Dynamic lymphocyte-CRP ratio as a predictor: a single-centre retrospective study on disease severity and progression in adult COVID-19 patients.

OBJECTIVE: To assess the efficacy of dynamic changes in lymphocyte-C-reactive protein ratio (LCR) on differentiating disease severity and predicting disease progression in adult patients with Coronavirus disease 2019 (COVID-19). METHODS: This single-centre retrospective study enrolled adult COVID-19 patients categorized into moderate, severe and critical groups according to the Diagnosis and Treatment of New Coronavirus Pneumonia (ninth edition). Demographic and clinical data were collected. LCR and sequential organ failure assessment (SOFA) score were calculated. Lymphocyte count and C-reactive protein (CRP) levels were monitored on up to four occasions. Disease severity was determined concurrently with each LCR measurement. RESULTS: This study included 145 patients assigned to moderate (n = 105), severe (n = 33) and critical groups (n = 7). On admission, significant differences were observed among different disease severity groups including age, comorbidities, neutrophil proportion, lymphocyte count and proportion, D-Dimer, albumin, total bilirubin, direct bilirubin, indirect bilirubin, CRP and SOFA score. Dynamic changes in LCR showed significant differences across different disease severity groups at different times, which were significantly inversely correlated with disease severity of COVID-19, with correlation coefficients of -0.564, -0.548, -0.550 and -0.429 at four different times. CONCLUSION: Dynamic changes in LCR can effectively differentiate disease severity and predict disease progression in adult COVID-19 patients.

COVID-19 patient with an incubation period of 27 d: A case report.

BACKGROUND: As a highly contagious disease, coronavirus disease 2019 (COVID-19) is wreaking havoc around the world due to continuous spread among close contacts mainly via droplets, aerosols, contaminated hands or surfaces. Therefore, centralized isolation of close contacts and suspected patients is an important measure to prevent the transmission of COVID-19. At present, the quarantine duration in most countries is 14 d due to the fact that the incubation period of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is usually identified as 1-14 d with median estimate of 4-7.5 d. Since COVID-19 patients in the incubation period are also contagious, cases with an incubation period of more than 14 d need to be evaluated. CASE SUMMARY: A 70-year-old male patient was admitted to the Department of Respiratory Medicine of The First Affiliated Hospital of Harbin Medical University on April 5 due to a cough with sputum and shortness of breath. On April 10, the patient was transferred to the Fever Clinic for further treatment due to close contact to one confirmed COVID-19 patient in the same room. During the period from April 10 to May 6, nucleic acid and antibodies to SARS-CoV-2 were tested 7 and 4 times, respectively, all of which were negative. On May 7, the patient developed fever with a maximum temperature of 39℃, and his respiratory difficulties had deteriorated. The results of nucleic acid and antibody detection of SARS-CoV-2 were positive. On May 8, the nucleic acid and antibody detection of SARS-CoV-2 by Heilongjiang Provincial Center for Disease Control were also positive, and the patient was diagnosed with COVID-19 and reported to the Chinese Center for Disease Control and Prevention. CONCLUSION: This case highlights the importance of the SARS-CoV-2 incubation period. Further epidemiological investigations and clinical observations are urgently needed to identify the optimal incubation period of SARS-CoV-2 and formulate rational and evidence-based quarantine policies for COVID-19 accordingly.

Standardization of critical care management of non-critically ill patients with COVID-19.

The large global outbreak of coronavirus disease 2019 (COVID-19) has seriously endangered the health care system in China and globally. The sudden surge of patients with severe acute respiratory syndrome coronavirus 2 infection has revealed the shortage of critical care medicine resources and intensivists. Currently, the management of non-critically ill patients with COVID-19 is performed mostly by non-intensive care unit (ICU) physicians, who lack the required professional knowledge, training, and practice in critical care medicine, especially in terms of continuous monitoring of the respiratory function, intervention, and feedback on treatment effects. This clinical problem needs an urgent solution. Therefore, here, we propose a series of clinical strategies for non-ICU physicians aimed at the standardization of the management of non-critically ill patients with COVID-19 from the perspective of critical care medicine. Isolation management is performed to facilitate the implementation of hierarchical monitoring and intervention to ensure the reasonable distribution of scarce critical care medical resources and intensivists, highlight the key patients, timely detection of disease progression, and early and appropriate intervention and organ function support, and thus improve the prognosis. Different management objectives are also set based on the high-risk factors and the severity of patients with COVID-19. The approaches suggested herein will facilitate the timely detection of disease progression, and thus ensure the provision of early and appropriate intervention and organ function support, which will eventually improve the prognosis.

Efficacy and safety of anti-interleukin-5 therapy in patients with asthma: A pairwise and Bayesian network meta-analysis.

