Antiprotozoal drug nitazoxanide enhances parasitemia, tissue lesions and mortality caused by Trypanosoma cruzi in murine model.

Chagas' disease is caused by unicellular parasite Trypanosoma cruzi (T. cruzi). It is endemic throughout Latin America, but nowadays has become a global challenge due to tourism and migration. Non-treated infection may result in health-threatening complications and lead to death. Current medications for this infection are nifurtimox (NFT) and benznidazol. Both drugs may cause side effects and are ineffective in the chronic phase. Therefore, new antichagasic compounds are urgently required. Nitazoxanide (NTZ) is a broad spectrum antiparasitic drug, proposed recently as a potential candidate to be added to the list of essential medicines for integrated neglected tropical disease control and elimination. Although the effect of NTZ against T. cruzi epimastigotes in vitro was reported, the corresponding experiments in animal models of T. cruzi infection have never been undertaken. The present work was designed to fill this gap and evaluate the effect of NTZ on experimental murine trypanosomiasis, in comparison with classical antichagasic agent NFT. Highly sensitive to T. cruzi BALB/c mice were infected using Albarrada T. cruzi strain, recently isolated in Mexico. Experimental groups were either left untreated, or otherwise treated with NFT, NTZ (100 and 1000 mg/kg), or with both drugs simultaneously. The severity of the infection was estimated based on criteria such as parasitemia, lesions in target tissues (heart, muscles and lungs) and mortality. Despite the expected protective effect, NTZ drastically aggravates the course of T. cruzi infection. Namely, parasitemia, tissue lesions and mortality caused by T. cruzi infection were significantly higher in NTZ-treated mice groups, even in comparison with untreated infected animals. NTZ by itself no produced mortality o tissue damage, and NFT showed an expected protective effect. Our results indicate that NTZ cannot be considered for Chagas' disease treatment. Moreover, NTZ should be used with caution in patients positive for T. cruzi infection.

Seroprevalence of Trypanosoma cruzi (TC) and risk factors in Colima, Mexico.

INTRODUCTION: The present study was conducted to estimate the incidence of seropositivity to anti-Trypanosoma cruzi antibodies and analyze potential risk factors in Colima, on the western coast of Mexico. METHODOLOGY: Longitudinal studies of 209 subjects with negative serology in 1999 for anti-Trypanosoma cruzi antibodies by hemagglutination inhibition test were tested again in 2005. At the same time, 716 children under six years of age were surveyed serologically (total n = 925); the history of Trypanosoma cruzi infection was determined by the same hemagglutination inhibition test. The variables analyzed were age, sex, living in triatomine-infested places, type of community, quality of housing, presence of pets, and number of inhabitants per house. RESULTS: Trypanosoma cruzi seropositivity in the period of six years was 22/925 cases, with a point prevalence of 2.73% and an adjusted rate of 7.3/1,000 person-years. The variable living in triatomine-infested areas showed association with seropositivity anti-Trypanosoma cruzi antibodies (RR: 5.5; 95% CI: 1.28-23.5). The remaining variables showed no significant association. CONCLUSIONS: This study confirms the active transmission of Chagas disease in Mexico´s western-central region, which merits greater epidemiological surveillance and vector control, particularly in localities infested with triatomines.

The protective effect of peanut, walnut, and almond consumption on the development of breast cancer.

BACKGROUND/AIMS: Breast cancer is the most common gynecologic malignancy known worldwide. The consumption of certain foods may modify the risk for its development. Peanuts and other seeds have shown anticarcinogenic effects in vitro, but there are a few studies that evaluate the effect of their consumption on the development of breast cancer. The aim of the present study was to determine whether there is an association between the consumption of peanuts, walnuts, and almonds and the development of breast cancer. METHODS: We analyzed 97 patients presenting with breast cancer and 104 control subjects that did not have the pathology (BIRADS 1-2). An analysis of the main clinical characteristics and lifelong seed consumption was carried out. The association between the consumption of these foods and the risk for breast cancer was estimated by odds ratios and 95% confidence intervals, controlling other risk factors, using the Mantel-Haenszel analysis. RESULTS: The high consumption of peanuts, walnuts, or almonds significantly reduced the risk for breast cancer by 2-3 times. This protective effect was not found with low or moderate seed consumption when compared with null consumption. CONCLUSIONS: High consumption of peanuts, walnuts, and almonds appears to be a protective factor for the development of breast cancer.

