COVID-19 and Therapeutic Apheresis

Abstract:

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, is an unprecedented challenge for the global community. The pathogenesis of COVID-19, its complications and long term sequelae (so called Long/Post-COVID) include, in addition to the direct virus-induced tissues injury, multiple secondary processes, such as autoimmune response, impairment of microcirculation, and hyperinflammation. Similar pathological processes, but in the settings of neurological, cardiovascular, rheumatological, nephrological, and dermatological diseases can be successfully treated by powerful methods of Therapeutic Apheresis (TA).

We describe here the rationale and the initial attempts of TA treatment in severe cases of acute COVID-19. We next review the evidence for the role of autoimmunity, microcirculatory changes and inflammation in pathogenesis of Long/Post COVID and the rationale for targeting those pathogenic processes by different methods of TA. Finally, we discuss the impact of COVID-19 pandemic on patients, who undergo regular TA treatments due to their underlying chronic conditions, with the specific focus on the patients with inherited lipid diseases being treated at the Dresden University Apheresis Center.

Source: Tselmin S, Julius U, Jarzebska N, Rodionov R. COVID-19 and Therapeutic Apheresis. Horm Metab Res. 2022 Aug;54(8):571-577. doi: 10.1055/a-1864-9482. Epub 2022 Aug 9. PMID: 35944525.  https://pubmed.ncbi.nlm.nih.gov/35944525/

Mast cell activation syndrome and the link with long COVID

Abstract:

Mast cells are innate immune cells found in connective tissues throughout the body, most prevalent at tissue-environment interfaces. They possess multiple cell-surface receptors which react to various stimuli and, after activation, release many mediators including histamine, heparin, cytokines, prostaglandins, leukotrienes and proteases.

In mast cell activation syndrome, excessive amounts of inflammatory mediators are released in response to triggers such as foods, fragrances, stress, exercise, medications or temperature changes. Diagnostic markers may be difficult to assess because of their rapid degradation; these include urinary N-methyl histamine, urinary prostaglandins D2, DM and F and serum tryptase (which is stable) in the UK. Self-management techniques, medications and avoiding triggers may improve quality of life. Treatments include mast cell mediator blockers, mast cell stabilisers and anti-inflammatory agents. ‘Long COVID’ describes post-COVID-19 syndrome when symptoms persist for more than 12 weeks after initial infection with no alternative diagnosis.

Both mast cell activation syndrome and long COVID cause multiple symptoms. It is theorised that COVID-19 infection could lead to exaggeration of existing undiagnosed mast cell activation syndrome, or could activate normal mast cells owing to the persistence of viral particles. Other similarities include the relapse-remission cycle and improvements with similar treatments. Importantly, however, aside from mast cell disorders, long COVID could potentially be attributed to several other conditions.

Source: Arun S, Storan A, Myers B. Mast cell activation syndrome and the link with long COVID. Br J Hosp Med (Lond). 2022 Jul 2;83(7):1-10. doi: 10.12968/hmed.2022.0123. Epub 2022 Jul 26. PMID: 35938771. https://pubmed.ncbi.nlm.nih.gov/35938771/

Complementary and Alternative Medicine for Long COVID: Scoping Review and Bibliometric Analysis

Abstract:

Prolonged symptoms after the clearance of acute coronavirus disease 2019 (COVID-19) infection, termed long COVID, are an emerging threat to the post-COVID-19 era. Complementary and alternative medicine (CAM) interventions may play a significant role in the management of long COVID. The present study aimed to identify published studies on the use of CAM interventions for long COVID and provide an overview of the research status using bibliometric analysis.

The present scoping review searched MEDLINE, Embase, and Cochrane Library from inception until November 2021 and identified published studies on CAM interventions for long COVID. A narrative analysis of the study types and effectiveness and safety of the CAM interventions are presented and a bibliometric analysis of citation information and references of the included publications were analyzed using the Bibliometrix package for R. An electronic database search identified 16 publications (2 clinical studies and 14 study protocols of systematic reviews or clinical studies) that were included in the present study. Dyspnea or pulmonary dysfunction, quality of life, olfactory dysfunction, and psychological symptoms after COVID-19 infection were assessed in the included publications.

The two clinical studies suggested that Chinese herbal medications were effective in relieving symptoms of pulmonary dysfunction. Bibliometric analysis revealed the current trend of research publication in this area was driven by study protocols written by Chinese, Korean, and Indian authors. Thus, the present scoping review and bibliometric analysis revealed that there are few studies published about the use of CAM for long COVID and long-term management for COVID-19 survivors. Original studies on CAM interventions, including randomized controlled trials and systematic reviews, are required to actively support evidence for their use in the management of long COVID. PROSPERO registration: this trial is registered with CRD42021281526.

