Epidemiology International Journal

ISSN: 2639-2038

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Repurposing Drugs for Covid-19 by a Developing Country
Valerio Pascua F1, Baires F2, Diaz O3, Sierra M4, Palou E5, Alvarado T6,
Hernández CI7, Lewis AS8, Durón M9, Valenzuela HD10, Flores A10, Alvarenga
LF11, Diaz T12, Chajtur DG13, Benítez LG14, Pineda E15, Vargas M16, Caraccioli
GG16, Garay J16, Godoy J16, Matamoros D16, Larios J17, Lara R15, Deras P18,
Leon V15, Videa EO19, Stevens ML20, Eberhard D20, Singh J21, Sekhon AK22*
and Sierra Hoffman M23

Research Article
Volume 6 Issue 2
Received Date: April 26, 2022

Published Date: May 20, 2022
DOI: 10.23880/eij-16000234

Department of Critical Care, Hospital CEMESA, Honduras
Universidad Nacional Autónoma de Honduras, Honduras
3
Department of Critical Care Hospital Regional del Norte Instituto Hondureño de Seguridad Social, Honduras
4
Universidad Tecnologica Centroamericana, Honduras
5Internal Medicine Department, Universidad Nacional Autónoma de Honduras, Honduras
6Internal Medicien Depatment, Universidad Nacional Autónoma de Honduras, Honduras
7
HEME Clinic, Honduras
8
Pharmacy Department, El Campo Memorial Hospital, United States of America
9
Laboratorios Durón, Honduras
10Emergency Department, Hospital Roberto Suazo Córdova, Honduras
11
Universidad Nacional Autónoma de Honduras, Honduras
12
La Paz Regional Health Department, Honduras
13
Universidad Católica de Honduras, Honduras
14
Universidad Nacional Autónoma de Honduras, Honduras
15
Emergency Department, Hospital CEMESA, Honduras
16
Emergency Department, Hospital Leonardo Martinez, Honduras
17
Emergency Department, Hospital Santa Bárbara Integrado, Honduras
18
Centro de Investigation de DEMEDICA, Honduras
19
Clinical de Attention Medical Integral CAMI, Honduras
20
Research Department, Texas A&M College of Medicine, United States of America
21
Cardiovascular Medicine, University of California, United States of America
22
Sleep Medicine, United States of America
23
Research and Infectious Disease Department, Texas A&M College of Medicine, United States of America
12*Corresponding author: Anupamjeet Kaur Sekhon, Sleep Medicine, Kaiser Permanente, 9961 Sierra Avenue, #7, Fontana, CA,
USA, Tel: 832-983-1131; Email: anupamsekhon@yahoo.com

Abstract
Background: Early treatment of COVID-19 disease with repurposed drugs has been controversial. Most guidelines in thedeveloped world recommend monoclonal antibodies or Ritonavir/Nirmatrelvir therapies for patients at risk of clinicaldeterioration, but accessibility to these in developing countries is a big challenge. The primary purpose of this study is to
Repurposing Drugs for Covid-19 by a Developing Country

