Tag: long covid treatment

COVID-19 immunopathology: From acute diseases to chronic sequelae

Abstract:

The clinical manifestation of coronavirus disease 2019 (COVID-19) mainly targets the lung as a primary affected organ, which is also a critical site of immune cell activation by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, recent reports also suggest the involvement of extrapulmonary tissues in COVID-19 pathology.

The interplay of both innate and adaptive immune responses is key to COVID-19 management. As a result, a robust innate immune response provides the first line of defense, concomitantly, adaptive immunity neutralizes the infection and builds memory for long-term protection. However, dysregulated immunity, both innate and adaptive, can skew towards immunopathology both in acute and chronic cases.

Here we have summarized some of the recent findings that provide critical insight into the immunopathology caused by SARS-CoV-2, in acute and post-acute cases. Finally, we further discuss some of the immunomodulatory drugs in preclinical and clinical trials for dampening the immunopathology caused by COVID-19.

Source: Arish M, Qian W, Narasimhan H, Sun J. COVID-19 immunopathology: From acute diseases to chronic sequelae. J Med Virol. 2022 Sep 3. doi: 10.1002/jmv.28122. Epub ahead of print. PMID: 36056655. https://onlinelibrary.wiley.com/doi/10.1002/jmv.28122 (Full text)

Long Covid and Apheresis – Where are we Standing?

Abstract:

A continual increase in cases of Long Covid constitutes a medical and socioeconomic challenge to health systems around the globe. While the true extent of this problem cannot yet be fully evaluated, recent data suggests that up to 20% of people with confirmed with SARS-CoV-2 suffer from clinically relevant symptoms of Long Covid several weeks to months after the acute phase. The clinical presentation is highly variable with the main symptoms being chronic fatigue, dyspnea and cognitive symptoms. Extracorporeal apheresis has been suggested to alleviate symptoms of Long Covid. Thus, numerous patients are currently treated with apheresis. However, at present there is no data from randomized controlled trials available to confirm the efficacy. Therefore, physicians rely on the experience of practitioners and centers performing this treatment. Here, we summarize clinical experience on extracorporeal apheresis in patients with Long Covid from centers across Germany.

Source: Steenblock C, Walther R, Tselmin S, Jarzebska N, Voit-Bak K, Toepfner N, Siepmann T, Passauer J, Hugo C, Wintermann G, Julius U, Babir M, Khan TZ, Puhan MA, Straube R, Hohenstein B, Bornstein SR, Rodionov R. Long Covid and Apheresis – Where are we Standing? Horm Metab Res. 2022 Sep 16. doi: 10.1055/a-1945-9694. Epub ahead of print. PMID: 36113501.  https://pubmed.ncbi.nlm.nih.gov/36113501/

Targeting endothelial dysfunction and oxidative stress in Long-COVID

Comment:

We thank Dr. Hsu and Dr. Lai for their interest in our work on COVID-19 and Long-COVID.

We fully agree with them on the fact that several factors need to be pondered in order to evaluate the risk of developing Long-COVID , . However, we respectfully believe that these considerations are not pertinent to our study . Indeed, we designed the LINCOLN (l-Arginine and Vitamin C improves Long-COVID) survey to determine whether a supplementation combining l-Arginine (to improve endothelial function) and Vitamin C (to reduce oxidation) could have favorable effects in patients with Long-COVID . Thus, in our study we did not assess the risk of developing Long-COVID; in fact, as clearly specified in our article, all the enrolled patients had Long-COVID when the survey was administered. Nevertheless, potential differences in health conditions between the group that had received l-Arginine + Vitamin C and the group that had received the alternative treatment were ruled out by their family physicians. When comparing the two groups, we did not observe any significant difference in terms of age, sex, hospitalization due to COVID-19, and time from SARS-Cov-2 negativization. Moreover, bearing in mind the limitations that all surveys have, we had concluded our article stating that further dedicated interventional studies were warranted to endorse our findings.

