INTERNATIONAL JOURNAL OF MULTIDISCIPLINARY RESEARCH AND ANALYSIS

ISSN(print): 2643-9840, ISSN(online): 2643-9875

Volume 04 Issue 08 August 2021
DOI: 10.47191/ijmra/v4-i8-02, Impact Factor: 6.072
Page No.- 1062-1071

A Retrospective Observational Study of Chlorine Dioxide

Effectiveness to Covid19-like Symptoms Prophylaxis in Relatives
Living with COVID19 Patients
Manuel Aparicio-Alonso1, Carlos A. Domínguez-Sánchez2, Marina Banuet-Martínez3
1,2,3
Centro Médico Jurica, Querétaro, México

ABSTRACT: To date, there is no effective prophylactic agent to prevent COVID-19. However, the development of symptoms similar
to covid19 could be prevented with an aqueous solution of chlorine dioxide (ClO2). This retrospective study evaluated the
effectiveness of an aqueous solution of ClO2 (CDS) as a prophylactic agent in 1,163 family members living with positive/suspected
COVID19 patients. Prophylactic treatment consisted of 0.0003% chlorine dioxide solution (CDS) orally for at least fourteen days.
Family members in whom no reports of the development of covid19-like symptoms were found in the medical history were
considered successful cases. The efficacy of CDS in preventing covid19-like symptoms was 90.4% (1,051 of 1,163 relatives did not
report any symptoms). The comorbidities, sex and severity of the illness of the sick patient did not contribute to the development
of symptoms similar to covid19 (P = 0.092, P = 0.351 and P = 0.574, respectively). However, older relatives were more likely to
develop covid19-like symptoms (ORa = 4.22, P = 0.002). There was no evidence of alterations in blood parameters or in the QTc
interval in relatives who consumed CDS. The recent findings regarding Chlorine Dioxide justify designing clinical trials to assess its
efficacy for preventing SARS-CoV-2 infection.

KEYWORDS: Chlorine Dioxide, prophylaxis, COVID19, Pandemic

I. INTRODUCTION
The coronavirus disease of 2019 (COVID19), caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is a
pathology transmitted directly or indirectly through aerosols and whose significant symptoms include mild to severe pneumonia
(da Rosa Mesquita et al. 2021; Yu et al. 2020). It has been shown that a high percentage of infections (mean 16.6%) occurs mainly
in family nuclei (Liu et al. 2020; Madewell et al. 2020) mostly because houses are closed environments that make it hard to
maintain social distance, there is a reduced use of personal protective equipment, and it is not possible to completely isolate a
sick family member (Madewell et al. 2020). Attributable to the global problems and the rapid spread of this disease, there are
research groups dedicated to testing drugs that contribute to prevent and improve the prognosis of the disease (e.g. Ivermectin,
Bryant et al., 2021; Vitamin D, Martineau & Forouhi, 2020; and Hydroxychloroquine, Rajasingham et al., 2021). However, the
global crisis continues, and it is necessary to test other substances that could effectively prevent the spread of SARS-CoV-2 and
develop COVID19.
Aqueous solutions of Chlorine Dioxide (ClO2) have antimicrobial potential due to the denaturation of the viral capsids’
specific proteins (Kály-Kullai et al. 2020). For example, ClO2 was shown to have the ability to inactivate Influenza Virus caused by
oxidating tryptophan 153 residue in the receptor-binding site (Ogata 2012). Considering SARS-CoV-2 spike protein composition
(12 tryptophan, 54 tyrosine, and 40 cysteine residues), it can be assumed that ClO 2 also has the potential to inactivate this virus
(Insignares-Carrione, Bolano Gómez, and Ludwig Kalcker 2020). There are a lot of unique properties that make ClO2 an ideal, non-
specific antimicrobial: It has been demonstrated that ClO2 is a size-selective antimicrobial agent that can neutralize
microorganisms rapidly (Noszticzius et al. 2013). Furthermore, it can be used in animals and humans without adverse effects in
proper concentrations because of its incapability to penetrate the tissues (Kály-Kullai et al. 2020; Noszticzius et al. 2013).
The current COVID-19 situation has shown the importance of having antiviral compounds available to act quickly.
Nowadays, there is no drug (prophylactic or therapeutic) approved by the Food and Drug Administration (FDA) against COVID-19,
and that had demonstrated high effectiveness (Gupta, Sahoo, and Singh 2020; Meo, Klonoff, and Akram 2020; Shamshina and

IJMRA, Volume 4 Issue 8 August 2021 www.ijmra.in Page 1062

A Retrospective Observational Study of Chlorine Dioxide Effectiveness to Covid19-like Symptoms Prophylaxis in
Relatives Living with COVID19 Patients
Rogers 2020). For this reason, it is essential to investigate new compounds that can help to reduce the impact of the current
pandemic. This study analyzed clinical information from healthy people who consumed an aqueous solution of ClO 2 as a
prophylactic agent when living with positive/suspected COVID19 patients. We evaluated the effectiveness of ClO 2 in preventing
the development of covid19-like symptoms.

