Earlier diagnosis improves COVID-19 prognosis: a nationwide retrospective cohort analysis.

BACKGROUND: Risk of adverse outcomes in COVID-19 patients by stratifying by the time from symptom onset to confirmed diagnosis status is still uncertain. METHODS: We included 1,590 hospitalized COVID-19 patients confirmed by real-time RT-PCR assay or high-throughput sequencing of pharyngeal and nasal swab specimens from 575 hospitals across China between 11 December 2019 and 31 January 2020. Times from symptom onset to confirmed diagnosis, from symptom onset to first medical visit and from first medical visit to confirmed diagnosis were described and turned into binary variables by the maximally selected rank statistics method. Then, survival analysis, including a log-rank test, Cox regression, and conditional inference tree (CTREE) was conducted, regarding whether patients progressed to a severe disease level during the observational period (assessed as severe pneumonia according to the Chinese Expert Consensus on Clinical Practice for Emergency Severe Pneumonia, admission to an intensive care unit, administration of invasive ventilation, or death) as the prognosis outcome, the dependent variable. Independent factors included whether the time from symptom onset to confirmed diagnosis was longer than 5 days (the exposure) and other demographic and clinical factors as multivariate adjustments. The clinical characteristics of the patients with different times from symptom onset to confirmed diagnosis were also compared. RESULTS: The medians of the times from symptom onset to confirmed diagnosis, from symptom onset to first medical visit, and from first medical visit to confirmed diagnosis were 6, 3, and 2 days. After adjusting for age, sex, smoking status, and comorbidity status, age [hazard ratio (HR): 1.03; 95% CI: 1.01-1.04], comorbidity (HR: 1.84; 95% CI: 1.23-2.73), and a duration from symptom onset to confirmed diagnosis of >5 days (HR: 1.69; 95% CI: 1.10-2.60) were independent predictors of COVID-19 prognosis, which echoed the CTREE models, with significant nodes such as time from symptom onset to confirmed diagnosis, age, and comorbidities. Males, older patients with symptoms such as dry cough/productive cough/shortness of breath, and prior COPD were observed more often in the patients who procrastinated before initiating the first medical consultation. CONCLUSIONS: A longer time from symptom onset to confirmed diagnosis yielded a worse COVID-19 prognosis.

Effect of Recombinant Human Granulocyte Colony-Stimulating Factor for Patients With Coronavirus Disease 2019 (COVID-19) and Lymphopenia: A Randomized Clinical Trial.

Importance: Lymphopenia is common and correlates with poor clinical outcomes in patients with coronavirus disease 2019 (COVID-19). Objective: To determine whether a therapy that increases peripheral blood leukocyte and lymphocyte cell counts leads to clinical improvement in patients with COVID-19. Design, Setting and Participants: Between February 18 and April 10, 2020, we conducted an open-label, multicenter, randomized clinical trial at 3 participating centers in China. The main eligibility criteria were pneumonia, a blood lymphocyte cell count of 800 per µL (to convert to ×109/L, multiply by 0.001) or lower, and no comorbidities. Severe acute respiratory syndrome coronavirus 2 infection was confirmed with reverse-transcription polymerase chain reaction testing. Exposures: Usual care alone, or usual care plus 3 doses of recombinant human granulocyte colony-stimulating factor (rhG-CSF, 5 µg/kg, subcutaneously at days 0-2). Main Outcomes and Measures: The primary end point was the time from randomization to improvement of at least 1 point on a 7-category disease severity score. Results: Of 200 participants, 112 (56%) were men and the median (interquartile range [IQR]) age was 45 (40-55) years. There was random assignment of 100 patients (50%) to the rhG-CSF group and 100 (50%) to the usual care group. Time to clinical improvement was similar between groups (rhG-CSF group median of 12 days (IQR, 10-16 days) vs usual care group median of 13 days (IQR, 11-17 days); hazard ratio, 1.28; 95% CI, 0.95-1.71; P = .06). For secondary end points, the proportion of patients progressing to acute respiratory distress syndrome, sepsis, or septic shock was lower in the rhG-CSF group (rhG-CSF group, 2% vs usual care group, 15%; difference, -13%; 95%CI, -21.4% to -5.4%). At 21 days, 2 patients (2%) had died in the rhG-CSF group compared with 10 patients (10%) in the usual care group (hazard ratio, 0.19; 95%CI, 0.04-0.88). At day 5, the lymphocyte cell count was higher in the rhG-CSF group (rhG-CSF group median of 1050/µL vs usual care group median of 620/µL; Hodges-Lehmann estimate of the difference in medians, 440; 95% CI, 380-490). Serious adverse events, such as sepsis or septic shock, respiratory failure, and acute respiratory distress syndrome, occurred in 29 patients (14.5%) in the rhG-CSF group and 42 patients (21%) in the usual care group. Conclusion and Relevance: In preliminary findings from a randomized clinical trial, rhG-CSF treatment for patients with COVID-19 with lymphopenia but no comorbidities did not accelerate clinical improvement, but the number of patients developing critical illness or dying may have been reduced. Larger studies that include a broader range of patients with COVID-19 should be conducted. Trial Registration: Chinese Clinical Trial Registry: ChiCTR2000030007.