Of note, we have previously conducted a randomized, double-blind, placebo-controlled, parallel-group, clinical trial testing the effects of l-Arginine oral supplementation in patients hospitalized for COVID-19, demonstrating that this treatment significantly decreases the length of hospitalization and reduces the respiratory support . Additionally, we have identified endothelial exosomes enriched in miR-24 as a reliable biomarker to predict cerebrovascular complications of COVID-19 , corroborating the fundamental role of endothelial dysfunction in the pathobiology of COVID-19 and its clinical sequelae .

Source: Trimarco V, Izzo R, Mone P, Trimarco B, Santulli G. Targeting endothelial dysfunction and oxidative stress in Long-COVID. Pharmacol Res. 2022 Sep 13;184:106451. doi: 10.1016/j.phrs.2022.106451. Epub ahead of print. PMID: 36108875; PMCID: PMC9467917. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9467917/ (Full text)

Fatigue in Covid-19 survivors: The potential impact of a nutritional supplement on muscle strength and function

Summary:

Background: Fatigue with reduced tolerance to exercise is a common persistent long-lasting feature amongst COVID-19 survivors. The assessment of muscle function in this category of patients is often neglected.

Aim: To evaluate the potential impact of a daily supplementation based on amino acids, minerals, vitamins, and plant extracts (Apportal®) on muscle function, body composition, laboratory parameters and self-rated health in a small group of COVID-19 survivors affected by fatigue.

Methods: Thirty participants were enrolled among patients affected by physical fatigue during or after acute COVID-19 and admitted to the post-COVID-19 outpatient service at Fondazione Policlinico Gemelli in Rome between 1st March 2021 and 30th April 2021. All participants were evaluated at first visit (t0) and at control visit (t1), after taking a daily sachet of Apportal® for 28 days. Muscle function was analyzed using hand grip strength test, exhaustion strength time and the number of repetitions at one-minute chair stand test. Body composition was assessed with bioelectrical impedance analysis (BIA). Laboratory parameters, including standard blood biochemistry and ferritin levels, were evaluated at the first visit and during the control visit. A quick evaluation of self-rated health, before COVID-19, at t0 and t1, was obtained through a visual analogue scale (VAS).

Results: Participants aged 60 years and older were 13 (43%). Females represented the 70% of the study sample. Participants hospitalized for COVID-19 with low-flow oxygen supplementation represented the 43.3% of the study sample while 3.3% received noninvasive ventilation (NIV) or invasive ventilation. Hand grip strength improved from 26.3 Kg to 28.9 Kg (p < 0.05) at t1 as compared to t0. The mean time of strength exhaustion increased from 31.7 s (sec) at t0 to 47.5 s at t1 (p < 0.05). Participants performed a higher number of repetitions (28.3 vs. 22.0; p < 0.05) during the one-minute chair stand test at t1 as compared to t0. A trend, although not significant, in reduction of ferritin levels was found after nutritional supplementation (94.4 vs. 84.3, respectively; p = 0.01). The self-rated health status increased by at least 13 points (t0, mean 57.6 ± 5.86; t1, mean 71.4 ± 6.73; p < 0.05).

Conclusion: After 28 days of nutritional supplementation with Apportal® in COVID-19 survivors affected by fatigue with reduced tolerance to exercise, we found a significant improvement in means of muscle strength and physical performance, associated with enhancement of self-rated health status between t0 and t1.

