Tag: antibiotics

Hypothesis: Matrix metalloproteinase inhibition with low-dose doxycycline in Long COVID and ME/CFS

Abstract:

Nonselective matrix metalloproteinase (MMP) inhibition with FDA approved subantimicrobial dose doxycycline formulations could improve systemic symptoms in at least a subset of patients with Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) as compared to those who receive placebo.

Source: Sanders, E.C. (2023). Hypothesis: Matrix metalloproteinase inhibition with low-dose doxycycline in Long COVID and ME/CFS. Patient-Generated Hypotheses Journal for Long COVID & Associated Conditions, Vol. 1, 21-29 https://patientresearchcovid19.com/hypothesis-matrix-metalloproteinase-inhibition-with-low-dose-doxycycline-in-long-covid-and-me-cfs-pghj-issue1-may2023/ (Full text)

Antihistamines as an early treatment for Covid-19

Abstract:

Infection with SARs-COV-2 results in COVID-19 disease. Between March 2020 and August 2021, 468 COVID-19 patients confirmed by PCR or antigen test, in Yepes, Spain, received early treatment with antihistamines, adding azithromycin in selected cases. The primary endpoint is the hospitalization rate of COVID-19 patients, and the secondary endpoints are ICU admission and mortality rates. All endpoints are compared with the official Spanish rates during the time period of the study.

There were 20 hospital admissions (hospitalization rate 4,3%), 5 ICU admissions (ICU admission rate 1,1%) and 3 deaths (fatality rate of 0,6%). No patients in the study required follow up treatment, which suggest they did not develop long COVID. Results from this retrospective trail indicate that early treatment of SARS-COV-2 positive patients with antihistamines may reduce the odds of hospitalization (OR: 0.490, CI: 0.313-0.767, p-value: 0.001). Randomized controlled clinical trials are needed to further evaluate the effects of early antihistamine treatment of SARS-CoV-2 patients to prevent hospitalization, ICU admission, mortality and long-covid.

Source: Morán Blanco JI, Alvarenga Bonilla JA, Fremont-Smith P, Villar Gómez de Las Heras K. Antihistamines as an early treatment for Covid-19. Heliyon. 2023 May;9(5):e15772. doi: 10.1016/j.heliyon.2023.e15772. Epub 2023 Apr 25. PMID: 37128299; PMCID: PMC10129342. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10129342/ (Full text)

Assessment of microbiota in the gut and upper respiratory tract associated with SARS-CoV-2 infection

Abstract:

Background: The human microbiome plays an important role in modulating the host metabolism and immune system. Connections and interactions have been found between the microbiome of the gut and oral pharynx in the context of SARS-CoV-2 and other viral infections; hence, to broaden our understanding of host-viral responses in general and to deepen our knowledge of COVID-19, we performed a large-scale, systematic evaluation of the effect of SARS-CoV-2 infection on human microbiota in patients with varying disease severity.

Results: We processed 521 samples from 203 COVID-19 patients with varying disease severity and 94 samples from 31 healthy donors, consisting of 213 pharyngeal swabs, 250 sputa, and 152 fecal samples, and obtained meta-transcriptomes as well as SARS-CoV-2 sequences from each sample. Detailed assessment of these samples revealed altered microbial composition and function in the upper respiratory tract (URT) and gut of COVID-19 patients, and these changes are significantly associated with disease severity. Moreover, URT and gut microbiota show different patterns of alteration, where gut microbiome seems to be more variable and in direct correlation with viral load; and microbial community in the upper respiratory tract renders a high risk of antibiotic resistance. Longitudinally, the microbial composition remains relatively stable during the study period.

Conclusions: Our study has revealed different trends and the relative sensitivity of microbiome in different body sites to SARS-CoV-2 infection. Furthermore, while the use of antibiotics is often essential for the prevention and treatment of secondary infections, our results indicate a need to evaluate potential antibiotic resistance in the management of COVID-19 patients in the ongoing pandemic. Moreover, a longitudinal follow-up to monitor the restoration of the microbiome could enhance our understanding of the long-term effects of COVID-19.