Histological changes caused by meclofenamic acid in androgen-independent prostate cancer tumors: evaluation in a mouse model.

Meclofenamic acid is a nonsteroidal anti-inflammatory drug that has shown therapeutic potential for different types of cancers, including androgen-independent prostate neoplasms. The antitumor effect of diverse nonsteroidal anti-inflammatory drugs has been shown to be accompanied by histological and molecular changes that are responsible for this beneficial effect. The objective of the present work was to analyze the histological changes caused by meclofenamic acid in androgen-independent prostate cancer. Tumors were created in a nude mouse model using PC3 cancerous human cells. Meclofenamic acid (10 mg/kg/day; experimental group, n=5) or saline solution (control group, n=5) was administered intraperitoneally for twenty days. Histological analysis was then carried out on the tumors, describing changes in the cellular architecture, fibrosis, and quantification of cellular proliferation and tumor vasculature. Meclofenamic acid causes histological changes that indicate less tumor aggression (less hypercellularity, fewer atypical mitoses, and fewer nuclear polymorphisms), an increase in fibrosis, and reduced cellular proliferation and tumor vascularity. Further studies are needed to evaluate the molecular changes that cause the beneficial and therapeutic effects of meclofenamic acid in androgen-independent prostate cancer.

Biofilm Eradication of Stenotrophomonas maltophilia by Levofloxacin and Trimethoprim-Sulfamethoxazole.

Stenotrophomonas maltophilia is a nonfermenting Gram-negative drug-resistant pathogen that causes healthcare-associated infections. Clinical isolates from Mexico were assessed for biofilm formation using crystal violet staining. Antimicrobial susceptibility was evaluated in planktonic and biofilm cells using the broth microdilution method. The effects of antibiotics on biofilms were visualized using fluorescence microscopy. Fifty isolates were included in this study, of which 14 (28%) were biofilm producers (9 [64%] from blood and 5 [36%] from respiratory samples). In planktonic cells 4/50 (8%) of isolates were resistant to levofloxacin (8.0%) and 22/50 (44%) were resistant to trimethoprim-sulfamethoxazole. All isolates were resistant to levofloxacin and trimethoprim-sulfamethoxazole in biofilm cells. Bacterial biofilms treated with different concentrations of both antibiotics were completely disrupted. In conclusion, S. maltophilia isolated from blood had higher biofilm production than those isolated from respiratory samples. Biofilm production was associated with increased antibiotic resistance. Antibiotic monotherapy might not be the best course of action for the treatment of S. maltophilia infections in Mexico, because it might cause biofilm production and antimicrobial resistance.

Polymorphisms in the genes related to angiogenesis are associated with uterine cervical cancer.

INTRODUCTION: The expression of plasminogen activator inhibitor type 1 (PAI-1), vascular endothelial growth factor (VEGF), and transforming growth factor ß1 (TGF-ß1) participates in the angiogenesis of several cancer types. The goal of this study was to investigate polymorphisms in genes related to angiogenesis (PAI-1-675 4G/5G, VEGF C936T, and TGF-ß1 G-800A) to evaluate the risk for developing uterine cervical cancer (UCC). METHODS: In a case-control study, 100 healthy subjects and 100 patients with UCC from Mexico were included. We determined the genetic profile of the polymorphic markers, which were evaluated by polymerase chain reaction using a sequence-specific primer. RESULTS: There was no statistical difference in the allele distribution from the intergroup comparisons of PAI-1 675 4G/5G and VEGF C936T data; however, a significant difference was observed within TGF-ß1 G-800A. The linkage disequilibrium analysis revealed that PAI-1 -675 4G and TGF-ß1 -800A pair-haplotype was in strong linkage disequilibrium with a significantly increased risk (odds ratio, 3.44; 95% confidence interval, 1.66-7.25) to UCC. CONCLUSIONS: The polymorphisms in the genes related to angiogenesis -675 4G/5G PAI-1 and G-800A TGF-ß1, segregated solely or combined, might contribute to the increased susceptibility to UCC in a Mexican population.