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review the impact of early treatment of COVID-19 with repurposed drugs on hospitalizations, oxygen requirement, andmortality in a limited resource setting.
Methods: This observational cohort study was Institutional Review Board (IRB) approved. Data was collected from medical
records from November 2020 until October 2021. A multiphasic multidrug protocol of repurposed drugs was used as
COVID-19 outpatient therapy in Honduras. Patients within 7 days of disease onset and mild symptoms received Ivermectin,
Aspirin, Colchicine, Fluvoxamine, and Famotidine. On day 7, patients received Prednisolone and Apixaban if CT-chest showedpulmonary infiltrates and inflammatory markers were elevated. Patients were followed every 24-72 hours, and pulse doses ofmethylprednisolone were given for clinical deterioration.
Results: Of 415 patients, 208 were men (50.1%), and 207 women (49.9%). Average age of the cohort was 47.4 years, and 94
patients were above age 60. 414 patients survived (99.7% survival). Twenty-six patients required hospitalization (6.5%, 95%
CI: 4.5% - 9.3%). All the hospitalized patients were unvaccinated. Other significant risk factors for hospitalization included
age ≥ 60 years, hypertension, diabetes, late Fluvoxamine start (>4 days), and steroid use prior to presentation. Only thirteen
patients required oxygen (3.1% 95% CI: 1.8% - 5.3%). Significant risk factors for oxygen requirement included age ≥ 60 years,
male gender, and prior steroid usage. All the thirteen patients that required oxygenation were unvaccinated. The average
length of hospital stay was 5.9 days.
Conclusion: Early outpatient treatment with affordable, easily accessible repurposed drugs focusing on the pathophysiology
of COVID-19 disease progression shows promising results vs. the standard of care by WHO, with only one death, 3.1% requiring
oxygen, 6.5% hospitalizations, and an average hospital stay of 5.9 days in a developing country.

Keywords: COVID-19; Repurposed Drugs; Fluvoxamine; Developing Country; Early Outpatient Treatment; Prednisolone;

Colchicine

Abbreviations: CCDC: Chinese Center for Disease Control

and Prevention; WHO: World Health Organization; SARSCOV-2: Severe Acute Respiratory Syndrome Coronavirus
2; COVID-19: Coronavirus Disease 2019; IRB: Institutional
Review Board; RT-PCR: Reverse Transcription Polymerase
Chain Reaction; CT: Chest Computed Tomography; CBC:
Complete Blood Counts; CRP: C-Reactive Protein; AST:
Aspartate Transaminase; ALT: Alanine Transaminase; LDH:
D-Dimer and lactate dehydrogenase; MERS-CoV: Middle
East Respiratory Syndrome Coronavirus; ACE: AngiotensinConverting Enzyme 2; SSRI: Selective Serotonin Reuptake
Inhibitor.

Introduction

In December 2019, even before mainstream media’s
first reports of the events to come, Sharon Sanders, an
online blogger from Florida, U.S.A. documented an unusual
pattern of occurrences from clinic reports in Wuhan, China[1]. An infectious outbreak involving an unknown cause wasoccurring among patients presenting with three common
factors: respiratory symptoms, hypoxia, and bilateral
opacities on imaging, among others [2]. Slowly, the local andinternational mainstream media began raising suspicion ofan epidemic caused by an agent yet to be determined at thattime. Days later, both the Chinese Center for Disease Control
and Prevention (CCDC) and the World Health Organization(WHO) jointly confirmed this suspicion and promised tocontinue informing the world of further developments [3-5].

Shortly after that, the world was introduced to a novel
coronavirus, later identified as Severe Acute Respiratory
Syndrome Coronavirus 2 (SARS-COV-2), the cause ofCoronavirus Disease 2019 (COVID-19), the worst pandemicof this century [6]. Few would have predicted that thispandemic would create multiple and extreme points of view
amongst physicians and scientists worldwide in regards
the approach to combat this new evolving catastrophe.
Unfortunately, this polarized positions still remain a hugearea of debate around the globe.

From the beginning of this ongoing and devastating
disease, there have been significant advancements
in managing hospitalized patients with SARS-CoV-2.
The RECOVERY Trial has conclusively proven thatdexamethasone reduces the mortality of patients requiring
oxygen [7]. Therapeutic anticoagulation also became avital care component for critical hospitalized patientswith SARS-CoV-2 given the now well-known COVID-19associated coagulopathy [8]. Additionally, the combinationof Interleukin-6 (IL-6) inhibitors, such as tocilizumab andsarilumab, with corticosteroids has been shown to further
reduce the mortality rate in COVID-19 in critical patients[9,10]. Unfortunately, advancements in COVID-19 disease
management in the first 12 months were almost exclusive inthe hospitalized patient with SARS-Cov-2 infection.

