Surging ICU during COVID-19 pandemic: an overview.

PURPOSE OF REVIEW: The coronavirus disease 2019 (COVID-19) pandemic has posed great challenges to intensive care units (ICUs) across the globe. The objective of this review is to provide an overview on how ICU surging was managed during COVID-19 pandemic, with a special focus on papers published in the last 18 months. RECENT FINDINGS: From the onset of the COVID-19 pandemic, it was apparent that the biggest challenge was the inequity of access to an adequately equipped and staffed ICU bed. The first wave was overwhelming; large surge of patients required critical care, resources were limited and non-COVID-19 care processes were severely compromised. Various approaches were used to address ICU staffing shortage and to expand the physical ICU space capacity. Because of restrictions to family visitations in most ICUs, the pandemic posed a threat to communication and family-centered ICU care. The pandemic, especially during the first wave, was accompanied by a high level of apprehension in the community, many uncertainties about clinical course and therapy and an influx of speculations and misinformation. SUMMARY: Although healthcare systems learned how to face some of the challenges with subsequent waves, the pandemic had persistent effects on healthcare systems.

Anti-C5a antibody (vilobelimab) therapy for critically ill, invasively mechanically ventilated patients with COVID-19 (PANAMO): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial.

BACKGROUND: Vilobelimab, an anti-C5a monoclonal antibody, was shown to be safe in a phase 2 trial of invasively mechanically ventilated patients with COVID-19. Here, we aimed to determine whether vilobelimab in addition to standard of care improves survival outcomes in this patient population. METHODS: This randomised, double-blind, placebo-controlled, multicentre phase 3 trial was performed at 46 hospitals in the Netherlands, Germany, France, Belgium, Russia, Brazil, Peru, Mexico, and South Africa. Participants aged 18 years or older who were receiving invasive mechanical ventilation, but not more than 48 h after intubation at time of first infusion, had a PaO2/FiO2 ratio of 60-200 mm Hg, and a confirmed SARS-CoV-2 infection with any variant in the past 14 days were eligible for this study. Eligible patients were randomly assigned (1:1) to receive standard of care and vilobelimab at a dose of 800 mg intravenously for a maximum of six doses (days 1, 2, 4, 8, 15, and 22) or standard of care and a matching placebo using permuted block randomisation. Treatment was not continued after hospital discharge. Participants, caregivers, and assessors were masked to group assignment. The primary outcome was defined as all-cause mortality at 28 days in the full analysis set (defined as all randomly assigned participants regardless of whether a patient started treatment, excluding patients randomly assigned in error) and measured using Kaplan-Meier analysis. Safety analyses included all patients who had received at least one infusion of either vilobelimab or placebo. This study is registered with ClinicalTrials.gov, NCT04333420. FINDINGS: From Oct 1, 2020, to Oct 4, 2021, we included 368 patients in the ITT analysis (full analysis set; 177 in the vilobelimab group and 191 in the placebo group). One patient in the vilobelimab group was excluded from the primary analysis due to random assignment in error without treatment. At least one dose of study treatment was given to 364 (99%) patients (safety analysis set). 54 patients (31%) of 177 in the vilobelimab group and 77 patients (40%) of 191 in the placebo group died in the first 28 days. The all-cause mortality rate at 28 days was 32% (95% CI 25-39) in the vilobelimab group and 42% (35-49) in the placebo group (hazard ratio 0·73, 95% CI 0·50-1·06; p=0·094). In the predefined analysis without site-stratification, vilobelimab significantly reduced all-cause mortality at 28 days (HR 0·67, 95% CI 0·48-0·96; p=0·027). The most common TEAEs were acute kidney injury (35 [20%] of 175 in the vilobelimab group vs 40 [21%] of 189 in the placebo), pneumonia (38 [22%] vs 26 [14%]), and septic shock (24 [14%] vs 31 [16%]). Serious treatment-emergent adverse events were reported in 103 (59%) of 175 patients in the vilobelimab group versus 120 (63%) of 189 in the placebo group. INTERPRETATION: In addition to standard of care, vilobelimab improves survival of invasive mechanically ventilated patients with COVID-19 and leads to a significant decrease in mortality. Vilobelimab could be considered as an additional therapy for patients in this setting and further research is needed on the role of vilobelimab and C5a in other acute respiratory distress syndrome-causing viral infections. FUNDING: InflaRx and the German Federal Government.

Perceptions of Critical Care Shortages, Resource Use, and Provider Well-being During the COVID-19 Pandemic: A Survey of 1,985 Health Care Providers in Brazil.

