Ivermectin to prevent hospitalizations in patients with COVID-19 (IVERCOR-COVID19) a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) has changed our lives. The scientific community has been investigating re-purposed treatments to prevent disease progression in coronavirus disease (COVID-19) patients. OBJECTIVE: To determine whether ivermectin treatment can prevent hospitalization in individuals with early COVID-19. DESIGN, SETTING AND PARTICIPANTS: A randomized, double-blind, placebo-controlled study was conducted in non-hospitalized individuals with COVID-19 in Corrientes, Argentina. Patients with SARS-CoV-2 positive nasal swabs were contacted within 48 h by telephone to invite them to participate. The trial randomized 501 patients between August 19th 2020 and February 22nd 2021. INTERVENTION: Patients were randomized to ivermectin (N = 250) or placebo (N = 251) arms in a staggered dose, according to the patient's weight, for 2 days. MAIN OUTCOMES AND MEASURES: The efficacy of ivermectin to prevent hospitalizations was evaluated as primary outcome. We evaluated secondary outcomes in relationship to safety and other efficacy end points. RESULTS: The mean age was 42 years (SD ± 15.5) and the median time since symptom onset to the inclusion was 4 days [interquartile range 3-6]. The primary outcome of hospitalization was met in 14/250 (5.6%) individuals in ivermectin group and 21/251 (8.4%) in placebo group (odds ratio 0.65; 95% confidence interval, 0.32-1.31; p = 0.227). Time to hospitalization was not statistically different between groups. The mean time from study enrollment to invasive mechanical ventilatory support (MVS) was 5.25 days (SD ± 1.71) in ivermectin group and 10 days (SD ± 2) in placebo group, (p = 0.019). There were no statistically significant differences in the other secondary outcomes including polymerase chain reaction test negativity and safety outcomes. LIMITATIONS: Low percentage of hospitalization events, dose of ivermectin and not including only high-risk population. CONCLUSION: Ivermectin had no significant effect on preventing hospitalization of patients with COVID-19. Patients who received ivermectin required invasive MVS earlier in their treatment. No significant differences were observed in any of the other secondary outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT04529525 .

Tracing the evolution of the chikungunya virus in Argentina, 2016-2023: independent introductions and prominence of Latin American lineages.

Chikungunya virus (CHIKV) has emerged as a significant public health concern due to its rapid spread and potential for causing debilitating epidemics. In Argentina, the virus has garnered attention since its introduction to the Americas in 2013, due to its growing incidence and impact in neighbouring countries. Here we present a comprehensive analysis of the spatiotemporal dynamics of CHIKV in Argentina, focusing on the evolutionary trajectory of its genetic variants. Through a combination of active surveillance, screening of historical and recent samples, and whole-genome sequencing, we traced the evolutionary history of CHIKV lineages circulating within the country. Our results reveal that two distinct genotypes circulated in Argentina: The Asian lineage during the 2016 epidemic and the ECSA lineage in 2023. This distribution reflects the dominance of particular variants across Latin America. Since 2023, the ECSA lineage has led to a surge in cases throughout the Americas, marking a significant shift. The replacement of lineages in the American region constitutes a major epidemiological event, potentially affecting the dynamics of virus transmission and the clinical outcomes in impacted populations. The spatiotemporal analysis highlights CHIKV's distribution across Argentina and underscores the significant role of human mobility, especially when considering recent epidemics in neighbouring countries such as Paraguay and Uruguay, which have facilitated the spread and introduction of the viral strain into different districts. By integrating epidemiological data with genomic insights, we elucidate the patterns of virus dissemination, highlighting key areas of transmission and potential factors contributing to its spread.

