Multiple BCG vaccinations for the prevention of COVID-19 and other infectious diseases in type 1 diabetes.

There is a need for safe and effective platform vaccines to protect against coronavirus disease 2019 (COVID-19) and other infectious diseases. In this randomized, double-blinded, placebo-controlled phase 2/3 trial, we evaluate the safety and efficacy of a multi-dose Bacillus Calmette-Guérin (BCG) vaccine for the prevention of COVID-19 and other infectious disease in a COVID-19-unvaccinated, at-risk-community-based cohort. The at-risk population is made of up of adults with type 1 diabetes. We enrolled 144 subjects and randomized 96 to BCG and 48 to placebo. There were no dropouts over the 15-month trial. A cumulative incidence of 12.5% of placebo-treated and 1% of BCG-treated participants meets criteria for confirmed COVID-19, yielding an efficacy of 92%. The BCG group also displayed fewer infectious disease symptoms and lesser severity and fewer infectious disease events per patient, including COVID-19. There were no BCG-related systemic adverse events. BCG's broad-based infection protection suggests that it may provide platform protection against new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and other pathogens.

Efficacy of two siddha polyherbal decoctions, Nilavembu Kudineer and Kaba Sura Kudineer, along with standard allopathy treatment in the management of mild to moderate symptomatic COVID-19 patients-a double-blind, placebo-controlled, clinical trial.

BACKGROUND AND AIM: Globally, the ongoing pursuit in exploring an effective drug to combat severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus has not met with significant success to date. Indian traditional medicines, especially polyherbal formulations like Nilavembu Kudineer (NVK) and Kaba Sura Kudineer (KSK) of the Siddha system of medicine, have been used as public health interventions for controlling viral epidemics like dengue and Chikungunya. These traditional therapies have been found safe, effective, and widely accepted. The current study evaluates the comparative efficacy of NVK and KSK as opposed to the placebo, in the management of mild to moderate COVID-19 disease. METHODS: The study was a double-blind, placebo-controlled comparative clinical trial, with the primary objective of determining the efficacy of KSK and NVK. Patients (n=125) diagnosed with mild to moderate COVID-19 symptoms were enrolled in the study over a period of 4 months (Aug 2020-Dec 2020). Participants were randomized into 3 arms; placebo-decaffeinated tea in Arm I, NVK in Arm II, and KSK in Arm III. Each arm received 60 ml of the respective treatment twice a day, post morning and evening meals, along with standard allopathy treatment for a maximum of 10 days. The main outcome measures of the study were the reduction in SARS-CoV-2 viral load, hospital stay, and time taken by the patients to become asymptomatic from symptomatic. Efficacy assessments included clinical symptoms (fever, cough, and breathlessness) each day and real-time reverse transcription-polymerase chain reaction (RT-PCR), liver function test (LFT), renal function test (RFT), and electrolytes and electrocardiogram (ECG) at baseline (day 0) and days 3, 6, and 10. Post-treatment, participants were followed up for 30 days via phone for adverse effects if any. Effects of drugs on inflammatory markers (IL6) at the end of treatment were also recorded. Adverse events (AE) were monitored throughout the study. RESULTS: The results revealed that when compared to patients in the placebo arm, those in NVK and KSK arms showed a statistically significant reduction in hospital stay time, reduction in viral load of SARS-CoV-2, and the time taken to become symptomatic from asymptomatic. Out of 125 COVID-19 patients recruited, 120 completed the study; two from the placebo group developed severe symptoms and were shifted to the intensive care unit (ICU) and three patients from Arms II and III withdrew from the study. The mean age of females (n=60) and males (n=60) enrolled was between 40.2 and 44.3 years, respectively. Results were more promising for all the patients in NVK and KSK arms as all enrolled participants (100%) under this group got discharged by day 6 as compared to only 42.5% (n=17) from the placebo group on that day. The hospital stay time for patients in Arm I was significantly longer (mean [SD]=8.4 [2.0] days) as compared to the Arms II and III (mean [SD]=4.7 [1.5] and 4.2 [1.5] days, respectively (Kruskal-Wallis test, P=0.0001). Patients in the three groups took a significantly different number of days to become asymptomatic. While Arm II and III patients took mean of 2.5 and 1.7 days, respectively, Arm I, patients took a mean of 4.2 days (Kruskal-Wallis test, P=0.0001). In all, two adverse events were recorded, one for vomiting and one for diarrhea lasting a day in Arm I and Arm II, respectively. The mean value of interleukin-6 (IL6) was significantly different in comparison to the placebo-decaffeinated tea arm (NVK=2.6 and KSK=2.2, placebo=4.0, P=0.02). The other blood biochemical parameters like C-reactive protein (CRP), lactate dehydrogenase (LDH), ferritin, and D-dimer that were analyzed at the baseline and at the time of discharge from the hospital, were not significantly different in the three arms. CONCLUSION: NVK and KSK arms showed a statistically significant reduction in hospital stay time, reduction in viral load of SARS-CoV-2, and time taken for patients to become asymptomatic from symptomatic, when compared to the placebo (decaffeinated tea). The primary outcome measures of the KSK arm were significantly better than those in the NVK arm.

Pre-exposure prophylaxis with hydroxychloroquine for high-risk healthcare workers during the COVID-19 pandemic: A structured summary of a study protocol for a multicentre, double-blind randomized controlled trial.

