long covid case series – American ME and CFS Society

New Alcohol Sensitivity in Patients With Post-acute Sequelae of SARS-CoV-2 (PASC): A Case Series

Abstract:

Post-acute sequelae of SARS-CoV-2 (PASC), or long COVID, is characterized by persistent symptoms after acute SARS-CoV-2 infection that can vary from patient to patient. Here, we present a case series of four patients with a history of SARS-CoV-2 infection referred to the Post-Acute COVID-19 Syndrome (PACS) Clinic at Stanford University for evaluation of persistent symptoms, who also experienced new-onset alcohol sensitivity.

Alcohol reactions and sensitivity are not well characterized in the literature as it relates to post-viral illness. While there have been some anecdotal reports of new alcohol sensitivity in PASC patients in the media, there is a paucity of published data in the medical literature about this topic. During their medical consultation, the patients self-reported new changes in their symptoms or behaviors following the use of alcohol. A new onset of alcohol sensitivities should be assessed along with other post-COVID-19 symptoms and may provide novel avenues to explore the pathobiology of illness and potential interventions.

Source: Eastin E F, Tiwari A, Quach T C, et al. (December 29, 2023) New Alcohol Sensitivity in Patients With Post-acute Sequelae of SARS-CoV-2 (PASC): A Case Series. Cureus 15(12): e51286. doi:10.7759/cureus.51286 https://www.cureus.com/articles/152512-new-alcohol-sensitivity-in-patients-with-post-acute-sequelae-of-sars-cov-2-pasc-a-case-series#!/ (Full text)

Identification of CD8 T-cell dysfunction associated with symptoms in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long COVID and treatment with a nebulized antioxidant/anti-pathogen agent in a retrospective case series

Highlights:

• Both Long COVID and ME/CFS are characterized by dysfunctional CD8 T-cells with severe deficiencies in their abilities to produce IFNγ and TNFα.

• In a small Long COVID and ME/CFS case series, patients’ immune deficiency and health improve during treatment period with a nebulized antioxidant, anti-pathogen and immune-modulatory pharmacological agent.

• This work provides evidence of a useful biomarker, CD8 T-cell dysfunction reminiscent of T cell exhaustion, that may assist diagnosis and have utility for tracking disease outcome during therapy, including response to a potential new treatment.

Abstract:

Background: Patients with post-acute sequelae of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection (PASC, i.e., Long COVID) have a symptom complex highly analogous to many features of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), suggesting they may share some aspects of pathogenesis in these similar disorders. ME/CFS is a complex disease affecting numerous organ systems and biological processes and is often preceded by an infection-like episode. It is postulated that the chronic manifestations of illness may result from an altered host response to infection or inability to resolve inflammation, as is being reported in Long COVID. The immunopathogenesis of both disorders is still poorly understood. Here, we show data that suggest Long COVID and ME/CFS may be due to an aberrant response to an immunological trigger-like infection, resulting in a dysregulated immune system with CD8 T-cell dysfunction reminiscent of some aspects of T-cell clonal exhaustion, a phenomenon associated with oxidative stress. As there is an urgent need for diagnostic tools and treatment strategies for these two related disabling disorders, here, in a retrospective case series, we have also identified a potential nebulized antioxidant/anti-pathogen treatment that has evidence of a good safety profile. This nebulized agent is comprised of five ingredients previously reported individually to relieve oxidative stress, attenuate NF-κB signaling, and/or to act directly to inhibit pathogens, including viruses. Administration of this treatment by nebulizer results in rapid access of small doses of well-studied antioxidants and agents with anti-pathogen potential to the lungs; components of this nebulized agent are also likely to be distributed systemically, with potential to enter the central nervous system.