II. METHODS
Baseline and clinical information
This retrospective study was carried out using clinical records of 1,163 healthy subjects (without covid19-like symptoms),
from now on referred to as relatives, who live with positive/suspected COVID19 patients (sick patients) in different cities (mainly
Queretaro) in Mexico; from May 30, 2020, to January 15, 2021. The inclusion criteria were as follows: 1) relatives living in the same
house with a sick patient diagnosed by Real-Time Reverse Transcriptase (RT)-PCR Viral Nucleic Acid Test to SARS-CoV-2(Park et al.
2020) and complementary tests like antigen detection test (Zainol Rashid et al. 2020), serology test for specific immunoglobulin
M (IgM) and immunoglobulin G (IgG) antibodies against SARS-CoV-2 (Xiang et al. 2020), computed tomography (Long et al. 2020),
chest radiography (Smith et al. 2020), or clinical manifestations such as fever, cough, dyspnea, malaise, and fatigue (da Rosa
Mesquita et al. 2021); 2) relatives whose voluntarily requested prophylactic management at home and that, after were informed
of the benefits and possible secondary effects of ClO2 consumption, signed informed consent. Baseline (sex, age, and
comorbidities) and clinical (date of prophylactic management request, partial oxygen saturation [SpO 2] and covid19-like
symptoms) information were collected from medical records. Moreover, the sick patient’s disease severity status (mild, moderate
or severe) was included.

Prophylactic Management: Chlorine Dioxide Solution

The production of ClO2 is not governed by any regulations in Mexico yet. Chemist-pharmacists or professional Chemical-
Engineers made the ClO2 by oxidation of sodium chlorite (NaClO2) using hydrochloric acid (HCl) as an activator, ensuring the
product’s concentration and safety. Being a chemical compound, exposure to light and temperature above 11 °C changes its
composition (Kály-Kullai et al. 2020). Relatives were informed to keep the CDS in the refrigerator (between 4-10 °C) and stored in
closed amber jars. Relatives began the oral prophylactic management in daily doses (0.3 mg/kg) of 0.0003% Chlorine Dioxide
aqueous Solution (CDS, 10 ml of ClO2 at 3000 ppm in 1000 ml of water), divided into ten intakes of 100 ml/hour. This dose had
been reported as adequate for human use (Lubbers and Bianchine 1984; Lubbers, Chauhan, and Bianchine 1981; Smith and
Willhite 1990); additionally, is ten times below the “No Observed Adverse Effect Level” (NOAEL), almost 20 times below the
“Lowest Observed Adverse Effect Level” (LOAEL), and nearly 300 times below the lethal dose 50 (LD50; Insignares-Carrione et al.,
2020; U.S. Environmental Protection Agency, 2000). Due to Mexico’s regulations during the pandemic, relatives stayed at home
for at least 14 days or offset symptoms of the sick patient. Medical records show a daily follow-up for a minimum of 20 days of
each relative.

Covid19-like symptoms Incidence and tracking overall physical well-being

Reported symptoms by relatives were used to calculated de incidence of covid19-like symptoms during the clinical follow-
up. Relatives who reported any symptom were considered as a non-successful case of prophylactic management. To evaluate
general physical well-being during prophylactic administration, 27 relatives that had a complete blood count (red blood cells,
white blood cells, and platelets) and a metabolic panel test (blood urea nitrogen, creatinine, alkaline phosphatase, alanine
aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, glucose, total protein, albumin, sodium, potassium,
chloride, bilirubin, cholesterol, and triglycerides) before (at least three months) and after CDS consumption, were included. Typical
values from the general Mexican adult population were used as reference values (Díaz Piedra et al. 2012; Olay Fuentes et al. 2013).
Additionally, data of 50 electrocardiograms (ECG) performed to the relatives after CDS consumption were collected to assess the
QTc interval (manually measured), using the Bazzet QT correction formula (Dahlberg et al. 2021).

Statistical analysis
Descriptive statistics were used to have an overall view of the basic features of the baseline information. Age was
categorized in five groups: 1-12, 13-19, 20-34, 35-64, >64 years. The incidence of covid19-like symptoms was calculated by dividing
the number of relatives with any symptom by the total number of relatives in prophylactic management. We fitted a logistic
regression model to analyze the association of age, sex, family size, comorbidities, and the sick patient’s disease severity with the
symptoms reported. Multicollinearity was analyzed and discarded. Adjusted odds ratio (aOR) and its 95% confidence intervals are
presented. Risk Ratio (RR) was calculated to compare the prophylactic effectiveness of CDS with current prophylactic drugs, and

IJMRA, Volume 4 Issue 8 August 2021 www.ijmra.in Page 1063

A Retrospective Observational Study of Chlorine Dioxide Effectiveness to Covid19-like Symptoms Prophylaxis in
Relatives Living with COVID19 Patients
we use an Ivermectin meta-analysis data (Bryant et al. 2021), which has presented the highest effectiveness so far. Wilcoxon rank-
sum tests were performed to compare outcomes between blood tests (complete blood counts and metabolic panel test) before
and after CDS consumption. To compare the QTc interval of relatives that consume CDS against COVID19 patients treated with
Hydroxychloroquine, we performed an Analysis of Variance (ANOVA). A p-value <0.05 was considered statistically significant. To
reduce information bias in this study, the treating physician was not involved in digitization or statistical analysis. All analyses were
conducted using STATA v.15.1.(StataCorp 2017)

Ethical approval
The Ethics Committee of the Centro Medico Jurica waived the need for ethical approval and the need to obtain consent
for the collection, analysis, and publication of retrospectively obtained data because it is a non-interventional study in which the
information was captured from old medical records, maintaining the anonymity of each person and because all patients signed
informed consent before treatment.

Data availability
The datasets used and analyzed during the current study are available from the corresponding author upon reasonable
request.

III. RESULTS
Background of study participants
Information was collected from 1,163 relatives belonging to 554 family nuclei, in 13 Mexico’s states, mainly from
Queretaro (52.25%) and Mexico City (12.61%). The sample comprised 567 women (48.75%), 442 men (38.00%) and 154 without
information (13.24%), with a mean at the onset of 40.37 (range 2-89) years. One hundred eighty-one relatives reported
concomitant diseases, predominantly hypertension (17.39%), diabetes (15.76%) and respiratory diseases (bronchitis, asthma and
chronic pneumonia; 7.06%). Other conditions like cancer, renal failure, hypothyroidism, heart diseases and arthritis were reported
in less than 1%.

