Objectives: To report the clinical features of 85 fatal cases of COVID-19 in two hospitals in Wuhan.
Methods: Medical records were collected of 85 fatal cases of COVID-19 between January 9, 2020, and February 15, 2020. Information recorded included medical history, exposure history, comorbidities, symptoms, signs, laboratory findings, computed tomographic scans, and clinical management.
Measurements and Main Results: The median age of the patients was 65.8 years, and 72.9% were male. Common symptoms were fever (78 [91.8%]), shortness of breath (50 [58.8%]), fatigue (50 [58.8%]), and dyspnea (60 [70.6%]). Hypertension, diabetes, and coronary heart disease were the most common comorbidities. Notably, 81.2% of patients had very low eosinophil counts on admission. Complications included respiratory failure (80 [94.1%]), shock (69 [81.2%]), acute respiratory distress syndrome (63 [74.1%]), and arrhythmia (51 [60%]), among others. Most patients received antibiotic (77 [90.6%]), antiviral (78 [91.8%]), and glucocorticoid (65 [76.5%]) treatments. A total of 38 (44.7%) and 33 (38.8%) patients received intravenous immunoglobulin and IFN-α2b, respectively.
Conclusions: In this depictive study of 85 fatal cases of COVID-19, most cases were males aged over 50 years with noncommunicable chronic diseases. The majority of the patients died of multiple organ failure. Early onset of shortness of breath may be used as an observational symptom for COVID-19 exacerbations. Eosinophilopenia may indicate a poor prognosis. A combination of antimicrobial drugs did not offer considerable benefit to the outcome of this group of patients.
In this retrospective study, we report what is, to date, the largest series of patients who have died from COVID-19, providing detailed clinical characteristics of this cohort of patients from two Wuhan hospitals. The 85 fatal cases of COVID-19 reported here account for 2.7% of the total mortality due to SARS-CoV-2 infection in Hubei province. Although the symptoms of the majority of patients in other provinces have been comparatively mild (11), the number of deaths from SARS-CoV-2 infection continues to increase, with more cases and fatalities occurring now in other provinces, countries, and regions. As of May 12, 2020, there have been 4,643 fatalities and 84,450 confirmed cases of COVID-19 in China, according to the World Health Organization (12). Early diagnosis and timely treatment to reduce mortality is of crucial importance. It is hoped that this work will have value in helping clinicians identify patients with poor prognosis at an early stage by being aware of some of the alarming clinical characteristics presented by patients before they died from COVID-19, and help guide appropriate and effective management for future patients.
A recent study by Zhou and colleagues of 191 patients, of whom 54 died, found that older age, high sequential organ failure assessment score, and D-dimer >1 μg/ml could assist in the early identification of patients who may have a poorer prognosis. In our study, the median age of nonsurvivors was 65.8 years, which is similar to the median age reported in nonsurvivors, but higher than that of the survivors (52 yr), reported in the previous study. Furthermore, our study found that the median (SD) level of D-dimer in nonsurvivors was 5.159 (4.679) μg/ml (range, 0.27–26 μg/ml), and 70.6% of our patients had a D-dimer >1 μg/ml, which was also consistent with the previous study. The sequential organ failure assessment score was not included in our study. However, we found that 29.4% of patients had a CURB-65 score >3, which was similar to the previous study (28% in nonsurvivors). In our study, about one-quarter of patients who died had an elevated procalcitonin level, which was consistent with the previous study, but Zhou and colleagues’ study also found that an elevated procalcitonin level >0.5 was associated with a 93% chance of death. In a non–COVID-19 study of patients with pneumonia, the CURB-65 score on admission correlated with mortality risk.
It was difficult to find age- and sex-matched control subjects for our study. In comparing our data to the previous study mentioned here, which did include survivors, we found that the hospital length of stay was the same in nonsurvivors between the two studies, but almost double the survivor length of stay (12 d) in the previous study. Interestingly, the use of intravenous immunoglobulin was higher in nonsurvivors in both the previous study and our study (36% and 38%, respectively), but much lower in survivors (10%) in the previous study. The increased use of intravenous immunoglobulin may be due to the severity of illness but also raises the question of whether intravenous immunoglobulin may be ineffective in severely ill patients. The use of corticosteroids was higher in our cohort of 85 patients than in the above-mentioned study (65% vs. 48% in nonsurvivors and 30% in survivors, respectively). Lymphopenia was identified as a risk factor for death in the previous study, but eosinopenia was not mentioned.
Previous studies found that nearly half of patients with COVID-19 are over the age of 50 years, and that men are more likely to be infected than women. The mortality rate in males is higher than that in females. In patients who develop SARS, advanced age is an independent predictor for an adverse outcome, but sex is not. In this report, we observed that, among the 85 deaths, there were 76 (89.3%) patients over the age of 50 years and 62 (72.9%) were male.The most common comorbidities of the patients with COVID-19 in our cohort are hypertension and diabetes, which is similar to findings of previous studies. However, the most common comorbidities in the patients with SARS were diabetes (16 [11%]) and cardiac disease (12 [8%]). The increased prevalence of hypertension in China may play a role in COVID-19–related deaths.