Ivermectin to prevent hospitalizations in patients with COVID-19 (IVERCOR-COVID19): a structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: To assess the efficacy of ivermectin in addition to standard treatment compared to standard treatment alone in reducing hospitalizations in the COVID-19 patient population. TRIAL DESIGN: IVERCOR-COVID19 will be a single-center, prospective, randomized, double-blind, parallel group (1:1 ratio), placebo-controlled study. PARTICIPANTS: Patients who meet the following criteria will be invited to participate: Inclusion criteria: (1) Over 18 years of age who reside in the province of Corrientes at the time of diagnosis. (2) Confirmed diagnosis of COVID-19 by polymerase chain reaction (PCR) test for detection of SARS-CoV2 in the last 48 h. (3) In the case of women of childbearing age, they must be using a contraceptive method of proven efficacy and safety (barrier, hormonal, or permanent contraceptives) for at least 3 months prior to inclusion in the present study and for the entire period of time for the duration of the study and until at least 30 days after the end of this study. A woman will be considered to have no reproductive capacity if she is postmenopausal (at least 2 years without her menstrual cycles) or if she has undergone surgical sterilization (at least 1 month before the time of inviting her to participate in this study). (4) Weight at the time of inclusion greater than 48 kg. (5) That they sign the informed consent for participation in the study. EXCLUSION CRITERIA: (1) pregnant or breastfeeding women; (2) known allergy to ivermectin or some of the components of ivermectin tablets or placebo; (3) current use of home oxygen; (4) require hospitalization due to COVID-19 at the time of diagnosis or history of hospitalization for COVID-19; (5) presence of mal-absorptive syndrome; (6) presence of any other concomitant acute infectious disease; (7) known history of severe liver disease, for example liver cirrhosis; (8) need or use of antiviral drugs at the time of admission for another viral pathology other than COVID-19; (9) need or use of hydroxychloroquine or chloroquine; (10) use of ivermectin up to 7 days prior to randomization; (11) patients on dialysis or who have required it in the last 2 months or who plan to do it in the next 2 months; and (12) current participation or in the last 30 days in a research study that has included the administration of a drug (Table 1). Table 1 Ivermectin/placebo dose according to patient weight Patient weight Ivermectin/placebo dose Total dose (mg) Equal to or greater than 48 kg and less than 80 kg 2 tablets of 6 mg each at the time of inclusion and 2 tablets 24 h after the first intake 24 Equal or greater than 80 kg and less than 110 kg 3 tablets of 6 mg each at the time of inclusion and 3 tablets 24 h after the first intake 36 Equal or greater than 110 kg 4 tablets of 6 mg each at the time of inclusion and 4 tablets 24 h after the first intake 48 The study will be carried out by the Ministry of Public Health of the Province of Corrientes (Argentina) in coordination with the Institute of Cardiology of Corrientes in the Province of Corrientes, Argentina. INTERVENTION AND COMPARATOR: Intervention group: patients who are randomized to ivermectin will receive the dose according to their weight (patients up to 80 kg will receive 2 tablets of 6 mg ivermectin; patients with more than 80 kg and up to 110 kg will receive 3 tablets of 6 mg of ivermectin; patients weighing more than 110 kg will receive 4 tablets of 6 mg ivermectin) the day they enter the study and the same dose 24 h after the first dose. CONTROL GROUP: patients who are randomized to placebo will receive the dose according to their weight (patients up to 80 kg will receive 2 tablets of 6 mg placebo; patients with more than 80 kg and up to 110 kg will receive 3 tablets of 6 mg of placebo; patients weighing more than 110 kg will receive 4 tablets of 6 mg placebo) on the day they enter the study and the same dose 24 h after the first dose (Table 2). Table 2 Inclusion and exclusion criteria Inclusion criteria Exclusion criteria 1. Over 18 years of age who reside in the province of Corrientes at the time of diagnosis 1. Pregnant or breastfeeding women 2.Confirmed diagnosis of COVID-19 by polymerase chain reaction test for detection of SARS-CoV2 in the last 48 h 2. Known allergy to ivermectin or some of the components of ivermectin tablets or placebo 3. In case of being women of childbearing