Methods and Findings: We conducted an analysis of CD8 T-cell function and severity of symptoms by self-report questionnaires in ME/CFS, Long COVID and healthy controls. We developed a CD8 T-cell functional assay, assessing CD8 T-cell dysfunction by intracellular cytokine staining (ICS) in a group of ME/CFS (n = 12) and Long COVID patients (n = 8), comparing to healthy controls (HC) with similar age and sex (n = 10). Magnet-enriched fresh CD8 T-cells in both patient groups had a significantly diminished capacity to produce both cytokines, IFNγ or TNFα, after PMA stimulation when compared to HC. The symptom severity questionnaire showed similar symptom profiles for the two disorders. Fortuitously, through a retrospective case series, we were able to examine the ICS and questionnaire data of 4 ME/CFS and 4 Long COVID patients in conjunction with their treatment (3–15 months). In parallel with the treatment pursued electively by participants in this retrospective case series, there was an increase in CD8 T-cell IFNγ and TNFα production and a decrease in overall self-reported symptom severity score by 54%. No serious treatment-associated side effects or laboratory anomalies were noted in these patients.

Conclusions: Here, in this small study, we present two observations that appear potentially fundamental to the pathogenesis and treatment of Long COVID and ME/CFS. The first is that both disorders appear to be characterized by dysfunctional CD8 T-cells with severe deficiencies in their abilities to produce IFNγ and TNFα. The second is that in a small retrospective Long COVID and ME/CFS case series, this immune dysfunction and patient health improved in parallel with treatment with an immunomodulatory, antioxidant pharmacological treatment with anticipated anti-pathogen activity. This work provides evidence of the potential utility of a biomarker, CD8 T-cell dysfunction, and suggests the potential for benefit from a new nebulized antioxidant/anti-pathogen treatment. These immune biomarker data may help build capacity for improved diagnosis and tracking of treatment outcomes during clinical trials for both Long COVID and ME/CFS while providing clues to new treatment avenues that suggest potential efficacy for both conditions.

Source: Gil, A., Hoag, G.E., Salerno, J.P., Hornig, M., Klimas, N., Selin, L.K. Identification of CD8 T-cell dysfunction associated with symptoms in myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS) and Long COVID and treatment with a nebulized antioxidant/antipathogen agent in a retrospective case series. Brain, Behavior, & Immunity – Health (2024), doi: https://doi.org/10.1016/j.bbih.2023.100720 https://www.sciencedirect.com/science/article/pii/S2666354623001345 (Full text)

Profound Symptom Alleviation in Long-Covid Patients After PAMP-Immunotherapy: Three Case Reports

Abstract:

Background: Long-Covid patients suffer from a range of symptoms with a largely varying degree of severity, including chronic fatigue syndrome (CFS), myalgic encephalomyelitis (ME), post-exertional malaise (PEM), postural orthostatic tachycardia syndrome (POTS), loss of smell and/or taste, cough, shortness of breath, headache, muscle ache, sleep disturbance, cognitive dysfunction, and depression.

Treatment: PAMP-immunotherapy was developed by one of us (UH), inspired by the old fever therapy a century ago, to treat cancer patients. Unintentionally, in three cases of Long-Covid, quick and profound symptom alleviation could be observed after only a few PAMP treatments.

Conclusion: PAMP-immunotherapy might be a treatment option for Long-Covid patients which is surprisingly brief, cheap, and effective.

Source: Raphaela Gaudek, Holger Porath, Uwe Hobohm. (2023). [Case Report] Profound Symptom Alleviation in Long-Covid Patients After PAMP-Immunotherapy: Three Case Reports. Qeios. doi:10.32388/69I32L. https://www.qeios.com/read/69I32L (Full text)

Remission of severe forms of long COVID following monoclonal antibody (MCA) infusions: A report of signal index cases and call for targeted research

Abstract:

Objective: Long COVID has afflicted tens of millions globally leaving many previously-healthy persons severely and indefinitely debilitated. The objective here was to report cases of complete, rapid remission of severe forms of long COVID following certain monoclonal antibody (MCA) infusions and review the corresponding pathophysiological implications.

