Complement and complement regulatory proteins are upregulated in lungs of COVID-19 patients.

We explored the pathological changes and the activation of local complement system in COVID-19 pneumonia. Lung paraffin sections of COVID-19 infected patients were analyzed by HE (hematoxylin-eosin) staining. The deposition of complement C3, the deposition of C3b/iC3b/C3d and C5b-9, and the expression of complement regulatory proteins, CD59, CD46 and CD55 were detected by immunohistochemistry. In COVID-19 patients' lung tissues, fibrin exudation, mixed with erythrocyte, alveolar macrophage and shed pneumocyte are usually observed in the alveoli. The formation of an "alveolar emboli" structure may contribute to thrombosis and consolidation in lung tissue. In addition, we also found that compared to normal tissue, the lung tissues of COVID-19 patients displayed the hyper-activation of complement that is represented by extensive deposition of C3, C3b/iC3b/C3d and C5b-9, and the increased expression level of complement regulatory proteins CD55, and especially CD59 but not CD46. The thrombosis and consolidation in lung tissues may contribute to the pathogenesis of COVID-19. The increased expression of CD55 and CD59 may reflect a feedback of self-protection on the complement hyper-activation. Further, the increased C3 deposition and the strongly activated complement system in lung tissues may suggest the rationale of complement-targeted therapeutics in conquering COVID-19.

Stress, Burnout, and Coping Strategies of Frontline Nurses During the COVID-19 Epidemic in Wuhan and Shanghai, China.

Background: Nurses at the frontline of caring for COVID-19 patients might experience mental health challenges and supportive coping strategies are needed to reduce their stress and burnout. The aim of this study was to identify stressors and burnout among frontline nurses caring for COVID-19 patients in Wuhan and Shanghai and to explore perceived effective morale support strategies. Method: A cross-sectional survey was conducted in March 2020 among 110 nurses from Zhongshan Hospital, Shanghai, who were deployed at COVID-19 units in Wuhan and Shanghai. A COVID-19 questionnaire was adapted from the previous developed "psychological impacts of SARS" questionnaire and included stressors (31 items), coping strategies (17 items), and effective support measures (16 items). Burnout was measured with the Maslach Burnout Inventory. Results: Totally, 107 (97%) nurses responded. Participants mean age was 30.28 years and 90.7% were females. Homesickness was most frequently reported as a stressor (96.3%). Seven of the 17 items related to coping strategies were undertaken by all participants. Burnout was observed in the emotional exhaustion and depersonalization subscales, with 78.5 and 92.5% of participants presenting mild levels of burnout, respectively. However, 52 (48.6%) participants experienced a severe lack of personal accomplishment. Participants with longer working hours in COVID-19 quarantine units presented higher emotional exhaustion (OR = 2.72, 95% CI 0.02-5.42; p = 0.049) and depersonalization (OR = 1.14, 95% CI 0.10-2.19; p = 0.033). Participants with younger age experienced higher emotional exhaustion (OR = 2.96, 95% CI 0.11-5.82; p = 0.042) and less personal accomplishment (OR = 3.80, 95% CI 0.47-7.13; p = 0.033). Conclusions: Nurses in this study experienced considerable stress and the most frequently reported stressors were related to families. Nurses who were younger and those working longer shift-time tended to present higher burnout levels. Psychological support strategies need to be organized and implemented to improve mental health among nurses during the COVID-19 pandemic.

Erratum to the effect of RAS blockers on the clinical characteristics of COVID-19 patients with hypertension.

[This corrects the article DOI: 10.21037/atm.2020.03.229.].

Low CD4 T cell count predicts radiological progression in severe and critically ill COVID-19 patients: a case control study.

