An observational study today in The Lancet that involved seriously ill adults hospitalized with confirmed COVID-19 early in the outbreak in Wuhan, China, found that advanced age, signs of sepsis, and blood clotting issues were all risk factors for in-hospital death.

Knowing these risk factors could help healthcare providers identify COVID-19 patients with a poor prognosis early on, according to the authors of the retrospective cohort study, which involved patients hospitalized from Dec 29, 2019, to Jan 31, 2020.

A high Sequential Organ Failure Assessment score (5.65; 95% confidence interval [CI], 2.61 to 12.23; P < 0.0001) —indicating sepsis—and a d-dimer test result greater than 1 microgram per milliliter (to identify serious blood clots) indicated a poor prognosis, the researchers found.

This is the first and largest study of the risk factors linked to severe COVID-19 infection and death in hospitalized adults who either died or were released from the hospital, the authors said. Of 191 patients, 137 were released, and 54 (28%) died in the hospital.

Co-existing conditions portend poor prognosis

The researchers compared clinical records, treatment data, laboratory results, and demographic data of survivors versus nonsurvivors. They evaluated the clinical course of symptoms, viral shedding, and changes in laboratory findings and used mathematical models.

On average, patients were middle-aged (median, 56 years), and 62% were men. The median time from illness onset to hospital release was 22 days, and the average time from onset to death was 18.5 days. Patients who died were, on average, 69 years old, versus 52 years in survivors.

Ninety-one (48%) patients had a coexisting condition, including high blood pressure (58 [30%]), diabetes (36 [19%]), and coronary heart disease (15 [8%]). Multivariable regression showed increasing odds of in-hospital death linked to advancing age (odds ratio, 1:10; 95% CI, 1.03 to 1.17; per-year increase, P = 0.0043). Half of the patients developed sepsis.

Coronary heart disease has also been linked to cardiac events and poor outcomes in patients with flu and other respiratory viral infections. "In this study, increased high-sensitivity cardiac troponin I during hospitalisation [indicating heart damage] was found in more than half of those who died," the authors wrote.

Complications such as respiratory failure (98%, 53/54 nonsurvivors vs 36%, 50/137 survivors), sepsis (100%, 54/54 vs 42%, 58/137), and secondary infections (50%, 27/54 vs 1%, 1/137) were also higher in those who died than in survivors.

The median length of fever was about 12 days in survivors, similar to that of nonsurvivors, and 45% of survivors still had a cough at hospital release. In survivors, shortness of breath ended after about 13 days.

Virus shed for as long as 37 days

The researchers also found that the median length of viral shedding in throat swabs was 20 days in survivors (range, 8 to 37) and that viral RNA was detectable until death. "The prolonged viral shedding provides the rationale for testing novel coronavirus antiviral interventions in efforts to improve outcomes," the authors wrote.

The researchers partially attribute poor outcomes in older people to age-related weakening of the immune system and increased inflammation that could stimulate viral replication and cause prolonged responses to inflammation, damaging the heart, brain, and other organs, according to the authors.

The number of deaths reported in this study does not reflect the true COVID-19 death rate, the authors wrote. The World Health Organization recently said the mortality rate is from 3% to 4%.

The authors also point out that not all lab tests, such as serum ferritin, were done on all patients, so the role of those tests in predicting in-hospital death may be underestimated. Lastly, they noted that a lack of effective antivirals, inadequate adherence to supportive therapy, high doses of corticosteroids, and transfer of some patients to the hospital late in their illness might also be tied to poor outcomes in some patients.