Covid19-like symptoms Incidence

The calculated incidence of covid19-like symptoms was 9.63%. In total, 112 relatives (67 women [59.82%], 41 men
[36.61%], and four without information [3.57%]) reported at least one sporadic-mild covid19-like symptom between 4-5 days after
the request for prophylactic management with CDS (Table 1). Thirteen relatives (1.12%) reported secondary effects (diarrhea,
headaches, gastritis, nausea, dizziness or throat pain) posterior to CDS intake, and two of the non-success cases (1.78%) suspended
the prophylactic management due to moderate headaches and gastritis. In those 112 ill relatives, the CDS consumption dosage
was increased immediately after the symptom onset was reported to a therapeutic dose (0.6 mg/kg) until symptoms’ resolution
(between two and four days). None of the relatives who presented covid19-like symptoms died.
The reported comorbidities were not statistically significant for covid19-like symptoms development (P = 0.092). There
was no statistical evidence that relative’s sex and sick patient’s disease severity contributed independently and were associated
with the presence of symptoms (P = 0.351 and P = 0.574). However, both variables were added to the model to adjust for
confounding. Adjusting for sex and sick patient’s diseases severity, relatives of all age categories had higher odds of present
covid19-like symptoms compared to younger patients, but only statistically significant in those of 35-64 years (aOR = 4.22, 95% CI:
1.71, 10.41, P = 0.002) and more than 64 years (aOR = 3.64, 95% CI: 1.30, 10.16, P = 0.014). When comparing the prophylactic
effectiveness of Ivermectin (average 86%; Bryant et al., 2021) against CDS, we observed that relatives who consume CDS are 31%
less likely to develop covid19-like symptoms (RR = 0.69, 95% CI = 0.54-0.89, P = 0.003).

Overall patient’s well-being

No parameters analyzed of the complete blood count (Table 2) were outside the average values before or after. The
Mean Cell Volume (MCV) was different (Wilcoxon rank-sum test, P < 0.02), being greater after prophylactic management with
CDS, although it was not outside the normal upper limit. In the metabolic test (Table 2), blood glucose was above expected values
before and after (mean, 102.65 mg/dL and 103.79 mg/dL, respectively). Nevertheless, there were no differences between both
periods, neither in this metabolite nor in the others evaluated. The mean QTc was 400.08 ms (95% CI: 394.34 ms, 405.76 ms), and
no ECG showed prolonged QTc (Fig. 1). Although, one male’s ECG showed a QTc = 442 ms. QTc interval of relatives was significantly
lower (ANOVA, P < 0.001) compared to the QTc of patients treated with conventional COVID19 treatment (Hydroxychloroquine
and Azithromycin; Chorin et al., 2020; Ramireddy et al., 2020).

