The Role of Nutrients in Prevention, Treatment and Post-Coronavirus Disease-2019 (COVID-19)

Abstract:

SARS-CoV-2 virus, infecting human cells via its spike protein, causes Coronavirus disease 2019 (COVID-19). COVID-19 is characterized by shortness of breath, fever, and pneumonia and is sometimes fatal. Unfortunately, to date, there is still no definite therapy to treat COVID-19. Therefore, the World Health Organization (WHO) approved only supportive care. During the COVID-19 pandemic, the need to maintain a correct intake of nutrients to support very weakened patients in overcoming disease arose. The literature available on nutrient intake for COVID-19 is mainly focused on prevention. However, the safe intake of micro- and/or macro-nutrients can be useful either for preventing infection and supporting the immune response during COVID-19, as well as in the post-acute phase, i.e., “long COVID”, that is sometimes characterized by the onset of various long lasting and disabling symptoms. The aim of this review is to focus on the role of nutrient intake during all the different phases of the disease, including prevention, the acute phase, and finally long COVID.

Source: Motti ML, Tafuri D, Donini L, Masucci MT, De Falco V, Mazzeo F. The Role of Nutrients in Prevention, Treatment and Post-Coronavirus Disease-2019 (COVID-19). Nutrients. 2022 Feb 26;14(5):1000. doi: 10.3390/nu14051000. PMID: 35267974; PMCID: PMC8912782. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8912782/ (Full text)

Individualizing medical treatment in chronic fatigue syndrome/ myalgic encephalomyelitis: Evidence for effective medications and possible relevance to “Long-Hauler Syndrome” in Covid-19 affected patients

Abstract:

Large controlled studies of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) have shown no effective medical treatment for this disorder. There are individual patients, however, with dramatic responses to some medications.

We report two patients with clear responses to rintatolimod and galantamine characterized by rapid reduction of symptoms on starting treatment and return of symptoms on withdrawal.

As in cancer, CFS/ME is a heterogeneous disorder but unlike most cancers, such as melanoma, breast cancer, and B-cell lymphoma, CFS/ME has no known biological marker that can distinguish between subtypes.

We suggest an approach to medical treatment of CFS/ME that could be utilized by primary caregivers that offer the possibility of more rapid and complete recovery from this debilitating disorder.

Current studies indicate that prolonged symptomatic recovery from infection with Covid-19 (“long hauler syndrome” or PASC, for post-acute sequelae of Covid-19) represents a severe form of CFS/ME and thus may also be amenable to personalized medicine with specific medications.

Source: Levine PH, Ajmera KM, Bjorke B, Peterson D. Individualizing medical treatment in chronic fatigue syndrome/myalgic
encephalomyelitis: Evidence for effective medications and possible relevance to “Long-Hauler Syndrome” in Covid-19 affected
patients. J Clin Images Med Case Rep. 2022; 3(1): 1681. https://jcimcr.org/pdfs/JCIMCR-v3-1681.pdf (Full text)

 

A central role for amyloid fibrin microclots in long COVID/PASC: origins and therapeutic implications

Abstract:

Post-acute sequelae of COVID (PASC), usually referred to as ‘Long COVID’ (a phenotype of COVID-19), is a relatively frequent consequence of SARS-CoV-2 infection, in which symptoms such as breathlessness, fatigue, ‘brain fog’, tissue damage, inflammation, and coagulopathies (dysfunctions of the blood coagulation system) persist long after the initial infection. It bears similarities to other post-viral syndromes, and to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Many regulatory health bodies still do not recognize this syndrome as a separate disease entity, and refer to it under the broad terminology of ‘COVID’, although its demographics are quite different from those of acute COVID-19. A few years ago, we discovered that fibrinogen in blood can clot into an anomalous ‘amyloid’ form of fibrin that (like other β-rich amyloids and prions) is relatively resistant to proteolysis (fibrinolysis). The result, as is strongly manifested in platelet-poor plasma (PPP) of individuals with Long COVID, is extensive fibrin amyloid microclots that can persist, can entrap other proteins, and that may lead to the production of various autoantibodies. These microclots are more-or-less easily measured in PPP with the stain thioflavin T and a simple fluorescence microscope.

Although the symptoms of Long COVID are multifarious, we here argue that the ability of these fibrin amyloid microclots (fibrinaloids) to block up capillaries, and thus to limit the passage of red blood cells and hence O2 exchange, can actually underpin the majority of these symptoms. Consistent with this, in a preliminary report, it has been shown that suitable and closely monitored ‘triple’ anticoagulant therapy that leads to the removal of the microclots also removes the other symptoms. Fibrin amyloid microclots represent a novel and potentially important target for both the understanding and treatment of Long COVID and related disorders.

