Corticosteroid treatment in severe patients with SARS-CoV-2 and chronic HBV co-infection: a retrospective multicenter study.

BACKGROUND: The impact of corticosteroids on patients with severe coronavirus disease 2019 (COVID-19)/chronic hepatitis B virus (HBV) co-infection is currently unknown. We aimed to investigate the association of corticosteroids on these patients. METHODS: This retrospective multicenter study screened 5447 confirmed COVID-19 patients hospitalized between Jan 1, 2020 to Apr 18, 2020 in seven centers in China, where the prevalence of chronic HBV infection is moderate to high. Severe patients who had chronic HBV and acute SARS-cov-2 infection were potentially eligible. The diagnosis of chronic HBV infection was based on positive testing for hepatitis B surface antigen (HBsAg) or HBV DNA during hospitalization and a medical history of chronic HBV infection. Severe patients (meeting one of following criteria: respiratory rate > 30 breaths/min; severe respiratory distress; or SpO2 ≤ 93% on room air; or oxygen index < 300 mmHg) with COVID-19/HBV co-infection were identified. The bias of confounding variables on corticosteroids effects was minimized using multivariable logistic regression model and inverse probability of treatment weighting (IPTW) based on propensity score. RESULTS: The prevalence of HBV co-infection in COVID-19 patients was 4.1%. There were 105 patients with severe COVID-19/HBV co-infections (median age 62 years, 57.1% male). Fifty-five patients received corticosteroid treatment and 50 patients did not. In the multivariable analysis, corticosteroid therapy (OR, 6.32, 95% CI 1.17-34.24, P = 0.033) was identified as an independent risk factor for 28-day mortality. With IPTW analysis, corticosteroid treatment was associated with delayed SARS-CoV-2 viral RNA clearance (OR, 2.95, 95% CI 1.63-5.32, P < 0.001), increased risk of 28-day and in-hospital mortality (OR, 4.90, 95% CI 1.68-14.28, P = 0.004; OR, 5.64, 95% CI 1.95-16.30, P = 0.001, respectively), and acute liver injury (OR, 4.50, 95% CI 2.57-7.85, P < 0.001). Methylprednisolone dose per day and cumulative dose in non-survivors were significantly higher than in survivors. CONCLUSIONS: In patients with severe COVID-19/HBV co-infection, corticosteroid treatment may be associated with increased risk of 28-day and in-hospital mortality.

Micronutrient Level Is Negatively Correlated with the Neutrophil-Lymphocyte Ratio in Patients with Severe COVID-19

Aim To explore the potential relationship between NLR and micronutrient deficiency in patients with severe COVID-19 infection. Methods Sixteen patients were categorized into the mild group (mild COVID-19) and severe group (severe COVID-19) based on the guideline of the management of COVID-19. The lactate dehydrogenase (LDH);superoxide dismutase (SOD), the inflammatory markers (neutrophil lymphocyte ratio (NLR)), erythrocyte sedimentation rate (ESR), c-reactive protein (CRP), selenium (Se), iron (Fe), zinc (Zn), nickel (Ni), copper (Cu), chromium (Cr), cadmium (Cd), arsenic (As), and manganese (Mn) were measured in the blood. Results Compared to the mild group, the NLR (P < 0.05) and the level of Se (P < 0.01), Fe (P < 0.05), and Zn (P < 0.05) were significantly decreased in the severe group. The level of Se, Fe, and Zn was significantly correlated to NLR levels. Furthermore, close positive correlation was found between NLR and severity of COVID-19. Conclusion The micronutrient deficiency in the blood is associated with NLR in the severity of COVID-19 patients.

Severe novel coronavirus pneumonia: a case report and literature review

Objective To describe the diagnosis and treatment of a patient with severe novel coronavirus pneumonia, and to improve the understanding and management of clinicians on novel coronavirus pneumonia. Methods The onset, development, treatment and outcome of a patient with severe 2019 novel coronavirus pneumonia were retrospectively analyzed and relevant literatures were reviewed. Results At the beginning of the disease, the patient presented fever and dry cough, and later the disease progressed to dyspnea. Chest CT showed bilateral exudation of the lung. Lopinavir/ritonavir, IFN-a and immunoglobulin were given to the patient according to the expert group's opinion. The pneumonia was cured and the patient was discharged two weeks later. Conclusion Appropriate management strategies are effective on diagnosis and treatment of new coronavirus pneumonia.

COVID-19 associated EBV reactivation and effects of ganciclovir treatment.