IJMRA, Volume 4 Issue 8 August 2021 www.ijmra.in Page 1064

A Retrospective Observational Study of Chlorine Dioxide Effectiveness to Covid19-like Symptoms Prophylaxis in
Relatives Living with COVID19 Patients
IV. DISCUSSION
This retrospective study collected information from 1,163 relatives who lived with sick patients and who consumed CDS
prophylactically. In this study, the incidence of the covid19-like symptoms was 9.63%, which is lower than the estimated overall
household secondary attack rate reported (16.6%, 95% CI: 14.0%, 19.3%; Madewell et al., 2020). It is clear that people commonly
take protective measures in public places such as washing their hands and wearing face masks, but neglect personal protection at
home because they consider it a “safe” place, which has generated a high incidence of infection among relatives (Madewell et al.
2020). This is why researchers are making a great effort to find an effective prophylactic alternative against COVID19.
A few studies had proof of the COVID19 prophylaxis effect. Vitamin D supplementation during the COVID19 pandemic
has been suggested as a preventive measure due to its beneficial effect on the immune system (Verdoia and De Luca 2021).
However, the effectiveness was only about 40% (Martineau and Forouhi 2020). On the other hand, Ivermectin has been studied
extensively to prove its prophylactic efficiency against SARS-CoV-2 infection (Alam et al. 2020; Elgazzar et al. 2020; Kory et al.
2021). The results of a meta-analysis were used to compare the effectiveness of CDS against Ivermectin. We show that CDS
prophylactic effectiveness was slightly higher than the reported for Ivermectin (90.4% vs 86%, respectively). Despite using similar
exposure and outcome variables, the conditions and design of the compared studies were different. Due to the few available
evidence of ClO2/CDS in humans, we consider it necessary to carry out randomized control trials or prospective cohorts to compare
the effect of these two substances in analogous groups.
One of the most studied drugs proposed as prophylactic is Hydroxychloroquine (Rajasingham et al. 2021; Rathi et al.
2020). However, it has not shown statistically significant hazard reduction (HR =0.72, 95% CI: 0.44, 1.16; P = 0.18; Rajasingham et
al., 2021). Furthermore, hematological alterations, liver and kidney function changes (Agrawal, Goel, and Gupta 2020; Galvañ et
al. 2007), and prolonged QTc interval (Chorin et al. 2020; Christos-Konstantinos et al. 2017; Ramireddy et al. 2020) have been
reported using this drug. Contrary to what we report in the present study, blood tests did not reveal any systemic alteration after
CDS consumption, similar to previously reported (Lubbers and Bianchine 1984; Smith and Willhite 1990). Regarding cardiac
function, the use of Hydroxychloroquine combined with azithromycin in COVID19 patients, induces a longer QTc interval (459 ±
36 ms, Ramireddy et al., 2020; and 463 ± 32 ms, Chorin et al., 2020). In this study, only one relative presented the QTc interval
(442 ms) in the borderline (431-450 ms), a limit established as usual for 1% of the population (Christos-Konstantinos et al. 2017).
In the rest of the relatives, the QTc interval was within normal ranges during prophylactic management with CDS. COVID19
infection has been associated with prolonged QTc, regardless of various clinical factors related to QTc prolongation. It has been
reported that the risk of having prolonged QTc, increases in patients treated with Hydroxychloroquine and Azithromycin,
regardless of the presence or absence of SARS-CoV-2 infection (Rubin et al. 2021), and could lead to a high risk of malignant
arrhythmia (Christos-Konstantinos et al. 2017). We did not find alterations in the QTc interval in healthy individuals who consumed
CDS prophylactically. The design of clinical trials in which a detailed follow-up is carried out is recommended to evaluate any
possible effect of Chlorine Dioxide on the QTc interval.
Concerning the risk associated with sex, women are the primary caregivers of other household members, which could
put them at risk in the event of a sick familiar (Wenham, Smith, and Morgan 2020). It has been reported a higher risk of infection
for COVID19 in females than in males (RR= 1.66, 95% CI: 1.39, 2.00) being the wife the most affected compared with a non-spouse
family member because of intimacy or direct contact (e.g. sleeping in the same room) with her husband (Liu et al. 2020). However,
in this study, no evidence was found that women have a higher risk of infection than men. Regarding age, we did not find statistical
evidence on covid19-like symptoms development in younger age groups. Relatives older than 35 were at higher risk, being those
with the highest probability of developing COVID19 worldwide (Liu et al. 2020; Madewell et al. 2020). Even though comorbidities
such as diabetes and hypertension have been recognized as risk factors for COVID19 development,(Liu et al. 2020) we did not find
statistical differences in the present study. This may be due to incorrect clinical data or due to CDS prophylactic effect. However,
this remains to be clarified in additional specific-designed studies.
This study shows that non-success cases started with covid19-like symptoms between 4-5 days after the request for
prophylactic management. This is consistent with previous studies where the highest transmissibility rate is at the end of the first
week of infection (To et al. 2020). Non-success cases reported sporadic and mild symptoms, mainly: headache, throat pain, cough,
fever, malaise, diarrhea, dizziness, abdominal pain, and fatigue, which have already been reported as COVID19 symptoms in other
studies (Madewell et al. 2020; da Rosa Mesquita et al. 2021). Nonetheless, without a confirmatory COVID19 diagnostic, it is
impossible to ensure that the relatives were infected with SARS-CoV-2.
ClO2 in other application forms and dosage have been categorized as a hazard compound due to a few reported side
effects. Additionally, some reported cases have been due to sodium hypochlorite (NaClO2) instead of ClO2. In general, social
networks have been flooded with misinformation through unjustified news about ClO 2. Even health authorities have issued
IJMRA, Volume 4 Issue 8 August 2021 www.ijmra.in Page 1065
A Retrospective Observational Study of Chlorine Dioxide Effectiveness to Covid19-like Symptoms Prophylaxis in
Relatives Living with COVID19 Patients
erroneous information (without scientific basis) about this compound in different media. While some of this information may be
harmless, another portion may be dangerous and may affect the development and implementation of possible treatments
(Osuagwu et al. 2021), such as this compound. Our results show that CDS in the used dosage is safe and does not have severe side
effects, even if used in higher doses (none of the non-success cases reported secondary effects after dose increase). This also is
supported since no blood parameter was out of the normal range after 14 days of prophylactic management. In this study, we
only report thirteen relatives with secondary effects, which disappear after dosage adjustment.

V. LIMITATIONS
Our study has some limitations. The first of all is that this is a retrospective observational study, which means that conclusive
evidence of the effectiveness of the CDS cannot be established because we could only use the information available in the medical
records of the relatives, and we could not have any control over the variables. Second, misinformation bias exists since baseline
and clinical information is reported by relatives. Third, many relatives did not undergo diagnostic or confirmatory tests for SARS-
Cov-2 due to the economic situation and the high cost of these in Mexico. Therefore, it was impossible to establish with certainty
that the relatives who reported any covid19-like symptoms had COVID19. Fourth, the studies’ results used to compare our results
are obtained from different populations and were collected under other conditions, so these comparisons should be interpreted
with caution. Fifth, the overall interpretation of the findings may be restrained due to the lack of additional information (e.g.
personal care, eating habits, proximity and relationship with patients, etc.). These and other variables should be taken into account
in future studies.

VI. CONCLUSION
This is the first study to try to determine the effectiveness of a Chlorine Dioxide aqueous Solution in preventing the development
of symptoms similar to COVID19. We demonstrated a 90.4% effectiveness of preventing the outbreak of covid19-like symptoms
under the given conditions. The blood test did not reveal any systemic alteration after CDS consumption. Our results suggest that
the correct use of ClO2 as a solution is safe for human consumption in an adequate concentration and dosage. Hence, we consider
that the recent findings regarding Chlorine Dioxide justify implementing RCTs to evaluate its efficacy against SARS-CoV-2.
Furthermore, this may open up a new field of research on the potential use of new compounds to solve current and future public
health problems. Finally, we invite more research groups to consider this solution for future studies.