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Nearing the end of 2021, most academicians andfrontline physicians would agree that the course of the
SARS-CoV-2 infection is anything but predictable. Thus,
implementing a therapeutic approach early in the disease
course becomes logical and essential to reducing COVID-19
related hospitalizations and mortality, making time a criticalfactor for COVID-19 management.

It became evident in the second year of the pandemic
that early outpatient treatment was essential to anticipate
the Covid 19 complications. However, the therapeutic wayof approaching this, became divergent with a clear distinct
between developed and underdeveloped countries. Most
guidelines in the developed world are supporting theuse of monoclonal antibodies or the recently approved
Ritonavir/Nirmatrelvir therapies for patients at risk ofclinical deterioration, but accessibility to these in developing
countries is still a challenge. Although these are outstanding
scientific achievements, the global disparity of vaccine
distribution in underdeveloped region has already proventhat these countries will not be able to prioritize these as
viable therapeutic options. Low-income countries havebeen more proactive by utilizing more easily accessible
medications, subsequently reporting success with early
ambulatory management of SARS-CoV-2 infection [11].
Proponents of this method have predicted that early
outpatient treatment with easily accessible, repurposed
medications is a more practical approach for preventing
COVID-19 related hospitalizations and complications, or atthe very least lessening the course of illness.

Medications that may demonstrate a theoretical impact
on the course of SARS-CoV-2 infection include Ivermectin,
Colchicine, Aspirin, and Fluvoxamine. Ivermectin is a safe
antiparasitic, with a wide spectrum of evidence throughout
the world with very controversial data supporting or against
its use when treating COVID-19 itself [12]. Colchicine
works by acting on the NLRP3 inflammasome, and Aspirin
is a well-known antiplatelet and anti-inflammatory agent[13,14]. Interestingly, there is new evidence that serotonin
acts as an essential molecule in COVID-19 pathology due toits effects on platelet adhesion [15]. The study presented
herein demonstrates the outcomes of a multifaceted protocol
utilizing repurposed, easily accessible medications for the
early management of SARS-CoV-2 infection in the ambulatory
setting of a developing country.

Definitions and Methods

Definitions of COVID 19 Severity
Mild Disease (COVID): Patients presenting with any of
the common signs or symptoms of SARS-CoV-2 infection,
including fever, cough, sore throat, malaise, headache,
myalgias, nausea, vomiting, diarrhea, or loss of taste andsmell, but do not have dyspnea, hypoxia, or abnormal chest
radiography.
Moderate Disease: Patients who show evidence of lower
respiratory disease (e.g., dyspnea) at clinical presentation
and/or abnormal chest radiography and who have pulse
oximetry of ≥ 94% on room air.
Severe Disease: Patients who show evidence of lower
respiratory disease with pulse oximetry of < 94% on room
air, a ratio of arterial partial pressure of oxygen to fraction of
inspired oxygen (PaO2/FiO2) < 300 mmHg, a respiratory rateof >30 breaths per min, and/or abnormal chest radiographydemonstrating > 50% pulmonary infiltrates.
Critical Illness: Individuals presenting with respiratory
failure, septic shock, and/or multiple organ dysfunction.

We conducted an observational cohort study, data wascollected from medical records according to the Institutional
Review Board (IRB) permission, from November 2020
until October 2021. This study was performed in the
COVID-19 outpatient clinic at the Hospital Centro Médico
Sanpedrano (CEMESA) in San Pedro Sula, Cortes, Honduras.
The institutional review board approved the study as aminimal risk for the retrospective character of the study, andinformed consent was not required. All patients fifteen yearsof age or older with mild or moderate signs and symptomsof COVID-19 with a positive SARS-COV-2 antigen or Reverse
Transcription Polymerase Chain Reaction (RT-PCR) were
included in the study. In addition, patients who developed
signs and symptoms of the disease and were in close contact
with one of the patients in the cohort were also treated andincluded in the study. Pregnant women, patients younger
than fifteen years of age, and patients presenting withsevere COVID-19 symptoms were excluded. A multidrug
multifaceted treatment protocol was used according to theclinical presentation and days of symptoms of the disease.