Integral approach to evaluation of the pathogenic activity of Trypanosoma cruzi clones as exemplified by the Mexican strain.

Comparative histopathological study and analysis of parasite load in different muscle groups were carried out in BALB/c mice during the acute phase of Chagas disease. Activities of C104 clone of T. cruzi strain TPAP/MX/2002/Albarrada and the parental strain were compared. Panoramic 2D-microscopy imaging of sample surface was used and quantitative analysis of parasitism and pathologic damage was performed. The infection rates in various muscle groups were as follows: myocardium=abdominal muscles=lumbar muscles=femoral muscles<--diaphragm for the clone and myocardium¬abdominal muscles=lumbar muscles=femoral muscles-->diaphragm for the parental strain.

Case Report: Outbreak of Nosocomial Myiasis by Cochliomyia macellaria (Diptera, Calliphoridae) in a Hospital in Colima, Mexico.

Myiasis in humans is a disease caused by larvae of various fly families. It mainly occurs in communities with poor sanitation and low socioeconomic status. Meanwhile intrahospital or nosocomial myiasis represents a rare phenomenon but is of relevance to public health. Here, we report an outbreak of myiasis caused by Cochliomyia macellaria in five patients hospitalized for several diseases at the Service of Internal Medicine of the Hospital Regional Universitario de Colima, Mexico during June and July 2021. Three patients were males and two were females, aged 37 to 83 years. All were affected by myiasis caused by larvae of the fly C. macellaria. Three patients underwent invasive mechanical ventilation; one had cutaneous basal cell cancer and one had advanced diabetic foot. This event occurred after 4 days of hospitalization and in the same hospital pavilion. Two patients died, and the others were discharged after treatment with antibiotics and ivermectin. We believe that this nosocomial cluster represents a more frequent phenomenon than reported in tropical countries, where authorities should pay attention to its timely detection, especially in vulnerable populations.

The Hypertriglyceridemic Waist Phenotype Is Associated with Several Cardiovascular Risk Factors in Women with Rheumatoid Arthritis.

Rheumatoid arthritis (RA) associates with cardiovascular risk factors (CVRF) such as dyslipidemias and systemic inflammation. Cardiovascular Disease (CVD) is the leading cause of mortality. The hypertriglyceridemic waist phenotype (HTWP) identifies increased CVRF; however, information about HTWP on RA is scarce. OBJECTIVE: To evaluate the association of HTWP with CVRF in RA. MATERIAL AND METHODS: Cross-sectional study. Women (125) with RA were included (ACR, 1987). Anthropometry, bioimpedance, body mass index (BMI), disease activity score 28 (DAS28), and health assessment questionnaire disability index (HAQ-Di) were determined. The lipid profile determination includes the atherogenic index (AI) (TC/HDL) and Framingham Risk Score. HTWP is defined as a waist circumference ≥88 cm and triglycerides ≥ 150 mg/dL. Chi-squared and Student's t-tests were applied for comparisons. RESULTS: HTWP was found in 38 (30.4%) patients. The subgroup with HTWP had a greater frequency of arterial hypertension (AHT) (57.9 vs. 37.9, p = 0.04), Type 2 DM (23.7 vs. 8.0, p= 0.02), BMI (29.7 ± 3.2, vs. 26.8 ± 4.3, p < 0.001), fat mass (39.3 ± 4.8 vs. 34.7 ± 6.8, p < 0.001), and AI (4.7 ± 1.2 vs. 3.7 ± 1.0, p < 0.001). No differences between DAS28 and HAQ-Di were found. HTWP was associated with the presence of MetS and CVR (p < 0.001 and p = 0.012, respectively). CONCLUSION: The HTWP in RA is associated with CVRF, and its potential predictive role should be evaluated in longitudinal studies.