REFERENCES
1) Agrawal, Sumita, Akhil Dhanesh Goel, and Nitesh Gupta. 2020. “Emerging Prophylaxis Strategies against COVID-19.”
Monaldi Archives for Chest Disease 90:169–72.
2) Alam, Mohammed Tarek, Rubaiul Murshed, Pauline Francisca Gomes, Zafor Md. Masud, Sadia Saber, Mainul Alam
Chaklader, Fatema Khanam, Monower Hossain, Abdul Basit Ibne Momen Momen, Naz Yasmin, Rafa Faaria Alam, Amrin
Sultana, and Rishad Choudhury Robin. 2020. “Ivermectin as Pre-Exposure Prophylaxis for COVID-19 among Healthcare
Providers in a Selected Tertiary Hospital in Dhaka – An Observational Study.” European Journal of Medical and Health
Sciences 2(6):1–5.
3) Bryant, Andrew, Theresa Lawrie, Edmund Fordham, Mitchell Scott, Sarah Hill, and Tony Tham. 2021. “Ivermectin for
Prevention and Treatment of COVID-19 Infection: A Systematic Review and Meta-Analysis.” PREPRINT (Version 1)
Available at Research Square 1–25.
4) Chorin, Ehud, Lalit Wadhwani, Silvia Magnani, Matthew Dai, Roi Bar-cohen, Edward Kogan, Chirag Barbhaiya, Anthony
Aizer, Douglas Holmes, Scott Bernstein, Michael Spinelli, David S. Park, Carugo Stefano, and Larry A. Chinitz. 2020. “QT
Interval Prolongation and Torsade de Pointes in Patients with COVID-19 Treated with Hydroxychloroquine/Azithromycin.”
Heart Rhythm 17:1425–33.
5) Christos-Konstantinos, Antoniou, Dilaveris Polychronis, Manolakou Panagiota, Galanakos Spyridon, Magkas Nikolaos,
Gatzoulis Konstantinos, and Tousoulis Dimitrios. 2017. “QT Prolongation and Malignant Arrhythmia: How Serious a
Problem?” European Cardiology Review 12(2):112–20.
6) Dahlberg, Pia, Ulla Britt Diamant, Thomas Gilljam, Annika Rydberg, and Lennart Bergfeldt. 2021. “QT Correction Using
Bazett’s Formula Remains Preferable in Long QT Syndrome Type 1 and 2.” Annals of Noninvasive Electrocardiology
26:e12804.
7) Díaz Piedra, Pablo, Gabriela Olay Fuentes, Ricardo Hernández Gómez, Daniel Cervantes-Villagrana, José Miguel Presno-
Bernal, and Luz Elena Alcántara Gómez. 2012. “Determinación de Los Intervalos de Referencia de Biometría Hemática En
IJMRA, Volume 4 Issue 8 August 2021 www.ijmra.in Page 1066
A Retrospective Observational Study of Chlorine Dioxide Effectiveness to Covid19-like Symptoms Prophylaxis in
Relatives Living with COVID19 Patients
Población Mexicana.” Revista Latinoamericana de Patología Clínica y Medicina de Laboratorio 59(4):243–50.
8) Elgazzar, Ahmed, Basma Hany, Shaimaa Abo Youssef, Mohy Hafez, Hany Moussa, and Abdelaziz Eltaweel. 2020. “Efficacy
and Safety of Ivermectin for Treatment and Prophylaxis of COVID-19 Pandemic.” PREPRINT (Version 2) Available at
Research Square 1–13.
9) Galvañ, Vicente Giner, María Rosa Oltra, Diego Rueda, María José Esteban, and Josep Redón. 2007. “Severe Acute
Hepatitis Related to Hydroxychloroquine in a Woman with Mixed Connective Tissue Disease.” Clinical Rheumatology
26(6):971–72.
10) Gupta, Dhyuti, Ajaya Kumar Sahoo, and Alok Singh. 2020. “Ivermectin: Potential Candidate for the Treatment of Covid
19.” Brazilian Journal of Infectious Diseases 24(4):369–71.
11) Insignares-Carrione, Eduardo, Blanca Bolano Gómez, and Andreas Ludwig Kalcker. 2020. “Chlorine Dioxide in COVID-19:
Hypothesis about the Possible Mechanism of Molecular Action in SARS-CoV-2.” Journal of Molecular and Genetic
Medicine 14(5):1–8.
12) Kály-Kullai, K., M. Wittmann, Z. Noszticzius, and László Rosivall. 2020. “Can Chlorine Dioxide Prevent the Spreading of
Coronavirus or Other Viral Infections? Medical Hypotheses.” Physiology International 107(1):1–11.
13) Kory, Pierre, Gianfranco Umberto Meduri, Joseph Varon, Jose Iglesias, and Paul E. Marik. 2021. “Review of the Emerging
Evidence Demonstrating the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19.” American Journal of
Therapeutics 28(3):e299–318.
14) Liu, Tao, Wenjia Liang, Haojie Zhong, Jianfeng He, Zihui Chen, Guanhao He, Tie Song, Shaowei Chen, Ping Wang, Jialing Li,
Yunhua Lan, Mingji Cheng, Jinxu Huang, Jiwei Niu, Liang Xia, Jianpeng Xiao, Jianxiong Hu, Lifeng Lin, Qiong Huang, Zuhua
Rong, Aiping Deng, Weilin Zeng, Jiansen Li, Xing Li, Xiaohua Tan, Min Kang, Lingchuan Guo, Zhihua Zhu, Dexin Gong,
Guimin Chen, Moran Dong, and Wenjun Ma. 2020. “Risk Factors Associated with COVID-19 Infection: A Retrospective
Cohort Study Based on Contacts Tracing.” Emerging Microbes and Infections 9(1):1546–53.
15) Long, Chunqin, Huaxiang Xu, Qinglin Shen, Xianghai Zhang, Bing Fan, Chuanhong Wang, Bingliang Zeng, Zicong Li, Xiaofen
Li, and Honglu Li. 2020. “Diagnosis of the Coronavirus Disease (COVID-19): RRT-PCR or CT?” European Journal of Radiology
126:108961.
16) Lubbers, J. R., and J. R. Bianchine. 1984. “Effects of the Acute Rising Dose Administration of Chlorine Dioxide, Chlorate
and Chlorite to Normal Healthy Adult Male Volunteers.” Journal of Environmental Pathology, Toxicology and Oncology :
Official Organ of the International Society for Environmental Toxicology and Cancer 5:215—228.
17) Lubbers, Judith R., Sudha Chauhan, and Joseph R. Bianchine. 1981. “Controlled Clinical Evaluations of Chlorine Dioxide,
Chlorite and Chlorate in Man.” Toxicological Sciences 1(4):334–38.
18) Madewell, Zachary J., Yang Yang, Ira M. Longini, Elizabeth Halloran, and Natalie E. Dean. 2020. “Household Transmission
of SARS-CoV-2: A Systematic Review and Meta-Analysis.” JAMA Network Open 3(12):e2031756.
19) Martineau, Adrian R., and Nita G. Forouhi. 2020. “Vitamin D for COVID-19: A Case to Answer?” The Lancet Diabetes and
Endocrinology 8:735–36.
20) Meo, S. A., D. C. Klonoff, and J. Akram. 2020. “Efficacy of Chloroquine and Hydroxychloroquine in the Treatment of COVID-
19.” European Review for Medical and Pharmacological Sciences 24(8):4539–47.
21) Noszticzius, Zoltán, Maria Wittmann, Kristóf Kály-Kullai, Zoltán Beregvári, István Kiss, László Rosivall, and János Szegedi.
2013. “Chlorine Dioxide Is a Size-Selective Antimicrobial Agent.” PLoS ONE 8(11):e79157.
22) Ogata, Norio. 2012. “Inactivation of Influenza Virus Haemagglutinin by Chlorine Dioxide: Oxidation of the Conserved
Tryptophan 153 Residue in the Receptor-Binding Site.” Journal of General Virology 93:2558–63.
23) Olay Fuentes, Gabriela, Pablo Díaz Piedra, Ricardo Hernández Gómez, Daniel Cervantes-Villagrana, José Miguel Presno-
