ABSTRACT
Key PointO_ST_ABSIMPORTANCEC_ST_ABSThe emergency of COVID-19 requires the implementation of urgent strategies to prevent the spread of the disease, mainly in health personnel, who are the most exposed and has the highest risk of becoming infected with the SARS-COV-2. Drug repurposing is a pragmatic strategy, a faster and cheaper option, compared to the new drug development that has proven successful for many drugs and can be a key tool in emergency situations such as the current one that requires quick action. In addition, considering the limited access to vaccines for developing countries, preventive use of ivermectin can be a palliative that minimizes the risks of infection. OBJECTIVETo evaluate the protective effect of the combination Ivermectin / Iota-Carrageenan (IVER/IOTACRC), intensive treatment with repeated administration in oral- and nasal-spray, respectively, as a prophylaxis treatment prior to exposure to SARS-CoV-2, in health personnel at Public Healthcare Centers. PARTICIPANTS, DESIGN AND SETTINGRandomized controlled 1-1 clinical trial in Personal Health, n = 234. The subjects were divided into experimental (EG: n=117; 39.6 {+/-} 9.4 years old, 65F) and control groups (CG: n=117; 38.4 {+/-} 7.4 years old, 61F). The EG received Ivermectin orally 2 tablets of 6 mg = 12 mg every 7 days, and Iota-Carrageenan 6 sprays per day for 4 weeks. All participants were evaluated by physical examination COVID-19 diagnosed with negative RT-PCR at the beginning, final, and follow-up of the protocol. Differences between the variables were determined using the Chi-square test. The proportion test almost contagious subject and the contagion risk (Odds Ratio) were calculated using software STATA. The level of statistical significance was reached when p-Value < 0.05. RESULTThe number of subjects who were diagnosed with COVID-19 in EG was lower, only 4 of 117 (3.4%) than subjects in CG: 25 of 117 (21.4%) (P-Value = 1.10-5). Nineteen patients had mild symptoms, 4 were in EG whereas, 15 were in CG (p-Value = 0.001). Seven subjects were moderate, and 3 with severe diagnostics, all them in CG. The probability (Odds Ratio) of becoming ill with COVID-19 was significantly lower in EG with values of 0.13, 95% 0.03 to 0.40; p-Value = 1.10-4, this value (<1) indicates a protective effect of the IVER/IOTACRC in the EG. Logistic regression test demonstrated that treatment was effective to prevent COVID-19 (Odds Ratio 0.11, 95% 0.03 to 0.33; p-Value = 1.10-4). We also found that when increase the age, decrease contagious risk (Odds Ratio 0, 93, 95% 0.88 to 0.98, p-Value= 0, 02). On the other hand, the probability of contracting COVID-19 was dependent on the patients preexisting comorbidity (Odds Ratio 5.58, 95% 2.20 to 14.16, p-Value = 1.10-5). The other variables sex and designation were independent. CONCLUSIONThe intensive preventive treatment (short-term) with IVER/IOTACRC was able to reduce the number of health workers infected with COVID-19. This treatment had also effect in preventing the severity of the disease, since all patients treated were mild. We propose a new therapeutic alternative for prevention and short-term intervention scheme (intensive) that is of benefit of the health worker in this pandemic accelerated time. This intervention did not produce lack of adherence to treatment or adverse effects. Trial RegistrationClinicalTrials.gov Identifier: NCT04701710
ABSTRACT
BackgroundThe emergence of COVID-19 requires alternative treatments based on the reuse of drugs as a strategy to prevent the progression of the disease in patients infected with SARS-COV-2. The goal was to evaluate the use of ivermectin in mild stage outpatients to heal and / or reverse the progression of COVID-19 disease towards the development of moderate or severe stages. MethodsCluster Assigned Clinical Trial (2:1) in outpatients, n = 234. The subjects were divided into experimental (EG: n = 110) and control groups (CG: n = 62). The EG received ivermectin orally 4 drops of 6 mg = 24 mg every 7 days for 4 weeks. All participants were diagnosed by positive RT-PCR for COVID-19 and were evaluated by clinical examination, at the beginning and the end of protocol. Data analyzed were applied the proportion, bivariate, and logical regression tests with level significance p < 0{middle dot}05. This study was registered at ClinicalTrials.gov Identifier NCT04784481. FindingsBoth groups were similar in age, sex, and comorbidities (EG: 56F, median age= 40{middle dot}0, range: 18{middle dot}0 - 75{middle dot}0; CG: 34F, median age = 37{middle dot}5, range: 18{middle