Background passive immunotherapy is a therapeutic alternative for patients with COVID-19. Equine polyclonal antibodies (EpAbs) could represent a source of scalable neutralizing antibodies against SARS-CoV-2. Methods we conducted a double-blind, randomized, placebo-controlled trial to assess efficacy and safety of EpAbs (INM005) in hospitalized adult patients with moderate and severe COVID-19 pneumonia in 19 hospitals of Argentina. Primary endpoint was improvement in at least two categories in WHO ordinal clinical scale at day 28 or hospital discharge (ClinicalTrials.gov number NCT04494984). Findings between August 1st and October 26th, 2020, a total of 245 patients were enrolled. Enrolled patients were assigned to receive two blinded doses of INM005 ( n = 118) or placebo ( n = 123). Median age was 54 years old, 65•1% were male and 61% had moderate disease at baseline. Median time from symptoms onset to study treatment was 6 days (interquartile range 5 to 8). No statistically significant difference was noted between study groups on primary endpoint (risk difference [95% IC]: 5•28% [-3•95; 14•50]; p = 0•15). Rate of improvement in at least two categories was statistically significantly higher for INM005 at days 14 and 21 of follow-up. Time to improvement in two ordinal categories or hospital discharge was 14•2 (± 0•7) days in the INM005 group and 16•3 (± 0•7) days in the placebo group, hazard ratio 1•31 (95% CI 1•0 to 1•74). Subgroup analyses showed a beneficial effect of INM005 over severe patients and in those with negative baseline antibodies. Overall mortality was 6•9% the INM005 group and 11•4% in the placebo group (risk difference [95% IC]: 0•57 [0•24 to 1•37]). Adverse events of special interest were mild or moderate; no anaphylaxis was reported. Interpretation Albeit not having reached the primary endpoint, we found clinical improvement of hospitalized patients with SARS-CoV-2 pneumonia, particularly those with severe disease.

Summary Background Influenza continues to have a significant socioeconomic and health impact despite a long established vaccine program and approved antivirals. Preclinical data suggest combination antivirals might be more effective than oseltamivir alone in the treatment of influenza. Methods We conducted a randomized, double-blinded, multicenter phase 2 trial of combination antivirals versus monotherapy for the treatment of influenza. Participants ≥18 years with influenza at increased risk of complications from influenza were randomized by an online computer-generated randomization system to receive either oseltamivir, amantadine, and ribavirin or oseltamivir alone for 5 days, and followed for 28 days. The primary endpoint was the percentage of participants with virus detectable by polymerase chain reaction in nasopharyngeal swab at Day 3. Among the secondary outcomes, there were safety and time to alleviation of influenza clinical symptoms. ClinicalTrials.gov Identifier: NCT01227967. Findings Between March 2011 and April 2016 we randomized 633 participants. Seven participants were excluded from analysis: 3 were given treatment without randomization, 3 withdrew before taking any medication, and 1 was lost to follow-up. The primary analysis included 394 participants, excluding 47 in the pilot phase, 172 without confirmed influenza, and 13 without an endpoint sample. 80 of 200 (40.0%) participants in the combination arm had virus detectable at Day 3 compared to 97 of 194 (50.0%) (95%C.I. 0.2–19.8%, p=0.046) in the control arm. There was no benefit, however, in multiple clinical secondary endpoints, such as median duration of symptoms (4.5 days in the combination arm vs 4.0 days in the oseltamivir arm; p = 0.21). Interpretation Although oseltamivir, amantadine, and ribavirin showed a statistically significant decrease in viral shedding at Day 3 relative to oseltamivir, this difference was not associated with improved clinical benefit. More work is needed to understand the lack of clinical benefit when a difference in virologic outcome was identified. Funding National Institute of Allergy and Infectious Diseases, National Institutes of Health, United States.

Background Clinical features and outcomes of SARS-CoV-2 infections diverge in different countries. The aim of this study was to describe clinical characteristics and outcomes in a cohort of patients hospitalized with SARS-CoV-2 in Argentina. Methods Multicenter prospective cohort study of ≥18 years-old patients with confirmed SARS-CoV-2 infection consecutively admitted to 19 hospitals in Argentina. Multivariable logistic regression models were used to identify variables associated with 30-day mortality and admission to intensive care unit (ICU). Results A total of 809 patients were analyzed. Median age was 53 years, 56% were males and 71% had at least one comorbidity. The most common comorbidities were hypertension (32%), obesity (23%) and diabetes (17%). Disease severity at admission was classified as mild 25%, moderate 51%, severe 17%, and critical 7%. Almost half of patients (49%) required supplemental oxygen, 18% ICU, and 12% invasive ventilation. Overall, 30-day mortality was 11%. Factors independently associated with ICU admission were male gender (OR 1.81; 95%CI 1.16–2.81), hypertension (OR 3.21; 95%CI 2.08–4.95), obesity (OR 2.38; 95%CI 1.51–3.7), oxygen saturation ≤93% (OR 6.45; 95%CI 4.20–9.92) and lymphopenia (OR 3.21; 95%CI 2.08–4.95). Factors independently associated with 30-day mortality included age ≥60 years-old (OR 2.68; 95% CI 1.63–4.43), oxygen saturation ≤93% (OR 3.19; 95%CI 1.97–5.16) and lymphopenia (OR 2.65; 95%CI 1.64–4.27). Conclusions This cohort validates crucial clinical data on patients hospitalized with SARS-CoV-2 in Argentina.

Tigecycline is the first of a new class of antibiotics named glycylcyclines and it was approved for the treatment of complicated intra-abdominal infections and complicated skin and skin structure infections. Notwithstanding this, tigecycline's pharmacological and microbiological profile which includes multidrug-resistant pathogens encourages physicians' use of the drug in other infections. We analyzed, during the first months after its launch, the tigecycline prescriptions for 113 patients in 12 institutions. Twenty-five patients (22%) received tigecycline for approved indications, and 88 (78%) for "off label" indications (56% with scientific support and 22% with limited or without any scientific support). The most frequent "off label" use was ventilator associated pneumonia (VAP) (63 patients). The etiology of infections was established in 105 patients (93%). MDR-Acinetobacter spp. was the microorganism most frequently isolated (50% of the cases). Overall, attending physicians reported clinical success in 86 of the 113 patients (76%). Our study shows that the "off label" use of tigecycline is frequent, especially in VAP. due to MDRAcinetobacter spp., where the therapeutic options are limited (eg: colistin). Physicians must evaluate the benefits/ risks of using this antibiotic for indications that lack rigorous scientific support.

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