Design: Case histories of the first three index events (among others) are presented. Unaware of others with similar remissions, each subject independently completed personal narratives and standardized surveys regarding demographics/occupation, past history, and the presence and respective severity grading of 33 signs/symptoms associated with long COVID, comparing the presence/severity of those symptoms during the pre-COVID, long-COVID, post-vaccination, and post-MCA phases.

Setting: Patient interviews, e-mails and telephone conversations.

Subjects: Three previously healthy, middle-aged, highly-functioning persons, two women and one man (ages 60, 43, and 63 years respectively) who, post-acute COVID-19 infection, developed chronic, unrelenting fatigue and cognitive impairment along with other severe, disabling symptoms. Each then independently reported incidental and unanticipated complete remissions within days of MCA treatment.

Interventions: The casirivimab/imdevimab cocktail.

Measurements and main results: Irrespective of sex, age, medical history, vaccination status, or illness duration (18, 8 and 5 months, respectively), each subject experienced the same complete remission of their persistent disabling disease within a week of MCA infusion. Each rapidly returned to normal health and previous lifestyles/occupations with normalized exercise tolerance, still sustained to date over two years later.

Conclusions: These index cases provide compelling clinical signals that MCA infusions may be capable of treating long COVID in certain cases, including those with severe debilitation. While the complete and sustained remissions observed here may only apply to long COVID resulting from pre-Delta variants and the specific MCA infused, the striking rapid and complete remissions observed in these cases also provide mechanistic implications for treating/managing other post-viral chronic conditions and long COVID from other variants.

Source: Scheppke KA, Pepe PE, Jui J, Crowe RP, Scheppke EK, Klimas NG, Marty AM. Remission of severe forms of long COVID following monoclonal antibody (MCA) infusions: A report of signal index cases and call for targeted research. Am J Emerg Med. 2023 Oct 4;75:122-127. doi: 10.1016/j.ajem.2023.09.051. Epub ahead of print. PMID: 37944296. https://www.sciencedirect.com/science/article/pii/S073567572300534X (Full text)

Long COVID-19 Symptoms Remedied by Anti-Viral Treatment in Neurosurgical Patients

Abstract:

The pandemic of COVID-19 is the largest in this century. Aside from the acute infection, some of the patients have been challenged with a complication that is known as long COVID-19. The symptoms of long COVID-19 are extensive and diverse. Long COVID-19 continues to plague many patients post-COVID-19 infection. No universal treatment has been found.

This study presents four patients who suffered from long COVID-19. Each patient presented with a different and diverse symptom of long COVID-19. Each of the patient’s symptoms resolved or greatly improved upon taking the anti-viral drug acyclovir. Acyclovir has been in use since 1981 and is generally considered safe. A novel theory as to the pathophysiology of long COVID-19 symptoms and the result of a new treatment is presented. The purpose of this study is to provide a foundation for much bigger studies and useful resources for further testing to halt long COVID-19.

Source: Beatty, R. M. (2023). Long COVID-19 Symptoms Remedied by Anti-Viral Treatment in Neurosurgical Patients. American Journal of Infectious Diseases, 19(3), 39-44. https://doi.org/10.3844/ajidsp.2023.39.44 https://thescipub.com/abstract/ajidsp.2023.39.44 (Full text available as PDF file)

Pathophysiology and potential treatment of long COVID: A report of signal index cases and call for targeted research

Abstract:

Setting: Patient interviews, e-mails and telephone conversations.

Subjects: Three previously healthy, middle-aged, highly-functioning persons, two women and one man (ages 60, 43, and 63 years respectively) who, post-acute COVID-19 infection, developed chronic, unrelenting fatigue and cognitive impairment along with other severe, disabling symptoms. Each then independently reported incidental and unanticipated complete remissions within days of MCA treatment.

Interventions: The casirivimab/imdevimab cocktail.

