Chlorpheniramine Maleate Nasal Spray In COVID-19 Patients: Case Series

Abstract

The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) posted a devastating global health crisis. Very little is known about this virus that it is difficult to find treatments of this novel virus. The vaccine that can potentially combat this virus is under works hence, the repurposing of existing medical treatments such as chlorpheniramine maleate (CPM) could be a possible treatment. CPM is a safe and effective antihistamine with potent antiviral activity against various strains of influenza A/B, thus highlighting its great antiviral potential. The coronavirus disease 2019 (COVID-19) has a droplet mode transmission with a notably high viral load especially the nose. Several studies postulated that the nose is possibly the primary route of entry of SARS-CoV-2 owing to the high expression of Angiotensin 2 converting enzyme receptors. We hypothesize that utilizing (CPM) nasal spray as an adjunct treatment to COVID-19 patients and reduce their clinical course and hasten their time to negativization via RT-PCR via nasopharyngeal swab. We present four symptomatic patients with mild-moderate risks. CPM nasal spray was added to their current supportive treatment. All four patients showed rapid improvement of their clinical symptoms with a shorter than average time to negativization on repeat nasopharyngeal swab via RT-PCR. No safety issues were encountered during the course of treatment. Given its years of excellent safety profile with remarkable clinical results as shown in this case series, we conclude that CPM nasal spray may be a potential adjunct treatment option in patients with mild to moderate COVID-19 symptoms.

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Research Article
Journal of
Clinical & Experimental Pharmacology
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ISSN: 2161-1459
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J Clin Exp Pharmacol, Vol.10 Iss. 2 No: 275 1
ABSTRACT
The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) posted a devastating global health crisis. Very
little is known about this virus that it is difficult to find treatments of this novel virus. The vaccine that can potentially combat
this virus is under works hence, the repurposing of existing medical treatments such as chlorpheniramine maleate (CPM)
could be a possible treatment. CPM is a safe and effective antihistamine with potent antiviral activity against various strains of
influenza A/B, thus highlighting its great antiviral potential.
The coronavirus disease 2019 (COVID-19) has a droplet mode transmission with a notably high viral load especially the nose.
Several studies postulated that the nose is possibly the primary route of entry of SARS-CoV-2 owing to the high expression
of Angiotensin 2 converting enzyme receptors. We hypothesize that utilizing (CPM) nasal spray as an adjunct treatment to
COVID-19 patients and reduce their clinical course and hasten their time to negativization via RT-PCR via nasopharyngeal
swab. We present four symptomatic patients with mild-moderate risks. CPM nasal spray was added to their current supportive
treatment. All four patients showed rapid improvement of their clinical symptoms with a shorter than average time to
negativization on repeat nasopharyngeal swab via RT-PCR. No safety issues were encountered during the course of treatment.
Given its years of excellent safety profile with remarkable clinical results as shown in this case series, we conclude that CPM
nasal spray may be a potential adjunct treatment option in patients with mild to moderate COVID-19 symptoms.
Key words: COVID19; Intranasal; Chlorpheniramine maleate; Therapeutics; Nasal spray; SARS-CoV-2
Chlorpheniramine Maleate Nasal Spray In COVID-19 Patients: Case
Series
Joselit Torres1, Camille Celeste Go2, Farah Chohan2, Genesis Camacho L2, Marcos A Sanchez-Gonzalez1, Gustavo
Ferrer2,3*
1Institute of Immunodiagnosis. Urb. El Rosal, Caracas, Venezuela; 2Division of Research & Academic Affairs, Larkin Health System, South
Miami, Florida, USA; 3Aventura Pulmonary Institute, Miami, Florida, USA; 4Nova Southeastern University Fort Lauderdale, Florida, USA
*Correspondence to: Gustavo Ferrer, Aventura Pulmonary Institute, Miami, Florida, USA, Tel: +1954482-474; E-mail: gferrer@pulmonary-institute.com
Received: January 08, 2021; Accepted: January 23, 2021; Published: January 30, 2021
Citation: Torres J, Go CC, Chohan F, Genesis Camacho L2, Sanchez-Gonzalez MA, Ferrer G (2021) Chlorpheniramine Maleate Nasal Spray In COVID-19
Patients: Case Series. J Clin Exp Pharmacol. 10:275. doi: 10.35248/2161-1459.21.10.275
Copyright: ©2021 Torres J, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which
permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
INTRODUCTION
The outbreak of severe acute respiratory syndrome coronavirus 2
(SARS-CoV-2) or coronavirus disease 2019 (COVID-19) led the
World Health Organization to recognize it as a global pandemic in
March 2020 [1].
There are no effective chemo-prophylactic drugs against SARS-
CoV-2 so the main intervention strategy is the control of
transmission. Scientists had to find alternative treatments, with
clinical trials focused on investigating potential therapeutic agents
and repurposing existing treatments.
Nasopharynx has been recognized as the port of entry of SARS-
CoV-2 and has a high viral shedding from the nasal cavity before
and after onset. [2] Nasal secretions are swept by rapid nasociliary
clearance into the oropharynx and aspirated into the lower
respiratory tract [3].
On the basis of a previously published case report, this study
is focused on understanding the potential effectiveness of
chlorpheniramine maleate (CPM) in suppressing the replication of
SARS-CoV-2 in the nose [4].
In a study conducted in vitro and in animal models by Xu et
al, carbinoxamine maleate (CAM) and S-(+)-chlorpheniramine
maleate (SCM) showed potent antiviral activity against influenza A
strains and one influenza B strain and protection from potentially
lethal avian H7N9 influenza virus. By penetrating the blood-brain
barrier, they inhibit the influenza virus by targeting the early stage
of virus life cycle, and its entry into the host cells. Additionally, they
can be used prophylactically in healthy individuals for prevention
of influenza virus infection [5].
We aim to utilize existing medications, particularly CPM nasal
spray, for reducing the clinical course of the disease and decrease