Source: Li J, Jing Q, Li J, Hua M, Di L, Song C, Huang Y, Wang J, Chen C, Wu AR. Assessment of microbiota in the gut and upper respiratory tract associated with SARS-CoV-2 infection. Microbiome. 2023 Mar 3;11(1):38. doi: 10.1186/s40168-022-01447-0. PMID: 36869345; PMCID: PMC9982190. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9982190/ (Full text)

Decolonization of staphylococcus aureus and therapeutic test to assist the diagnosis in me/cfs, long covid, post-vaccine covid syndrome and other diseases with fatigue and/or chronic pain

Abstract:

Nasal Decolonization is performed with an antiseptic such as Povidone-iodine. For the Therapeutic Test an Antibiotic such as Flucloxacillin plus Probiotics or other supplements with an effect against S.aureus is indicated.

There is a Subgroup of patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long COVID Syndrome or PACS who present a persistent bacterial infection that affects the upper respiratory tract, and especially at the level of the nostrils.

We estimate that this Subgroup of patients presenting this persistent infection as a causal or contributing factor would be around a third of all cases.

The most frequent causative agent of these persistent and/or recurrent infections is the Staphylococcus aureus bacterium. According to the studies carried out, this bacterium is present in the nasal passages of between 16 and 36% of the general population, who are asymptomatic carriers of Staphylococcus aureus, and are often unaware of it.

In health professionals who carry out care work, the percentage of carriers can exceed 50%. In a recent study carried out in health workers and medical students, 65% of nasal carriers of S. aureus were reported, and of these, 74% were multidrug-resistant (MDR) bacteria and 69% were biofilm-forming bacteria [1].

Source: Gustavo Aguirre Chang and Aurora Natividad Trujillo Figueredo. Decolonization of staphylococcus aureus and therapeutic test to assist the diagnosis in me/cfs, long covid, post-vaccine covid syndrome and other diseases with fatigue and/or chronic pain. ResearchGate [Preprint] 2/17/23. https://www.researchgate.net/publication/368646387_DECOLONIZATION_OF_STAPHYLOCOCCUS_AUREUS_AND_THERAPEUTIC_TEST_TO_ASSIST_THE_DIAGNOSIS_IN_MECFS_LONG_COVID_POST-VACCINE_COVID_SYNDROME_AND_OTHER_DISEASES_WITH_FATIGUE_ANDOR_CHRONIC_PAIN (Full text)

Clinical Characteristics in the Acute Phase of COVID-19 That Predict Long COVID: Tachycardia, Myalgias, Severity, and Use of Antibiotics as Main Risk Factors, While Education and Blood Group B Are Protective

Abstract:

Background: Risk factors for developing long COVID are not clearly established. The present study was designed to determine if any sign, symptom, or treatment of the acute phase, or personal characteristics of the patient, is associated with the development of long COVID.
Methods: A cohort study was carried out, randomly selecting symptomatic COVID-19 patients and not vaccinated. The severity of the acute illness was assessed through the number of compatible COVID-19 symptoms, hospitalizations, and the symptom severity score using a 10-point visual analog scale.
Results: After multivariate analysis, a severity score ≥8 (RR 2.0, 95%CI 1.1–3.5, p = 0.022), hospitalization (RR 2.1, 95%CI 1.0–4.4, p = 0.039), myalgia (RR 1.9, 95%CI 1.08–3.6, p = 0.027), tachycardia (RR 10.4, 95%CI 2.2–47.7, p = 0.003), and use of antibiotics (RR 2.0, 95%CI 1.1–3.5, p = 0.022), was positively associated with the risk of having long COVID. Higher levels of education (RR 0.6, 95%CI 0.4–0.9, p = 0.029) and type positive B blood group (B + AB, RR 0.44, 95%CI 0.2–0.9, p = 0.044) were protective factors. The most important population attributable fractions (PAFs) for long COVID were myalgia (37%), severity score ≥8 (31%), and use of antibiotics (27%).
Conclusions: Further studies in diverse populations over time are needed to expand the knowledge that could lead us to prevent and/or treat long COVID.
Source: Guzman-Esquivel J, Mendoza-Hernandez MA, Guzman-Solorzano HP, Sarmiento-Hernandez KA, Rodriguez-Sanchez IP, Martinez-Fierro ML, Paz-Michel BA, Murillo-Zamora E, Rojas-Larios F, Lugo-Trampe A, Plata-Florenzano JE, Delgado-Machuca M, Delgado-Enciso I. Clinical Characteristics in the Acute Phase of COVID-19 That Predict Long COVID: Tachycardia, Myalgias, Severity, and Use of Antibiotics as Main Risk Factors, While Education and Blood Group B Are Protective. Healthcare. 2023; 11(2):197. https://doi.org/10.3390/healthcare11020197 https://www.mdpi.com/2227-9032/11/2/197 (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)