age, they must be using a contraceptive method of proven efficacy and safety (barrier, hormonal, or permanent contraceptives) for at least 3 months prior to inclusion in the present study, during the entire period of time for the duration of the study, and until at least 30 days after the end of this study. A woman will be considered to have no reproductive capacity if she is postmenopausal (at least 2 years without her menstrual cycles) or if she has undergone surgical sterilization (at least 1 month before the time of inviting her to participate in this study) 3. Current use of home oxygen 4. Weight at the time of inclusion equal to or greater than 48 kg 4. That require hospitalization due to COVID-19 at the time of diagnosis or history of hospitalization for COVID-19 5. That they sign the informed consent for participation in the study 5. Presence of mal-absorptive syndrome 6. Presence of any other concomitant acute infectious disease 7. Known history of severe liver disease, for example liver cirrhosis 8. Need or use of antiviral drugs at the time of admission for another viral pathology other than COVID-19 9. Need or use of hydroxychloroquine or chloroquine 10. Use of ivermectin up to 7 days prior to randomization 11. Patients on dialysis or who have required it in the last 2 months or who plan to do it in the next 2 months 12. Current participation or in the last 30 days in a research study that has included the administration of a drug MAIN OUTCOMES: Primary outcome will be the percentage of hospitalizations in patients with COVID-19 in the intervention and control groups. SECONDARY OUTCOMES: time to hospitalization in each of the arms of the study: number of days elapsed from the inclusion in the study until the hospitalization of the patient; percentage of use of invasive mechanical ventilation in each of the study arms: every patient who is connected to invasive mechanical ventilation after signing the informed consent and before the final study visit; time to invasive mechanical ventilation in each of the arms of the study: number of days elapsed from inclusion in the study to connection to invasive mechanical ventilation of the patient; percentage of patients requiring dialysis in each of the study arms: all patients who require renal replacement therapy of any kind, temporary or permanent, and which begins after signing the informed consent and before the final visit; mortality from all causes in each of the two trial groups: death of the patient, from any cause. Negative PCR swab at 3 ± 1 and 12 ± 2 days after entering the study. Ivermectin safety: it will be analyzed according to the incidence of adverse events that patients present in the intervention and control groups. The end of study (EOS) is recorded as the day the patient is discharged or death. Discharge will be granted according to the current recommendations of the Ministry of Public Health of the Province of Corrientes. A follow-up visit (EOF) will be made by phone 30 days after the EOS when vital status will be verified. RANDOMIZATION: Randomization will be done through a web system with randomly permuted blocks. Randomization will be carried out by one of the investigators who will not participate in the inclusion of patients or in the delivery of medication (Table 3). Table 3 EOS end of study, EOF end of follow-up Visit Basal and randomization, day 0 Day 3 ± 1 Day 12 ± 2 V#1 V#2 V#3 EOS EOF Informed consent X - - - - Inclusion/exclusion criteria X - - - - Demographic data and medical history X - - - - Concomitant medication X - - - - Vital signs* X X - - - Anthropometric data^ X - - - - Basal laboratory X - - - - PCR swab - X X - - Assessment of adverse events - X X X - Final objective evaluation - X X X X Randomization X - - - - Adherence to treatment X X - - - *Includes heart rate, temperature, and oxygen saturation by a digital saturometer ^Includes weight and height BLINDING (MASKING): The participants, investigators, care providers, and outcome assessors will be blinded. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): We will include a total of 500 patients (250 patients in each group). TRIAL STATUS: This is version 1.0, 17 August 2020. The recruitment started on 19 August 2020, and we anticipate the trial will finish recruitment on 31 December 2020. TRIAL REGISTRATION: ClinicalTrials.gov NCT04529525 . Registered on 26 August 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting the dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol.

