Efficacy and safety of convalescent plasma and intravenous immunoglobulin in critically ill COVID-19 patients. A controlled clinical trial.

BackgroundThe proportion of critically ill COVID-19 patients has collapsed hospital care worldwide. The need for alternative therapies for this group of patients is imperative. This study aims to compare the safety and efficacy of convalescent plasma (CP) compared with human immunoglobulin (IVIg) in patients requiring the administration of high oxygen levels or mechanical ventilation. MethodsThis is a controlled, randomized, open clinical trial of patients with pneumonia secondary to SARS-CoV-2 infection, that fulfilled criteria for severe or critical disease. They were randomized in a 1:2 ratio; group 1 was administered IVIg at a dose of 0.3 grams per kilogram of ideal weight, in an 8-hour infusion every 24 hours, for 5 days. Group 2 was administered 200 ml of CP infused in 2 hours, for 2 days. The primary outcomes were duration of hospitalization and mortality at 28 days. ResultsOne hundred and ninety (190) patients were randomized; 130 to the CP group, and 60 to the IVIg group. Their average age was 58 years (IQR 47 - 72), and most were male (n= 119, 62.6 %). On inclusion, 85.2 % of patients (n=162) were on invasive mechanical ventilation therapy. Overall mortality in all included patients was 53 % (n= 102), with a median follow-up of 14 days (IQI 8 - 26). Mortality at 28 days was 45.2 % (n=86). In the intention-to-treat analysis, there was no difference between groups neither in mortality on follow-up (53.8 vs. 53.3, p =1.0) nor at 28 days (46.2 vs 43 %, p=0.75, Log Rank p = 0.83). Per-protocol analysis between treatment groups revealed no difference in mortality throughout hospitalization (51.5 vs 51.4 %, p=1.0) nor after 28 days (42.1 vs 42.87 %, p=0.92 Log Rank p = 0.54). Only 23 patients in the CP group received plasma with detectable anti-SARS-CoV-2 antibodies. ConclusionsIn critically ill patients or on invasive mechanical ventilation for treatment of Covid-19, the use of CP is not superior to IVIg in terms of hospitalization duration or mortality. The use of CP is based on complex logistics and requires an assured level of antibodies if used therapeutically. IVIg does not appear to be useful in this group of patients. clinicaltrials.gov identifier: NCT04381858.

Factors associated with increased mortality in critically ill COVID-19 patients in a Mexican public hospital: the other faces of health system oversaturation.

BACKGROUNDThe lethality rate of COVID-19 in Mexico is one of the highest worldwide, but in-hospital factors associated with this increased rate have yet to be explored. This study aims to evaluate those factors that could be associated with mortality at 28-days in critically ill COVID-19 patients in Mexico. METHODSThis is a retrospective analysis of the patients included in the clinical trial (NCT04381858) which recruited patients with severe COVID-19 with high oxygen requirement or mechanical ventilation from May to October 2020. The primary outcome, death at 28, was analyzed. RESULTSBetween May and October 2020, 196 predominantly male patients (n=122, 62.2%) with an average of 58.1 years ({+/-} 15.5), were included in the cohort. Mortality at 28 days was 44.3 % (n= 84). Patients included in the second trimester had a greater mortality rate when compared with those recruited in the first trimester (54.1 vs 32.1, p< 0.01). On multivariate analysis, the detected protective factors were the use of fentanyl HR 0.51 (95%CI 0.31 - 0.85, p=0.01), the use of antibiotics HR 0.22 (95% CI 0.13 - 0.36, p<0.01), and a previously healthy state (no comorbidities other than obesity) HR 0.58 (95%CI 0.35 - 0.94, p =0.03); risk factors were severe kidney injury (AKIN3) HR 1.74 (95%CI 1.04 - 2.9, p=0.035), elevated D-Dimer levels HR 1.02 (95%CI 1.007 - 1.04, p=0.005), shock OR 5.8 (2.4 - 13.8, p<0.01), and recruitment in the second trimester OR 2.3 ((1.1 - 4.8, p=0.02). CONCLUSIONSIn-hospital mortality in critically ill COVID-19 patients has increased in our center. The appropriate use of antibiotics, the type of sedation, and AKIN3 are modifiable factors directly related to this increased mortality. The increase in mortality observed in the second trimester is explained by hospital overcrowding that began in August 2020.

Efficacy and safety of Ivermectin and Hydroxychloroquine in patients with severe COVID-19. A randomized controlled trial

BackgroundIn the search for active drugs against COVID-19, the indications of many have been redirected. Ivermectin and Hydroxychloroquine are drugs that inhibit viral replication in vitro and that have been used in several medical centers. ObjectivesThis clinical trial analyzes the efficacy of Ivermectin and Hydroxychloroquine in patients with moderate COVID-19 and in need of hospitalization. MethodsThis a controlled, clinical, randomized, double-blind trial that included patients with COVID-19-induced pneumonia and hospitalization criteria, but no severe respiratory failure. Patients were randomized to one of three groups: Group1-hydroxychloroquine, 400 mg every 12 hours on the first day and subsequently, 200 mg every 12 hours for 4 days, Group 2-ivermectin, 12 mg or 18 mg, according to patient weight and, Group 3-placebo. At inclusion, blood samples for arterial blood gases and biochemical markers associated with a poor prognosis were obtained. The primary outcome was established as the duration of hospitalization until discharge due to patient improvement, the total duration of hospitalization, and the safety outcomes were either respiratory deterioration or death. ResultsDuring the month of August, the admission of patients requiring hospitalization mostly encompassed cases with severe respiratory failure, so we ended the recruitment process and analyzed the data that was available at the time. One hundred and six (106) patients with an average age of 53 yrs. ({+/-}16.9) were included, with a greater proportion of males (n=66, 62.2 %). Seventy-two percent (72%) (n= 76) had an associated comorbidity. Ninety percent (90 %) of patients were discharged due to improvement (n=96). The average duration of hospitalization was 6 days (IQR, 3 - 10). No difference in hospitalization duration was found between the treatment groups (Group1: 7 vs Group 2: 6 vs Group 3: 5, p=0.43) nor in respiratory deterioration or death (Group 1: 18 % vs Group 2: 22.2 % vs Group 3: 24.3 %, p =0.83). ConclusionsIn non-critical hospitalized patients with COVID-19 pneumonia, neither ivermectin nor hydroxychloroquine decreases the number of in-hospital days, respiratory deterioration, or deaths. ClinicalTrials identifier NCT04391127