Inflammation, Thrombosis Biomarkers Tied to COVID-19 Deaths


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Biomarkers for inflammation and thrombosis may predict deaths from COVID-19 among critically ill patients, researchers say.

Their prospective cohort study of 1150 patients hospitalized with the disease in New York City also revealed a high proportion of racial and ethnic minorities, and confirmed high rates of critical illness and mortality.

“Of particular interest is the finding that over three quarters of critically ill patients required a ventilator and almost one third required renal dialysis support,” Max O’Donnell, MD, MPH, assistant professor of medicine and epidemiology at Columbia University in New York City, said in a press release.

O’Donnell and colleagues published the results of their study online today in The Lancet. It is the largest prospective cohort study published in the United States, they said.

“Although the clinical spectrum of disease has been characterised in reports from China and Italy, until now, detailed understanding of how the virus is affecting critically ill patients in the US has been limited to reports from a small number of cases,” said Natalie Yip, MD, assistant professor of medicine at Columbia University.

In the cohort, drawn from two NewYork-Presbyterian hospitals, the researchers focused on the 257 (22%) patients who required intensive care. When they estimated inflammation through interleukin-6 (IL-6) concentrations and thrombosis through D-dimer concentrations, they found a 10% increased risk for death with every 10% increase of IL-6 (adjusted hazard ratio [aHR], 1.11; 95% confidence interval [CI], 1.02–1.20) or D-dimer concentration (aHR, 1.10; 95% CI, 1.01–1.19).

“The association of mortality with higher concentrations of IL-6 and D-dimer is particularly relevant for two reasons,” write Giacomo Grasselli, from the Fondazione IRCCS Ca’ Granda Ospediale Maggiore Policlinico, and Alberto Zanella, from the University of Milan, Italy, in an accompanying commentary.

“First, it confirms the key pathogenic role played by the activation of systemic inflammation and endothelial-vascular damage in the development of organ dysfunction,” they write. “Second, it provides the rationale for the design of clinical trials for measuring the efficacy of treatment with immunomodulating and anticoagulant drugs.”

Seventeen percent of patients received interleukin receptor antagonists and 26% received corticosteroids, but the authors did not report any data on the effects of these treatments, or any data about anticoagulant therapies administered.

Severe Disease Common

The study also highlighted a high proportion of ethnic and racial minorities. Sixty-two percent of the critically ill patients were Hispanic or Latinx, 19% Black, 32% White, and 3% Asian.

Their median age was 62 years and 67% were men. Eighty-two percent had at least one chronic illness, most commonly hypertension (63%), followed by diabetes (36%). Forty-six percent were obese.

As of April 28, 2020, 101 (39%) of the critically ill patients had died following a median of 9 days (interquartile range (IQR), 5–15) in the hospital and 94 (37%) remained hospitalized. Of the 203 patients who received invasive mechanical ventilation, 84 (41%) had died.

The poor prognosis of patients requiring ventilation is consistent with data from a report on patients treated in National Health Service intensive care units in England, Wales, and Northern Ireland through May 15. Overall, 11,292 patients with COVID-19 required critical care, and 4855 needed advanced respiratory support. Approximately half of the patients receiving mechanical ventilation had died 30 days after starting critical care.

In the New York study, patients spent an average of 18 days on a ventilator (IQR, 9–28 days). This is a longer period than reported in smaller studies of cases from Washington state, but corresponds with a recent report from Italy, the researchers said.

Remarkably, O’Donnell and colleagues report that almost a third (31%) of critically ill patients developed severe kidney damage and required dialysis.

Mortality was associated with several baseline factors, including older age (aHR, 1.31 [95% CI, 1.09–1.57] per 10-year increase), chronic cardiac disease (aHR, 1.76; 95% CI, 1.08–2·86), and chronic pulmonary disease (aHR, 2.94; 95% CI, 1.48–5.84).

Authors of the New York study reported financial relationships to ICE Neurosystems, ALung Technologies, Baxter, BREETHE, Xenios, Hemovent, Gilead Sciences, Amazon, and Karyopharm Therapeutics.

Grasselli reports personal fees from Biotest, Draeger, Fisher & Paykel, Maquet, Merck Sharp & Dohme, and Pfizer, all outside the area of work commented on here. Zanella has disclosed no relevant financial relationships.

The Lancet. Published online May 19, 2020. Full text

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