Source: Vincenzo Galluzzo, Maria Beatrice Zazzara, Francesca Ciciarello, Giulia Savera, Cristina Pais, Riccardo Calvani, Anna Picca, Emanuele Marzetti, Francesco Landi, Matteo Tosato, Steering Committee, Francesco Landi, Elisa Gremese, Coordination, Roberto Bernabei, Massimo Fantoni, Antonio Gasbarrini, Field investigators, Gastroenterology team, Serena Porcari, Carlo Romano Settanni, Geriatric team, Francesca Benvenuto, Giulia Bramato, Vincenzo Brandi, Angelo Carfì, Francesca Ciciarello, Sofia Fabrizi, Vincenzo Galluzzo, Maria Rita Lo Monaco, Anna Maria Martone, Emanuele Marzetti, Carmen Napolitano, Francesco Cosimo Pagano, Cristina Pais, Sara Rocchi, Elisabetta Rota, Andrea Salerno, Matteo Tosato, Marcello Tritto, Maria Beatrice Zazzara, Riccardo Calvani, Lucio Catalano, Anna Picca, Giulia Savera, Francesco Paolo Damiano, Alessandra Rocconi, Alessandro Galliani, Giovanni Spaziani, Salvatore Tupputi, Camilla Cocchi, Flavia Pirone, Federica D’Ignazio, Stefano Cacciatore, Infectious disease team, Roberto Cauda, Enrica Tamburrini, A. Borghetti, Simona Di Gianbenedetto, Rita Murri, Antonella Cingolani, Giulio Ventura, E. Taddei, D. Moschese, A. Ciccullo, A. Dusina, Internal Medicine team, Leonardo Stella, Giovanni Addolorato, Francesco Franceschi, Gertrude Mingrone, M.A. Zocco, Microbiology team, Maurizio Sanguinetti, Paola Cattani, Simona Marchetti, Brunella Posteraro, M. Sali, Neurology team, Alessandra Bizzarro, Alessandra Lauria, Ophthalmology team, Stanislao Rizzo, Maria Cristina Savastano, G. Gambini, G.M. Cozzupoli, C. Culiersi, Otolaryngology team, Giulio Cesare Passali, Gaetano Paludetti, Jacopo Galli, F. Crudo, G. Di Cintio, Y. Longobardi, L. Tricarico, M. Santantonio, Pediatric team, Danilo Buonsenso, P. Valentini, D. Pata, D. Sinatti, C. De Rose, Pneumology team, Luca Richeldi, Francesco Lombardi, A. Calabrese, Paolo Maria Leone, Maria Rosaria Calvello, Enrica Intini, Giuliano Montemurro, Psychiatric team, Gabriele Sani, Delfina Janiri, Alessio Simonetti, G. Giuseppin, M. Molinaro, M. odica, Radiology team, Luigi Natale, Anna Rita Larici, Riccardo Marano, Rheumatology team, Annamaria Paglionico, Luca Petricca, Luca Gigante, G. Natalello, A.L. Fedele, M.M. Lizzio, B. Tolusso, Clara Di Mario, S. Alivernini, Vascular team, Angelo Santoliquido, Luca Santoro, Angela Di Giorgio, Antonio Nesci, V. Popolla, Fatigue in Covid-19 survivors: The potential impact of a nutritional supplement on muscle strength and function, Clinical Nutrition ESPEN, 2022, ISSN 2405-4577, https://doi.org/10.1016/j.clnesp.2022.08.029. (Full text)

Hyperbaric oxygen therapy improves neurocognitive functions and symptoms of post-COVID condition: randomized controlled trial

Abstract:

Post-COVID-19 condition refers to a range of persisting physical, neurocognitive, and neuropsychological symptoms after SARS-CoV-2 infection. The mechanism can be related to brain tissue pathology caused by virus invasion or indirectly by neuroinflammation and hypercoagulability. This randomized, sham-control, double blind trial evaluated the effect of hyperbaric oxygen therapy (HBOT or HBO2 therapy) on post-COVID-19 patients with ongoing symptoms for at least 3 months after confirmed infection.

Seventy-three patients were randomized to receive daily 40 session of HBOT (n = 37) or sham (n = 36). Follow-up assessments were performed at baseline and 1-3 weeks after the last treatment session. Following HBOT, there was a significant group-by-time interaction in global cognitive function, attention and executive function (d = 0.495, p = 0.038; d = 0.477, p = 0.04 and d = 0.463, p = 0.05 respectively). Significant improvement was also demonstrated in the energy domain (d = 0.522, p = 0.029), sleep (d = – 0.48, p = 0.042), psychiatric symptoms (d = 0.636, p = 0.008), and pain interference (d = 0.737, p = 0.001).