Diagnóstico y vigilancia epidemiológica de virus respiratorios en la provincia de Corrientes / Diagnosis and Epidemiological Surveillance of Respiratory Viruses in the Province of Corrientes

Durante el otoño e invierno de 2016 se advirtió un cambio de comportamiento en la circulación y prevalencia de los virus de influenza y sincicial respiratorio en las muestras de la provincia de Corrientes.

Circulación de Bocavirusen niños menores de 5 años con infección respiratoria aguda de la provincia del Chaco: análisis de los años 2014 y 2015 / Bocavirus circulation in children under 5 years with acute respiratory infection in the province of Chaco: analysis of 2014 and 2015

Acute respiratory infection (ARI) is the most frequent pathology along human life, being the most common cause of morbidity and mortality in children under 5 years old. The aim of this study was to determine the circulation of HBoV in infants under 5 years old with symptoms of ARI from north Argentina (Chaco province). Were analyzed 882 nasopharyngeal aspirates obtained during the years 2014 and 2015. The samples were tested by real time PCR and the overal frequency of HBoV was 7.6%. The period with the major detection report was June-September with 77.6% of all positive cases. It is interesting that 98.5% of all cases were in infants aged 0 to 2 years of life. HBoV positive cases were given as single infection in 46.3% of patients and the remaining 53.7% as concomitant infections with other viruses. The evaluation of two full years calendar of molecular epidemiological study in northern Argentina of HBoV, reflects more accurately the current situation and could lead to re-formulate strategies for diagnosis, treatment and prognosis of this disease. We intend to highlight the importance of investigate this new virus capable of produce an acute respiratory disease by providing information about it to the community.

A infecção respiratória aguda (IRA) é a mais frequente ao longo da vida de uma patologia individual e é a causa mais comum de mortalidade/morbidade em crianças com menos de 5 anos. O objetivo deste estudo foi determinar o movimento do Bocavírus Humano (HBoV) em crianças menores de 5 anos com um diagnóstico presuntivo de IRA numa capital estadual do norte da Argentina (Resistencia, Chaco). Foram analizados 882 aspirados nasofaríngeos, obtidos durante os anos 2014 e 2015. As pessoas foram testeadas por PCR em tempo real, onde se encontrou uma frequência de HBoV do 7,6% (67/882), dando a maior concentração de casos positivos no período de junho a setembro (77,6%). Curiosamente, 98,5% dos casos foram em crianças de 0 a 2 anos de vida. Os casos positívos de HBoV foram dados como única infecção em 46,3% dos pacientes e os restantes 53,7% como infecções concomitantes com outros vírus. A avaliação de dois anos, calendário completo de estudo de epidemiologia molecular HBoV no norte da Argentina, reflete com mais precisão a realidade, e pode reformular as estratégias para o diagnóstico, tratamento e prognóstico da patología. Temos a intenção de destacar a importância de se investigar o novo vírus capaz de gerar doença respiratória aguda, fornecendo informações dele para a comunidade

La infección respiratoria aguda (IRA) es la patología más frecuente a lo largo de la vida de una persona y es la causa más común de morbi-motalidad en niños menores de 5 años. El objetivo de este trabajo fue determinar la circulación del Bocavirus Humano (HBoV) en niños menores de 5 años con diagnóstico presuntivo de IRA en una ciudad capital del norte argentino (Resistencia, Chaco). Ruiz Díaz, Natalia; y Col. Rev. Fac. Med. UNNE XXXVI: 3, 5-12, 2016 Se analizaron 882 aspirados nasofaríngeos obtenidos durante los años 2014 y 2015. Los mismos fueron testeados por PCR en tiempo real encontrándose una frecuencia de HBoV de 7.6% (67/882), dándose la mayor concentración de casos positivos en el período junio-septiembre (77,6%) y es interesante destacar que el 98,5% del total de casos se registraron en infantes entre 0 a 2 año de vida. Los casos positivos para HBoV se dieron como infección única en el 46.3% de los pacientes y el 53.7% restante como infecciones concomitantes con otros virus. La evaluación de dos años -calendarios completos- de estudio epidemiológico molecular de HBoV en el norte argentino, refleja de manera más fiel la realidad ya que permite reformular las estrategias en cuanto al diagnóstico, el tratamiento y el pronóstico de esta patología. Pretendemos destacar la importancia de investigar los nuevos virus capaces de generar patología respiratoria aguda brindando información sobre el mismo a la comunidad