BACKGROUND: Systemic reactivation of Epstein-Barr virus (EBV) may occur in novel coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). However, the clinical consequences of EBV reactivation remain uncertain. METHODS: In this retrospective study, we screened 1314 patients with confirmed COVID-19 who died or were discharged between January 1, 2020 and March 12, 2020, in Wuhan Infectious Disease Hospital, Wuhan, China. Patients who had complete data for EBV serology and cytomegalovirus (CMV) serology were eligible. Serum levels of viral capsid antigen (VCA)-immunoglobulin G (IgG), Epstein-Barr nuclear antigen-IgG, VCA-IgM, early antigen (EA)-IgG, CMV-IgG, and CMV-IgM were compared between survivors and nonsurvivors. Dynamic changes of laboratory tests and outcomes were compared in patients with and without ganciclovir treatment. We used 1:1 matching based on age, gender, and illness severity to balance baseline characteristics. RESULTS: EBV reactivation was present in 55 of 217 patients. EBV reactivation was associated with age (57.91 [13.19] vs. 50.28 [12.66] years, p < .001), female gender (31 [56%] vs. 60 [37%], p = .02). Patients with EBV reactivation have statistically nonsignificant higher mortality rate (12 [22%] vs. 18 [11%], p = .08). EA-IgG levels were significantly higher in nonsurvivors than in survivors (median difference: -0.00005, 95% confidence interval, CI [-3.10, 0.00], p = .05). As compared to patients with COVID-19 who did not receive ganciclovir therapy, ganciclovir-treated patients had improved survival rate (0.98, 95% CI [0.95, 1.00] vs. 0.88, 95% CI [0.81, 0.95], p = .01). Hemoglobin (p < .001) and prealbumin (p = .02) levels were significantly higher in ganciclovir-treated patients. CONCLUSION: A high proportion of COVID-19 patients had EBV reactivation that may be associated with an increased risk of death. Whether treatment with ganciclovir may decrease the mortality of COVID-19 patients complicated with EBV reactivation warrants to be addressed in a placebo-controlled randomized trial in the future.

Micronutrient Level Is Negatively Correlated with the Neutrophil-Lymphocyte Ratio in Patients with Severe COVID-19.

Aim: To explore the potential relationship between NLR and micronutrient deficiency in patients with severe COVID-19 infection. Methods: Sixteen patients were categorized into the mild group (mild COVID-19) and severe group (severe COVID-19) based on the guideline of the management of COVID-19. The lactate dehydrogenase (LDH); superoxide dismutase (SOD), the inflammatory markers (neutrophil lymphocyte ratio (NLR)), erythrocyte sedimentation rate (ESR), c-reactive protein (CRP), selenium (Se), iron (Fe), zinc (Zn), nickel (Ni), copper (Cu), chromium (Cr), cadmium (Cd), arsenic (As), and manganese (Mn) were measured in the blood. Results: Compared to the mild group, the NLR (P < 0.05) and the level of Se (P < 0.01), Fe (P < 0.05), and Zn (P < 0.05) were significantly decreased in the severe group. The level of Se, Fe, and Zn was significantly correlated to NLR levels. Furthermore, close positive correlation was found between NLR and severity of COVID-19. Conclusion: The micronutrient deficiency in the blood is associated with NLR in the severity of COVID-19 patients.

Sex Differences on Clinical Characteristics, Severity, and Mortality in Adult Patients With COVID-19: A Multicentre Retrospective Study.

Background: Coronavirus disease-2019 (COVID-19) epidemic is spreading globally. Sex differences in the severity and mortality of COVID-19 emerged. This study aims to describe the impact of sex on outcomes in COVOD-19 with a special focus on the effect of estrogen. Methods: We performed a retrospective cohort study which included 413 patients (230 males and 183 females) with COVID-19 from three designated hospitals in China with a follow up time from January 31, 2020, to April 17, 2020. Women over 55 were considered as postmenopausal patients according to the previous epidemiological data from China. The interaction between age and sex on in-hospital mortality was determined through Cox regression analysis. In addition, multivariate Cox regression models were performed to explore risk factors associated with in-hospital mortality of COVID-19. Results: Age and sex had significant interaction for the in-hospital mortality (P < 0.001). Multivariate Cox regression showed that age (HR 1.041, 95% CI 1.009-1.073, P = 0.012), male sex (HR 2.033, 95% CI 1.007-2.098, P = 0.010), the interaction between age and sex (HR 1.118, 95% CI 1.003-1.232, P = 0.018), and comorbidities (HR 9.845, 95% CI 2.280-42.520, P = 0.002) were independently associated with in-hospital mortality of COVID-19 patients. In this multicentre study, female experienced a lower fatality for COVID-19 than male (4.4 vs. 10.0%, P = 0.031). Interestingly, stratification by age group revealed no difference in-hospital mortality was noted in women under 55 compared with women over 55 (3.8 vs. 5.2%, P = 0.144), as well as in women under 55 compared with the same age men (3.8 vs. 4.0%, P = 0.918). However, there was significantly difference in women over 55 with men of the same age group (5.2 vs. 21.0%, P = 0.007). Compared with male patients, female patients had higher lymphocyte (P < 0.001) and high-density lipoprotein (P < 0.001), lower high sensitive c reaction protein level (P < 0.001), and lower incidence rate of acute cardiac injury (6.6 vs. 13.5%, P = 0.022). Conclusion: Male sex is an independent risk factor for COVID-19 in-hospital mortality. Although female mortality in COVID-19 is lower than male, it might not be directly related to the effect of estrogen. Further study is warranted to identify the sex difference in COVID-19 and mechanisms involved.