The Gut Microbiome in Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS)

Abstract:

Myalgic encephalomyelitis (ME) or Chronic Fatigue Syndrome (CFS) is a neglected, debilitating multi-systemic disease without diagnostic marker or therapy. Despite evidence for neurological, immunological, infectious, muscular and endocrine pathophysiological abnormalities, the etiology and a clear pathophysiology remains unclear. The gut microbiome gained much attention in the last decade with manifold implications in health and disease. Here we review the current state of knowledge on the interplay between ME/CFS and the microbiome, to identify potential diagnostic or interventional approaches, and propose areas where further research is needed.

We iteratively selected and elaborated on key theories about a correlation between microbiome state and ME/CFS pathology, developing further hypotheses. Based on the literature we hypothesize that antibiotic use throughout life favours an intestinal microbiota composition which might be a risk factor for ME/CFS. Main proposed pathomechanisms include gut dysbiosis, altered gut-brain axis activity, increased gut permeability with concomitant bacterial translocation and reduced levels of short-chain-fatty acids, D-lactic acidosis, an abnormal tryptophan metabolism and low activity of the kynurenine pathway. We review options for microbiome manipulation in ME/CFS patients including probiotic and dietary interventions as well as fecal microbiota transplantations. Beyond increasing gut permeability and bacterial translocation, specific dysbiosis may modify fermentation products, affecting peripheral mitochondria. Considering the gut-brain axis we strongly suspect that the microbiome may contribute to neurocognitive impairments of ME/CFS patients.

Further larger studies are needed, above all to clarify whether D-lactic acidosis and early-life antibiotic use may be part of ME/CFS etiology and what role changes in the tryptophan metabolism might play. An association between the gut microbiome and the disease ME/CFS is plausible. As causality remains unclear, we recommend longitudinal studies. Activity levels, bedridden hours and disease progression should be compared to antibiotic exposure, drug intakes and alterations in the composition of the microbiota. The therapeutic potential of fecal microbiota transfer and of targeted dietary interventions should be systematically evaluated.

Source: König RS, Albrich WC, Kahlert CR, Bahr LS, Löber U, Vernazza P, Scheibenbogen C, Forslund SK. The Gut Microbiome in Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS). Front Immunol. 2022 Jan 3;12:628741. doi: 10.3389/fimmu.2021.628741. PMID: 35046929; PMCID: PMC8761622. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8761622/ (Full text)

 

Oral Minocycline Therapy Improves Symptoms of Myalgic Encephalomyelitis, Especially in the Initial Disease Stage

Abstract:

Objective: Central nervous system dysfunction associated with myalgic encephalomyelitis (ME) has been suggested to be the main cause of chronic fatigue syndrome. In animal models of chronic fatigue, minocycline was reported to act as a suppressor of neural inflammation. Minocycline may thus exert favorable therapeutic effects in patients with ME.