Source: Tae-Hun Kim, Sae-Rom Jeon, Jung Won Kang, Sunoh Kwon, “Complementary and Alternative Medicine for Long COVID: Scoping Review and Bibliometric Analysis“, Evidence-Based Complementary and Alternative Medicine, vol. 2022, Article ID 7303393, 7 pages, 2022. https://doi.org/10.1155/2022/7303393 https://www.hindawi.com/journals/ecam/2022/7303393/ (Full text)

Long COVID endotheliopathy: hypothesized mechanisms and potential therapeutic approaches

Abstract:

SARS-CoV-2–infected individuals may suffer a multi–organ system disorder known as “long COVID” or post-acute sequelae of SARS-CoV-2 infection (PASC). There are no standard treatments, the pathophysiology is unknown, and incidence varies by clinical phenotype.

Acute COVID-19 correlates with biomarkers of systemic inflammation, hypercoagulability, and comorbidities that are less prominent in PASC. Macrovessel thrombosis, a hallmark of acute COVID-19, is less frequent in PASC. Female sex at birth is associated with reduced risk for acute COVID-19 progression, but with increased risk of PASC. Persistent microvascular endotheliopathy associated with cryptic SARS-CoV-2 tissue reservoirs has been implicated in PASC pathology.

Autoantibodies, localized inflammation, and reactivation of latent pathogens may also be involved, potentially leading to microvascular thrombosis, as documented in multiple PASC tissues. Diagnostic assays illuminating possible therapeutic targets are discussed.

Source: Ahamed J, Laurence J. Long COVID endotheliopathy: hypothesized mechanisms and potential therapeutic approaches. J Clin Invest. 2022 Aug 1;132(15):e161167. doi: 10.1172/JCI161167. PMID: 35912863; PMCID: PMC9337829. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9337829/ (Full text)

Use of 1-MNA to Improve Exercise Tolerance and Fatigue in Patients after COVID-19

Abstract:

COVID-19 is not only a short-term infection, as patients (pts) recovering from SARS-CoV-2 infection complain of persisting symptoms, which may lead to chronic fatigue syndrome. There is currently no evidence that nutritional supplements can assist in the recovery of pts with chronic fatigue syndrome. 1-Methylnicotinamide (1-MNA) is an endogenic substance that is produced in the liver when nicotinic acid is metabolized. 1-MNA demonstrates anti-inflammatory and anti-thrombotic properties. Therefore, we investigated whether 1-MNA supplements could improve exercise tolerance and decrease fatigue among patients recovering from SARS-CoV-2.

Methods: The study population was composed of 50 pts who had recovered from symptomatic COVID-19. The selected pts were randomized into two groups: Gr 1 (NO-1-MNA)-without supplementation; Gr 2 (1-MNA) with 1-MNA supplementation. At the beginning of the study (Phase 0), in both groups, a 6-minute walk test (6MWT) was carried out and fatigue assessment was performed using the Fatigue Severity Scale (FSS). Both FSS and 6MWT were repeated after 1 month.

Results: A significant improvement in the mean distance covered in the 6MWT was noted at follow-up in Gr 1-MNA, compared with Gr NO-1-MNA. We also noted that in Gr 1-MNA, the 6MWT distance was significantly higher after 1 month of supplementation with 1-MNA, compared with the beginning of the study (515.18 m in Phase 0 vs. 557.8 m in Phase 1; p = 0.000034). In Gr 1-MNA, significantly more pts improved their distance in the 6MWT (23 out of 25 pts, equal to 92%), by a mean of 47 m, compared with Gr NO-1-MNA (15 of 25 pts, equal to 60%) (p = 0.0061). After one month, significantly more patients in the group without 1-MNA had severe fatigue (FSS ≥ 4) compared with the group with supplementation (Gr 1-MNA = 5 pts (20%) vs. Gr NO-1-MNA = 14pts (56%); p = 0.008).

Conclusions: 1-MNA supplementation significantly improved physical performance in a 6-min walk test and reduced the percentage of patients with severe fatigue after COVID-19. The comprehensive action of 1-MNA, including anti-inflammatory and anticoagulant effects, may be beneficial for the recovery of patients with persistent symptoms of fatigue and low tolerance to exercise after COVID-19.