Source: Kell DB, Laubscher GJ, Pretorius E. A central role for amyloid fibrin microclots in long COVID/PASC: origins and therapeutic implications. Biochem J. 2022 Feb 17;479(4):537-559. doi: 10.1042/BCJ20220016. PMID: 35195253. https://portlandpress.com/biochemj/article/479/4/537/230829/A-central-role-for-amyloid-fibrin-microclots-in (Full text)

Antihistamines for Postacute Sequelae of SARS-CoV-2 Infection

Abstract:

Postacute sequelae of SARS-CoV2 (PASC) infection is an emerging global health crisis, variably affecting millions worldwide. PASC has no established treatment. We describe 2 cases of PASC in response to opportune administration of over-the-counter antihistamines, with significant improvement in symptoms and ability to perform activities of daily living. Future studies are warranted to understand the potential role of histamine in the pathogenesis of PASC and explore the clinical benefits of antihistamines in the treatment of PASC.

Source: Melissa D. Pinto, Natalie Lambert, Charles A. Downs, Heather Abrahim, Thomas D. Hughes, Amir M. Rahmani, Candace W. Burton, Rana Chakraborty. Antihistamines for Postacute Sequelae of SARS-CoV-2 Infection. The Journal for Nurse Practitioners, 2022, ISSN 1555-4155, https://doi.org/10.1016/j.nurpra.2021.12.016.
https://www.sciencedirect.com/science/article/pii/S155541552100547X  (Full text)

Oral Minocycline Challenge as a Potential First-Line Therapy for Myalgic Encephalomyelitis and Long Covid-19 Syndrome

Abstract:

Chronic fatigue syndrome characterized by severe disabling fatigue, prolonged post-exertional malaise, and unrefreshing sleep markedly reduces the activities of daily living and impairs the quality of life.

Central nervous system dysfunction associated with myalgic encephalomyelitis (ME) has been postulated as the main cause of chronic fatigue syndrome.

Recently, oral minocycline therapy has been reported to exert favorable therapeutic effects in some patients with ME, especially in the initial stage of the disease, although many patients discontinued treatment in the first few days because of acute adverse effects such as nausea and/or dizziness.

Minocycline appeared to exert a variety of biologic actions against neural inflammation that are independent of their anti-microbial activity, including anti-inflammatory, immunomodulatory, and neuroprotective effects.

In recent years, it has been noted that COVID-19 disease may cause persistent signs and symptoms described as post-COVID syndrome or long COVID, in which the clinical presentation is remarkably similar to those seen in patients with ME.

A wide range of infectious agents have been suggested to trigger the development of ME, and one of such pathogens may be the COVID-19 virus.

Recently, I had a valuable experience of a 22-year-old female patient with a 14-month duration of long COVID who completely recovered from ME-like symptoms after treatment with minocycline. This case suggests that oral minocycline could be an effective first-line therapy for long COVID-19, although a large scale of trial is obviously needed to justify the therapy.

Source: Miwa K. Oral Minocycline Challenge as a Potential First-Line Therapy for Myalgic Encephalomyelitis and Long Covid-19 Syndrome. Ann Clin Med Case Rep. 2022; V8(7): 1-4 https://acmcasereport.com/wp-content/uploads/2022/01/ACMCR-v8-1710.pdf  (Full article available as PDF file)

Oral Bacteriotherapy Reduces the Occurrence of Chronic Fatigue in COVID-19 Patients

Abstract:

Long COVID refers to patients with symptoms as fatigue, “brain fog,” pain, suggesting the chronic involvement of the central nervous system (CNS) in COVID-19. The supplementation with probiotic (OB) would have a positive effect on metabolic homeostasis, negatively impacting the occurrence of symptoms related to the CNS after hospital discharge. On a total of 58 patients hospitalized for COVID-19, 24 (41.4%) received OB during hospitalization (OB+) while 34 (58.6%) taken only the standard treatment (OB-). Serum metabolomic profiling of patients has been performed at both hospital acceptance (T0) and discharge (T1). Six months after discharge, fatigue perceived by participants was assessed by administrating the Fatigue Assessment Scale. 70.7% of participants reported fatigue while 29.3% were negative for such condition. The OB+ group showed a significantly lower proportion of subjects reporting fatigue than the OB- one (p < 0.01). Furthermore, OB+ subjects were characterized by significantly increased concentrations of serum Arginine, Asparagine, Lactate opposite to lower levels of 3-Hydroxyisobutirate than those not treated with probiotics. Our results strongly suggest that in COVID-19, the administration of probiotics during hospitalization may prevent the development of chronic fatigue by impacting key metabolites involved in the utilization of glucose as well as in energy pathways.