Methods: Oral minocycline (100 mg ×2 on the first day, followed by 100 mg/day for 41 days) was administered to 100 patients with ME. The performance status score (0-9), orthostatic intolerance during the 10-min standing test, neurologic disequilibrium, and neuropathic pain were compared before and after treatment.

Results: After therapy completion, favorable effects were observed with a decrease in the performance status score of ≥2 points in 27 patients (27%). Before treatment, 6 of the 27 patients had orthostatic intolerance with an inability to complete the 10-min standing test; after treatment, this symptom resolved in 4 and improved in 2 patients. In addition, after treatment, postural orthostatic tachycardia resolved in five of eight patients, disequilibrium resolved in five of eight patients, and fibromyalgia or neuropathic pain was attenuated in four of five patients. The favorable effects appeared dependent on a shorter disease duration, primarily for a duration of less than three years and most frequently within six months of the disease onset. However, acute adverse effects with nausea and/or dizziness caused 38 patients (38%) to discontinue treatment in the first few days.

Conclusion: Oral minocycline therapy may be an effective treatment option for patients with ME, especially in the initial stage of the disease.

Source: Miwa K. Oral Minocycline Therapy Improves Symptoms of Myalgic Encephalomyelitis, Especially in the Initial Disease Stage. Intern Med. 2021 Apr 26. doi: 10.2169/internalmedicine.6082-20. Epub ahead of print. PMID: 33896862. https://pubmed.ncbi.nlm.nih.gov/33896862/

From IBS to ME – The dysbiotic march hypothesis

Abstract:

Irritable bowel syndrome (IBS) is often associated with other unexplained complaints like chronic fatigue syndrome (CFS), fibromyalgia and myalgic encephalopathy (ME). The pathogenesis of the relationship is unknown. Intestinal dysbiosis may be a common abnormality, but based on 1100 consecutive IBS patients examined over a nine years period, we hypothesize that the development of the disease, often from IBS to ME, actually manifests a “dysbiotic march”. In analogy with “the atopic march” in allergic diseases, we suggest “a dysbiotic march” in IBS; initiated by extensive use of antibiotics during childhood, often before school age. Various abdominal complaints including IBS may develop soon thereafter, while systemic symptom like CFS, fibromyalgia and ME may appear years later.

Source: Berstad A, Hauso O, Berstad K, Berstad JER. From IBS to ME – The dysbiotic march hypothesis. Med Hypotheses. 2020 Feb 26;140:109648. doi: 10.1016/j.mehy.2020.109648. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/32126475

Successful treatment of postural orthostatic tachycardia and mast cell activation syndromes using naltrexone, immunoglobulin and antibiotic treatment

Abstract:

A patient with severe postural orthostatic tachycardia syndrome (POTS) and mast cell activation syndrome (MCAS) received immunotherapy with low-dose naltrexone (LDN) and intravenous immunoglobulin (IVIg) and antibiotic therapy for small intestinal bacterial overgrowth (SIBO). A dramatic and sustained response was documented. The utility of IVIg in autoimmune neuromuscular diseases has been published, but clinical experience with POTS is relatively unknown and has not been reported in MCAS. As a short-acting mu-opioid antagonist, LDN paradoxically increases endorphins which then bind to regulatory T cells which regulate T-lymphocyte and B-lymphocyte production and this reduces cytokine and antibody production. IVIg is emerging as a promising therapy for POTS. Diagnosis and treatment of SIBO in POTS is a new concept and appears to play an important role.

Source: Leonard B Weinstock, Jill B Brook, Trisha L Myers, Brent Goodman. Successful treatment of postural orthostatic tachycardia and mast cell activation syndromes using naltrexone, immunoglobulin and antibiotic treatment. Case Report. BMJ Case Rep. 2018; 2018: bcr2017221405. Published online 2018 Jan 11. doi: 10.1136/bcr-2017-221405 PMCID: PMC5778345 PMID: 29326369. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5778345/ (Full article)