On March 9th, local time, The Lancet, an international authoritative medical journal, published a research article by 19 academics, “Clinical course and risk factors for adult inpatients”. s with COVID-19 in Wuhan, China: a retrospective cohort study” review edifying risk factors associated with mortality in the clinical process of adult patients in the early stages of the new coronary pneumonia (COVID-19) outbreak, and the spread of the virus Ability.
The author of this article is a team of medical personnel from Beijing and Wuhan, including Beijing Sino-Japanese Friendship Hospital, Beijing Concord Hospital, Wuhan Lung Hospital (Wuhan City Tuberculosis Prevention and Control Institute), Wuhan Jinyintan Hospital, etc., and the author of the article is Cao Bin, Director of Respiratory Department of Beijing Sino-Japanese Friendship Hospital, and Chen Hua, Director of Tuberculosis Department of Jinyintan Hospital.
In this retrospective, multicenter cohort study, the authors identified all COVID-19 adult inpatients diagnosed in the laboratory of Jinyintan Hospital and Wuhan Lung Hospital, which were discharged or died before January 31, 2020, through demographic, clinical, and statistical, clinical, Treatment and laboratory data, a series of samples for viral RNA testing, compare differences between survivors and non-survivors.
By using single-variable and multivariate logistic regression methods, the authors concluded that older, sequential organ failure scores (SOFA) and higher levels of D-dipolymer in the blood were potential risk factors for adult patients with neo-coronary pneumonia, often with poor prognosis.
In addition, it is worth noting that the authors also found that confirmed patients carried the new coronavirus for a longer period of time, i.e. the duration of the spread of the virus, which would provide a theoretical basis for later isolation of infected patients and optimal antiviral interventions.
The study included 191 patients (135 at Jinyintan Hospital and 56 cases in Wuhan Lung Hospital), of which 137 were discharged and 54 died in hospital.
Of these patients, 91 (48%) had comorbidities, with hypertension being the most common (58,30%), followed by diabetes (36,19%) and coronary heart disease (15,8%).
Earlier, on March 3rd, The Lancet published the results of research by teams such as Wuhan Concord Hospital, which explored some of the factors associated with the risk of death. The study also found an increase in mortality among older people (especially those over 60 years of age) and more underlying diseases (comorbidities).
Analysis of risk factors for death in the first batch of adult patients
The authors looked at patients who died or were discharged between December 29, 2019 (the time of admission to the first COVID-19 patients) and January 31, 2020. As until February 1, Jinyintan Hospital and Wuhan Lung Hospital were the only designated hospitals in Wuhan to refer COVID-19 patients at the time, the study included all adult patients admitted to COVID-19 at the beginning of the outbreak and the results were clear (death or discharge).
Since the results of RNA tests for the new coronavirus were not available in electronic medical records until January 11, 2020, the study did not include all 41 of the first patients in Wuhan to be diagnosed with new coronary pneumonia, including only 29 of them.
To explore the risk factors associated with death in the hospital, the researchers used a single-variable and multivariate logistic regression model. Taking into account that the total number of deaths in the sample was 54, to avoid overfitting the model, the authors selected five variables for multivariate analysis based on previous studies and clinical constraints.
The five variables are: blood lymphocyte count, D-dipolymer, SOFA score, coronary heart disease, and age.
The study found that the median age of the 191 patients was 56 years (IQR 46-0-67.0), ranging from 18 to 87 years old, with the majority of the patients being male.
Nearly half of patients had comorbidities, and the proportion of patients who died was as high as 67 percent.
The most common symptoms of admission are fever and cough, followed by sputum production and fatigue. Lymphocytic reduced disease occurred in 77 (40%) patients. 181 patients (95%) received antibiotic treatment and 41 (21%) received antiviral therapy (Lopinavir/Litonavir).
There were significant differences in the use of systemic corticosteroid hormones and intravenous immunoglobulin synods among mortals and survivors, with 36 cases, or 67 per cent, in the death group, far higher than among survivors (10,7 per cent).
The median time from the onset of the disease (before admission) to discharge is 22 days, and the median time from the onset of the disease to death is 18.5 days.
Of all the patients in the study, 32 patients who needed invasive mechanical ventilation were involved, of which 31 (97%) died. The median time between onset and mechanical ventilation was 14.5 days.
Three patients were given an in vitro membrane pulmonary oxygenation (ECMO), but all three died. The incidence of complications in mortal itys was higher than among survivors, with sepsis being the most common complication, followed by respiratory failure, acute respiratory distress syndrome (ARDS), heart failure and septic shock.
Half of all deaths had secondary infections, and 10 (31%) of the 32 patients who had invasive mechanical ventilation had respiratory-related pneumonia.
In a single variable analysis, patients with diabetes or coronary heart disease had higher in-hospital mortality.