Bernal, and Luz Elena Alcántara Gómez. 2013. “Determinación de Intervalos de Referencia Para Química Clínica En
Población Mexicana.” Revista Latinoamericana de Patología Clínica y Medicina de Laboratorio 60(1):43–51.
24) Osuagwu, Uchechukwu L., Chundung A. Miner, Dipesh Bhattarai, Khathutshelo Percy Mashige, Richard Oloruntoba,
Emmanuel Kwasi Abu, Bernadine Ekpenyong, Timothy G. Chikasirimobi, Piwuna Christopher Goson, Godwin O. Ovenseri-
Ogbomo, Raymond Langsi, Deborah Donald Charwe, Tanko Ishaya, Obinna Nwaeze, and Kingsley Emwinyore Agho. 2021.
“Misinformation about COVID-19 in Sub-Saharan Africa: Evidence from a Cross-Sectional Survey.” Health Security
19(1):44–56.
25) Park, Myungsun, Joungha Won, Byung Yoon Choi, and Justin C. Lee. 2020. “Optimization of Primer Sets and Detection
Protocols for SARS-CoV-2 of Coronavirus Disease 2019 (COVID-19) Using PCR and Real-Time PCR.” Experimental and
Molecular Medicine 52(6):963–77.
IJMRA, Volume 4 Issue 8 August 2021 www.ijmra.in Page 1067
A Retrospective Observational Study of Chlorine Dioxide Effectiveness to Covid19-like Symptoms Prophylaxis in
Relatives Living with COVID19 Patients
26) Rajasingham, Radha, Ananta S. Bangdiwala, Melanie R. Nicol, Caleb P. Skipper, Katelyn A. Pastick, Margaret L. Axelrod,
Matthew F. Pullen, Alanna A. Nascene, Darlisha A. Williams, Nicole W. Engen, Elizabeth C. Okafor, Brian I. Rini, Ingrid A.
Mayer, Emily G. McDonald, Todd C. Lee, Peter Li, Lauren J. MacKenzie, Justin M. Balko, Stephen J. Dunlop, Katherine H.
Hullsiek, David R. Boulware, and Sarah M. Lofgren. 2021. “Hydroxychloroquine as Pre-Exposure Prophylaxis for
Coronavirus Disease 2019 (COVID-19) in Healthcare Workers: A Randomized Trial.” Clinical Infectious Diseases : An Official
Publication of the Infectious Diseases Society of America 72(11):e835–43.
27) Ramireddy, Archana, Harpriya Chugh, Kyndaron Reinier, Joseph Ebinger, Eunice Park, Michael Thompson, Eugenio
Cingolani, Susan Cheng, Eduardo Marban, Christine M. Albert, and Sumeet S. Chugh. 2020. “Experience with
Hydroxychloroquine and Azithromycin in the Coronavirus Disease 2019 Pandemic: Implications for Qt Interval
Monitoring.” Journal of the American Heart Association 9(12):e017144.
28) Rathi, Sahaj, Pranav Ish, Ashwini Kalantri, and Shriprakash Kalantri. 2020. “Hydroxychloroquine Prophylaxis for COVID-19
Contacts in India.” The Lancet Infectious Diseases 20(10):1118–19.
29) da Rosa Mesquita, Rodrigo, Luiz Carlos Francelino Silva Junior, Fernanda Mayara Santos Santana, Tatiana Farias de
Oliveira, Rafaela Campos Alcântara, Gabriel Monteiro Arnozo, Etvaldo Rodrigues da Silva Filho, Aisla Graciele Galdino dos
Santos, Euclides José Oliveira da Cunha, Saulo Henrique Salgueiro de Aquino, and Carlos Dornels Freire de Souza. 2021.
“Clinical Manifestations of COVID-19 in the General Population: Systematic Review.” The Central European Journal of
Medicine 133(377):382.
30) Rubin, Geoffrey A., Amar D. Desai, Zilan Chai, Aijin Wang, Qixuan Chen, Amy S. Wang, Cameron Kemal, Haajra Baksh,
Angelo Biviano, Jose M. Dizon, Hirad Yarmohammadi, Frederick Ehlert, Deepak Saluja, David A. Rubin, John P. Morrow,
Uma Mahesh R. Avula, Jeremy P. Berman, Alexander Kushnir, Mark P. Abrams, Jessica A. Hennessey, Pierre Elias, Timothy
J. Poterucha, Nir Uriel, Christine J. Kubin, Elijah Lasota, Jason Zucker, Magdalena E. Sobieszczyk, Allan Schwartz, Hasan
Garan, Marc P. Waase, and Elaine Y. Wan. 2021. “Cardiac Corrected QT Interval Changes among Patients Treated for
COVID-19 Infection during the Early Phase of the Pandemic.” JAMA Network Open 4:1–14.
31) Shamshina, Julia L., and Robin D. Rogers. 2020. “Are Myths and Preconceptions Preventing Us from Applying Ionic Liquid
Forms of Antiviral Medicines to the Current Health Crisis?” International Journal of Molecular Sciences 21(17):1–16.
32) Smith, David L., John-Paul Grenier, Catherine Batte, and Bradley Spieler. 2020. “A Characteristic Chest Radiographic
Pattern in the Setting of the COVID-19 Pandemic.” Radiology: Cardiothoracic Imaging 2(5):e200280.
33) Smith, Roger P., and Calvin C. Willhite. 1990. “Chlorine Dioxide and Hemodialysis.” Regulatory Toxicology and
Pharmacology 11(1):42–62.
34) StataCorp. 2017. “Stata Statistical Software: Release 15.”
35) To, Kelvin Kai Wang, Owen Tak Yin Tsang, Wai Shing Leung, Anthony Raymond Tam, Tak Chiu Wu, David Christopher Lung,
Cyril Chik Yan Yip, Jian Piao Cai, Jacky Man Chun Chan, Thomas Shiu Hong Chik, Daphne Pui Ling Lau, Chris Yau Chung
Choi, Lin Lei Chen, Wan Mui Chan, Kwok Hung Chan, Jonathan Daniel Ip, Anthony Chin Ki Ng, Rosana Wing Shan Poon,
Cui Ting Luo, Vincent Chi Chung Cheng, Jasper Fuk Woo Chan, Ivan Fan Ngai Hung, Zhiwei Chen, Honglin Chen, and Kwok
Yung Yuen. 2020. “Temporal Profiles of Viral Load in Posterior Oropharyngeal Saliva Samples and Serum Antibody
Responses during Infection by SARS-CoV-2: An Observational Cohort Study.” The Lancet Infectious Diseases 20(5):565–
74.
36) U.S. Environmental Protection Agency. 2000. “Toxicological Review of Chlorine Dioxide and Chlorite.” CAS Nos. 10049-
04-4 and 7758-19-2 (September):1–49.
37) Verdoia, M., and G. De Luca. 2021. “Potential Role Pf Hypovitaminosis D and Vitamin D Supplementation during COVID-
19 Pandemic.” QJM: An International Journal of Medicine 114(1):3–10.
38) Wenham, Clare, Julia Smith, and Rosemary Morgan. 2020. “COVID-19: The Gendered Impacts of the Outbreak.” The
Lancet 395(10227):846–48.
39) Xiang, Fei, Xiaorong Wang, Xinliang He, Zhenghong Peng, Bohan Yang, Jianchu Zhang, Qiong Zhou, Hong Ye, Yanling Ma,
Hui Li, Xiaoshan Wei, Pengcheng Cai, and Wan Li Ma. 2020. “Antibody Detection and Dynamic Characteristics in Patients
with Coronavirus Disease 2019.” Clinical Infectious Diseases 71(8):1930–34.
40) Yu, Xiaoqi, Dong Wei, Yongyan Chen, Donghua Zhang, and Xinxin Zhang. 2020. “Retrospective Detection of SARS-CoV-2
in Hospitalized Patients with Influenza-like Illness.” Emerging Microbes and Infections 9:1–12.
41) Zainol Rashid, Zetti, Siti Norlia Othman, Muttaqillah Najihan Abdul Samat, Umi Kalsom Ali, and Kon Ken Wong. 2020.
“Diagnostic Performance of COVID-19 Serology Assays.” Malaysian Journal of Pathology 42(1):13–21.

