For patients admitted to the hospital and confirmed to have the new coronavirus disease (COVID-19), the key risk factors for death are:
- Advanced age
- Signs of sepsis
- Blood clotting issues
These risk factors come from a new retrospective study that evaluated data records for 191 patients—137 survivors and 54 non-survivors. Each patient had been admitted to one of two hospitals in Wuhan, China.
The study, which appeared March 9 in The Lancet—in a paper entitled “Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study”—could help clinicians identify patients with poor prognosis at an early stage.
“Multivariable regression showed increasing odds of in-hospital death associated with older age, higher Sequential Organ Failure Assessment (SOFA) score, and d-dimer greater than 1 μg/L on admission,” the study’s authors wrote. The age range for survivors was 45.0–58.0; that for non-survivors was 63.0–76.0.
Besides specifying risk factors for death, the authors presented new findings on viral shedding, which indicate that the median duration of viral shedding was 20 days in survivors (ranging from 8 to 37 days), and that the virus was detectable until death in the 54 non-survivors.
While prolonged viral shedding suggests that patients may still be capable of spreading COVID-19, the authors caution that 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. Moreover, the estimated duration of viral shedding was limited by the low frequency of respiratory specimen collection and the lack of measurable genetic material detection in samples.
“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,” explained co-lead author professor Bin Cao from the China-Japan Friendship Hospital and Capital Medical University, 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.
“We recommend that negative tests for COVID-19 should be required before patients are discharged from hospital. 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.”
According to co-author Dr. Zhibo Liu from Jinyintan Hospital, China: “Older age, showing signs of sepsis on admission, underlying diseases like high blood pressure and diabetes, and the prolonged use of noninvasive ventilation were important factors in the deaths of these patients. 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.”
The current study adds new details to our picture of how COVID-19 progresses. The median duration of fever was about 12 days in survivors, which was similar in non-survivors. But the cough may last for a long time—45% of survivors still had a cough on discharge. In survivors, dyspnoea (shortness of breath) would cease after about 13 days, but it would last until death in non-survivors. The study also illustrates the time of the occurrence of different complications such as sepsis, acute respiratory distress syndrome (ARDS), acute cardiac injury, acute kidney injury, and the secondary infection.
The new analysis includes all adults (aged 18 or older) with laboratory-confirmed COVID-19 admitted to Jinyintan Hospital and Wuhan Pulmonary Hospital after December 29, 2019, who had been discharged or died by January 31, 2020. These were the two designated hospitals for transferring patients with severe COVID-19 from across Wuhan up until February 1, 2020.
During the study, the researchers compared clinical records, treatment data, laboratory results, and demographic data between survivors who had been discharged from hospital and non-survivors. They looked at the clinical course of symptoms, viral shedding, and changes in laboratory findings during hospitalization (such as blood examinations, chest X-rays, and CT scans), and they used mathematical modeling to examine risk factors associated with dying in hospital.
On average, patients were middle-aged (median age 56 years), most were men (62%, 119 patients), and around half had underlying chronic conditions (48%, 91 patients)—the most common being high blood pressure (30%, 58 patients) and diabetes (19%, 36 patients). From illness onset, the median time to 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 (average age 69 years vs. 52 years), and have a higher score on the Sequential Organ Failure Assessment (SOFA) indicating sepsis, and elevated blood levels of the d-dimer protein (a marker for coagulation) on admission to hospital.
Additionally, lower lymphocyte (a type of white blood cell) count, elevated levels of Interleukin 6 (IL-6, a biomarker for inflammation and chronic disease), and increased high-sensitivity troponin I concentrations (a marker of heart attack), were more common in severe COVID-19 illness.
The frequency of complications such as respiratory failure (98%, 53/54 non-survivors 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 survivors.
The authors noted several limitations of the study. For example, it excluded patients who were still in hospital as of Jan 31, 2020. Since these patients had relatively more severe disease at an earlier stage, the number of deaths found by the study does not reflect the true mortality of COVID-19.
The authors also pointed out that not all laboratory tests (such as the d-dimer test) were done in all patients, so their exact role in predicting in-hospital death might be underestimated. Finally, a lack of effective antivirals, inadequate adherence to standard supportive therapy, and high doses of corticosteroids, as well as the transfer of some patients to the hospital late in their illness, might have also contributed to the poor outcomes in some patients.