图说：与院内死亡相关的风险因素，OR（odds ratio）为定义比数比，Univariable OR为单变量OR，Multivariable OR为多变量OR，OR越大则该项与疾病的关联强度越大
The researchers found that age, lymphocyte reduction, white blood cell growth, and elevated alanine amino transferase (ALT), lactic acid dehydrogenase, highly sensitive myocardial calcitonin I, creatine kinase, d-dipolymer, serum ferritin, IL-6 (leukin-6), ceagulase time, Creatine and calcium-reducing also are associated with death in patients.
The baseline lymphocyte count of survivors was significantly higher than in the patients who died, and among the survivors, the lymphatic cell count was lowest on the 7th day after the onset of the disease, and improved during hospitalization, while in the patients who died, the researchers observed severe lymphocytic cell reduction to death.
Age, sepsis and heart muscle injury
The researchers said it had previously been reported that age was an important independent predictor associated with mortality rates from SARS (Severe Acute Respiratory Syndrome) and MERS (MerS). Current studies have confirmed that increased age in PATIENTS WITH COVID-19 is associated with death.
The authors suggest that age-dependent deficiency in the function of T and B cells in the human body, as well as overproduction of type 2 cytokines with age, may lead to inadequate viral replication control and longer-term inflammatory reactions, which in turn may lead to undesirable results.
The authors say the SOFA score is a good indicator of sepsis and septicaemia shock, reflecting the state and extent of multi-organ dysfunction. Although bacterial infections are often considered the main cause of sepsis, viral infections can also cause sepsis syndrome.
Previously, researchers found that nearly 40 percent of adults develop edified sepsis in community-acquired pneumonia as a result of a viral infection.
In this study, however, more than half of the patients suffered from sepsis. In addition, the authors found that more than 70 percent of patients with white blood cell counts below 10.0 x 10 g/L or calcitonin than 0.25 ng / mL, and that these patients were not found with bacterial pathogens when admitted to hospital.
Sepsis is a common complication that may be directly caused by neo-coronavirus infection, but the authors say further research is needed to determine the pathogenesis of sepsis in COVID-19.
Compared to survivors, d-dipolymer, highly sensitive myocardial troponin I, serum ferritin, lactic acid dehydrogenase and IL-6 levels increased significantly compared to survivors, and increased as the disease worsened.
Normal quantification of D-dipolymer in human blood is generally less than 200 ?g/L, D-dipolymer elevation may be caused by myocardial infarction, cerebral infarction, pulmonary embolism, venous thrombosis, infection and tissue necrosis.
About 90% of patients hospitalized with pneumonia have increased blood clotting activity, characterized by increased concentration of D-dipolymer. In this study, the authors found that the level sofore of D-dipolymers was higher than 1?g/L and the fatal results of COVID-19.
High levels of D-dipolymer were reported to be associated with 28-day mortality (28-mortality) in patients with infection or sepsis found in emergency departments.
The mechanism of the disease includes a systemic protophilis cytokine reaction, a medium of atherosclerosis that directly contributes to plaque rupture through local inflammation, leading to the induction of coagulation factors and hemodynamic changes, and ultimately lead to local ischemia and thrombosis.
Heart complications (including new or worsening heart failure, new or worsening heart rhythms, or myocardial infarction) are common in patients with pneumonia. For the new coronavirus, its receptor angiotensin conversion enzyme 2 (ACE2) is expressed in myocardial cells and vascular endothelial cells, so at least in theory it can be proved that the new coronavirus infection has the potential to directly cause heart damage.
It is worth noting that although no specific virus testing studies have been reported, among the deaths of COVID-19, there have been studies that indicate the presence of interstitial mononucleitis in the patient’s heart tissue.
The “detox period” averages 20 days and can be up to 37 days
Among survivors, the median patient had a “viral period” of 20 days (IQR 17.0-24.0), but in the case of death, they were able to continue to spread the virus until the patient died, the study found. Among the survivors, the authors observed a minimum detox period of 8 days and a maximum of 37 days.
Of the 29 patients treated and discharged from the hospital, the median time from onset to the start of antiviral treatment was 14 days, with a median detox age of 22 days.
It is important to explore the detoxseason period of the virus (i.e., when the new coronavirus RNA can be detected in the patient’s body) for both the patient’s isolation policy and the guidance of antiviral treatment time. In severe influenza virus infections, longer detox periods are associated with fatal consequences, and timely and longer antiviral treatments may shorten the detox period, the researchers said.
Similarly, effective antiviral therapy may improve the prognosis of COVID-19, although no reduction in the post-toxic period of lopinavir/Litonavir treatment has been observed in the current study.
In terms of the severity of the condition, the authors found that the average detox period for severe (severe) patients was 19 days, compared with 24 days for critically ill patients.
The median time from onset to sepsis was 9 days to about 12 days of ARDS, followed by acute heart injury (15 days), acute kidney injury (15 days) and secondary infection (17 days).