IJMRA, Volume 4 Issue 8 August 2021 www.ijmra.in Page 1068

A Retrospective Observational Study of Chlorine Dioxide Effectiveness to Covid19-like Symptoms Prophylaxis in
Relatives Living with COVID19 Patients
TABLE 1. Covid19-lik symptoms (mild, moderate and severe) that were reported by relatives
n %
Relatives that reported covid19-like symptoms
Total (non-success cases) 112 9.63
Female 67 59.82
Male 41 36.61
No informed sex 4 3.57
Covid19-like symptom (sporadic-mild)
Headache 36 3.10
Throat pain 24 2.06
Cough 23 1.98
Fever 22 1.89
Malaise 14 1.20
Diarrhea 12 1.03
Dizziness 11 0.95
Abdominal Pain 10 0.86
Fatigue 10 0.86
Nasal Congestion 10 0.86
Nasal Secretion 10 0.86
Nausea 9 0.77
Chest Pain 8 0.69
Dyspnea 7 0.60
Ageusia 4 0.34
Vomit 4 0.34
Anosmia 3 0.26
Gastritis 3 0.26
Appetite Loss 3 0.26
Joint Pain 3 0.26
Myalgia 1 0.09
Disorientation 1 0.09
Sneeze 1 0.09
Relatives that reported moderate covid19-like symptoms and suspended CDS
Total 2 0.17
Covid19-like symptom (moderate)
Headache 1 0.08
Gastritis 1 0.08
Relatives that reported severe covid19-like symptoms
Total 0 0
Relatives that reported secondary effects after CDS consumption
Total 13 1.12

