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Identification of Distinct Clinical Subphenotypes in Critically Ill Patients With COVID-19.
Vasquez, Charles R; Gupta, Shruti; Miano, Todd A; Roche, Meaghan; Hsu, Jesse; Yang, Wei; Holena, Daniel N; Reilly, John P; Schrauben, Sarah J; Leaf, David E; Shashaty, Michael G S.
  • Vasquez CR; Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA. Electronic address: Charles.vasquez@pennmedicine.upenn.edu.
  • Gupta S; Harvard Medical School, Boston, MA; Division of Renal Medicine, Brigham and Women's Hospital, Boston, MA.
  • Miano TA; Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
  • Roche M; Renal-Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
  • Hsu J; Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
  • Yang W; Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
  • Holena DN; Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
  • Reilly JP; Pulmonary, Allergy and Critical Care Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
  • Schrauben SJ; Renal-Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
  • Leaf DE; Harvard Medical School, Boston, MA; Division of Renal Medicine, Brigham and Women's Hospital, Boston, MA.
  • Shashaty MGS; Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; Pulmonary, Allergy and Critical Care Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
Chest ; 160(3): 929-943, 2021 09.
Article in English | MEDLINE | ID: covidwho-1220138
ABSTRACT

BACKGROUND:

Subphenotypes have been identified in patients with sepsis and ARDS and are associated with different outcomes and responses to therapies. RESEARCH QUESTION Can unique subphenotypes be identified among critically ill patients with COVID-19? STUDY DESIGN AND

METHODS:

Using data from a multicenter cohort study that enrolled critically ill patients with COVID-19 from 67 hospitals across the United States, we randomly divided centers into discovery and replication cohorts. We used latent class analysis independently in each cohort to identify subphenotypes based on clinical and laboratory variables. We then analyzed the associations of subphenotypes with 28-day mortality.

RESULTS:

Latent class analysis identified four subphenotypes (SP) with consistent characteristics across the discovery (45 centers; n = 2,188) and replication (22 centers; n = 1,112) cohorts. SP1 was characterized by shock, acidemia, and multiorgan dysfunction, including acute kidney injury treated with renal replacement therapy. SP2 was characterized by high C-reactive protein, early need for mechanical ventilation, and the highest rate of ARDS. SP3 showed the highest burden of chronic diseases, whereas SP4 demonstrated limited chronic disease burden and mild physiologic abnormalities. Twenty-eight-day mortality in the discovery cohort ranged from 20.6% (SP4) to 52.9% (SP1). Mortality across subphenotypes remained different after adjustment for demographics, comorbidities, organ dysfunction and illness severity, regional and hospital factors. Compared with SP4, the relative risks were as follows SP1, 1.67 (95% CI, 1.36-2.03); SP2, 1.39 (95% CI, 1.17-1.65); and SP3, 1.39 (95% CI, 1.15-1.67). Findings were similar in the replication cohort.

INTERPRETATION:

We identified four subphenotypes of COVID-19 critical illness with distinct patterns of clinical and laboratory characteristics, comorbidity burden, and mortality.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Critical Illness / Renal Replacement Therapy / Acute Kidney Injury / Pandemics / COVID-19 Type of study: Cohort study / Experimental Studies / Observational study / Prognostic study / Randomized controlled trials Limits: Aged / Female / Humans / Male / Middle aged Country/Region as subject: North America Language: English Journal: Chest Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Critical Illness / Renal Replacement Therapy / Acute Kidney Injury / Pandemics / COVID-19 Type of study: Cohort study / Experimental Studies / Observational study / Prognostic study / Randomized controlled trials Limits: Aged / Female / Humans / Male / Middle aged Country/Region as subject: North America Language: English Journal: Chest Year: 2021 Document Type: Article