Viral Replication Phase treatment

Patients with less than seven days of disease onset in
the viral replication phase with mild symptoms received
the first phase (viral replication phase) of treatment, which
consisted of Ivermectin 0.4 milligrams per kilogram (mg/kg)
orally daily for five days, Aspirin 100 milligrams (mg) orally
per day for fourteen days if no history of allergy, Colchicine
0.5 mg orally twice per day for fourteen days, Fluvoxamine
50 mg orally twice daily for three days, which, dependingon patient tolerance, was increased to 100 mg orally twice
daily to complete fourteen days, and Famotidine 40 mg orally
twice daily for fourteen days.

Early Pulmonary Inflammatory Phase treatment

Patients were clinically evaluated on the eighth day
following symptom onset or earlier for dyspnea, worsening
cough, or a three percent reduction in oxygen saturation,

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measured by a home pulse oximeter. Chest computed
tomography (CT) or chest radiograph and inflammatory
markers, including complete blood counts (CBC), C-reactive
protein (CRP), aspartate transaminase (AST), alaninetransaminase (ALT), D-Dimer and lactate dehydrogenase(LDH), were obtained.
If the patient had clinical deterioration or had pulmonary
infiltrates present on imaging studies and associatedelevation of inflammatory markers, treatment with oralcorticosteroids in association with oral anticoagulation
was started even if they did not have oxygen desaturationconsidering they were developing an early pulmonary
inflammatory phase. Prednisolone 1 mg/kg orally per day
was used. All patients were reassessed after three days ofusing corticosteroids. If improving, a total five days of same
treatment was completed followed by slow weaning ofsteroids (i.e fifty percent every three days).

If any inflammatory markers increased or clinicaldeterioration was present, which was defined as a progressive
elevation of C-reactive protein, D-Dimer, or LDH, worsening
dyspnea or oxygen saturation of less than 94% after threedays of initiating oral corticosteroids, then intravenous (IV)methylprednisolone 250 mg per day for three days wasadministered, and oral prednisolone was discontinued.
This was followed by a close daily clinical assessment at

the COVID-19 clinic site to address whether the patient
required hospital admission. If the patient’s clinical course
and inflammatory markers improved, prednisolone wastapered down from a dose of 1 mg/kg per day with fifty
percent reduction every three days. Apixaban 5 mg orally
every twelve hours was given to patients who had elevatedinflammatory markers or had worsening signs or symptoms
and radiologic evidence of pulmonary disease progression
by Chest CT or radiography.
If the patient had an oxygen saturation of less than 95%,
then the dose of Ivermectin was escalated from 0.4 mg/kg
to 0.6 mg/kg orally per day for five days. Additionally, thefrequency of Fluvoxamine 100 mg was escalated from every
twelve hours to every eight hours. If patients presented
after day seven of the onset of symptoms and had clinicaland radiologic evidence of pulmonary disease, they weretreated with the viral replication phase medication as well as
prednisolone and oral anticoagulation.

Statistical Analysis

Descriptive analysis was performed to find the averageand median values for quantitative analysis. Univariate
analysis using Chi-square analysis was performed on the
categorical variables to establish the risk association. SPSS
Version 26 was used for statistical analysis (Figure 1).

Figure 1: Descriptive analysis was performed to find the average and median values for quantitative analysis.

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Results

A total of 415 patients participated in the study. 208 weremen (50.1%) and 207 were women (49.9%). The average
age was 47.4 years (46.8 in men and 47.9 in women, p = 0.5).
Only 94 patients (22.6%) were older adults i.e age ≥60 years.
158 (38.1%) were overweight (BMI 25.0 – 29.9 kg/m2), and117 (28.2%) patients were obese (BMI ≥30 kg/m2). Ninetyeight (23.6%) patients had hypertension. Forty-seven(11.3%) were diabetic, and twenty-four (5.8%) patients
had hyperlipidemia. Bronchial asthma and hypothyroidism
were seen in sixteen (3.9%) patients each. Eleven (2.7%) had
psychiatric illnesses. A total of 176 (47.8%) had at least oneof the comorbidities.