Measurements and main results: Irrespective of sex, age, vaccination status, or illness duration (18, 8 and 5 months, respectively), each subject experienced the same complete remission of their persistent disabling disease within a week of MCA infusion. Each rapidly returned to normal health and previous lifestyles/occupations with normalized exercise tolerance, still sustained to date nearly two years later.

Key points

•Question: Considering that long COVID-19 has been devastating for many millions worldwide, what is the proposed pathophysiology and are there any effective treatments?
Findings: Previously-healthy middle-aged persons who had developed persistent debilitating post-acute SARS-CoV-2 sequelae, each experienced complete remission their symptoms within days of receiving a specific monoclonal anti-body infusion despite relative differences in sex, age, vaccination status, and long COVID duration.
Meaning: Certain monoclonal antibody infusions may be capable of reversing severe long COVID. Beyond providing an effective potential treatment for long COVID, these findings have mechanistic implications for treating other post-viral chronic conditions, including future long COVID variants.

Source: Kenneth A. Scheppke, Paul E. Pepe, Jonathan Jui, Remle P. Crowe, Eric K. Scheppke, Nancy G. Klimas, Aileen M. Marty. Pathophysiology and potential treatment of long COVID: A report of signal index cases and call for targeted research, The American Journal of Emergency Medicine, 2023. ISSN 0735-6757. https://doi.org/10.1016/j.ajem.2023.09.051. https://www.sciencedirect.com/science/article/abs/pii/S073567572300534X

Immune Adsorption for the Treatment of Fatigue-Dominant Long-/Post-COVID Syndrome

Introduction:

Following an infection with SARS-CoV-2, a relevant proportion of patients suffer from fatigue-dominant long-/post-COVID syndrome. In 57% of patients with long-/post-COVID syndrome, who were treated in a university hospital, increased levels of autoantibodies (AABs) to G-protein-coupled neurotransmitter receptors (including ß-adrenergic and muscarinic) were detected (1).

Reduction of ß-adrenergic AABs by immunoadsorption therapy was associated with clinical improvement in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) (2). Increasingly, reports of individual cases of successful treatment of long/post-COVID syndrome with the help of apheresis techniques have been widely disseminated via social media. By contrast, cases or studies with negative outcomes are much less likely to receive proper attention. Given the overall lack of data to date, medical societies are calling for a broader scientific basis, to which we would like to contribute with this case series.

Source: Ruhe J, Giszas B, Schlosser M, Reuken PA, Wolf G, Stallmach A. Immune Adsorption for the Treatment of Fatigue-Dominant Long-/Post-COVID Syndrome: A Series of Cases With Standardized Individual Experimental Therapy. Dtsch Arztebl Int. 2023 Jul;120(29-30):499–500. doi: 10.3238/arztebl.m2023.0073. Epub 2023 Jul 24. PMCID: PMC10511006. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10511006/ (Full text)

Long COVID: Cognitive and FDG PET evolutions in six patients

Abstract:

Long COVID is often characterized by cognitive complaints and deficits occurring immediately or several weeks after the infectious disease. Neuropsychological tests can revealed attention and executive function anomalies and FDG PET can display hypometabolic areas affecting various regions including frontal and cingulate cortices as well as precuneus and brainstem. We report here the cognitive and FDG PET evolutions over one year in 6 patients suffering from long COVID. Our study shows cognitive and FDG PET improvements in most of the cases and highlight the importance of a careful neurological follow-up in these patients.

Source: Jacques Hugon, Karim Farid, Mathieu Queneau et al. Long COVID: Cognitive and FDG PET evolutions in six patients, 03 April 2023, PREPRINT (Version 1) available at Research Square. https://doi.org/10.21203/rs.3.rs-2703691/v1 https://www.researchsquare.com/article/rs-2703691/v1 (Full text)

Severe Course of COVID-19 and Long-COVID-19 in Children: Difficulties in Diagnosis

Abstract:

The question of COVID-19 and long-COVID-19 course in children remains unsolved. This infection in children, which is associated with COVID-19, can vary from asymptomatic to systemic damage of various systems. Multisystem inflammatory syndrome in children, associated with SARS-CoV-2 (MIS-C), is a serious condition in children and adolescents after experiencing COVID-19.