Using Artificial Intelligence to Develop a Multivariate Model with a Machine Learning Model to Predict Complications in Mexican Diabetic Patients without Arterial Hypertension (National Nested Case-Control Study): Metformin and Elevated Normal Blood Pressure Are Risk Factors, and Obesity Is Protective.

Diabetes mellitus is a disease with no cure that can cause complications and even death. Moreover, over time, it will lead to chronic complications. Predictive models have been used to identify people with a tendency to develop diabetes mellitus. At the same time, there is limited information regarding the chronic complications of patients with diabetes. Our study is aimed at creating a machine-learning model that will be able to identify the risk factors of a diabetic patient developing chronic complications such as amputations, myocardial infarction, stroke, nephropathy, and retinopathy. The design is a national nested case-control study with 63,776 patients and 215 predictors with four years of data. Using an XGBoost model, the prediction of chronic complications has an AUC of 84%, and the model has identified the risk factors for chronic complications in patients with diabetes. According to the analysis, the most crucial risk factors based on SHAP values (Shapley additive explanations) are continued management, metformin treatment, age between 68 and 104 years, nutrition consultation, and treatment adherence. But we highlight two exciting findings. The first is a reaffirmation that high blood pressure figures across patients with diabetes without hypertension become a significant risk factor at diastolic > 70 mmHg (OR: 1.095, 95% CI: 1.078-1.113) or systolic > 120 mmHg (OR: 1.147, 95% CI: 1.124-1.171). Furthermore, people with diabetes with a BMI > 32 (overall obesity) (OR: 0.816, 95% CI: 0.8-0.833) have a statistically significant protective factor, which the paradox of obesity may explain. In conclusion, the results we have obtained show that artificial intelligence is a powerful and feasible tool to use for this type of study. However, we suggest that more studies be conducted to verify and elaborate upon our findings.

Correlation between percentage of fat mass and level of disease activity in rheumatoid arthritis.

Introduction: Controversies exist regarding the relationship between body fat and disease activity in patients with rheumatoid arthritis. The evaluation of the disease is critical for establishing treatment and prognosis. Fat mass could be a predictive factor for poor prognosis in rheumatoid arthritis because of its association with low- and high-grade inflammation. Objective: To evaluate the correlation between fat mass values and disease activity in patients with rheumatoid arthritis. Materials and methods: This was a cross-sectional study. Eighty female patients diagnosed with rheumatoid arthritis (American College of Rheumatology of 1987) were evaluated. For each one, the evaluation determined fat mass using bioelectrical impedance analysis and disease activity using the Disease Activity Score on 28 joints (DAS28). Results: The mean age was 59.11 ± 9.92 years, with an average disease duration of 14.13 ± 10.13 years; 85% of patients showed a high body fat percentage. Pearson's correlation between DAS28 values and fat mass was r = 0.035 (p = 0.76). Conclusion: The levels of DAS28 showed no correlation with fat mass percentage. Further studies are required to clarify the factors that can modify these levels.

Detection of sequences from a potentially novel strain of cell fusing agent virus in Mexican Stegomyia (Aedes) aegypti mosquitoes.

Flaviviruses (FVs) are a very heterogeneous group of viruses that includes viruses capable of infecting insects and/or vertebrates. Different human-disease-causing FVs are disseminated by mosquitoes, and therefore, the search for FV in these insects has recently been proposed in order to evaluate their potential transmission in a given community. An entomological survey was carried out in Colima (the hyperendemic dengue fever transmission zone in Mexico) to collect culicidae in urban and wild areas. No human-pathogenic FVs were found, but sequences related to a potentially novel strain of cell fusing agent virus (CFAV) were detected in Stegomyia (Aedes) aegypti mosquitoes.

Demographic and climatic factors associated with dengue prevalence in a hyperendemic zone in Mexico: an empirical approach.