Clinical characteristics and outcomes of hospitalised patients with COVID-19 treated in Hubei (epicentre) and outside Hubei (non-epicentre): a nationwide analysis of China.

BACKGROUND: During the outbreak of coronavirus disease 2019 (COVID-19), consistent and considerable differences in disease severity and mortality rate of patients treated in Hubei province compared to those in other parts of China have been observed. We sought to compare the clinical characteristics and outcomes of patients being treated inside and outside Hubei province, and explore the factors underlying these differences. METHODS: Collaborating with the National Health Commission, we established a retrospective cohort to study hospitalised COVID-19 cases in China. Clinical characteristics, the rate of severe events and deaths, and the time to critical illness (invasive ventilation or intensive care unit admission or death) were compared between patients within and outside Hubei. The impact of Wuhan-related exposure (a presumed key factor that drove the severe situation in Hubei, as Wuhan is the epicentre as well the administrative centre of Hubei province) and the duration between symptom onset and admission on prognosis were also determined. RESULTS: At the data cut-off (31 January 2020), 1590 cases from 575 hospitals in 31 provincial administrative regions were collected (core cohort). The overall rate of severe cases and mortality was 16.0% and 3.2%, respectively. Patients in Hubei (predominantly with Wuhan-related exposure, 597 (92.3%) out of 647) were older (mean age 49.7 versus 44.9 years), had more cases with comorbidity (32.9% versus 19.7%), higher symptomatic burden, abnormal radiologic manifestations and, especially, a longer waiting time between symptom onset and admission (5.7 versus 4.5 days) compared with patients outside Hubei. Patients in Hubei (severe event rate 23.0% versus 11.1%, death rate 7.3% versus 0.3%, HR (95% CI) for critical illness 1.59 (1.05-2.41)) have a poorer prognosis compared with patients outside Hubei after adjusting for age and comorbidity. However, among patients outside Hubei, the duration from symptom onset to hospitalisation (mean 4.4 versus 4.7 days) and prognosis (HR (95%) 0.84 (0.40-1.80)) were similar between patients with or without Wuhan-related exposure. In the overall population, the waiting time, but neither treated in Hubei nor Wuhan-related exposure, remained an independent prognostic factor (HR (95%) 1.05 (1.01-1.08)). CONCLUSION: There were more severe cases and poorer outcomes for COVID-19 patients treated in Hubei, which might be attributed to the prolonged duration of symptom onset to hospitalisation in the epicentre. Future studies to determine the reason for delaying hospitalisation are warranted.

Comorbidity and its impact on 1590 patients with COVID-19 in China: a nationwide analysis.

BACKGROUND: The coronavirus disease 2019 (COVID-19) outbreak is evolving rapidly worldwide. OBJECTIVE: To evaluate the risk of serious adverse outcomes in patients with COVID-19 by stratifying the comorbidity status. METHODS: We analysed data from 1590 laboratory confirmed hospitalised patients from 575 hospitals in 31 provinces/autonomous regions/provincial municipalities across mainland China between 11 December 2019 and 31 January 2020. We analysed the composite end-points, which consisted of admission to an intensive care unit, invasive ventilation or death. The risk of reaching the composite end-points was compared according to the presence and number of comorbidities. RESULTS: The mean age was 48.9 years and 686 (42.7%) patients were female. Severe cases accounted for 16.0% of the study population. 131 (8.2%) patients reached the composite end-points. 399 (25.1%) reported having at least one comorbidity. The most prevalent comorbidity was hypertension (16.9%), followed by diabetes (8.2%). 130 (8.2%) patients reported having two or more comorbidities. After adjusting for age and smoking status, COPD (HR (95% CI) 2.681 (1.424-5.048)), diabetes (1.59 (1.03-2.45)), hypertension (1.58 (1.07-2.32)) and malignancy (3.50 (1.60-7.64)) were risk factors of reaching the composite end-points. The hazard ratio (95% CI) was 1.79 (1.16-2.77) among patients with at least one comorbidity and 2.59 (1.61-4.17) among patients with two or more comorbidities. CONCLUSION: Among laboratory confirmed cases of COVID-19, patients with any comorbidity yielded poorer clinical outcomes than those without. A greater number of comorbidities also correlated with poorer clinical outcomes.

Optical coherence tomography in imaging of peripheral pulmonary arteries.