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2J Clin Exp Pharmacol, Vol.10 Iss. 2 No: 275
but with mild presentation of nasal symptoms and persistent eye
pain. On day 6, she reported mild eye pain. On day 7, her sense of
smell completely recovered. She was retested on day 7 and tested
negative. She returned to baseline health on day 14.
Case 4
A young adult white female, with history of chronic rhinitis treated
with desloratadine. She tested positive for COVID-19 on October
2020. She is a non-smoker, with no surgical history. She reported
fatigue, restless, runny, itchy and stuffy nose, anosmia and eye pain,
fatigue, shortness of breath with minimum physical activity, eye
pain, runny nose, anosmia, ageusia and diarrhea two days prior.
A consultation was followed by a COVID-19 RT-PCR test which
was positive. She was enrolled in this case series and was given the
experimental treatment. On day 1, she complained of a stuffy nose,
anosmia, ageusia, tiredness, cough, and congestion. She reported
mild symptoms on SAS, rated generalized pain as nine on the VAS
and the NRS. She had diarrhea on day 3 and 4. Improvement of
symptoms was noted on day 7 and a repeat COVID-19 RT-PCR via
nasopharyngeal swab was done with negative results. She reported
return to baseline health by day 14.
DISCUSSION AND CONCLUSION
The above-mentioned cases are showing the potential efficacy of
utilizing CPM containing nasal spray as a possible adjunct treatment
against COVID-19 and augment the time to negativization on
nasal RT-PCR. Although this does not guarantee definite proof
of efficacy, this case series provides a framework for initiating a
broader scope randomized placebo-controlled clinical trial in the
potential efficacy of chlorpheniramine nasal spray in COVID-19
patients.
Patients in this study reported several risk factors that could
potentially increase morbidity and mortality in COVID-19
infected individuals. Patient 1 was an elderly, with hypertension
and asthma, patient 2, 3 and 4 had chronic rhinitis and sinusitis.
These patients had more than average risk of morbidity and
mortality of COVID-19. [6] All patients had a benign course of
disease and all showed improvement of symptoms with the use of
chlorpheniramine.
Patients were asked to spray two puffs of CPM nasal spray per
nostrils two times per day for seven days. A study conducted on
SARS-cov-2 stock to highlight the virucidal potential of CPM
showed a reduction of 99.7% in viral load in Vero 76 infected
cells [7].
Mostafa et al in a study on FDA approved drugs that have antiviral
activity against SARS-CoV-2 concluded that besides antimicrobial
drugs like Azithromycin, Niclosamide, and Nitazoxanide, several
antihistamines and anti-inflammatory drugs could reduce SARS-
CoV-2 replication. CPM, a competitive histamine H1 receptor
antagonist, exhibited strong virucidal activity against a variety of
influenza viruses [8].
In addition, CPM is generally safe and effective for use with the
main side effect being drowsiness. A study also reviewed the
systemic bioavailability and overall safety of a nasal spray solution
that delivers doses of 1.12 and 2.24 mg CPM intranasally (0.4%
nasal spray) and has found no adverse events [9].
Lastly, the improvement of symptoms and time to negative PCR test
are important to highlight. A study conducted by Vaira, L.A. found
the time to negativization.
This case series will show how four COVID-19 positive patients
enrolled in a study utilizing CPM nasal spray showed positive
outcomes. All patients have expressed written informed consents.
CASE PRESENTATION
Case 1
An elderly white female, with hypertension with unknown
treatment and asthma treated with desloratadine and albuterol,
tested positive for COVID-19 in September 202. The patient is
a non-smoker, no past surgical history. After testing positive with
COVID-10, she was enrolled in this case series and was given the
experimental treatment. She was instructed to spray two puffs
of CPM nasal spray per nostrils twice a day for seven days. She
continued to use albuterol as needed, and supportive treatment.
She was followed for seven days and was assessed for symptoms.
On day 1, she complained of waking up at night due to the cough,
fever and diarrhea, runny, itchy and stuffy nose, sandy sensation
in her eyes, chest pain, anosmia, ageusia, fatigue, cough. She had
mild symptoms most of the time on Symptoms Assessment Score
(SAS). She rated generalized pain as nine on the Visual Analogue
Score (VAS) and the Numerical Rating Scale (NRS). On day 2,
oxygenation was 91%. On day 4, she noted improvement in her
runny, itchy and stuffy nose. On day 6, VAS was reported as three.
She also had mild to nonexistent congestion. Although mild
anosmia was still present, it was markedly improved compared to
day 1. She remained afebrile after the fourth day of the trial. She
was tested via nasopharyngeal swab RT-PCR and tested negative
on day 7. A follow-up was done on day 14 and reported return to
baseline health.
Case 2
A young adult white woman with chronic rhinitis and sinusitis
treated with cetirizine, tested positive for COVID-19 in September
2020. She is a non-smoker with no past surgical history. Three
days prior, she started experiencing runny and stuffy nose,
itchy and painful eyes, anosmia, chest pain, fatigue and fever at
102.2 Fahrenheit (F). She also reported difficulty in sleep due to
nasal symptoms and has been using albuterol as needed. Upon
consultation, she was tested for COVID-19 RT-PCR via the
nasopharyngeal swab. Following the positive test, she was enrolled
in the case series experimental group. On day 1, she complained
of stuffy nose, sneezing, congestion, sandy and watery eyes, fever
102.2ºF, anosmia, and eye pain. she reported fever 100.4º (F)
and mid-effort shortness of breath that was worse on day 3 when
saturation was 92%. On Day 4, she was afebrile and was able to
smell strong substances. On day 7, she reported all the symptoms
were mild or non-existent. Repeat nasal swab RT-PCR was negative.
She returned to baseline health on Day 14.
Case 3
An elderly Hispanic female, with history of chronic rhinitis and
allergies treated with cetirizine, tested positive for COVID-19
in October 2020. She is a non-smoker with no past surgical
history reported. She sought consult on day 3 and was tested
for COVID-19 via nasal swab RT-PCR with positive results. On
day 1, she had runny and stuffy nose, anosmia, tiredness, itchy
and painful eyes and mild cough. Normal oxygen saturation was
detected. On day 3, she noticed an improvement of symptoms