BACKGROUND: Many models for predicting dengue epidemics use incidence and short-term changes in climate variables, however, studies in real-life scenarios for correlations of seroprevalence (SP) with long-term climate variables and with integration of socio-economic factors are scarce. Our objective was to analyse the combined correlation between socio-economic and climate variables with the SP of dengue in Mexico. METHODS: We performed a seroepidemiological ecological study on the Mexican Pacific coast. Dengue SP was estimated by the presence of immunoglobulin G antibodies in 1278 inhabitants. We implemented multiple correlations with socio-economic, climatic and topographic characteristics using logistic regression, generalized linear models and non-linear regressions. RESULTS: Dengue SP was 58%. The age-adjusted correlation was positive with the male sex, while a negative correlation was seen with socio-economic status (SES) and scholl level (SL). The annual temperature showed a positive correlation, while the altitude was negative. It should be noted that these correlations showed a marked 'S' shape in the non-linear model, suggesting three clearly defined scenarios for dengue risk. CONCLUSION: Low SES and SL showed an unexpected paradoxical protective effect. Altitude above sea level and annual temperature are the main determinants for dengue in the long term. The identification of three clearly delineated scenarios for transmission could improve the accuracy of predictive models.

"I prefer to get coronavirus than to stop working": the street vendor's perspective.

During phase 2 of the COVID-19 pandemic in a Mexican City, informal street vendors (cases) and formal employees (controls) were interviewed. A total of 82.6% of street vendors preferred to expose themselves to the coronavirus than to stop working, compared with 18.4% of formal employees (adjusted OR = 19.4, 95%CI: 4.6-81.7, p < 0.001). Street vendors had 7 times less fear of dying from coronavirus (adjusted OR = 0.14, 95% CI: 0.03-0.5, p = 0.005) and showed a 16-times greater lack of real concern for the increase in cases in their community than the formal employees (adjusted OR = 0.06, 95% CI: 0.01-0.3, p = 0.002). Street vendors were the group with the poorest adherence to household and work area containment measures that continued to be in contact with others. The corresponding authorities must plan specific strategies that allow street vendors to survive economically, while at the same time, protecting community health.

Safety and efficacy of a COVID-19 treatment with nebulized and/or intravenous neutral electrolyzed saline combined with usual medical care vs. usual medical care alone: A randomized, open-label, controlled trial.

Coronavirus disease 2019 (COVID-19) is currently the major public health problem worldwide. Neutral electrolyzed saline solution that contains reactive chlorine and oxygen species may be an effective therapeutic. In the present study, the treatment efficacy of intravenous and/or nebulized neutral electrolyzed saline combined with usual medical care vs. usual medical care alone was evaluated in ambulatory patients with COVID-19. A prospective, 2-arm, parallel-group, randomized, open-label, multi-center, phase I-II clinical trial including 214 patients was performed. The following two outcomes were evaluated during the 20-day follow-up: i) The number of patients with disease progression; and ii) the patient acceptable symptom state. Serial severe acute respiratory syndrome coronavirus 2 naso/oro-pharyngeal detection by reverse transcription-quantitative (RT-q) PCR was performed in certain patients of the experimental group. Biochemical and hematologic parameters, as well as adverse effects, were also evaluated in the experimental group. The experimental treatment decreased the risk of hospitalization by 89% [adjusted relative risk (RR)=0.11, 95% confidence interval (CI): 0.03-0.37, P<0.001] and the risk of death by 96% (adjusted RR=0.04, 95% CI: 0.01-0.42, P=0.007) and also resulted in an 18-fold higher probability of achieving an acceptable symptom state on day 5 (adjusted RR=18.14, 95% CI: 7.29-45.09, P<0.001), compared with usual medical care alone. Overall, neutral electrolyzed saline solution was better than usual medical care alone. Of the patients analyzed, >50% were negative for the virus as detected by RT-qPCR in naso/oro-pharyngeal samples on day 4, with only a small number of positive patients on day 6. Clinical improvement correlated with a decrease in C-reactive protein, aberrant monocytes and increased lymphocytes and platelets. Cortisol and testosterone levels were also evaluated and a decrease in cortisol levels and an increase in the testosterone-cortisol ratio were observed on days 2 and 4. The experimental treatment produced no serious adverse effects. In conclusion, neutral electrolyzed saline solution markedly reduced the symptomatology and risk of progression in ambulatory patients with COVID-19. The present clinical trial was registered in the Cuban public registry of clinical trials (RPCEC) database (May 5, 2020; no. TX-COVID19: RPCEC00000309).