BACKGROUND: Brazil has been disproportionately affected by COVID-19, placing a high burden on ICUs. RESEARCH QUESTION: Are perceptions of ICU resource availability associated with end-of-life decisions and burnout among health care providers (HCPs) during COVID-19 surges in Brazil? STUDY DESIGN AND METHODS: We electronically administered a survey to multidisciplinary ICU HCPs during two 2-week periods (in June 2020 and March 2021) coinciding with COVID-19 surges. We examined responses across geographical regions and performed multivariate regressions to explore factors associated with reports of: (1) families being allowed less input in decisions about maintaining life-sustaining treatments for patients with COVID-19 and (2) emotional distress and burnout. RESULTS: We included 1,985 respondents (57% physicians, 14% nurses, 12% respiratory therapists, 16% other HCPs). More respondents reported shortages during the second surge compared with the first (P < .05 for all comparisons), including lower availability of intensivists (66% vs 42%), ICU nurses (53% vs 36%), ICU beds (68% vs 22%), and ventilators for patients with COVID-19 (80% vs 70%); shortages were highest in the North. One-quarter of HCPs reported that families were allowed less input in decisions about maintaining life-sustaining treatments for patients with COVID-19, which was associated with lack of intensivists (adjusted relative risk [aRR], 1.37; 95% CI, 1.05-1.80) and ICU beds (aRR, 1.71; 95% CI, 1.16-2.62) during the first surge and lack of N95 masks (aRR, 1.43; 95% CI, 1.10-1.85), noninvasive positive pressure ventilation (aRR, 1.56; 95% CI, 1.18-2.07), and oxygen concentrators (aRR, 1.50; 95% CI, 1.13-2.00) during the second surge. Burnout was higher during the second surge (60% vs 71%; P < .001), associated with witnessing colleagues at one's hospital contract COVID-19 during both surges (aRR, 1.55 [95% CI, 1.25-1.93] and 1.31 [95% CI, 1.11-1.55], respectively), as well as worries about finances (aRR, 1.28; 95% CI, 1.02-1.61) and lack of ICU nurses (aRR, 1.25; 95% CI, 1.02-1.53) during the first surge. INTERPRETATION: During the COVID-19 pandemic, ICU HCPs in Brazil experienced substantial resource shortages, health care disparities between regions, changes in end-of-life care associated with resource shortages, and high proportions of burnout.

Tocilizumab and remdesivir in hospitalized patients with severe COVID-19 pneumonia: a randomized clinical trial.

PURPOSE: Trials of tocilizumab in patients with severe COVID-19 pneumonia have demonstrated mixed results, and the role of tocilizumab in combination with other treatments is uncertain. Here we evaluated whether tocilizumab plus remdesivir provides greater benefit than remdesivir alone in patients with severe COVID-19 pneumonia. METHODS: This randomized, double-blind, placebo-controlled, multicenter trial included patients hospitalized with severe COVID-19 pneumonia requiring > 6 L/min supplemental oxygen. Patients were randomly assigned (2:1 ratio) to receive tocilizumab 8 mg/kg or placebo intravenously plus ≤ 10 days of remdesivir. The primary outcome was time from randomization to hospital discharge or "ready for discharge" (defined as category 1, assessed by the investigator on a 7-category ordinal scale of clinical status) to day 28. Patients were followed for 60 days. RESULTS: Among 649 enrolled patients, 434 were randomly assigned to tocilizumab plus remdesivir and 215 to placebo plus remdesivir. 566 patients (88.2%) received corticosteroids during the trial to day 28. Median time from randomization to hospital discharge or "ready for discharge" was 14 (95% CI 12-15) days with tocilizumab plus remdesivir and 14 (95% CI 11-16) days with placebo plus remdesivir [log-rank P = 0.74; Cox proportional hazards ratio 0.97 (95% CI 0.78-1.19)]. Serious adverse events occurred in 128 (29.8%) tocilizumab plus remdesivir and 72 (33.8%) placebo plus remdesivir patients; 78 (18.2%) and 42 (19.7%) patients, respectively, died by day 28. CONCLUSIONS: Tocilizumab plus remdesivir did not shorten time to hospital discharge or "ready for discharge" to day 28 compared with placebo plus remdesivir in patients with severe COVID-19 pneumonia.

Case Study of Two Post Vaccination SARS-CoV-2 Infections with P1 Variants in CoronaVac Vaccinees in Brazil.

The rapid development of efficacious and safe vaccines against coronavirus disease 2019 (COVID-19) has been instrumental in mitigating the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Moreover, the emergence of SARS-CoV-2 variants raised concerns on the efficacy of these vaccines. Herein, we report two cases of breakthrough infections with the P1 variant in patients vaccinated with CoronaVac, which is one of the two vaccines authorized for emergency use in the Brazilian immunization program. Our observations suggest that the vaccine reduced the severity of the disease and highlight the potential risk of illness following vaccination and subsequent infection with the P1 variant as well as for continued efforts to prevent and diagnose infection in vaccinated persons.

Presentation of fatal stroke due to SARS-CoV-2 and dengue virus coinfection.

Herein, we report a case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and dengue coinfection, presented as a fatal stroke in our hospital, in São José do Rio Preto, São Paulo State, a Brazilian city hyperendemic for dengue viruses and other arthropod-borne viruses (arboviruses) and currently facing a surge of SARS-CoV-2 cases. This case is the first described in the literature and contributes to the better understanding of clinical presentations of two important diseases in a tropical setting.