Tag: antihistamines

Antihistamines improve cardiovascular manifestations and other symptoms of Long-COVID attributed to Mast Cell Activation

Abstract:

Introduction: Long-COVID is a hardly defined condition and there are no effective therapies. Cardiovascular manifestations of Long-COVID include high heart rate, postural tachycardia, and palpitations. Previous studies have suggested that mast cell activation (MCA) may play a role in the pathophysiology of Long-COVID, including in the mechanisms of its cardiovascular manifestations. The aim of the study was to evaluate the effectiveness of a treatment with blockers of histamine receptors in Long-COVID patients who did not respond to other therapies.

Methods: Fourteen patients (F/M=9/5; 49.5±11.5 years) and 13 controls (F/M=8/5; 47.3±8.0 years) with Long-COVID symptoms attributed to MCA were evaluated. Patients were treated with fexofenadine (180 mg/day) and famotidine (40 mg/day). Fatigue, brain fog, abdominal disorders, and increased heart rate were evaluated in treated and untreated patients at baseline and 20 days later.

Results: Long-COVID symptoms disappeared completely in 29% of treated patients. There was significant improvement in each of the considered symptoms (improved or disappeared) in all treated patients, and the improvement grade was significantly greater in treated patients with respect to controls. No significant differences in the outcomes were observed in the controls.

Our data confirm that histamine receptors blockade may be an effective target to successfully treat long-COVID. Our finding supports the underlying role of MCA in the pathophysiology of Long-COVID.

Source: Fabrizio Salvucci, Roberto Codella, ADRIANA COPPOLA, Irene Zacchei, Gabriella Grassi, Maria L. Anti, Nicolita Nitisoara, Livio Luzi, and Carmine Gazzaruso. Antihistamines improve cardiovascular manifestations and other symptoms of Long-COVID attributed to Mast Cell Activation. Front. Cardiovasc. Med. Sec. General Cardiovascular Medicine. Volume 10 – 2023 | doi: 10.3389/fcvm.2023.1202696 https://www.frontiersin.org/articles/10.3389/fcvm.2023.1202696/abstract

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)

Pathophysiology of Post-COVID syndromes: a new perspective

Abstract:

Most COVID-19 patients recovered with low mortality; however, some patients experienced long-term symptoms described as “long-COVID” or “Post-COVID syndrome” (PCS). Patients may have persisting symptoms for weeks after acute SARS-CoV-2 infection, including dyspnea, fatigue, myalgia, insomnia, cognitive and olfactory disorders. These symptoms may last for months in some patients.

PCS may progress in association with the development of mast cell activation syndrome (MCAS), which is a distinct kind of mast cell activation disorder, characterized by hyper-activation of mast cells with inappropriate and excessive release of chemical mediators. COVID-19 survivors, mainly women, and patients with persistent severe fatigue for 10 weeks after recovery with a history of neuropsychiatric disorders are more prone to develop PCS. High D-dimer levels and blood urea nitrogen were observed to be risk factors associated with pulmonary dysfunction in COVID-19 survivors 3 months post-hospital discharge with the development of PCS. PCS has systemic manifestations that resolve with time with no further complications. However, the final outcomes of PCS are chiefly unknown.

Persistence of inflammatory reactions, autoimmune mimicry, and reactivation of pathogens together with host microbiome alterations may contribute to the development of PCS. The deregulated release of inflammatory mediators in MCAS produces extraordinary symptoms in patients with PCS. The development of MCAS during the course of SARS-CoV-2 infection is correlated to COVID-19 severity and the development of PCS. Therefore, MCAS is treated by antihistamines, inhibition of synthesis of mediators, inhibition of mediator release, and inhibition of degranulation of mast cells.