dot}0 - 71{middle dot}0). A significant reduction in the symptom numbers was observed in the EG when the medical examination was performed from 5th to 9th days, after starting treatment (p = 0{middle dot}0026). Although, medical examination from 10th to 14th day, showed a progressive reduction of the percentage symptom numbers, these were not significative in both groups. A higher proportion of medical release was observed in EG (98{middle dot}2%) vs CG (87{middle dot}1%) (p = 0{middle dot}003). EG showed 8 times more chance of receiving medical release than CG (OR 7{middle dot}99, 95% CI: 1{middle dot}64 -38{middle dot}97, p = 0{middle dot}003). The treatment effect with ivermectin to obtain medical release was analyzed by the logistic regression model based in the following control variables: sex, age, and comorbidities. Then, the chance to obtain medical release was maintained in EG (OR 10{middle dot}37, 95% CI: 2{middle dot}05 - 52{middle dot}04, p = 0{middle dot}005). InterpretationTreatment with ivermectin in outpatients with mild stage COVID-19 disease managed to slightly reduce the symptom numbers. Also, this treatment improved the clinical state to obtain medical release, even in the presence of comorbidities. The treatment with ivermectin could significantly prevent the evolution to serious stages since the EG did not present any patient with referral to critical hospitalization. Clinical Trials registry number is NCT04784481 FundingMinistry of Public Health. Tucuman, Argentina. Research in ContextO_ST_ABSEvidence before this studyC_ST_ABSCurrently there are no specific therapies approved for COVID-19 treatment by the FDA, that is why different repositionable drugs are being studied in clinical trials and compassionate use protocols based on in vitro activity. ivermectin is a broad spectrum antiparasitic agent that has been shown to have antiviral activity against a wide range of viruses. A study by Caly et al. (2020) suggested thatnuclear transport inhibitory activity of ivermectin may be effective against SARS-CoV-2. Since the publication of that work, numerous clinical trials were started to study ivermectin potential for COVID-19 treatment. At the end of March 2021, there were about 60 studies registered in https://www.clinicaltrials.gov, and 43 studies listened https://www.who.int/clinical-trials-registry-platform about the safety and effectiveness of ivermectin in COVID-19 patients, for treatment and prophylaxis. Most of these studies are from developing countries, which shows the need of emerging economies to find alternative therapies to contain the spread of the disease and the collapse of health systems. Added value of this studyWe found that an early intervention with ivermectin has impacted on the score of symptoms related to COVID-19 in ambulatory patients, between the 5th and 9th day. The patients who received the treatment changed from score 2 to score 1 in the WHO ordinal scale. In any case, patients evolved to higher scores. Also the treatment increased the probability to obtain medical release, even in the presence of comorbidities. Implications of all available evidenceAccording to the COVID-19 Treatment Guidelines by the NIH, most trials have several limitations. It needs results from adequately powered and well-designed clinical trials to provide evidence-based guidance on the role of ivermectin in the treatment of COVID-19. However, our study shows overlaps in benefits with other authors, and taking together, these results are encouraging for further study about repurposing ivermectin for the treatment of COVID-19.
ABSTRACT
We hypothesized that in individuals with previous SARS-CoV-2 infection, the first vaccine dose would work as a booster, eliciting a faster and more intense immune response. We herein describe antibody responses to the first and second doses of Gam-COVID-Vac (SPUTNIK V) vaccine in health personnel of Tucuman, Argentina, with previous COVID-19 and compared it with uninfected personnel. Individuals with anti-SARS-CoV-2 titers at baseline showed significantly higher responses to the first dose than people with no prior history of disease (p <0.0001), with titers higher to those registered after the second dose in the control group, representing a clear secondary antibody response. This suggests that a single dose of SPUTNIK V for people with previous SARS-CoV-2 infection could contribute to a better use of available doses. One-Sentence SummaryFirst vaccine dose in subjects with prior COVID19 elicits a higher antibody response than two doses in uninfected individuals
