Posted on Mar 12, 2020, 4 p.m.
Based on patients admitted to the hospital and confirmed to be infected with COVID-19 the key risk factors for death are: signs of sepsis, blood clotting issues, diabetes, heart disease, and advanced age, according to a new retrospective study published in The Lancet evaluating data record for 191 patients of which 54 did not survive and all patients had been admitted to one of 2 hospitals in the epicenter of Wuhan, China.
“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; age range for survivors was 45-58; that for non-survivors was 63-76.
This study also provided new findings on viral shedding which indicate that the median duration of viral shedding was 20 days in survivors ranging from 8-37 days and that the virus was detectable up until death in the non-survivors.
Prolonged viral shedding suggests that patients may still be able to spread COVID-19, but it was noted that the duration of viral shedding is influenced by the severity of infection and of those in the study two thirds had severe or critical illness, and the estimated duration was limited by low frequency of respiratory specimen collection and 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.”
“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,” said co-author Dr. Zhibo Liu from Jinyintan Hospital, China.
Median duration of fever was 12 days in survivors, while the cough can remain for a long time as 45% of the survivors still had a cough at discharge. Dyspnoea ceased after 13 days in survivors, but the shortness of breath lasted until death in non-survivors. Findings also describe the time of occurrence of different complications such as sepsis, acute respiratory distress syndrome, acute cardiac injury, acute kidney injury, and secondary infection.
This analysis included patients aged 18+ who were laboratory confirmed to have been infected with COVID-19 and were admitted to either Jinyintan Hospital and Wuhan Pulmonary Hospital after December 29, 2019, who had been discharged or died by January 31, 2020; these 2 sites were the designated hospitals for transferring patients to with severe COVID-19 in Wuhan until February 1. 2020.
For this study clinical records, treatment data, lab results and demographic data was compared between survivors and nonsurvivors examining the clinical source of symptoms, viral shedding, and changes in lab results during hospitalization using mathematical modeling to examine risk factors associated with mortality.
Findings showed that on average patients were middle aged with a median age of 56 year; 62% were men, and 48% had underlying chronic conditions of which the most common was high blood pressure at 30% and diabetes at 19%. From illness onset to discharge the median duration was 22 days, the average duration until death was 18.5 days.
Those who did not survive were more likely to be older, and have a higher score on the Sequential Organ Failure Assessment indicating sepsis, and elevated blood levels of the d-dimer protein on hospital admission which is a marker for coagulation.
Lower lymphocyte white blood cell count, elevated levels of Interleukin 6 which is a biomarker for inflammation and chronic disease, and increased high sensitivity to troponin I concentration were more common in those with severe cases of COVID-19 infection.
Frequency of complications such as respiratory failure was 98% for nonsurvivors and 36% for survivors; sepsis was 100% for non survivors and 42% for survivors; and the secondary infections were 50% for nonsurvivors and only 1% in survivors.
It was noted that there were several limitations to the study including that it excluded patients who were still in hospitals as of January 31,202 as they had relatively more severe disease at an earlier stage, thus the number of deaths found by the study does not include any of those patients and may not reflect the true mortality of COVID-19.
Also it was pointed out that not all laboratory test were done on all patients, so their exact role in predicting in hospital deaths may be underestimated; and lack of effective antivirals, inadequate adherence to standard supportive therapy, and high doses of corticosteroids, as well as transfer of some patients late in illness may have contributed to poor outcomes in some of the patients.
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