Ferrer G, et al.
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3J Clin Exp Pharmacol, Vol.10 Iss. 2 No: 275
that olfactory and gustatory dysfunctions are common symptoms
in COVID-19 patients. [9] Furthermore, Al-Ani RM et al. also
highlighted that patients who have nasal and paranasal problems
have longer time in recovery from the smell because of interference
with air current from reaching the olfactory epithelium to the roof
of the nose. [10] Spethet. Al also stated that patients with allergic
rhinitis, chronic rhinosinusitis, and asthma, have increased severity
in symptoms. [11] In our study, resolution of symptoms was notable
as early as Day 4 with no progression to severity. Furthermore,
when patients were tested via nasal RT-PCR on Day 7, all of them
tested negative, a 50 % reduction to negativization compared to
the average 14-day course of the disease [12].
In summary, the cases reported in this case series, who have minimal
to moderate morbidity and mortality risk from COVID-19 showed
significant improvement in symptoms and a 50% reduction in
the clinical course with the use of CPM nasal spray. This could
potentially pave the way in improving clinical outcome and reduce
clinical burden in areas heavily affected with COVID-19. We
recommend a larger randomized, placebo-controlled clinical trials
which could further shed light on this potential treatment.
COMPETING INTERESTS
The authors declared that they do not have any conflict of interest.
FUNDING
Not applicable
AUTHORS’ CONTRIBUTION
T.J, G.F. are the one who conceptualized and gathered the data.
C.C.G, F.C, G.C.L and M.S.G collated and analyzed the data
for this case series. All authors have equal contribution with this
paper. All authors agreed to the final manuscript and submission
of this case report.
ACKNOWLEDGMENT
None.
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