BACKGROUND: To establish an optical coherence tomography (OCT)-based method for imaging peripheral pulmonary arteries. METHODS: We recruited eight patients (five men; average age, 48±12 years; peripheral pulmonary artery thrombosis, three patients; idiopathic pulmonary hypertension, three patients; interstitial lung disease, two patients) who underwent OCT of the peripheral pulmonary arteries in the First Affiliated Hospital of Guangzhou Medical University and Guangzhou Institute of Respiratory Diseases, between September 2009 and September 2010. OCT was performed using both the conventional OCT imaging method (COI) and the improved pulmonary artery imaging method (IPI). In the IPI, contrast agent was used as an indicator of balloon inflation meanwhile increases in flushing speed of the replacement fluid. The percentage of optimal images, inflation pressure, flushing speeds and complications were compared between the two methods. RESULTS: We performed OCT of 33 vessel segments by both methods. IPI produced more optimal images than COI (88% vs. 24%). Mean inflation pressure and flushing speed were higher during IPI than COI (0.62±0.15 vs. 0.43±0.08 atm; 1 atm =101.3 kPa; 0.82±0.10 vs. 0.42±0.06 mL/s; both P<0.01). Decreased blood oxygen saturation (SaO2) was associated with 9% and 30% segments (P<0.01) in the COI (mean decrease, 8.4%±3.6%) and IPI groups (mean decrease, 12.1%±5.3%; P<0.05) respectively. SaO2 recovered to pre-imaging levels after oxygen inhalation. CONCLUSIONS: IPI is safe and effective for OCT of peripheral pulmonary arteries.

Visualization of peripheral pulmonary artery red thrombi utilizing optical coherence tomography.

Optical coherence tomography (OCT) is a new imaging technique capable of obtaining high-resolution intravascular images and has been used in interventional cardiology. However, an application of OCT in pulmonary arteries had seldom been documented. In this case, OCT imaging is performed in peripheral pulmonary arteries and shows mural red thrombi. Subsequently, the red thrombi are aspirated and confirmed by a histological examination. These findings suggest that OCT may be a useful tool to depict peripheral pulmonary artery thrombi.

[Bronchoesophageal fistula secondary to mediastinal lymph node tuberculosis: a case report and review of the literature].

OBJECTIVE: To analyze the clinical features of 1 case of bronchoesophageal fistula (BEF) secondary to mediastinal lymph node tuberculosis. METHODS: The clinical, auxiliary examinational and pathological data of 1 case with BEF were presented, and the literatures were reviewed. RESULTS: The patient was a 19 year old female, who was admitted to hospital because of fever and cough associated with liquid intake. It was diagnosed by chest CT scan, endobronchial ultrasound biopsy of mediastinal lymph nodes, and clinical testing (methylene blue). The BEF was closed after anti-tuberculosis therapy and preventing contamination of the fistula by indwelling stomach tube. CONCLUSIONS: Bronchoesophageal fistula secondary to mediastinal lymph node tuberculosis is rare. Chest CT scan, fiberoptic bronchoscopy, and clinical testing (methylene blue) are useful diagnostic tools for BEF.

[Clinical characteristics and prognostic factors of pulmonary embolism in different age groups].

OBJECTIVE: To explore the clinical characteristics of pulmonary embolism (PE) in different age-groups and to analyze prognostic factors of PE. METHODS: Data of 209 PE patients diagnosed in our hospital from 2004 to 2009 were reviewed retrospectively. RESULTS: Of the 209 patients with PE, 95 subjects (45.5%) were over the age of 65, and 114 were ≤ 65 years. The third leading comorbidity were activity limitation that were banding in bed, chronic obstructive pulmonary disease, neoplasm and hypertension, accounting for 42.1%, 24.4% and 21.5%, respectively. The typical clinical presentations included dyspnea(83.7%), cough (74.2%), chest pain (29.2%), haemoptysis (15.3%) and syncope (3.8%). In 186(92.1%) patients, D-dimer was above the normal level, 37.8% (79) and 54.0% (81/150) subjects were found having got a venous thrombosis in lower extremity and pulmonary hypertension, respectively by using ultrasonic visualization. 16.7% (35) and 80.9% (169) had received thrombolytic and anticoagulant therapy, respectively. The death rate of PE was 6.7%. A difference in clinical characteristics was observed between younger and older patients. The later had more comorbidity such as COPD, neoplasm and hypertension, the older patients had fewer complaints of chest pain, haemoptysis, fever, hypotension and typical electrocardiogram (ECG), but had more cough with sputum, pulmonary rales and lower extremity edema, in comparison to the younger patients. The older PE patients were less likely to suffer from large thrombosis and pulmonary infarction, and to received thrombolytic therapy. Multivariate logistic regression showed that PaO(2) < 60 mm Hg (1 mm Hg = 0.133 kPa), having pulmonary rales, having abnormal neutrophilic granulocyte counts, not receiving thrombolysis and anticoagulant therapy, suffering from emergency rescue, having comorbidities with tumor and pneumonia were important prognostic factors. CONCLUSION: The clinical features of PE were various and non-specific. More attention should be paid to PE patients, in particular to older patients who usually had more comorbidities and non-specific clinical manifestations.