Clinical Features for Severely and Critically Ill Patients with COVID-19 in Shandong: A Retrospective Cohort Study.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel pathogen, has caused an outbreak of coronavirus disease 2019 (COVID-19) that has spread rapidly around the world. Determining the risk factors for death and the differences in clinical features between severely ill and critically ill patients with SARS-CoV-2 pneumonia has become increasingly important. AIM: This study was intended to provide insight into the difference between severely ill and critically ill patients with SARS-CoV-2 pneumonia. METHODS: In this retrospective, multicenter cohort study, we enrolled 62 seriously ill patients with SARS-CoV-2 pneumonia who had been diagnosed by March 12, 2020. Clinical data, laboratory indexes, chest images, and treatment strategies collected from routine medical records were compared between severely ill and critically ill patients. Univariate and multivariate logistic regression analyses were also conducted to identify the risk factors associated with the progression of patients with severe COVID-19. RESULTS: Of the 62 patients with severe or critical illness, including 7 who died, 30 (48%) patients had underlying diseases, of which the most common was cardiovascular disease (hypertension, 34%, and coronary heart disease, 5%). Compared to patients with severe disease, those with critical disease had distinctly higher white blood cell counts, procalcitonin levels, and D-dimer levels, and lower hemoglobin levels and lymphocyte counts. Multivariate regression showed that a lymphocyte count less than 109/L (odds ratio 20.92, 95% CI 1.76-248.18; p=0.02) at admission increased the risk of developing a critical illness. CONCLUSION: Based on multivariate regression analysis, a lower lymphocyte count (<109/L) on admission is the most critical independent factor that is closely associated with an increased risk of progression to critical illness. Age, underlying diseases, especially hypertension and coronary heart disease, elevated D-dimer, decreased hemoglobin, and SOFA score, and APACH score also need to be taken into account for predicting disease progression. Blood cell counts and procalcitonin levels for the later secondary bacterial infection have a certain reference values.

Risk factors for severe COVID-19 in middle-aged patients without comorbidities: a multicentre retrospective study.

BACKGROUND: Information regarding characteristics and risk factors of COVID-19 amongst middle-aged (40-59 years) patients without comorbidities is scarce. METHODS: We therefore conducted this multicentre retrospective study and collected data of middle-aged COVID-19 patients without comorbidities at admission from three designated hospitals in China. RESULTS: Among 119 middle-aged patients without comorbidities, 18 (15.1%) developed into severe illness and 5 (3.9%) died in hospital. ARDS (26, 21.8%) and elevated D-dimer (36, 31.3%) were the most common complications, while other organ complications were relatively rare. Multivariable regression showed increasing odds of severe illness associated with neutrophil to lymphocyte ratio (NLR, OR, 11.238; 95% CI 1.110-1.382; p < 0.001) and D-dimer greater than 1 µg/ml (OR, 16.079; 95% CI 3.162-81.775; p = 0.001) on admission. The AUCs for the NLR, D-dimer greater than 1 µg/ml and combined NLR and D-dimer index were 0.862 (95% CI, 0.751-0.973), 0.800 (95% CI 0.684-0.915) and 0.916 (95% CI, 0.855-0.977), respectively. SOFA yielded an AUC of 0.750 (95% CI 0.602-0.987). There was significant difference in the AUC between SOFA and combined index (z = 2.574, p = 0.010). CONCLUSIONS: More attention should be paid to the monitoring and early treatment of respiratory and coagulation abnormalities in middle-aged COVID-19 patients without comorbidities. In addition, the combined NLR and D-dimer higher than 1 µg/ml index might be a potential and reliable predictor for the incidence of severe illness in this specific patient with COVID-19, which could guide clinicians on early classification and management of patients, thereby relieving the shortage of medical resource. However, it is warranted to validate the reliability of the predictor in larger sample COVID-19 patients.