INTRODUCTION: Anti-interleukin-5 therapy has been proposed as a novel and promising treatment option in asthma treatment. However, the optimum monoclonal antibodies for asthma treatment remain uncertain. METHODS: We searched the PubMed, EMBASE and Cochrane databases from their inceptions to June 2018 for randomized controlled trials that reported pulmonary function, adverse events, Asthma Quality of Life Questionnaire (AQLQ) scores, and asthmatic exacerbations resulting from anti-interleukin-5 therapy in asthma patients. Extracted data were analyzed by pairwise and network meta-analysis. RESULTS: Twenty-one randomized studies were identified for this analysis. By pairwise meta-analysis using a placebo as the reference, patients treated with monoclonal antibodies were associated with significantly improved forced expiratory volume (FEV1) values (standard mean difference [SMD], 0.18; 95% confidence interval [CI], 0.12-0.23; P < 0.001), lower rates of adverse events (risk ratio [RR], 0.93; 95% CI, 0.90-0.97; P < 0.001) and significant improvements in the AQLQ scores (SMD, 0.20; 95% CI, 0.13-0.26; P < 0.001). There were no significant differences in exacerbations risks (RR, 0.68; 95% CI, 0.11-4.14; P = 0.097). According to network meta-analysis, adverse events-related benefits were seen only with reslizumab, while AQLQ scores benefits, and pulmonary function benefits were still seen with all three monoclonal antibodies. The assessment of rank probabilities indicated that reslizumab presented the greatest likelihood of having benefits for pulmonary function, reducing adverse events and improving AQLQ scores when compared with the placebo, and mepolizumab presented the best benefits for reducing asthmatic exacerbations. CONCLUSIONS: Anti-interleukin-5 therapy appears to be a safe and effective treatment for asthma patients with respect to pulmonary lung function, adverse events and AQLQ scores, and do not increase asthmatic exacerbations. Our network meta-analysis in patients with asthma suggests that reducing adverse events benefits due to reslizumab, and pulmonary lung function benefits as well as good AQLQ scores are seen with respect to the three antibodies. Network meta-analysis indicates the probability that the best anti-interlukin-5 therapy for asthma patients might be reslizumab, but further trials are required to determine the most effective asthma treatment drug.

Artesunate Protects Against Sepsis-Induced Lung Injury Via Heme Oxygenase-1 Modulation.

Artesunate, a derivative of artemisinin, has anti-inflammatory properties and exerts protective roles in sepsis. Heme oxygense-1 (HO-1) inhibits the inflammatory response through reduction of proinflammatory cytokines and leukocyte influx into tissues. The present study investigated the effects of artesunate on HO-1 and septic lung injury. Cecal ligation and puncture (CLP) was employed to induce septic lung injury. Mice pretreated with artesunate (AS) (15 mg/kg) exhibited decreased sepsis-induced mortality and lung injury and alleviated lung pathological changes and neutrophil infiltration. In addition, AS lowered the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the serum and bronchoalveolar lavage fluid (BALF) and inhibited cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase isoform (iNOS) expression and NF-κB activation in lung tissue. In addition, AS enhanced NF-E2-related factor-2 (Nrf2) activation and HO-1 expression and enzymatic activity in lung tissue. However, the protective effects of AS on sepsis-induced lung injury were eliminated by ZnPP IX, an HO-1 competitive inhibitor. Therefore, AS plays protective roles in septic lung injury related to the upregulation of HO-1. These findings suggest an effective and applicable treatment to sepsis-induced lung injury and provide new insights into the molecular mechanisms and actions of AS.

Hemin inhibits NLRP3 inflammasome activation in sepsis-induced acute lung injury, involving heme oxygenase-1.

NLRP3 inflammasome activation contributes to acute lung injury (ALI), accelerating caspase-1 maturation, and resulting in IL-1ß and IL-18 over-production. Heme oxygenase-1 (HO-1) plays a protective role in ALI. This study investigated the effect of hemin (a potent HO-1 inducer) on NLRP3 inflammasome in sepsis-induced ALI. The sepsis model of cecal ligation and puncture (CLP) was used in C57BL6 mice. In vivo induction and suppression of HO-1 were performed by pretreatment with hemin and zinc protoporphyrin IX (ZnPP, a HO-1 competitive inhibitor) respectively. CLP triggered significant pulmonary damage, neutrophil infiltration, increased levels of IL-1ß and IL-18, and edema formation in the lung. Hemin pretreatment exerted inhibitory effect on lung injury and attenuated IL-1ß and IL-18 secretion in serum and lung tissue. In lung tissues, hemin down-regulated mRNA and protein levels of NLRP3, ASC and caspase-1. Moreover, hemin reduced malondialdehyde and reactive oxygen species production, and inhibited NF-κB and NLRP3 inflammasome activity. Meanwhile, hemin significantly increased HO-1 mRNA and protein expression and HO-1 enzymatic activity. In contrast, no significant differences were observed between the CLP and ZnPP groups. Our study suggests that hemin-inhibited NLRP3 inflammasome activation involved HO-1, reducing IL-1ß and IL-18 secretion and limiting the inflammatory response.

[Molecular biologic study on heme oxygenase in experiment pulmonary thromboembolism].

OBJECTIVE: To investigate the changes in heme oxygenase (HO) system expression in pulmonary thromboembolism (PTE), and the influence to the pulmonary artery blood pressure as a result of the changes. METHODS: In 23 healthy adult male dogs, autologous thrombus was injected through the jugular vein to reproduce the PTE model. They were divided randomly into 4 groups: A (pulmonary embolism 3 hours group), B (pulmonary embolism 8 hours group), C (pulmonary embolism 24 hours group) and D (control group). Swan-Ganz catheter was placed via the femoral vein to observe the changes in hemodynamics. Pulmonary artery was obtained to detect the expression of HO-1 using semi-quantity reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical method. RESULTS: The pulmonary artery mean pressure (PAMP), pulmonary artery systolic pressure (PASP) and pulmonary artery diastolic pressure (PADP) of the experimental groups were increased obviously after the pulmonary embolism as compared with those of before the embolism (all P<0.05), and were decreased obviously 1 hour after the embolism (all P<0.05). The decrease was gradual and stopped after 4-5 hours, but the pressure 8 hours after embolism was still higher than that of before embolism. HO-1 was not expressed in pulmonary artery in control group, but expressed after embolism in each experimental group. The expression was increased gradually after pulmonary embolism, and it was remarkable 24 hours after embolism (all P<0.05). CONCLUSION: The expression of HO-1 increased in PTE, and the increased pulmonary artery blood pressure decreased at the same time. The results suggest that HO-1 is related with dilatation of pulmonary artery after PTE.