Out of 415, only 100 people were adequately vaccinated,
whether they had two doses or a single dose (Johnson andJohnson), and at least 14 days had elapsed since the last
dose. All 415 patients received Fluvoxamine and ivermectin.
Aspirin was given to 379 patients. 375 received Famotidine,and 388 received colchicine. Only 191 were prescribed
Apixaban and 186 received steroids. Only five patientsrequired Tocilizumab (1.2%, 95% CI: 0.5% - 2.8%). Ninetythree patients (22.4%) had received premedication before
presenting to the study clinic. Only eleven patients had priordocumented steroid usage.
Of the 415 patients, 414 survived (99.7% survival).
Only one patient died. She was a 50-year-old unvaccinatedfemale with class I Obesity, who was self-medicating withprednisolone 50 mg/day and Azithromycin 500 mg/day
since day one of symptom onset. She presented on the fifth
day of symptoms. Upon evaluation, she was classified asmoderate disease needing supplemental oxygen and was
hospitalized.

Of 415 patients, twenty-six patients required
hospitalization (6.5%, 95% CI: 4.5% - 9.3%). All of thehospitalized patients were unvaccinated. Other significant
risk factors for hospitalization included age ≥ 60 years (RR =2.6, 95% CI: 1.2-5.4, p = 0.009), hypertension (RR = 2.1, 95%
CI: 1.0-4.5, p = 0.003), Diabetes Mellitus type 2 (RR = 2.9,
95% CI: 1.3-6.8, p = 0.01), late Fluvoxamine start (>4 days)(RR = 2.8, 95% CI: 1.2-6.9, p = 0.007), and steroid use in theearly viral replication phase (RR = 5.1, 95% CI: 1.9-13.5, p =0.01).
The average length of hospital stay (LOS) was 5.9 days
(P25 4.0, P50 5.5, P75 7.7). Only thirteen patients required
oxygen (3.1% 95% CI: 1.8% - 5.3%). Significant risk factors
for oxygen requirement included age ≥ 60 years (RR = 3.5,
95% CI: 1.2-10.1, p = 0.01), male gender (RR = 3.2, 95% CI:
0.9-11.4, p = 0.03), and use of steroids in the early replication

phase (RR = 7.3, 95% CI: 1.9-28.2, p = 0.02). All of the thirteen
patients that required oxygenation were unvaccinated.

Discussion

History will remember the COVID-19 pandemic for
multiple reasons, but the most striking will likely be theconflict and diversity of opinions in all areas of modern
society. Among scientists, academicians, and frontline
healthcare providers, there has been an unrelenting debate
revolving around whether to wait for the evidence provided
by randomized controlled trials before proceeding with atherapeutic strategy or utilizing the best available evidence
at present to develop a targeted therapeutic approach. Thiswas exemplified by the early debate over the responsivenessof SARS-CoV-2 to corticosteroids, as six months wentby before a randomized controlled trial answered thiscritical question. However, many frontline healthcare
providers were already implementing corticosteroids
into their therapeutic approach for SARS-CoV-2 infection
despite enduring criticism. Underdeveloped countries, like
Honduras, did not have the luxury of awaiting the results ofrandomized controlled studies because of the potential forcollapse of their healthcare system without developing atreatment strategy. In contrast to New York City, which has
a population of 8.9 million, 1060 critical care physicians,
and 1644 intensive care unit (ICU) beds, Honduras has
only nineteen critical care physicians and 125 ICU beds fora population of 9.9 million [16,17]. This has led to the needto develop a multifaceted therapeutic approach utilizing
repurposed medications that are more readily accessible tounderdeveloped countries like Honduras.
Early in the COVID-19 pandemic, there was considerable
controversy and debate at all levels of government, and the
medical community, regarding how to mitigate the impactof this rapidly progressing coronavirus infection. Logically,
medical authorities looked to past experiences with theepidemics caused by Severe Acute Respiratory SyndromeCoronavirus 1 (SARS-CoV-1) and Middle East Respiratory
Syndrome Coronavirus (MERS-CoV). These epidemics wereapproached with large-scale quarantines of infected patientsand close contacts alike in all settings, including healthcare.
Because this seemed to be an effective strategy, this approach
was utilized in the initial phases of SARS-CoV-2 infection,with isolation of ill patients followed by contact tracing,progressing to closures, even with fervent debate, of large
sectors of the populace. However, it has now become clearthat this was not an effective means of control, given a better
understanding of the pathogenesis of SARS-CoV-2 comparedto SARS-CoV-1 and MERS-CoV. When discussing SARS-CoV-1,
MERS-CoV, and SARS-CoV-2, one cannot assume that theycan each be managed similarly, simply because they are