BACKGROUND: Novel coronavirus disease (COVID-19) has spread globally and caused over 3 million deaths, posing great challenge on public health and medical systems. Limited data are available predictive factors for disease progression. We aim to assess clinical and radiological predictors for pulmonary aggravation in severe and critically ill COVID-19 patients. METHODS: Patients with confirmed COVID-19 in Renmin Hospital of Wuhan University, China, between Feb. 6th, 2020 and Feb. 21st, 2020 were retrospectively collected. Enrolled patients were divided into non-progression group and progression group based on initial and follow-up chest CTs. Clinical, laboratory, and radiological variables were analyzed. RESULTS: During the study period, 162 patients were identified and a total of 126 patients, including 97 (77.0%) severe cases and 29 (23.0%) critically ill cases were included in the final analysis. Median age was 66.0 (IQR, 56.0-71.3) years. Median time from onset to initial chest CT was 15.0 (IQR, 12.0-20.0) days and median interval to follow-up was 7.0 (IQR, 5.0-7.0) days. Compared with those who did not progress (n=111, 88.1%), patients in the progression group (n=15, 11.9%) had significantly higher percentage of peak body temperature >38 °C (P=0.002), lower platelet count (P=0.011), lower CD4 T cell count (P=0.002), lower CD8 count (P=0.011), higher creatine kinase level (P=0.002), and lower glomerular filtration rate (P=0.018). On both univariate and multivariable analysis, only CD4 T cell count <200/µL was significant (OR, 6.804; 95% CI, 1.450-31.934; P=0.015) for predicting pulmonary progression. CONCLUSIONS: Low CD4 T cell count predicts progression of pulmonary change in severe and critically ill patients with COVID-19.

Effect of liver injury on prognosis and treatment of hospitalized patients with COVID-19 pneumonia.

BACKGROUND: Liver injury is common in patients with coronavirus disease 2019 (COVID-19), although its effect on patient outcomes has not been well studied. This study aimed to evaluate the effect of liver injury on the prognosis and treatment of patients with COVID-19 pneumonia. METHODS: In this retrospective, single-center study, data on 109 hospitalized patients with COVID-19 pneumonia were extracted and analyzed. The primary composite end-point event was the use of mechanical ventilation or death. RESULTS: At admission, of the 109 patients enrolled, 56 patients (51.4%) were diagnosed with severe disease, and 39 (35.8%) presented with liver injury, which mainly manifested as elevated levels of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) accompanied simultaneously by an increase in the level of γ-glutamyl transferase. A primary composite end-point event occurred in 21 patients (19.3%). Liver injury was more prevalent in patients with severe disease than in those with non-severe disease (46.4% vs. 24.5%, P=0.017). However, there was no significant difference found between severe and non-severe patients in the use of mechanical ventilation, mortality, hospital stay, or use and dosage of glucocorticoids between individuals with and without liver injury (all P>0.05). The degree of disease severity (OR =7.833, 95% CI, 1.834-31.212, P=0.005) and presence of any coexisting illness (OR =4.736, 95% CI, 1.305-17.186, P=0.018) were predictable risk factors for primary composite end-point events, whereas liver injury had no significance in this aspect (OR =0.549, 95% CI, 0.477-5.156, P=0.459). CONCLUSIONS: Liver injury was more common in severe cases of COVID-19 pneumonia than in non-severe cases. However, liver injury had no negative effect on the prognosis and treatment of COVID-19 pneumonia.

Myocardial injury and COVID-19: Serum hs-cTnI level in risk stratification and the prediction of 30-day fatality in COVID-19 patients with no prior cardiovascular disease.