[Clinical and pathological analysis of allergic bronchopulmonary aspergillosis in China].

OBJECTIVE: To describe the clinical features and diagnosis of allergic bronchopulmonary aspergillosis (ABPA). METHODS: Three cases of ABPA from this hospital were presented. Chinese Biomedical Disk (CBM-Disk) was searched to identify Chinese ABPA cases from 1991 to 2008, and a retrospective analysis of all the cases was made. RESULTS: Fifty-seven cases of ABPA were collected, including 33 male and 24 female patients, with a mean age of (41 +/- 15) yrs. The main clinical manifestations included cough (n = 51), expectoration (n = 50), wheeze (n = 47), dyspnea (n = 44), fever (n = 33), hemoptysis (n = 28), sputum plugs (n = 18), chest pain (n = 13) and weight loss (n = 8). Forced expired volume in one second (FEV1) was (64 +/- 25)% predicted, and FEV1/forced vital capacity (FVC) was (63 +/- 11)%. Chest CT was performed in 33 cases. Patchy infiltration was present in 32, central bronchiectasis in 25, mucoid impaction (glover-finger/band linear opacities) in 12, nodular opacities in 11, consolidation in 8 and mediastinal adenopathy in 13 cases, while 24 cases presented fleeting infiltrations. CONCLUSION: ABPA is a rare disease. Measurement of total IgE, A. fumigatus-specific IgE, and immediate cutaneous reaction to A. fumigatus are help for confirmation of the diagnosis.

[Lymphoma presenting with unusual combination of clinical features: a case report and literature review].

OBJECTIVE: To describe a case of lymphoma presenting with multi-organ involvement, and to review similar cases reported in the English and Chinese literatures since 1994. METHODS: The clinical and pathological features of a patient admitted to our hospital on September 6, 2007 with lymphoma presenting with some unusual clinical symptoms including subcutaneous nodules, pleural effusion and orbital tumor were analyzed and related literatures were reviewed. RESULTS: The patient was a 60-year-old male. The primary manifestations were subcutaneous nodules. The reason for his hospitalization was pleural effusion. Orbital tumor was present. Computed tomography of the chest and the abdomen reveal systemic lymphadenopathy. Lymphoma was proved by pathological study. CONCLUSIONS: Complicated clinical manifestations of lymphoma may have multi-system involvement. Lymphoma with extranodal presentations as the first sign may lead to misdiagnosis.

[Expiratory flow limitation detected by negative expiratory pressure in patients with bronchial asthma].

OBJECTIVE: To evaluate the relationship between expiratory flow limitation (EFL) and chronic dyspnea and the effect of bronchodilator on EFL in patients with bronchial asthma. METHODS: Sixty-five patients with bronchial asthma were treated for pre- and post-bronchodilation of 400 microg salbutamol. RESULTS: EFL was detected in 26 (40%) of the 65 bronchial asthma patients, 11 only in supine position and 15 in both sitting and supine positions. There was a significant difference in FEV(1) percentage of the predicted value (FEV(1)% pred) between patients with and without EFL (t = 5.822, P < 0.01); the mean values of FEV(1)% pred in non-EFL group and EFL group was (77 +/- 18)% and (52 +/- 15)% respectively, and the value was lowest in patients who showed EFL both in seated and supine positions [(43 +/- 12)%]; the mean values of FEV(1)% pred in those showing EFL only in sitting position (S-EFL) and both in sitting and supine position (SS-EFL) were (64 +/- 10)% and (43 +/- 12)% respectively (t = 2.283, 6.694 respectively, P < 0.01, < 0.05). Both three-point EFL and five-point EFL were significantly correlated with FEV(1) (r = -0.637, -0.630 respectively, all P < 0.01). There was a significant negative correlation between as proposed by the Canadian Medical Research Council (MRC) dyspnea scale and FEV(1) (r = -0.501, P < 0.01), and a significant positive correlation between dyspnea scale and 3-point EFL and five-point EFL (r = 0.627, 0.636 respectively, all P < 0.01). After salbutamol, of the 17 patients having EFL and < 70% pre FEV(1) at baseline, EFL completely reversed in 9, and changed from SS-EFL to S-EFL in 5, with significant improvements in 3-point and 5-point EFL as compared with before salbutamol (t = 6.769, 6.010 respectively, all P < 0.01). CONCLUSIONS: EFL as measured by NEP (negative expiratory pressure) technique may be more useful in the evaluation of dyspnea in bronchial asthma patients than routine lung function measurements. The EFL in bronchial asthma patients is reversible after bronchodilator administration.