IJMRA, Volume 4 Issue 8 August 2021 www.ijmra.in Page 1069

A Retrospective Observational Study of Chlorine Dioxide Effectiveness to Covid19-like Symptoms Prophylaxis in
Relatives Living with COVID19 Patients
TABLE 2. Complete blood count and metabolic parameters of 27 relatives before and after the CDS prophylactic management
to prevent covid19-like symptoms development
Before CDS AFTER CDS p-value Reference
Parameter
mean±SD mean±SD α = 0.05 values
Red blood cells (106/µL) 5.02 ± 0.59 4.69 ± 0.89 0.22 4.39 - 6.10
Hemoglobine (gr/dL) 17.44 ± 7.26 14.11 ± 2.69 0.13 13.80 - 18.50
Hematocrit (%) 45.59 ± 12.80 42.73 ± 7.85 0.36 35.40 - 49.40
MCV (fL) 80.05 ± 22.56 90.36 ± 8.23 0.02* 84.40 - 100.00
MCH (pg) 36.82 ± 17.50 30.97 ± 2.40 0.45 27.10 - 33.5
MCHC (gr/dL) 30.79 ± 5.44 32.11 ± 1.45 0.84 31.60 - 34.80
3
Platelets (10 ) 264.21 ± 59.78 239.62 ± 39.11 0.27 147 - 384
MPV (fL) 9.47 ± 1.75 9.60 ± 1.39 0.73 9.60 - 13.40
3
White blood cells (10 ) 6.93 ± 1.73 6.94 ± 1.81 0.79 3.84 - 9.79
Neutrophils (%) 62.31 ± 7.29 61.05 ± 7.77 0.39 39.60 - 76.10
Lymphocytes (%) 29.42 ± 6.37 29.51 ± 8.48 0.73 15.50 - 48.60
Monocytes (%) 5.43 ± 2.13 5.97 ± 1.81 0.43 3.40 - 10.10
Eosinophils (%) 2.21 ± 2.43 1.88 ± 1.70 0.91 0.30 - 4.50
Basophils (%) 0.56 ± 0.56 0.41 ± 0.48 0.35 0.00 - 1.60
Lactic Dehydrogenase (UI/L) 147.43 ± 24.30 194.95 ± 72.57 0.22 139 - 205
Aspartate aminotransferase
(UI/L) 26.21 ± 8.43 27.41 ± 9.47 0.34 12 - 35
Alaline aminotransferase
(UI/L) 31.08 ± 13.27 26.72 ± 13.09 0.22 9 - 47
Gamma-glutamyl Transferase
(UI/L) 33.77 ± 21.88 43.18 ± 29.18 0.28 13- 82
Sodium (mmol/L) 139.24 ± 1.56 138.78 ± 1.72 0.79 136 - 145
Chloride (mmol/L) 104.00 ± 3.78 103.94 ± 4.11 0.69 102 - 112
Potassium (mmol/L) 4.37 ± 0.38 4.48 ± 0.48 0.44 3.70 - 5.20
Glucose (mg/dL) 102.65 ± 15.76 103.79 ± 20.40 0.73 < 100
Urea (mg/dL) 34.57 ± 16.91 45.18 ± 47.43 0.16 19 - 58
Blood Urea Nitrogen (mg/dL) 19.19 ± 8.61 18.87 ± 15.54 0.04 9 - 27
Creatinine (mg/dL) 0.90 ± 0.20 0.90 ± 0.23 0.74 0.77 - 1.32
Cholesterol total (mg/dL) 191.25 ± 66.91 174.09 ± 58.41 0.76 < 200
Triglycerids (mg/dL) 151.78 ± 75.02 141.71 ± 63.80 0.28 < 150
Total Bilirubin (mg/dL) 0.64 ± 0.39 0.73 ± 0.36 1 0.22 - 1.04
Direct Bilirubin (mg/dL) 0.16 ± 0.13 0.31 ± 0.20 0.64 0.12- 0.42
Indirect Bilirubin (mg/dL) 0.48 ± 0.37 0.42 ± 0.32 1 0.09 - 0.65
Alkaline phosphatase (UI/L) 79.94 ± 30.42 78.55 ± 29.11 0.48 40 - 130
Total Protein (g/dL) 7.03 ± 0.66 6.99 ± 1.14 0.26 6.50- 8.10
Seric Albumin (g/dL) 4.14 ± 0.53 4.19 ± 0.85 0.71 3.50 - 5.20

Abbreviations: MCV, mean cell volume; MCH, mean corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin
concentration; MPV, mean platelets volume; SD, standard deviation.
*Statistical significance

IJMRA, Volume 4 Issue 8 August 2021 www.ijmra.in Page 1070

A Retrospective Observational Study of Chlorine Dioxide Effectiveness to Covid19-like Symptoms Prophylaxis in
Relatives Living with COVID19 Patients

FIG. 1. QTc interval (ms) of 50 relatives (females and males) after prophylactic management with CDS to prevent covid19-like
symptoms development.

IJMRA, Volume 4 Issue 8 August 2021 www.ijmra.in Page 1071