OBJECTIVES: The aim of this study is to assess the efficacy of the use of pre-exposure prophylaxis (PrEP) with hydroxychloroquine against placebo in healthcare workers with high risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in reducing their risk of coronavirus disease 2019 (COVID-19) disease during an epidemic period. As secondary objectives, we would like to: i) assess the efficacy of the use of PrEP with hydroxychloroquine against placebo in healthcare workers with high risk of SARS-CoV-2 infection in reducing their risk of exposure to SARS-CoV-2 (defined by seroconversion) during an epidemic period, ii) evaluate the safety of PrEP with hydroxychloroquine in adults, iii) describe the incidence of SARS-CoV-2 infection among healthcare workers at high risk of SARS-CoV-2 infection, iv) identify clinical, analytical and microbiological predictors of COVID-19 among healthcare workers at high risk of SARS-CoV-2 infection, v) set up a repository of serum samples obtained from healthcare workers at high risk of SARS-CoV-2 infection for future research on blood markers to predict SARS-CoV-2 infection. TRIAL DESIGN: Multicentre double-blind parallel design (ratio 1:1) randomized controlled clinical trial. PARTICIPANTS: Approximately 440 healthcare workers of four Spanish hospitals (Hospital Clínic of Barcelona, Hospital de la Santa Creu i Sant Pau of Barcelona, Hospital Plató of Barcelona, Hospital General de Granollers, Barcelona) will be recruited. Participants are considered to be at high-risk of SARS-CoV-2 infection due to their frequent contact with suspected and confirmed cases of COVID-19. For eligibility, healthcare workers with 18 years old or older working at least 3 days a week in a hospital with both negative SARS-CoV-2 polymerase chain reaction (PCR) assays and serological COVID-19 rapid diagnostic tests (RDT) are invited to participate. Participants with any of the following conditions are excluded: pregnancy, breastfeeding, ongoing antiviral, antiretroviral or corticosteroids treatment, chloroquine or hydroxychloroquine uptake the last month or any contraindication to hydroxychloroquine treatment. INTERVENTION AND COMPARATOR: Eligible participants will be allocated to one of the two study groups: Intervention group (PrEP): participants will receive the standard of care and will take 400mg of hydroxychloroquine (2 tablets of 200 mg per Dolquine® tablet) daily the first four consecutive days, followed by 400 mg weekly for a period of 6 months. CONTROL GROUP: participants will receive placebo tablets with identical physical appearance to hydroxychloroquine 200 mg (Dolquine®) tablets following the same treatment schedule of the intervention group. Both groups will be encouraged to use the personal protection equipment (PPE) for COVID-19 prevention according to current hospital guidelines. MAIN OUTCOMES: The primary endpoint will be the number of confirmed cases of a COVID-19 (defined by a positive PCR for SARS-CoV-2 or symptoms compatible with COVID-19 with seroconversion) in the PrEP group compared to the placebo group at any time during the 6 months of the follow-up in healthcare workers with negative SARS-CoV-2 PCR and serology at day 0. As secondary endpoints, we will obtain: i) the SARS-CoV-2 seroconversion in the PrEP group compared to placebo during the 6 months of follow-up in healthcare workers with negative serology at day 0; ii) the occurrence of any adverse event related with hydroxychloroquine treatment; iii) the incidence of SARS-CoV-2 infection and COVID-19 among healthcare workers in the non-PrEP group, among the total of healthcare workers included in the non-PrEP group during the study period; iv) the risk ratio for the different clinical, analytical and microbiological conditions to develop COVID-19; v) a repository of serum samples obtained from healthcare workers confirmed COVID-19 cases for future research on blood markers to predict SARS-CoV-2 infection. RANDOMISATION: Participants meeting all eligibility requirements will be allocated to one of the two study arms (PrEP with hydroxychloroquine or non-PrEP control group) in a 1:1 ratio using simple randomisation with computer generated random numbers. BLINDING (MASKING): Participants, doctors and nurses caring for participants, and investigators assessing the outcomes will be blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Each intervention group will have 220 participants, giving a total of 440 participants. TRIAL STATUS: The current protocol version is 1.5, 2nd of June 2020. Two hundred and seventy-fiveparticipants were recruited and completed first month follow-up until date. The estimated sample size could not be reached yet due to the declining national epidemic curve. Thus, 275 is the total number of participants included until date. The study has been suspended (26th of June) until new epidemic curve occurs. TRIAL REGISTRATION: This trial was registered on April 2nd 2020 at clinicaltrials.gov with the number NCT04331834. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Narratives between science and politics in chloroquine activism

The current sanitary and pandemic crisis generated a set of global tensions, schemes and conflicts in different scientific, politic-party and economic spaces. The drugs hydroxychloroquine and chloroquine gained fame and expectations. What until then served only to treat malaria, now had a "cure possibility" for Covid-19. In this article we sought to understand the debate between science and politics that was generated through a research with chloroquine (Chlorocovid-19) and developed in Manaus, Amazonas. Through an ethnography woven with documents such as videos, notes, letters and messages broadcast on social media, we described and analyzed: (a) what we call chloroquine activity in Manaus and its offensive;(b) the consequent academic reaction to the attacks. Both poles-pro and contra-made efforts in the construction of a truth, in which science and politics cross-link. © 2020.