Article originally published in The Journal for Nurse Practitioners; Feb. 7, 2022; Melissa D. Pinto, Natalie Lambert, Charles A. Downs, Heather Abrahim, Thomas D. Hughes, Amir M. RahmaniCandace W. Burton, Rana Chakraborty; DOI: doi.org/10.1016/j.nurpra.2021.12.016 With Commentary by Betty Mekdeci

This report on two long Covid cases successfully treated with over-the-counter antihistamines is very intriguing.
I have to offer a warning, however.  I have ME/CFS, first diagnosed in 1984.  Some of the earliest symptoms were of mast cell disturbance where I became reactive to exposures that had never bothered me before.
At one point, I decided to be tested for Mast Cell Disorder.  This involved allergy testing which confirmed that I had become reactive to all kinds of drugs and chemicals.  This was followed by a trial of small doses of medications they use to treat MCAS: two antihistamines, Tagamet and Singulair.  
The morning after taking these small doses, I woke up with blurry vision.  I decided to stop all the medicines, but things didn’t get better.
I went to an optometrist who found that I had sky high eye pressure and referred me immediately to a glaucoma specialist who recommended laser surgery which I had.  Everything seemed okay for two weeks until we took a long, long plane ride to visit our daughter in Hawaii.
When we arrived, my left eye turned bright red and started dropping.  I also had the most horrid headache of my life.  We sent pictures to the glaucoma specialist who was very concerned.  He sent me to his former partner who was practicing on Maui.  
As soon as we returned to Florida, I was rushed to a neuroradiologist for evaluation.  The artery behind my left eye had ruptured and connected with the vein.  This was an emergency that could result in a fatal stroke or the loss of vision in that eye.
I had a 7 hour brain surgery to separate the vein and artery with platinum coils. For several months, I had double vision in the left eye which eventually resolved, but I will have to use eye pressure drops for the rest of my life to preserve (I hope) my vision.
The only ironic part of this report is that years ago I had been the second grade gifted teacher for the neuroradiologist who did my surgery. We both remembered all the students in that class.
The point of sharing this is that both ME/CFS and long Covid are tricky diseases and believe me (after 40 years) there are no sure cures and much care must be taken with the medications, supplements, herbal remedies, etc. that you try.

By Betty Mekdeci, Executive Director, Birth Defect Research for Children

Article Highlights

•Postacute sequelae of SARS-Co-V 2 infection (PASC) is a public health crisis.

•Currently there are no treatments for PASC.

•Two patients with PASC report rapid symptom resolution with antihistamine use.

•Antihistamines may be a high accessible therapy for PASC.

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.

Keywords

antihistamineCOVID-19long-COVIDlong-haul COVIDpostacute SARS-CoV-2 infection (PASC)SARS-CoV-2 infection (PASC)treatment

Introduction

Postacute sequelae of SARS-CoV-2 infection (PASC) is a new, ill-defined disease characterized by persistent symptoms that extend beyond the expected resolution time frame. Symptoms also tend to evolve, with more than 200 patient-reported symptoms reflecting multiple organ system involvement.1 PASC is an emerging global health crisis, with an estimated prevalence of 30%.2 PASC is often painful, debilitating, and impairs daily functioning.3 The United States (US) Centers for Disease Control and Prevention (CDC) reports that two-thirds of patients hospitalized with SARS-CoV-2 develop PASC within 6 months after infection.4 Among nonhospitalized patients with COVID-19 in California, Huang et al5 found that 11% continued to report symptoms at least 6 months after infection.

As of August 2021, an estimated 54 million people globally had PASC. There is no treatment for PASC, and the World Health Organization has urgently requested that countries prioritize PASC research and care.6 We present 2 patients, previously healthy middle-aged women who developed signs and symptoms consistent with PASC in early 2020. Both patients report nearly complete resolution of symptoms after administration of over-the-counter histamine antagonists. These case reports are consistent with recent studies showing endothelial injury and aberrant immune response with histamine release during COVID-19.78910

Methods

These case reports were deemed exempt by the Indiana University and the University of California, Irvine Institutional Review Boards. Cases were obtained from members of Survivor Corps, a virtual COVID-19 research and advocacy organization hosted on Facebook. Survivor Corps has more than 170,000 members who post about their COVID-19–related experiences, symptoms, and self-management of PASC. In the time frame of March 24, 2020, until July 23, 2021, survivors mentioned using antihistamines on Survivor Corps’ Facebook page more than 900 times (Lambert et al, unpublished data, 2021). To our knowledge, no reports yet document the potential for antihistamine use in managing PASC.

Results

Patient One

Patient 1 is a White woman in her 40s who works in health care. Past medical history includes idiopathic Raynaud phenomenonpolycystic ovarian syndrome, heterozygous factor V Leiden mutation, and an immunoglobulin E-confirmed milk allergy managed with a modified diet. The patient has no history of vascular occlusiondeep vein thrombosispulmonary emboli, or stroke. She is a nonsmoker and uses alcohol occasionally. Her body mass index (BMI) is within the reference range for normal weight, and she received annual influenza immunization 3 months before onset of SARS-CoV-2 infection. Before her illness, she engaged in moderate-to-intense physical activity for 1 to 2 hours 4 to 5 times per week.

The patient was likely infected with SARS-CoV-2 in early January 2020 while attending a dance festival in southern California. At this time, SARS-CoV-2 testing was limited, and there was no COVID-19 screening protocol in the US. Within 72 hours of probable exposure, the patient developed profound fatigue, malaise, and headache. Within 10 days, she developed a disseminated rash over her anterior and posterior trunk (Figure 1). She experienced inspiratory chest pain, bilateral flank pain, dry cough, fever, night sweats, dysgeusia, and ulcerations of the tongue, soft palate, and inside lower lip. The acute illness phase lasted approximately 24 days, at which time she experienced partial resolution of symptoms. To date, however, she experiences persistent rashes in multiple locations as well as flank pain, bilateral chest pain, and right-sided headache.

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