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6categorized as coronaviruses. With SARS-CoV-1 and MERSCoV, infected patients develop symptoms before the peak ofviral load.

Therefore, there are no asymptomatic carriers, which
is why patient and contact isolation is effective. There was
no indication for the development of an early outpatient
treatment approach to slow transmission because
symptomatic patients were placed in isolation early in the
disease process. This is in direct contrast to SARS-CoV-2. Intheir study, Benefield A, et al. [18] clearly demonstrated that
the SARS-CoV-2 viral load peaks before symptom onset andremains elevated for approximately twenty days [18]. This
allows for asymptomatic persons to propagate SARS-CoV-2
early on, before progression to more severe, complicatedillness, even as viral load declines. Thus, along with aggressive
testing, an early aggressive outpatient therapeutic approach
becomes of the utmost importance to mitigating the impactof SARS-CoV-2.
Since January 2020, there has been a plethora of
emerging evidence by scientists worldwide regarding thepathophysiology of SARS-CoV-2 infection. A consensus
exists that there is an initial viral stage whereby symptoms
may vary from a minimal to a mild undifferentiated viral
syndrome in some, which may progress in others to apulmonary phase with hypoxia and associated organizing
pneumonia. COVID-19 is multi-systemic, most of the time,and follows the pattern of Angiotensin-Converting Enzyme
2 (ACE) receptors in various body organ systems, including
the cardiovascular, renal, and gastrointestinal systems[19]. There is also a significant body of evidence that thetiming of interferon release plays a crucial role in the severe
inflammatory phase. The dysfunction caused by SARSCoV-2 promotes a vigorous activation of the nucleotidebinding oligomerization domain, Leucine-rich repeat andPyrin domain-containing protein 3 (NLRP3) inflammasome,
caspase, interleukin-1 (IL-1) and interleukin-6 (IL-6)
pathways [20]. Another point of convergence among experts
is the fact that COVID-19 causes endothelitis. This gives riseto an unregulated prothrombotic state that ultimately leads
to endothelial cell dysfunction, dysregulation of angiotensin
II, and a vicious pro-inflammatory state leading to unabatedimmune thrombosis. In addition, immobilization, hypoxia
and disseminated intravascular coagulation can increase theprothrombotic state of these patients. It has been speculated
that microvascular thrombosis may play a critical role inhypoxemia and multiorgan failure [21,22].
Another important pathway in COVID-19 pathogenesis
is excessive platelet activation. An excess of free plasma
serotonin derived from platelets leads to excessive plateletfibrin aggregation and the formation of microthrombi

Epidemiology International Journal[23]. Fluvoxamine, a medication classified as a selective
serotonin reuptake inhibitor (SSRI), has been shown toplay a significant role in modulating this pathway throughagonistic activity on the sigma 1 receptor. This, in turn,
mediates inflammation, potentiates an antiplatelet effect,and reduces mast cell degranulation and cytokine storm,
among other actions specific to the pathophysiology of SARSCoV-2 infection. Further, Aspirin, a well-known antiplatelet
agent, also plays a role in limiting SARS-CoV-2 pathogenesis
through inhibition of the Cyclooxygenase-1 (COX-1)
pathway, leading to a decrease in Thromboxane-A2 (TX-A2),
subsequently decreasing platelet aggregation [24]. Evidence
from autopsies and bronchoscopy samples shows a clear
macrophage activation syndrome that perpetuates all theabove pathways. With all this knowledge acquired since thefirst days of the COVID-19 pandemic, it would be logical toanticipate the activation of all these pathologic pathways andattempt to effectively intervene with a targeted therapeutic
approach early in the disease course rather than later.