Common clinical features of patients with COVID-19 include fever (83%), cough (82%), shortness of breath (31%), and muscle ache (11%). For SARS, the common clinical features included fever (99%), cough (69%), myalgia (49%), and dyspnea (42%). It is worth noting that the overall rates of shortness of breath in our cohort were higher than that in patients with SARS. We suggest that early onset of shortness of breath may be indicative of poor prognosis.
We found that the absolute eosinophil count in peripheral blood was reduced in almost all patients who died. The number of patients with reduced eosinophil count in patients with nonsevere and severe COVID-19 who survived has been reported elsewhere to be 39/82 (47.6%) and 34/56 (60.7%), respectively. Previous studies have reported that there is a rapid and persistent decrease in the numbers of circulating eosinophils in acute infection or inflammation. A study on 30-day mortality and eosinopenia showed that eosinopenia is an independent predictor of death in patients with pneumonia, but without chronic respiratory disease. This effect was not related to steroid use. In the case of COVID-19, this may be related to CD8 T-cell depletion and eosinophil consumption caused by SARS-CoV-2. IL-5, produced by CD8 T cells, contributes to eosinophil proliferation and activation in blood. Lower numbers of CD8 T cells has been found in patients infected with SARS-CoV-2. Moreover, ECP and EDN, two eosinophil granule proteins, can neutralize viruses.Therefore, the decrease of eosinophils in patients with COVID-19 may be related to a higher viral load of SARS-CoV-2 and SARS-CoV-2–triggered eosinophil granule protein consumption.
We thus speculate that eosinophilopenia may be used as a prognostic indicator for patients with COVID-19. In addition, the ratio of neutrophil to eosinophil counts may be another measure that can minimize variability in absolute eosinophil counts from different hospitals. Another laboratory abnormality found in this study was decreased total lymphocytes, which is consistent with the conclusions of existing research indicating that lymphocytopenia is more often seen in nonsurvivors of SARS-CoV-2 infection.
Similarly, prolonged PT and elevated lactate dehydrogenase were noted in our cohort, whereas a previous study found that 13% of patients had creatine kinase and 3% of patients had serum creatinine above the normal ranges at the time of admission. Wang and colleagues reported that the levels of blood urea and creatinine, as measured by dynamic profiling of laboratory data, progressively increased before death. We observed that 56.5% of our patients had renal dysfunction, as indicated by the increased levels of blood urea or creatinine at the time of admission. Therefore, we suggest that an increased level of creatinine and urea nitrogen may also indicate poor prognosis.
Copathogens of patients with COVID-19 have not been previously reported in the literature. Testing for copathogens was done in some, but not all, patients in our cohort, and we found that <10% of tested patients were positive for influenza A virus, influenza B virus, and parainfluenza virus. It is worth noting that the antibody-positive rate of mycoplasma and Chlamydia were relatively high.
The initial admission CURB-65 score of most patients was not high, and yet the outcome of all the patients was death. This indicates that the clinical course of COVID-19 develops rapidly, so the CURB-65 at the beginning of admission cannot be used as a guide of severity. Patients with COVID-19 need to be closely monitored after admission
From a practical standpoint, doctors equipped with protective suits and helmets have great difficulties in closely examining patients with standard techniques, such as auscultation and observing for signs of shortness of breath. Therefore, laboratory findings and chest CT scan become critical in monitoring disease progress and treatment outcome. We determined that the presence of bilateral pneumonia and progressive radiographic deterioration on follow-up CT scan may be risk factors for poor prognosis (26). It should be noted that the administration of multiple antibiotics did not change the outcome of the disease in our series. Rational use of antibiotics should thus be exercised. It is also not known if any of the therapies used in COVID-19, such as steroids, may actually be counterproductive and lead to increased morbidity or mortality.
This study has some limitations. First, only fatal cases of COVID-19 were included. A prospective study including patients with fatal and nonfatal disease will provide more conclusive and valuable data. Second, pathological findings were not available. Third, although eosinophilopenia was found in almost all patients in this series, it can also occur in many patients with nonfatal severe and moderate disease, based on our clinical observations (unpublished results). Therefore, additional studies are needed to confirm the prognostic value of eosinophilopenia in patients with COVID-19.
Conclusions In summary, most cases of death from COVID-19 were males over 50 years of age with noncommunicable chronic diseases, such as hypertension, diabetes, and coronary heart diseases. The patients mainly died of multiple organ failure. Early onset of shortness of breath might be predictive of demise, and eosinophilopenia may indicate a poor prognosis. The use of a combination of more than three antimicrobial drugs appears to offer no benefit to the outcome of this group of patients
Reference & source information: https://www.atsjournals.org/
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