Published data on MIS-C have indicated that the inflammation can be registered in the gastrointestinal tract (60–100%), as well as in cardiovascular (80%), nervous (29–58%), and respiratory (21–65%) systems. However, with the changing characteristics of SARS-CoV-2, the manifestations of COVID-19 and long-COVID-19 in children have also been changing. Currently, there is no clear understanding of the development of severe COVID-19 and MIS-C in children, especially after being exposed to patients with COVID-19.

We presented two new clinical courses of multisystem inflammatory syndrome in children with severe multisystem damage after close contact to relatives with COVID-19 or long-COVID-19. Thus, high-risk children, who are positive for SARS-CoV-2 infection after contact with COVID-19 patients, should be clinically managed during the first few months. The identification of the disease complexity requires the involvement of neurologists, cardiologists, and other specialists.

Source: Vasichkina E, Kofeynikova O, Fetisova S, Starshinova AY, Sheyanova E, Vershinina T, Ryzhkov A, Skripnik A, Alekseeva D, Nechaeva E, Glushkova A, Kudlay D, Pervunina T, Starshinova A. Severe Course of COVID-19 and Long-COVID-19 in Children: Difficulties in Diagnosis. Life. 2023; 13(3):781. https://doi.org/10.3390/life13030781 https://www.mdpi.com/2075-1729/13/3/781 (Full text)

Not myopathic, but autonomic changes in patients with long-COVID syndrome: a case series

Abstract:

Introduction: Neurological sequelae following SARS-CoV-2 infection still represent a serious concern both for neurologists and neuroscientists. In our paper, we investigated pain, myalgia, and fatigue as symptoms in long-COVID patients with an electrophysiological approach, comprising the evaluation of sympathetic skin responses (SSRs) and quantitative electromyography (qEMG).

Materials and methods: Twelve patients were enrolled (mean age, 47.7 ± 11.6 years), referred to our attention because of myalgia, pain, or muscle cramps, which persisted about 6 months after the diagnosis of SARS-CoV-2 infection. They underwent conventional electroneurography (ENG), needle electromyography (EMG), and SSRs; moreover, qEMG was performed by sampling at least 20 motor unit potentials (20-30 MUPs) during weak voluntary contraction in deltoid and tibialis anterior muscles. The mean duration, amplitude, and percentage of polyphasic potentials were assessed and compared with healthy and age-matched volunteers.

Results: ENG did not disclose significant changes compared to healthy subjects; needle EMG did not reveal denervation activity. In addition, qEMG showed MUPs similar to those recorded in healthy volunteers in terms of polyphasia (deltoid: p = 0.24; TA: p = 0.35), MUP area (deltoid: p = 0.45; TA: p = 0.44), mean duration (deltoid: p = 0.06; TA: p = 0.45), and amplitude (deltoid: p = 0.27; TA: p = 0.63). SSRs were not recordable from lower limbs in seven patients (58%) and from the upper ones in three of them (25%).

Conclusion: Our data suggest an involvement of the autonomic system, with a focus on cholinergic efferent sympathetic activity, without any evidence of myopathic changes.

Source: Bocci T, Bertini A, Campiglio L, Botta S, Libelli G, Guidetti M, Priori A. Not myopathic, but autonomic changes in patients with long-COVID syndrome: a case series. Neurol Sci. 2023 Apr;44(4):1147-1153. doi: 10.1007/s10072-023-06637-8. Epub 2023 Feb 3. PMID: 36735149; PMCID: PMC9896447. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9896447/ (Full study)