Pro Inflammatory Cytokines Profiles of Patients With Long COVID Differ Between Variant Epochs.

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-1ß, 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 1ß (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.

Longitudinal Progression of Patients with Long COVID Treated in a Post-COVID Clinic: A Cross-Sectional Survey.

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.

Association between obesity and female sexual dysfunction: a review.

INTRODUCTION: Obesity is a global health crisis that has been growing over the past few decades. The economic burden associated with obesity is substantial as it is associated with multiple disabling chronic diseases, such as cardiovascular disease, certain cancers, osteoarthritis, chronic pain, and mental illness. Obesity is known to be a risk factor for sexual dysfunction in men, but this association is less well understood in women. AIMS: To provide a narrative review of the available literature on the relationship between overweight/obesity and female sexual dysfunction, elaborate on the possible mechanisms explaining this association, and discuss the effects of weight loss on sexual function in those with obesity. METHODS: A search of the medical literature was carried out in PubMed and Medline, focusing on original research and systematic reviews of original research on obesity and sexual function in women. RESULTS: The relationship between obesity and female sexual function is not consistent across studies. While women with obesity are more likely to have worse sexual function and avoid sexual activity, many studies have failed to identify these associations. Lifestyle changes resulting in weight loss lead to better sexual function, and bariatric surgery has been shown to improve sexual function in the first couple of years following the procedure; yet, the long-term effects of weight loss and bariatric surgery are still uncertain. CONCLUSIONS: The evidence on the relationship between obesity and female sexual function is mixed. Nevertheless, weight loss has been shown to improve sexual function in women with obesity. The impact of weight loss medications and the long-term effect of bariatric surgery on female sexual function require further study.

Diagnosis and Management of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic neurologic disease often preceded by infection. There has been increased interest in ME/CFS recently because of its significant overlap with the post-COVID syndrome (long COVID or post-acute sequelae of COVID), with several studies estimating that half of patients with post-COVID syndrome fulfill ME/CFS criteria. Our concise review describes a generalist approach to ME/CFS, including diagnosis, evaluation, and management strategies.

The use of MRI, PET/CT, and nuclear scintigraphy in the imaging of pyogenic native vertebral osteomyelitis: a systematic review and meta-analysis.

BACKGROUND CONTEXT: Native vertebral osteomyelitis (NVO) is a severe infection with an increasing incidence globally. Although there is no widely agreed upon reference standard for diagnosis of the disease, imaging plays a crucial role. Magnetic resonance imaging (MRI) is currently the imaging modality of choice. In recent years, advances in imaging have allowed for a larger role for alternative imaging techniques in the setting of NVO. PURPOSE: Our aim was to evaluate the diagnostic accuracy of MRI, PET/CT, and nuclear imaging, namely 67Gallium and 99mTechnetium scintigraphy, in the diagnosis of pyogenic NVO. STUDY DESIGN/SETTING: We conducted a systematic review of five medical databases and included all studies from 1970 to September 2021 that compared imaging techniques and provided sufficient data for diagnostic test accuracy meta-analysis. METHODS: Abstract screening, full text review, and data extraction were done by a pair of independent reviewers. Nonnative and nonpyogenic patients were excluded. A bivariate random effect model was used for meta-analysis. RESULTS: Twenty studies were included in the meta-analysis, encompassing a total of 1,123 imaging studies. The meta-analysis sensitivity and specificity of MRI were 90% and 72% respectively; those of PET/CT were 93% and 80%; those of 67Ga were 95% and 88%; those of 99mTc were 86% and 39%; and the sensitivity and specificity of combined Ga and Tc were 91% and 92% respectively in the setting of suspected NVO. CONCLUSIONS: 67Ga has the highest sensitivity for NVO, and its specificity is augmented when combined with 99mTc. MRI and PET/CT are both highly sensitive modalities, although the specificity of PET/CT is slightly better. MRI remains an appropriate initial test depending on the availability of other modalities.

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.

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.

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.

A sticky situation: a case of Actinomyces viscosus vertebral osteomyelitis.

Actinomyces viscosus is an oral bacterium that is rarely virulent in humans, with most case presentations involving dental and maxillofacial infections. We describe the first reported case of A. viscosus vertebral osteomyelitis in a patient who had a significant response to penicillin after minimal response to cephalosporin therapy.

Factor XII inhibition reduces thrombus formation in a primate thrombosis model.

The plasma zymogens factor XII (fXII) and factor XI (fXI) contribute to thrombosis in a variety of mouse models. These proteins serve a limited role in hemostasis, suggesting that antithrombotic therapies targeting them may be associated with low bleeding risks. Although there is substantial epidemiologic evidence supporting a role for fXI in human thrombosis, the situation is not as clear for fXII. We generated monoclonal antibodies (9A2 and 15H8) against the human fXII heavy chain that interfere with fXII conversion to the protease factor XIIa (fXIIa). The anti-fXII antibodies were tested in models in which anti-fXI antibodies are known to have antithrombotic effects. Both anti-fXII antibodies reduced fibrin formation in human blood perfused through collagen-coated tubes. fXII-deficient mice are resistant to ferric chloride-induced arterial thrombosis, and this resistance can be reversed by infusion of human fXII. 9A2 partially blocks, and 15H8 completely blocks, the prothrombotic effect of fXII in this model. 15H8 prolonged the activated partial thromboplastin time of baboon and human plasmas. 15H8 reduced fibrin formation in collagen-coated vascular grafts inserted into arteriovenous shunts in baboons, and reduced fibrin and platelet accumulation downstream of the graft. These findings support a role for fXII in thrombus formation in primates.