Clinical outcomes were associated with significant improvement in brain MRI perfusion and microstructural changes in the supramarginal gyrus, left supplementary motor area, right insula, left frontal precentral gyrus, right middle frontal gyrus, and superior corona radiate.

These results indicate that HBOT can induce neuroplasticity and improve cognitive, psychiatric, fatigue, sleep and pain symptoms of patients suffering from post-COVID-19 condition. HBOT’s beneficial effect may be attributed to increased brain perfusion and neuroplasticity in regions associated with cognitive and emotional roles.

Source: Zilberman-Itskovich S, Catalogna M, Sasson E, Elman-Shina K, Hadanny A, Lang E, Finci S, Polak N, Fishlev G, Korin C, Shorer R, Parag Y, Sova M, Efrati S. Hyperbaric oxygen therapy improves neurocognitive functions and symptoms of post-COVID condition: randomized controlled trial. Sci Rep. 2022 Jul 12;12(1):11252. doi: 10.1038/s41598-022-15565-0. PMID: 35821512; PMCID: PMC9276805. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9276805/ (Full text)

Lots of long COVID treatment leads, but few are proven

As the current crisis phase of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic winds down—and the world nervously awaits potentially dangerous new variants—research into the nature and treatment of so-called long coronavirus disease (COVID) is beginning to ramp up. The White House has promised funding and a federal research roadmap, and dedicated clinics have started cropping up at academic medical centers across the country.

But attempts to understand and treat long COVID have been underway almost since the pandemic began. For more than 2 years, clinicians have been coping—mostly on their own—with streams of patients complaining of persistent symptoms or mysterious new ones after a bout with COVID-19 had seemingly resolved ( 1 ). And collectively, doctors and researchers have already made headway toward identifying some of the mechanisms underlying the condition—formally known as post-acute sequelae of COVID (PASC).

Read the rest of this article HERE.

Source: Leah Shaffer. Lots of long COVID treatment leads, but few are proven. Vol. 119 | No. 36. https://www.pnas.org/doi/10.1073/pnas.2213524119 (Full text)

Coenzyme Q10 + alpha lipoic acid for chronic COVID syndrome

Abstract:

Chronic COVID syndrome is characterized by chronic fatigue, myalgia, depression and sleep disturbances, similar to chronic fatigue syndrome (CFS) and fibromyalgia syndrome. Implementations of mitochondrial nutrients (MNs) with diet are important for the clinical effects antioxidant. We examined if use of an association of coenzyme Q10 and alpha lipoic acid (Requpero®) could reduce chronic covid symptoms.

The Requpero study is a prospective observational study in which 174 patients, who had developed chronic-covid syndrome, were divided in two groups: The first one (116 patients) received coenzyme Q10 + alpha lipoic acid, and the second one (58 patients) did not receive any treatment. Primary outcome was reduction in Fatigue Severity Scale (FSS) in treatment group compared with control group. complete FSS response was reached most frequently in treatment group than in control group. A FSS complete response was reached in 62 (53.5%) patients in treatment group and in two (3.5%) patients in control group. A reduction in FSS core < 20% from baseline at T1 (non-response) was observed in 11 patients in the treatment group (9.5%) and in 15 patients in the control group (25.9%) (p < 0.0001).

To date, this is the first study that tests the efficacy of coenzyme Q10 and alpha lipoic acid in chronic Covid syndrome. Primary and secondary outcomes were met. These results have to be confirmed through a double blind placebo controlled trial of longer duration.

Source: Barletta MA, Marino G, Spagnolo B, Bianchi FP, Falappone PCF, Spagnolo L, Gatti P. Coenzyme Q10 + alpha lipoic acid for chronic COVID syndrome. Clin Exp Med. 2022 Aug 22. doi: 10.1007/s10238-022-00871-8. Epub ahead of print. PMID: 35994177.  https://link.springer.com/article/10.1007/s10238-022-00871-8 (Full text)

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 F2α 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)