Introduction: To explore the involvement of the cardiovascular system in coronavirus disease 2019 (COVID-19), we investigated whether myocardial injury occurred in COVID-19 patients and assessed the performance of serum high-sensitivity cardiac Troponin I (hs-cTnI) levels in predicting disease severity and 30-day in-hospital fatality. Methods: We included 244 COVID-19 patients, who were admitted to Renmin Hospital of Wuhan University with no preexisting cardiovascular disease or renal dysfunction. We analyzed the data including patients' clinical characteristics, cardiac biomarkers, severity of medical conditions, and 30-day in-hospital fatality. We performed multivariable Cox regressions and the receiver operating characteristic analysis to assess the association of cardiac biomarkers on admission with disease severity and prognosis. Results: In this retrospective observational study, 11% of COVID-19 patients had increased hs-cTnI levels (>40 ng/L) on admission. Of note, serum hs-cTnI levels were positively associated with the severity of medical conditions (median [interquartile range (IQR)]: 6.00 [6.00-6.00] ng/L in 91 patients with moderate conditions, 6.00 [6.00-18.00] ng/L in 107 patients with severe conditions, and 11.00 [6.00-56.75] ng/L in 46 patients with critical conditions, P for trend=0.001). Moreover, compared with those with normal cTnI levels, patients with increased hs-cTnI levels had higher in-hospital fatality (adjusted hazard ratio [95% CI]: 4.79 [1.46-15.69]). The receiver-operating characteristic curve analysis suggested that the inclusion of hs-cTnI levels into a panel of empirical prognostic factors substantially improved the prediction performance for severe or critical conditions (area under the curve (AUC): 0.71 (95% CI: 0.65-0.78) vs. 0.65 (0.58-0.72), P=0.01), as well as for 30-day fatality (AUC: 0.91 (0.85-0.96) vs. 0.77 (0.62-0.91), P=0.04). A cutoff value of 20 ng/L of hs-cTnI level led to the best prediction to 30-day fatality. Conclusions: In COVID-19 patients with no preexisting cardiovascular disease, 11% had increased hs-cTnI levels. Besides empirical prognostic factors, serum hs-cTnI levels upon admission provided independent prediction to both the severity of the medical condition and 30-day in-hospital fatality. These findings may shed important light on the clinical management of COVID-19.

The effect of RAS blockers on the clinical characteristics of COVID-19 patients with hypertension.

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by a novel coronavirus (designated as SARS-CoV-2) has become a pandemic worldwide. Based on the current reports, hypertension may be associated with increased risk of sever condition in hospitalized COVID-19 patients. Angiotensin-converting enzyme 2 (ACE2) was recently identified to functional receptor of SARS-CoV-2. Previous experimental data revealed ACE2 level was increased following treatment with ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). Currently doctors concern whether these commonly used renin-angiotensin system (RAS) blockers-ACEIs/ARBs may increase the severity of COVID-19. METHODS: We extracted data regarding 50 hospitalized hypertension patients with laboratory confirmed COVID-19 in the Renmin Hospital of Wuhan University from Feb 7 to Mar 03, 2020. These patients were grouped into RAS blockers group (Group A, n=20) and non-RAS blockers group (Group B, n=30) according to the basic blood pressure medications. All patients continued to use pre-admission antihypertensive drugs. Clinical severity (symptoms, laboratory and chest CT findings, etc.), clinical course, and short time outcome were analyzed after hospital admission. RESULTS: Ten (50%) and seventeen (56.7%) of the Group A and Group B participants were males (P=0.643), and the average age was 52.65±13.12 and 67.77±12.84 years (P=0.000), respectively. The blood pressure of both groups was under effective control. There was no significant difference in clinical severity, clinical course and in-hospital mortality between Group A and Group B. Serum cardiac troponin I (cTnI) (P=0.03), and N-terminal (NT)-pro hormone BNP (NT-proBNP) (P=0.04) showed significant lower level in Group A than in Group B. But the patients with more than 0.04ng/mL or elevated NT-proBNP level had no statistical significance between the two groups. In patients over 65 years or under 65 years, cTnI or NT-proBNP level showed no difference between the two groups. CONCLUSIONS: We observed there was no obvious difference in clinical characteristics between RAS blockers and non-RAS blockers groups. These data suggest ACEIs/ARBs may have few effects on increasing the clinical severe conditions of COVID-19.