[Domestic violence and risk of suicidal behavior among university students]. / Violencia doméstica y riesgo de conducta suicida en universitarios adolescentes.

OBJECTIVE: To estimate the degree of association between domestic violence -physical, verbal or sexual- with suicidal behavior among university students. MATERIAL AND METHODS: A matched case-control study was done with students attending the University of Colima, Mexico. The cases were 235 teenagers who presented both suicidal ideation and suicide attempt; the controls were 470 individuals of the same age and sex. RESULTS: Sexual abuse showed the highest degree of association with suicidal behavior (OR= 27.4), followed by verbal violence (OR= 9.28), drug use (OR= 8.6), physical violence (OR= 5.5) and smoking (OR= 3.6). Multivariate logistic regression showed that verbal violence was associated with suicidal behavior independently of the other variables, while physical violence, sexual abuse, smoking and drug use seem to depend on verbal violence. CONCLUSIONS: Domestic violence, particularly verbal or sexual, is strongly associated with suicidal behavior in adolescents and should be considered in suicide prevention programs.

Effect of an ecosystem-centered community participation programme on the incidence of dengue. A field randomized, controlled trial.

OBJECTIVES: The purpose of this study is to analyse the effect of a community participation programme based on the ecosystem model on the incidence of dengue in urban communities. METHODS: A randomized controlled field trial was conducted in the state of Colima, Mexico. The intervention consisted of a community participation programme focused on the ecosystem; simultaneously, the control groups were communities that only received the usual official prevention programs. The incidence of dengue was estimated in people of both groups due to the appearance of de novo IgM antibodies during the follow-up period. RESULTS: The incidence of dengue in the intervened group was 2.58%/month (n = 818) and in control group 2.26%/month (n = 994), with a risk ratio of 1.14 (95% CI 0.89-1.45) and a PAF of 0.06 (95% CI - 0.056 to 0.16). The A. aegypti larval density (Breteau Index) was reduced in the treated group. CONCLUSIONS: The implementation of a community participation programme in the cities of Colima, Mexico, showed a slightly counterproductive effect on the incidence of dengue. This happened even with a reduction in the A. aegypti index.

Presence of Acute Chagas Disease Among Febrile Patients in the Western Coast of Mexico.

Chagas disease (ChD) is a parasitosis caused by the protozoan Trypanosoma cruzi (Tc). It is endemic to almost all Latin American countries, including the southern United States. The acute form of ChD and its actual incidence have rarely been described in Mexico, despite the extensive presence of favorable niches for its transmission. The objective of this study was to estimate the frequency of acute ChD in febrile patients at the central Pacific coast of Mexico. For this, we surveyed patients with persistent fever (5 to 10 days) in five hospitals at the Mexican states of Jalisco, Colima, and Nayarit in 2012. Samples were taken from a total of 485 patients to detect Tc in blood using the polymerase chain reaction (PCR) test and direct microscopic examination. Of these subjects, 10 were positive for PCR and none for microscopic examination (2% in 12 months). We adjusted this rate by the total people at risk in the area and obtained an incidence of 7.4/100,000 habs./year. The positive cases showed no association with sex, rural settlement, or pet ownership, only with the contact with Triatominae insects (odds ratio = 9.22 and confidence interval: 1.93-44.06). The clinical picture of positive patients showed an association with the diagnosis of lower respiratory tract infections. Meanwhile, only one fatal case showed the typical picture of acute fatal cardiomyopathy. The pulmonary manifestations of our patients suggest possible lung pathogenicity of Tc, which merits further investigation. Our findings differ markedly from the official reports for ChD. This difference suggests an underestimation of the disease. These findings urge the Mexican health authorities to implement more vigorous actions aimed at improving medical skills in the timely diagnosis of ChD, as well as to apply efficient preventive programs.