Colchicine is an anti-inflammatory medication thathas been available for centuries and the mechanism ofaction interferes with microtubules auto formation within
the cytoplasm of cells. It is thought to interfere with these
inflammatory pathways through microtubule inhibition andinhibiting the neutrophil recruitment and adhesion in thesite of inflammation. It interferes with the proinflammatory
protein complex, the nod-like receptor protein 3 (NLRP3)
inflammasome, which produces inflammatory pathways
and enzymes such as caspase-1 which are responsible foractivating interleukin 1Beta, that induce macrophages torelease large quantities of additional pro-inflammatory
cytokines, one of them being IL-6, a cytokine that induces
C-reactive protein that has been deeply associated as animportant proinflammatory component of the cytokine
storm that is characteristic in COVID-19 patients. The
concentration of colchicine in inflammatory cells such as
leukocytes is very high, its concentrated about 16 times morethan in serum, hence the importance of anti-inflammatory
properties in the entire COVID-19 pathophysiology [25].
New released evidence states that these pathways need tobe blocked very early on the disease course [26]. A recent
review by Kory P, et al. [27] shows that Ivermectin has
antiviral properties against an increasing number of RNA
viruses including SARS-COV2. Its mechanism of action in the
disease to name a few, is due to the high binding activity ofthe medication to the spike protein on SARS-COV2, whichmakes it harder for the virus to bind to the ACE2 receptors
located all around the body and therefore a decrease on viralcellular entry. It is also noticeable that Ivermectin inhibits
viral replication by binding and blocking the RNA-dependent
RNA polymerase. For a more detailed review we invite thereader to see the excellent manuscript of Kory P, et al. [27]Sekhon AK, et al. Repurposing Drugs for Covid-19 by a Developing Country. Epidemol Int J
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A recent metanalysis by Bryant et al showed that using
Ivermectin early in the clinical course may reduce numbers
progressing to severe disease having a significant impact on
the SARS-CoV2 pandemic [28].

A multi-mechanistic and stepwise approach in theoutpatient setting, which is initiated early in the disease
course and has been geared toward these pathogenic
pathways, is not only logical but scientifically founded.
Recently, Valerio Pascua FV et al. [29] proposed a multimechanistic approach for the management of hospitalized
patients with COVID-19, which has since been adopted
by many countries with very minimal differences in
implementation. This treatment approach consists of highdose corticosteroids, preferentially methylprednisolone,
tocilizumab as a rescue agent, high-intensity, or therapeutic
anticoagulation, Ivermectin, high-flow oxygen systems, andself-proning, if possible, to improve oxygenation [29]. An
early outpatient treatment based on clear pathophysiologic
states of the disease is an extension of these principles.
The basis for this clinical study is to apply these principles
and investigate their impact on the course of COVID-19 in
an outpatient clinic in Honduras, utilizing readily available
repurposed medications.