Source: Chudzik M, Burzyńska M, Kapusta J. Use of 1-MNA to Improve Exercise Tolerance and Fatigue in Patients after COVID-19. Nutrients. 2022 Jul 22;14(15):3004. doi: 10.3390/nu14153004. PMID: 35893858.  https://www.mdpi.com/2072-6643/14/15/3004/htm (Full text)

The Use of Palmitoylethanolamide in the Treatment of Long COVID: A Real-Life Retrospective Cohort Study

COVID-19 can cause symptoms that last weeks or months after the infection has gone, with a significant impairment of quality of life. Palmitoylethanolamide (PEA) is a naturally occurring lipid mediator that has an entourage effect on the endocannabinoid system mitigating the cytokine storm. The aim of this retrospective study is to evaluate the potential efficacy of PEA in the treatment of long COVID.
Patients attending the Neurological Out Clinic of the IRCCS Centro Neurolesi Bonino-Pulejo (Messina, Italy) from August 2020 to September 2021 were screened for potential inclusion in the study. We included only long COVID patients who were treated with PEA 600 mg two times daily for about 3 months. All patients performed the post-COVID-19 Functional Status (PCFS) scale. Thirty-three patients (10 males, 43.5%, mean age 47.8 ± 12.4) were enrolled in the study. Patients were divided into two groups based on hospitalization or home care observation. A substantial difference in the PCFS score between the two groups at baseline and after treatment with PEA were found. We found that smoking was a risk factor with an odds ratio of 8.13 CI 95% [0.233, 1.167]. Our findings encourage the use of PEA as a potentially effective therapy in patients with long COVID.
Source: Raciti L, De Luca R, Raciti G, Arcadi FA, Calabrò RS. The Use of Palmitoylethanolamide in the Treatment of Long COVID: A Real-Life Retrospective Cohort Study. Medical Sciences. 2022; 10(3):37. https://doi.org/10.3390/medsci10030037  https://www.mdpi.com/2076-3271/10/3/37/htm (Full text)

Improvement in Long-COVID Symptoms Using Acupuncture: A Case Study

Abstract:

Background: The long-COVID syndrome (LCS), defined by residual symptoms from acute COVID-19 for <60 days, affects about one-third of all COVID survivors and is an emerging public health challenge. Empirical data about the range of symptoms or the utility of acupuncture alone for the LCS are very limited.

Case: This observational case study of a 46-year-old male with LCS was conducted to preliminarily define the range of symptoms, a Traditional Chinese Medicine (TCM) diagnostic structure, and evaluate the potential utility of prescribed acupuncture for LCS.

Results: The primary TCM diagnostic patterns from this patient’s LCS presentation included Lung Qi and Yin Deficiency, Qi and Blood Stagnation, and Spleen Qi Deficiency with dampness. Acupuncture for this patient was associated with reduced symptoms and signs of LCS.

Conclusion: A preliminary TCM diagnostic structure for LCS was defined. Acupuncture appears to have been helpful for a patient with LCS. Further research is needed to demonstrate the efficacy of acupuncture and/or other TCM modalities for LCS.

Source: Hollifield M, Cocozza K, Calloway T, Lai J, Caicedo B, Carrick K, Alpert R, Hsiao AF. Improvement in Long-COVID Symptoms Using Acupuncture: A Case Study. Med Acupunct. 2022 Jun 1;34(3):172-176. doi: 10.1089/acu.2021.0088. Epub 2022 Jun 16. PMID: 35832108; PMCID: PMC9248334. https://www.liebertpub.com/doi/10.1089/acu.2021.0088 (Full text)

The Role of Acupuncture for Long COVID: Mechanisms and Models

Abstract:

Objective: To establish an evidence-based role for acupuncture as a safe and effective treatment for managing Long COVID in the integrative medical setting.

Background: COVID-19 progresses to a chronic state, termed Long COVID, in about 30% of cases with estimates as high as 40% for prolonged illness. Symptoms are diverse and range over several body systems, including unrelenting fatigue, persistent malaise, chronic pain, and mood changes. Early clinical reports suggest acupuncture can effectively address both symptoms and the underlying causes of Long COVID.

Evidence: Historically, acupuncture is well defined in Traditional Chinese Medicine writings to treat influenza-like febrile illnesses. Contemporary scientific literature and case studies support the value of acupuncture for symptoms associated with acute and chronic respiratory viral infections, such as influenza, including SARS and COVID-19. Recent reports provide early evidence of acupuncture’s effectiveness in managing Long COVID symptoms and may also have disease-modifying benefits.