Source: Santinelli L, Laghi L, Innocenti GP, Pinacchio C, Vassalini P, Celani L, Lazzaro A, Borrazzo C, Marazzato M, Tarsitani L, Koukopoulos AE, Mastroianni CM, d’Ettorre G, Ceccarelli G. Oral Bacteriotherapy Reduces the Occurrence of Chronic Fatigue in COVID-19 Patients. Front Nutr. 2022 Jan 12;8:756177. doi: 10.3389/fnut.2021.756177. PMID: 35096923; PMCID: PMC8790565. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8790565/ (Full text)

Using condition specific patient reported outcome measures for long covid

Management expert Peter Drucker’s famous words “if you can’t measure it, you can’t manage it” holds good for post-covid syndrome, or long covid, which affects an estimated two million individuals in the UK 1 and extrapolated prevalence data suggests more than 50 million individuals may be affected worldwide.2 Long covid is a multisystem condition with over 200 symptoms reported across most of the organ systems, often with a chronic fluctuating pattern of presentation.3 With up to 30% of covid-19 health burden being related to covid induced disability, long covid presents substantial challenges for healthcare systems worldwide.4 Management of this complex syndrome, in part, requires new integrated long covid services with expertise drawn from a range of specialists across disciplines from both primary and secondary care.56 Healthcare services globally are investing in these new pathways of care, but there are no agreed measurement metrics yet to comprehensively capture patient experience or the effectiveness of treatments, partly due to lack of clear biomarkers for the condition.

Patient reported outcome measures (PROMs) are questionnaire tools to ascertain patients’ views of their symptoms, their functional status, and their health-related quality of life.7 PROM use in other routine clinical contexts have been shown to facilitate communication, engage patients in their care, tailor care to individual patients’ needs, and show value for money for those investing in the services.89 Clinical outcome assessments should include clinically important concepts that define the disease in the target population, assess the impact of disease, and reflect the lived experience of those with the condition. Given the large scale, relative novelty, and multifariousness of long covid syndrome, coupled with shortcomings in understanding viral-onset illness, it is unsurprising that standardised assessments of functioning, disability, and health are lacking.1011

Currently long covid services are using PROMs developed for other conditions such respiratory conditions (Medical Research Council Dyspnea Scale), anxiety disorder (Generalised Anxiety Disorder Assessment) and depression (Patient Health Questionnaire) and a range of other symptom-specific PROMs that have not yet been validated for use with long covid. However, this approach has several limitations. Such measures, in our experience, are cognitively burdensome to long covid patients, do not comprehensively capture the spectrum of symptoms, cannot directly engage with the underlying biological mechanisms, and are reported not to be meaningful by patients, families, and clinicians. Using a range of symptom specific measures makes it challenging to repeat the measures frequently to capture day by day fluctuations and are difficult to implement in busy services overburdened with managing such a large caseload of patients. There is the added danger of misleading management, for example individuals scoring highly on anxiety scores may get diverted to psychological services when their anxiety is being driven by underlying dysautonomia (increased heart rate) which needs medical optimisation.

Read the rest of this article HERE.

Source: Sivan M, Wright S, Hughes S, Calvert M. Using condition specific patient reported outcome measures for long covid. BMJ. 2022 Jan 28;376:o257. doi: 10.1136/bmj.o257. PMID: 35091425. https://www.bmj.com/content/376/bmj.o257 (Full text)

Trigger point injections and dry needling can be effective in treating long COVID syndrome-related myalgia: a case report

Abstract:

Introduction: Myofascial pain is a complex health condition that affects the majority of the general population. Myalgia has been recognized as a symptom of long COVID syndrome. The treatment for long COVID syndrome-related myalgia lacks research. Dry needling is a technique that involves the insertion of a needle into the tissue of, or overlaying, a pain point. Wet needling is the addition of an injection of an analgesic substance such as lidocaine while performing needling. Both dry and wet needling have are practiced as treatment modalities for myofascial pain. Limited literature exists to define long COVID syndrome-related myalgia and its relation to myofascial pain, or to examine the utility of needling techniques for this pain. We report a case of dry and wet needling as effective treatments for long COVID-related myofascial pain.

Case presentation: A 59-year-old, previously healthy Hispanic male with no comorbid conditions was diagnosed with COVID-19 pneumonia. The patient suffered moderate disease without hypoxia and was never hospitalized. Three months later, the patient continued to suffer from symptoms such as exertional dyspnea, “brain fog,” and myalgia. An extensive multisystem workup revealed normal cardiac, pulmonary, and end organ functions. The patient was then diagnosed with long COVID syndrome. The nature and chronicity of the patient’s myalgia meet the criteria for myofascial pain. Both wet and dry needling were used to treat the patient’s myofascial pain, with good short- and long-term therapeutic effects.

