ABSTRACT
BackgroundClinical presentation of severe Coronavirus disease 2019 (COVID-19) is associated to an intense inflammatory response and thrombogenesis. The benefits of the association of interleukin-6 receptor blockade (tocilizumab) and therapeutic-dose anticoagulation remains unclear. We aimed to assess whether heparin and tocilizumab could effectively reduce inflammation and thrombogenesis in severe COVID-19 patients. MethodsThis is an open-label, multicenter, randomized, clinical trial, involving patients with severe COVID-19 infection. Eligible patients were randomly assigned in a 1:1:1:1 ratio to receive either therapeutic or prophylactic anticoagulation with heparin, with or without an intravenous single dose of tocilizumab. The participants in the study were assigned to one of the four distinct arms: 1) therapeutic anticoagulation; 2) prophylactic anticoagulation; 3) therapeutic anticoagulation plus a single intravenous dose of tocilizumab; and 4) prophylactic anticoagulation plus a single intravenous dose of tocilizumab. The primary outcome was clinical improvement at day 30, defined as a composite of hospital discharge and/or a reduction of at least 2 points of the modified ordinal scale of 7 points recommended by the World Health Organization. ResultsWe enrolled 308 patients. Patients randomized to receive therapeutic anticoagulation more frequently had clinical improvement at day 30 when compared to the prophylactic anticoagulation patients [64/75 (85%) versus 51/80 (64%), odds ratio, 3.31; 95% confidence interval, 1.51; 7.26 P=0.003]. Major bleeding was more frequent in the therapeutic anticoagulation group (6.7%) and in the therapeutic anticoagulation plus tocilizumab group (5.0%), compared to the prophylactic anticoagulation group (P=0.02). All-cause mortality at day 30 was significantly lower in therapeutic anticoagulation group (9.3%), when compared to prophylactic anticoagulation group (28.7%), therapeutic anticoagulation plus tocilizumab group (21.5%) and prophylactic anticoagulation plus tocilizumab group (25.7%), P=0.02. ConclusionsIn this randomized clinical trial involving severe COVID-19 patients, therapeutic anticoagulation resulted in clinical improvement at 30 days. Even if therapeutic anticoagulation increased bleeding, it was associated with a reduced overall mortality. Tocilizumab did not provide additional benefits to heparin in COVID-19 patients. Trial registrationClinicaltrials.gov NCT04600141. Registered October 22, 2020. https://www.clinicaltrials.gov/study/NCT04600141?term=NCT04600141&rank=1
Subject(s)
COVID-19 , Hemorrhage , InflammationABSTRACT
Effective vaccination against coronavirus (COVID) mitigates the risk of hospitalizations and mortality but it is unclear whether the vaccination status may influence the post-COVID symptoms in patients who required hospitalization. The available evidence is limited to outpatients with mild cases. Here, we evaluated 412 patients (age: 60 ± 16 years, 65% males) consecutively admitted at two Hospitals in Brazil due to a confirmed case of COVID-19. As compared to patients with complete vaccination (n = 185) before infection/hospitalization, those with no/incomplete vaccination (n = 227) were younger and had a lower frequency of several comorbidities. Data during hospitalization revealed that the no/incomplete vaccination group required more admissions in the intensive care unit, used more corticosteroids and had higher rates of pulmonary embolism/deep venous thrombosis than the complete vaccination group. At 90 days after hospital discharge, patients with no/incomplete vaccination presented a higher frequency of ≥ 1 symptom than patients with complete vaccination: 40 vs. 27%; p = 0.013. After adjustments for confounders, no/incomplete vaccination (OR = 1.819; 95% CI:1.175–2.815), females (OR = 2.435; 95% CI:1.575–3.764) and intensive care unit admission during hospitalization (OR = 1.697; 95% CI:1.062–2.712) were independently associated with ≥ 1 symptom 90-days after hospital discharge. In conclusion, even in patients with more severe COVID-19 infection, vaccination mitigate the probability of long-COVID symptoms.
Subject(s)
COVID-19ABSTRACT
INTRODUCTIONCOVID-19 convalescent plasma (CCP) transfusion has emerged in the past months as an alternative approach to treat pneumonia cases of SARS-CoV-2. Current evidence regarding characteristics of the plasma product, the titer of neutralizing antibodies (nAbs) in the transfused units, time to onset of intervention, and impact of nAbs produced by the patient are limited and heterogeneous. MATERIAL AND METHODSWe describe the preliminary results of 104 patients with severe pneumonia due to SARS-CoV-2 transfused with CCP at three medical centers in Brazil. All enrolled patients were transfused with doses between 200 mL through 600mL of ABO compatible CCP on days 0-2 after enrolment. Clinical parameters were monitored and nAbs titration was performed using the cytopathic effect-based virus neutralization test with SARS-CoV-2 (GenBank MT126808.1). RESULTSForty-one patients achieved clinical improvement on day 14, and multivariable logistic regression showed that nAbs T (from CCP units transfused) (p= 0.001), nAbs P0 (on day of enrolment) (p=0.009) and use of other supportive therapies (p<0.001) were associated with higher odds for this clinical improvement. Considering ICU length of stay (LOS) and length of mechanical ventilation, in our analysis, nAbs P0 were associated with a significant reduction in ICU LOS (p=0.018) and duration of mechanical ventilation (p<0.001). Administration of CCP after 10 days of symptom onset was associated with increases in ICU length of stay (p<0.001). DISCUSSION/CONCLUSIONDespite the study limitations, our data have shown an association between patients previously acquired nAbs and clinical outcomes. The potential value of timely administration of CCP transfusion before day 10 of disease onset was demonstrated and nAbsP0, but not nAbsT, were associated with ICU LOS, and duration of mechanical ventilation on the improvement of clinical outcomes was also demonstrated. In conclusion, we consider these data are useful parameters to guide future CPP transfusion strategies to COVID-19.