In findings published Monday by The Lancet, researchers from Wuhan, China, ground zero for the ongoing outbreak, document trends in adults who ultimately died after acquiring the virus, known as COVID-19.
They observe that those infected appear to be contagious “for longer than expected.”
The study is the first in which researchers have examined risk factors associated with severe disease and death in hospitalized adults who have either died or been discharged from the hospital, because they were cured.
However, the clinicians also caution their findings — based on analysis of data from 191 patients at two hospitals in Wuhan — may be skewed, given the severe illness of those included in the study and limited samples and genetic material available for testing.
“Poorer outcomes in older people may be due, in part, to the age-related weakening of the immune system and increased inflammation that could promote viral replication and more prolonged responses to inflammation, causing lasting damage to the heart, brain and other organs,” Zhibo Liu, from Jinyintan Hospital in China, said in a press release.
In general, Liu and the other researchers, who have been working at the front lines of the outbreak, found that being of older age, having sepsis — a common infection — and having a history of blood clotting are all key risk factors associated with higher risk for death from COVID-19.
Additionally, Liu said that “underlying diseases like high blood pressure and diabetes and the prolonged use of non-invasive ventilation were important factors in the deaths of these patients.”
Of the 191 COVID-19 patients included in the analysis, 137 were discharged from the hospital and 54 died in the hospital while still receiving treatment.
Among the surviving patients, the authors found the median duration of viral shedding — how long they were contagious — was 20 days, and as high as 37 days in some. The virus was detectable until death in the 54 non-survivors.
“The extended viral shedding noted in our study has important implications for guiding decisions around isolation precautions and antiviral treatment in patients with confirmed COVID-19 infection,” said co-author Bin Cao from the China-Japan Friendship Hospital and Capital Medical University in China. “However, we need to be clear that viral shedding time should not be confused with other self-isolation guidance for people who may have been exposed to COVID-19 but do not have symptoms, as this guidance is based on the incubation time of the virus.”
While prolonged viral shedding suggests patients may be capable of spreading COVID-19, the authors said, they caution the duration of viral shedding is influenced by disease severity, and note that all patients in the study were hospitalized — two-thirds of whom had severe or critical illness.
“We recommend that negative tests for COVID-19 should be required before patients are discharged from hospital,” Cao said. “In severe influenza, delayed viral treatment extends how long the virus is shed, and together these factors put infected patients at risk of dying. Similarly, effective antiviral treatment may improve outcomes in COVID-19, although we did not observe shortening of viral shedding duration after antiviral treatment in our study.”
Among study participants, the median duration of fever was about 12 days in survivors, which was similar in non-survivors. However, the cough associated with COVID-19 may last for a long time — in fact, 45 percent of the survivors still had a cough on discharge — and shortness of breath persisted for about 13 days in survivors, but would last until death in non-survivors.
On average, patients in the study were middle-aged — median age 56 years — and most were men, while roughly half had underlying chronic conditions, the most common being high blood pressure and diabetes.
From illness onset, the median time to hospital discharge was 22 days, and the average time to death was 18.5 days.
Compared with survivors, patients who died were more likely to be older — with an average age of 69 years, versus 52 years for survivors — and have a higher score on the Sequential Organ Failure Assessment indicating sepsis and elevated blood levels of the d-dimer protein, which is a biomarker for coagulation or clotting, upon admission to the hospital.
In addition, lower lymphocyte white blood cell counts, elevated levels of Interleukin 6 — common in those with inflammation and chronic disease — and increased high-sensitivity troponin I concentrations, a common sign of heart attack, were more common in those with severe COVID-19 illness.
Perhaps not surprisingly, the frequency of complications such as respiratory failure, sepsis and secondary infections were also higher in those who died than in survivors.