Source: Batiha, G.ES., Al-kuraishy, H.M., Al-Gareeb, A.I. et al. Pathophysiology of Post-COVID syndromes: a new perspective. Virol J 19, 158 (2022). https://doi.org/10.1186/s12985-022-01891-2  https://virologyj.biomedcentral.com/articles/10.1186/s12985-022-01891-2 (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)

Levocetirizine and montelukast in the COVID-19 treatment paradigm

Abstract:

Levocetirizine, a third-generation antihistamine, and montelukast, a leukotriene receptor antagonist, exhibit remarkable synergistic anti-inflammatory activity across a spectrum of signaling proteins, cell adhesion molecules, and leukocytes. By targeting cellular protein activity, they are uniquely positioned to treat the symptoms of COVID-19. Clinical data to date with an associated six-month follow-up, suggests the combination therapy may prevent the progression of the disease from mild to moderate to severe, as well as prevent/treat many of the aspects of ‘Long COVID,’ thereby cost effectively reducing both morbidity and mortality. To investigate patient outcomes, 53 consecutive COVID-19 test (+) cases (ages 3-90) from a well-established, single-center practice in Boston, Massachusetts, between March – November 2020, were treated with levocetirizine and montelukast in addition to then existing protocols [2]. The data set was retrospectively reviewed.

Thirty-four cases were considered mild (64%), 17 moderate (32%), and 2 (4%) severe. Several patients presented with significant comorbidities (obesity: n = 22, 41%; diabetes: n = 10, 19%; hypertension: n = 24, 45%). Among the cohort there were no exclusions, no intubations, and no deaths. The pilot study in Massachusetts encompassed the first COVID-19 wave which peaked on April 23, 2020 as well as the ascending portion of the second wave in the fall. During this period the average weekly COVID-19 case mortality rate (confirmed deaths/confirmed cases) varied considerably between 1 and 7.5% [37]. FDA has approved a multicenter, randomized, placebo-controlled, Phase 2 clinical trial design, replete with electronic diaries and laboratory metrics to explore scientific questions not addressed herein.

Source: May BC, Gallivan KH. Levocetirizine and montelukast in the COVID-19 treatment paradigm. Int Immunopharmacol. 2021 Dec 15;103:108412. doi: 10.1016/j.intimp.2021.108412. Epub ahead of print. PMID: 34942461; PMCID: PMC8673734. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8673734/ (Full text)

Double-blind placebo-controlled study of the efficacy of oral terfenadine in the treatment of chronic fatigue syndrome

Abstract:

BACKGROUND: There is no established treatment for chronic fatigue syndrome (CFS), an illness characterized by disabling fatigue exacerbated by physical activity. A variety of immunologic abnormalities have been reported, including a high incidence of atopy and hypoergy or anergy.

OBJECTIVE: Because of anecdotal reports and uncontrolled trials showing antihistamine efficacy in CFS, we evaluated the clinical efficacy of the antihistamine terfenadine (60 mg twice daily) in a placebo-controlled study.

METHODS: Thirty patients with CFS were enrolled in a 2-month, double-blind, placebo-controlled trial of terfenadine. Participants underwent a battery of both immediate- and delayed-type hypersensitivity skin tests and completed a self-assessment questionnaire used to measure severity of symptoms, physical and social functioning, health perceptions, and mental health before each of six biweekly visits.

RESULTS: Twenty-eight patients completed the trial. History of atopy and positive immediate skin test results were prevalent, 73% and 53%, respectively. No evidence for hypoergy or anergy after delayed-type hypersensitivity skin testing was found. No therapeutic benefit from terfenadine could be detected in terms of symptom amelioration, improved physical or social functioning, health perceptions, or mental health. A high incidence of atopy in patients with CFS was confirmed.

CONCLUSION: Although this trial involved a small number of patients, the results suggest that terfenadine is unlikely to be of clinical benefit in treating CFS symptoms.

 

Source: Steinberg P, McNutt BE, Marshall P, Schenck C, Lurie N, Pheley A, Peterson PK. Double-blind placebo-controlled study of the efficacy of oral terfenadine in the treatment of chronic fatigue syndrome. J Allergy Clin Immunol. 1996 Jan;97(1 Pt 1):119-26. http://www.ncbi.nlm.nih.gov/pubmed/8568124