Limitations

Vaccination has been the first globally acceptedpharmaceutical contingency measure for the COVID-19
pandemic and it has become within reach for underdeveloped
countries, including Honduras. The massive vaccination
campaign programs promoted by the WHO may impact theseverity of some cases in this research. Some patients were
fully vaccinated, while others had only one dose, affecting thestudy outcome. The lack of ethnic diversity, the absence of acontrol group, and the fact that this study was conducted in asingle hospital during the COVID-19 pandemic are all limiting
factors with respect to the study outcomes. However, the lackof significant research performed on this topic makes thisstudy a strong starting point for further investigations. Also,
it has been so deeply rooted in the population to stay at homeand not search for an early treatment that some cases thatwere not in an early stage were included, limiting the study
outcomes. However, it was a small percentage of the whole
population in the study. Despite all these limitations there’s
a counterbalance when applying this protocol accessibility
in an underdeveloped nation like the one doing the study.
The pandemic has proven to the world that there have been
disparities in the distribution of novel therapies directed to
SarsCov2, in the vaccines and monoclonal antibodies. Whenthe manuscript was being written two new antivirals werereleased: molnupiravir and ritonavir/nirmatrelvir in the
United States for early outpatient treatment [30]. Given ourprior experiences in the distribution of new therapies, itwould be naïve to believe that Honduras will be a priority
to these two big pharmaceutical companies producing theseproducts.

Confounding Factors

Individual Socioeconomic Status
This study was conducted at a private hospital. Therefore,
due to specific social considerations, some patients wereadmitted despite not meeting the criteria. As a result of this,the rate of hospitalizations increased by a small percentage.
We don’t think that this will play a role in mortality rate andlength of hospital stay since patients were treated under
the same circumstances and same criteria were used per
our protocol in the entire cohort, not being influenced bytheir socioeconomic status. All patients that were admitted
and treated in our study were able to afford a private healthsetting which gave us the opportunity to use the same
resources in all our patients.

Number of Comorbidities

Another confounding factor is the comorbidities in thepatient group, among these comorbidities were: obesity,
hypertension, diabetes, bronchial asthma, hypothyroidism,
hyperlipidemia, and psychiatric illnesses which may havecontributed to the increase of length of stay and mortality
in some patients. Also is very important to clarify that the
comorbidities needed to be seen in every patient individually,
because the outcomes of every patient could also be
determined if those comorbidities were under control or not.

Hospital Care Quality

The hospital care quality was the same in the entire
patients under the study, since they were treated just in one
hospital which was private, with the same conditions for allof them. We will consider that this confounding will play arole on our results if we were comparing patients between
a private and public hospital, since the care quality cansometimes be diminished in a public hospital setting because
there are less resources available for healthcare workers andeven for the patients itself. Our entire cohort were under thesame circumstances regarding hospital care quality which
would not affect the mortality and hospitalizations rate, nor
the length of hospital stay.

Social and Economic Impact

When repurposed drugs for the treatment of COVID-19
are referenced herein, it is innovative and beneficial forpatients overall and essential for managing the disease
within developing countries, such as Honduras. In addition,

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8Epidemiology International Journal

by using a redirected drug, Fluvoxamine, this study presents
a proposal for a low-cost option that is within financial reachfor a large portion of a developing society, within which many
live in extreme poverty. Therefore, the evidence presented inthis study will have both an economic and social impact on
the management of ambulatory patients with COVID-19.

7.

The study provided an undeniable insight into the conceptof early outpatient treatment in COVID-19 disease in a cohortof unvaccinated, partially, and fully vaccinated patients
within a country with such limited resources as Honduras.
This regimen focused on an early multi-mechanism approach
to better understand the pathophysiology and phases of thisviral infection. Emphasizing the use of affordable, easily
accessible repurposed drugs for COVID-19 decreased criticalepidemiological markers like hospitalization, oxygen need,mean hospital stay, and death, which are fundamentally
crucial in the COVID-19 puzzle. Despite the study’s limitations,
it proves that the intention of treatment is lifesaving. Thesefindings merit further investigation in a comparative, multiinstitutional study to reinforce/replicate its results.

9.

8.

Conclusion

Acknowledgments

We wish to thank Mrs. Waleska Solis-Hoffman, Mr.
Edgardo Melgar and Mr. Daniel Antonio Fortin and Ing.
Robert Maas Chavez for their altruism during the pandemicin Honduras, the success and outcome of this study required
their voluntarily constant dedication and hard work.

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