One-step nested RT-PCR for COVID-19 detection: A flexible, locally developed test for SARS-CoV2 nucleic acid detection.

INTRODUCTION: Due to the coronavirus pandemic, identifying the infected individuals has become key to limiting its spread. Virus nucleic acid real-time RT-PCR testing has become the current standard diagnostic method but high demand could lead to shortages. Therefore, we propose a detection strategy using a one-step nested RT-PCR. METHODOLOGY: The nucleotide region in the ORF1ab gene that has the greatest differences between the human coronavirus and the bat coronavirus was selected. Primers were designed after that sequence. All diagnostic primers are species-specific since the 3´ end of the sequence differs from that of other species. A primer set also creates a synthetic positive control. Amplified products were seen in a 2.5% agarose gel, as well as in an SYBR Green-Based Real-Time RT-PCR. RESULTS: Amplification was achieved for the positive control and specific regions in both techniques. CONCLUSIONS: This new technique is flexible and easy to implement. It does not require a real-time thermocycler and can be interpreted in agarose gels, as well as adapted to quantify the viral genome. It has the advantage that if the coronavirus mutates in one of the key amplification nucleotides, at least one pair can still amplify, thanks to the four diagnostic primers.

Patient-Reported Health Outcomes After Treatment of COVID-19 with Nebulized and/or Intravenous Neutral Electrolyzed Saline Combined with Usual Medical Care Versus Usual Medical care alone: A Randomized, Open-Label, Controlled Trial.

Background: Coronavirus disease (COVID-19) is currently the main public health problem worldwide. The administration of neutral electrolyzed saline, a solution that contains reactive species of chlorine and oxygen (ROS), may be an effective therapeutic alternative due to its immunomodulating characteristics, in systemic inflammation control, as well as in immune response improvement, promoting control of the viral infection. The present study evaluated the efficacy of treatment with intravenous and/or nebulized neutral electrolyzed saline combined with usual medical care versus usual medical care alone, in ambulatory patients with COVID-19. Methods: A prospective, 2-arm, parallel group, randomized, open-label, phase I-II clinical trial included 39 patients in the control group (usual medical care alone) and 45 patients in the experimental group (usual medical care + intravenous and/or nebulized electrolyzed saline, with dose escalation). Two aspects were evaluated during the twenty-day follow-up: i) the number of patients with disease progression (hospitalization or death); and ii) the Patient Acceptable Symptom State (PASS), a single-question outcome that determines patient well-being thresholds for pain and function. Biochemical and hematologic parameters, as well as adverse effects, were evaluated in the experimental group. Results: The experimental treatment decreased the risk for hospitalization by 92% (adjusted RR=0.08, 95% CI: 0.01-0.50, P=0.007), with a 43-fold increase in the probability of achieving an acceptable symptom state on day 5 (adjusted RR= 42.96, 95% CI: 9.22-200.0, P<0.001). Intravenous + nebulized administration was better than nebulized administration alone, but nebulized administration was better than usual medical care alone. Clinical improvement correlated with a decrease in C-reactive protein, and aberrant monocytes and an increase of lymphocytes, and platelets. Cortisol and testosterone levels were also evaluated, observing a decrease in cortisol levels and an increment of testosterone-cortisol ratio, on days 2 and 4. Conclusions: The experimental treatment produced no serious adverse effects. In conclusion, intravenous and/or nebulized neutral electrolyzed saline importantly reduced the symptomatology and risk of progression (hospitalization and death), in ambulatory patients with COVID-19. Trial registration: Cuban Public Registry of Clinical Trials (RPCEC) Database RPCEC00000309. Registered: 05. May 2020. https://rpcec.sld.cu/en/trials/RPCEC00000309-En.