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Crit Care Med ; 49(4): 598-622, 2021 04 01.
Article in English | MEDLINE | ID: covidwho-1085323


OBJECTIVES: To identify research priorities in the management, pathophysiology, and host response of coronavirus disease 2019 in critically ill patients. DESIGN: The Surviving Sepsis Research Committee, a multiprofessional group of 17 international experts representing the European Society of Intensive Care Medicine and Society of Critical Care Medicine, was virtually convened during the coronavirus disease 2019 pandemic. The committee iteratively developed the recommendations and subsequent document. METHODS: Each committee member submitted a list of what they believed were the most important priorities for coronavirus disease 2019 research. The entire committee voted on 58 submitted questions to determine top priorities for coronavirus disease 2019 research. RESULTS: The Surviving Sepsis Research Committee provides 13 priorities for coronavirus disease 2019. Of these, the top six priorities were identified and include the following questions: 1) Should the approach to ventilator management differ from the standard approach in patients with acute hypoxic respiratory failure?, 2) Can the host response be modulated for therapeutic benefit?, 3) What specific cells are directly targeted by severe acute respiratory syndrome coronavirus 2, and how do these cells respond?, 4) Can early data be used to predict outcomes of coronavirus disease 2019 and, by extension, to guide therapies?, 5) What is the role of prone positioning and noninvasive ventilation in nonventilated patients with coronavirus disease?, and 6) Which interventions are best to use for viral load modulation and when should they be given? CONCLUSIONS: Although knowledge of both biology and treatment has increased exponentially in the first year of the coronavirus disease 2019 pandemic, significant knowledge gaps remain. The research priorities identified represent a roadmap for investigation in coronavirus disease 2019.

COVID-19 , Critical Care , Research , Sepsis/therapy , Humans
Crit Care Explor ; 2(10): e0230, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-873085


OBJECTIVES: To assess the early physiologic response to angiotensin-II treatment in patients with coronavirus disease 2019-induced respiratory failure and distributive shock. DESIGN: Retrospective consecutive-sample cohort study. SETTING: Three medical ICUs in New York during the coronavirus disease 2019 outbreak. PATIENTS: All patients were admitted to the ICU with respiratory failure and were receiving norepinephrine for distributive shock. INTERVENTIONS: The treatment groups were patients who received greater than or equal to 1 hour of angiotensin-II treatment. Time-zero was the time of angiotensin-II initiation. Controls were identified using a 2:1 hierarchical process that matched for 1) date and unit of admission; 2) specific organ support modalities; 3) age; 4) chronic lung, cardiovascular, and kidney disease; and 5) sex. Time-zero in the control group was 21 hours post vasopressor initiation, the mean duration of vasopressor therapy prior to angiotensin-II initiation in the treated group. MEASUREMENTS AND MAIN RESULTS: Main outcomes were trajectories of vasopressor requirements (in norepinephrine-equivalent dose) and mean arterial pressure. Additionally assessed trajectories were respiratory (Pao2/Fio2, Paco2), metabolic (pH, creatinine), and coagulation (d-dimer) dysfunction indices after time-zero. We also recorded adverse events and clinical outcomes. Trajectories were analyzed using mixed-effects models for immediate (first 6 hr), early (48 hr), and sustained (7 d) responses. Twenty-nine patients (n = 10 treated, n = 19 control) were identified. Despite matching, angiotensin-II-treated patients had markedly greater vasopressor requirements (mean: 0.489 vs 0.097 µg/kg/min), oxygenation impairment, and acidosis at time-zero. Nonetheless, angiotensin-II treatment was associated with an immediate and sustained reduction in norepinephrine-equivalent dose (6 hr model: ß = -0.036 µg/kg/min/hr; 95% CI: -0.054 to -0.018 µg/kg/min/hr, p interaction=0.0002) (7 d model: ß = -0.04 µg/kg/min/d, 95% CI: -0.05 to -0.03 µg/kg/min/d; p interaction = 0.0002). Compared with controls, angiotensin-II-treated patients had significantly faster improvement in mean arterial pressure, hypercapnia, acidosis, baseline-corrected creatinine, and d-dimer. Three thrombotic events occurred, all in control patients. CONCLUSIONS: Angiotensin-II treatment for coronavirus disease 2019-induced distributive shock was associated with rapid improvement in multiple physiologic indices. Angiotensin-II in coronavirus disease 2019-induced shock warrants further study.

Lancet Respir Med ; 8(12): 1233-1244, 2020 12.
Article in English | MEDLINE | ID: covidwho-867256


The description of a so-called cytokine storm in patients with COVID-19 has prompted consideration of anti-cytokine therapies, particularly interleukin-6 antagonists. However, direct systematic comparisons of COVID-19 with other critical illnesses associated with elevated cytokine concentrations have not been reported. In this Rapid Review, we report the results of a systematic review and meta-analysis of COVID-19 studies published or posted as preprints between Nov 1, 2019, and April 14, 2020, in which interleukin-6 concentrations in patients with severe or critical disease were recorded. 25 COVID-19 studies (n=1245 patients) were ultimately included. Comparator groups included four trials each in sepsis (n=5320), cytokine release syndrome (n=72), and acute respiratory distress syndrome unrelated to COVID-19 (n=2767). In patients with severe or critical COVID-19, the pooled mean serum interleukin-6 concentration was 36·7 pg/mL (95% CI 21·6-62·3 pg/mL; I2=57·7%). Mean interleukin-6 concentrations were nearly 100 times higher in patients with cytokine release syndrome (3110·5 pg/mL, 632·3-15 302·9 pg/mL; p<0·0001), 27 times higher in patients with sepsis (983·6 pg/mL, 550·1-1758·4 pg/mL; p<0·0001), and 12 times higher in patients with acute respiratory distress syndrome unrelated to COVID-19 (460 pg/mL, 216·3-978·7 pg/mL; p<0·0001). Our findings question the role of a cytokine storm in COVID-19-induced organ dysfunction. Many questions remain about the immune features of COVID-19 and the potential role of anti-cytokine and immune-modulating treatments in patients with the disease.

COVID-19/blood , Cytokine Release Syndrome/blood , Interleukin-6/blood , Biomarkers/blood , COVID-19/immunology , Cytokine Release Syndrome/immunology , Humans , Interleukin-6/immunology , Respiratory Distress Syndrome/blood , Respiratory Distress Syndrome/immunology , Sepsis/blood , Sepsis/immunology , Severity of Illness Index