Conclusions: COVID-19 infection has been shown to exacerbate preexisting myofascial pain syndrome. Our case report indicates that long COVID syndrome-related myalgia is likely a form of new-onset myofascial pain. Additionally, both wet and dry needling can be utilized as an effective treatment modality for this pain syndrome, with short- and long-term benefits.

Source: Zha M, Chaffee K, Alsarraj J. Trigger point injections and dry needling can be effective in treating long COVID syndrome-related myalgia: a case report. J Med Case Rep. 2022 Jan 17;16(1):31. doi: 10.1186/s13256-021-03239-w. PMID: 35039086; PMCID: PMC8763132. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8763132/ (Full text)

“LONG COVID”-A hypothesis for understanding the biological basis and pharmacological treatment strategy

Abstract:

Infection of humans with SARS-CoV-2 virus causes a disease known colloquially as “COVID-19” with symptoms ranging from asymptomatic to severe pneumonia. Initial pathology is due to the virus binding to the ACE-2 protein on endothelial cells lining blood vessels and entering these cells in order to replicate. Viral replication causes oxidative stress due to elevated levels of reactive oxygen species. Many (~60%) of the infected people appear to have eliminated the virus from their body after 28 days and resume normal activity. However, a significant proportion (~40%) experience a variety of symptoms (loss of smell and/or taste, fatigue, cough, aching pain, “brain fog,” insomnia, shortness of breath, and tachycardia) after 12 weeks and are diagnosed with a syndrome named “LONG COVID.”

Longitudinal clinical studies in a group of subjects who were infected with SARS-CoV-2 have been compared to a non-infected matched group of subjects. A cohort of infected subjects can be identified by a battery of cytokine markers to have persistent, low level grade of inflammation and often self-report two or more troubling symptoms. There is no drug that will relieve their symptoms effectively.

It is hypothesized that drugs that activate the intracellular transcription factor, nuclear factor erythroid-derived 2-like 2 (NRF2) may increase the expression of enzymes to synthesize the intracellular antioxidant, glutathione that will quench free radicals causing oxidative stress. The hormone melatonin has been identified as an activator of NRF2 and a relatively safe chemical for most people to ingest chronically. Thus, it is an option for consideration of re-purposing studies in “LONG COVID” subjects experiencing insomnia, depression, fatigue, and “brain fog” but not tachycardia. Appropriately designed clinical trials are required to evaluate melatonin.

Source: Jarrott B, Head R, Pringle KG, Lumbers ER, Martin JH. “LONG COVID”-A hypothesis for understanding the biological basis and pharmacological treatment strategy. Pharmacol Res Perspect. 2022 Feb;10(1):e00911. doi: 10.1002/prp2.911. PMID: 35029046. https://bpspubs.onlinelibrary.wiley.com/doi/10.1002/prp2.911 (Full text)

Successful application of pulsed electromagnetic fields in a patient with post-COVID-19 fatigue: a case report

Abstract:

Background: Post-COVID-19 fatigue is a frequent symptom in COVID-19 survivors, which substantially limits patients to achieve full recovery and potentially restrains return to work. The previous literature has not yet reported the use of pulsed electromagnetic fields in this indication.

Methods: Over the course of 5 weeks, 10 sessions of pulsed electromagnetic field treatment with a high magnetic flux density were applied to a patient suffering from post-COVID-19 fatigue syndrome. Fatigue, work ability, quality of life as well as anxiety, depression, stress level, and resilience were evaluated using validated patient-reported outcome measures.

Results: Fatigue, work ability, quality of life, and psychological well-being improved clearly over the course of the treatment and showed stable results 6 weeks later.

Conclusion: The use of pulsed electromagnetic field therapy with a device that allows sufficient penetration of the body tissue might be a promising physical modality to manage post-COVID-19 fatigue syndrome, which could reduce clinical and economic health consequences. Clinical sham-controlled studies are needed to evaluate the effect of pulsed electromagnetic fields in this indication.

Source: Wagner B, Steiner M, Markovic L, Crevenna R. Successful application of pulsed electromagnetic fields in a patient with post-COVID-19 fatigue: a case report. Wien Med Wochenschr. 2022 Jan 10:1–6. doi: 10.1007/s10354-021-00901-2. Epub ahead of print. PMID: 35006516; PMCID: PMC8743351. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8743351/ (Full text)