: In addition to the morbidity and mortality associated with acute infection, COVID-19 has been associated with persistent symptoms (>30 days), often referred to as Long COVID (LC). LC symptoms often cluster into phenotypes, resembling conditions such as fibromyalgia, postural orthostatic tachycardiac syndrome (POTS), and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). LC clinics have been established to best address the needs of LC patients and continuity of care. We developed a cross-sectional survey to assess treatment response through our LC Clinic (LCC). Methods: A 25-question survey (1-10 Likert scale) was expert- and content-validated by LCC clinicians, patients, and patient advocates. The survey assessed LC symptoms and the helpfulness of different interventions, including medications and supplements. A total of 852 LCC patients were asked to complete the survey, with 536 (62.9%) responding. Results: The mean time from associated COVID-19 infection to survey completion was 23.2 ± 6.4 months. The mean age of responders was 52.3 ± 14.1 (63% females). Self-reported symptoms were all significantly improved ( P < .001) from the initial visit to the LCC (baseline) to the time of the follow-up survey. However, only 4.5% (24/536) of patients rated all symptoms low (1-2) at the time of the survey, indicating low levels of full recovery in our cohort. The patients rated numerous interventions as being helpful, including low-dose naltrexone (45/77; 58%), vagal nerve stimulation (18/34; 53%), and fisetin (28/44; 64%). Conclusions: Patients report general improvements in symptoms following the initial LCC visit, but complete recovery rates remain low at 23.2 ± 6.4 months.

Background: Over 30% of patients with COVID-19 have persistent symptoms that last beyond 30 days and referred to as Long COVID. Long COVID has been associated with a persistent elevation in peripheral cytokines including interleukin-6, interleukin-1β, and tumor necrosis factor-α. This study reports cytokine profiles of patients in our clinic across SARS-COV-2 variant epochs. Methods: The clinical cytokine panel was analyzed in patients with Long COVID during periods that were stratified according to variant epoch. The 4 variant epochs were defined as: (1) wild-type through alpha, (2) alpha/beta/gamma, (3) delta, and (4) omicron variants. Results: A total of 390 patients had the clinical cytokine panel performed; the median age was 48 years (IQR 38-59) and 62% were female. Distribution by variant was wild-type and alpha, 50% (n = 196); alpha/beta/gamma, 7.9% (n = 31); delta, 18% (n = 72); and omicron, 23% (n = 91). Time to cytokine panel testing was significantly longer for the earlier epochs. Tumor necrosis factor-α ( P < .001) and interleukin 1β ( P < .001) were significantly more elevated in the earlier epochs (median of 558 days in wild-type through Alpha epoch vs 263 days in omicron epoch, P < .001)). Nucleocapsid antibodies were consistently detected across epochs. Discussion: When stratified by variant epoch, patients with early epoch Long COVID had persistently elevated peripheral pro-inflammatory cytokine levels when compared to later epoch Long COVID. Patients with Long COVID have similar clusters of symptoms across epochs, suggesting that the underlying pathology is independent of the peripheral cytokine signature.

Background Over the past few years, a growing number of studies have explored massage robots. However, to date, a dedicated systematic review focused solely on robot-assisted massage has not been conducted. Objective To systematically identify and summarize evidence from studies concerning robot-assisted massage in healthcare settings. Methods An extensive literature search, involving electronic databases Ovid and Scopus, was conducted from the inception of the databases up to March 2023. This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, and relevant papers were chosen based on the predefined inclusion criteria. Given the substantial methodological diversity among the included studies, a qualitative analysis was conducted. Results Seventeen studies met the inclusion criteria, comprising 15 preliminary trials, one quasi-experimental study, and one randomized controlled trial. Approximately 29% of the studies focused on the application of robotic massage for patients, 24% targeted both healthy volunteers and patients, and the remaining 47% were preclinical trials assessing the effectiveness of robotic massage solely on healthy volunteers. Primary interventions included robotic massage for oral rehabilitation, scalp massage, low back massage, shoulder massage, and full-body massage. All studies provided evidence that robotic massage interventions can enhance health and well-being, indicating a promising future for the integration of robotics in the field of massage therapy. Conclusions In general, robotic massage interventions offer physical and mental health benefits. Robot-assisted massage may be integrated into care provision as an adjunct to enhance human well-being. Nonetheless, further research is needed to confirm these findings.

Background: Electronic massagers have gained popularity for their non-invasive and cost-effective approach to healthcare. However, existing electronic massagers require manual manipulation, leading to inconsistency. Objective: To investigate the feasibility and acceptability of the Electronic Massager—Expert Manipulative Massage Automation (EMMA) among the American population. Methods: A single-arm pilot study was conducted at Mayo Clinic Rochester campus. Participants received massage therapy with the EMMA treatment model and completed a demographics and Satisfaction Survey Questionnaire. Data were collected using REDCap, and statistical analysis was performed. Results: Twenty healthy volunteers (13 women, 7 men; median age, 47 years) participated and completed the intervention within 2 weeks. No adverse events were reported. Overall, the acceptability and satisfaction of massage utilizing EMMA were high, with all participants finding the study worthwhile, willing to participate again, and willing to recommend the study to others. Regarding the overall experience, 65.0% reported a better-than-expected experience. Responses to open-ended post-treatment questions showed that most participants enjoyed the warmth (35%), pressure (25%), and relaxation (20%) provided by EMMA, with the majority suggesting no changes or improvements were needed. However, some participants expressed a desire for an expanded massage area (20%). Conclusions: This study suggests that the EMMA massager has high acceptability and satisfaction among healthy volunteers, thus demonstrating its feasibility. However, further research is needed to optimize EMMA and assess its clinical effectiveness.

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.