Conclusion: Acupuncture is a viable adjunctive health care modality as part of a multidisciplinary approach for symptom control and disease management to improve quality of life in Long COVID patients. Since acupuncture may favorably modify the length and outcome of this condition, the model of acupuncture presented in this article warrants broader use in the integrative clinical setting and for further research.

Source: Williams JE, Moramarco J. The Role of Acupuncture for Long COVID: Mechanisms and Models. Med Acupunct. 2022 Jun 1;34(3):159-166. doi: 10.1089/acu.2021.0090. Epub 2022 Jun 16. PMID: 35832109; PMCID: PMC9248327. https://www.liebertpub.com/doi/10.1089/acu.2021.0090 (Full text)

Conceptualizing a Traditional Chinese Medicine and Pathology of Arousal Diagnostic and Pathophysiological Framework for Postacute Sequelae of COVID-19

Abstract:

Introduction: The postacute sequelae of COVID-19 (PASC) is a serious heterogeneous condition that affects a significant minority of those who endured COVID-19. PASC involves multiple body systems and an illness trajectory that has stages now being identified in medical research.

Objective: Traditional Chinese Medicine (TCM) and acupuncture are well suited to conceptualize and treat PASC and other postviral conditions. No description of TCM theory and its relationship with modern medical theory about PASC and its illness trajectory currently exists.

Conclusion: The authors provide an overview of the potential value of TCM for conceptualizing and treating PASC with a few examples and clarify directions for research.

Source: Calloway T, Hsiao AF, Brand M, Lai J, Geise C, Caceido B, Alpert R, Hollifield M. Conceptualizing a Traditional Chinese Medicine and Pathology of Arousal Diagnostic and Pathophysiological Framework for Postacute Sequelae of COVID-19. Med Acupunct. 2022 Jun 1;34(3):167-171. doi: 10.1089/acu.2022.0022. Epub 2022 Jun 16. PMID: 35832113; PMCID: PMC9248333. https://www.liebertpub.com/doi/10.1089/acu.2022.0022 (Full text)

Can aquatic exercises contribute to the improvement of the gait stereotype function in patients with Long COVID outcomes?

Abstract:

A variety of rehabilitation programmes can be offered to Long COVID patients, specifically physical training. Indeed 90% of these patients reports impairments of verticalization, stability and spatial orientation, making difficult exercise in the gym. The aim of our study was to assess the effectiveness and safety of aquatic exercise techniques as part of a comprehensive rehabilitation program for patients with Long COVID.

The first of a two-stage program involved development of aquatic exercises technique, which was evaluated in 12 patients with impaired upright posture control before and after exercising by “Habilect” video gait analysis system. During the second phase, effectiveness and safety of aqua exercises were tested in water pool as part of a comprehensive rehabilitation programme conducted in 23 patients with Long COVID outcomes. Physical examination, 6-minute step test, Euro-QL-5D questionnaire, Borg scale, laser Doppler flowmetry, cardiointervalography, and spirometry were performed before and after the aquatic exercises program.

After the training with aquatic exercises, indices of deviations of the main body axes of the head and the body mass centre ameliorated, as well as direction of body movement vector decreased (p<0.05). This study demonstrated a statistically significant improvement in exercise tolerance in both groups, as measured by the 6-minute step test after rehabilitation. The comparison group averaged 236.7 metres [126; 380] (T=8, p=0.047) after the rehabilitation course and the intervention group averaged 233.71 metres [150; 320] (T=8.0, p=0.047). When tested with the Euro-QL-5D questionnaire, a post-treatment improvement was noted in the comparison group on the anxiety/depression subscale (3 [3;3] (T=0, p=0.043)).

In the intervention group, laser Doppler flowmetry revealed a statistically significant increase in microcirculation (6.36 standard units after rehabilitation) [5.54; 8.17] (T=7.0, p=0.004), and a decrease of oxidative metabolism index of 6.89 standard units. [4.76; 6.96] (T=4.0, p=0.03). No serious adverse events were reported. In conclusion, the developed aquatic exercises technique seems to contribute to recovery of impaired upright posture and motor function, normalizing the walking pattern.

Source: Lobanov AA, Irina A Grishechkina, Andronov SV, Gleb N Barashkov, Andrey I Popov, Anatoliy D Fesyun, Elena P Ivanova, Maccarone MC, Stefano Masiero. Can aquatic exercises contribute to the improvement of the gait stereotype function in patients with Long COVID outcomes? Eur J Transl Myol. 2022 Jul 14. doi: 10.4081/ejtm.2022.10698. Epub ahead of print. PMID: 35833897.  https://pubmed.ncbi.nlm.nih.gov/35833897/ (Full text: Follow link on page)