Exhausting T Cells During HIV Infection May Improve the Prognosis of Patients with COVID-19.

T-cell reduction is an important characteristic of coronavirus disease 2019 (COVID-19), and its immunopathology is a subject of debate. It may be due to the direct effect of the virus on T-cell exhaustion or indirectly due to T cells redistributing to the lungs. HIV/AIDS naturally served as a T-cell exhaustion disease model for recognizing how the immune system works in the course of COVID-19. In this study, we collected the clinical charts, T-lymphocyte analysis, and chest CT of HIV patients with laboratory-confirmed COVID-19 infection who were admitted to Jin Yin-tan Hospital (Wuhan, China). The median age of the 21 patients was 47 years [interquartile range (IQR) = 40-50 years] and the median CD4 T-cell count was 183 cells/µl (IQR = 96-289 cells/µl). Eleven HIV patients were in the non-AIDS stage and 10 were in the AIDS stage. Nine patients received antiretroviral treatment (ART) and 12 patients did not receive any treatment. Compared to the reported mortality rate (nearly 4%-10%) and severity rate (up to 20%-40%) among COVID-19 patients in hospital, a benign duration with 0% severity and mortality rates was shown by 21 HIV/AIDS patients. The severity rates of COVID-19 were comparable between non-AIDS (median CD4 = 287 cells/µl) and AIDS (median CD4 = 97 cells/µl) patients, despite some of the AIDS patients having baseline lung injury stimulated by HIV: 7 patients (33%) were mild (five in the non-AIDS group and two in the AIDS group) and 14 patients (67%) were moderate (six in the non-AIDS group and eight in the AIDS group). More importantly, we found that a reduction in T-cell number positively correlates with the serum levels of interleukin 6 (IL-6) and C-reactive protein (CRP), which is contrary to the reported findings on the immune response of COVID-19 patients (lower CD4 T-cell counts with higher levels of IL-6 and CRP). In HIV/AIDS, a compromised immune system with lower CD4 T-cell counts might waive the clinical symptoms and inflammatory responses, which suggests lymphocyte redistribution as an immunopathology leading to lymphopenia in COVID-19.

Retrospective Study of Critically Ill COVID-19 Patients With and Without Extracorporeal Membrane Oxygenation Support in Wuhan, China.

Background: Extracorporeal membrane oxygenation (ECMO) might benefit critically ill COVID-19 patients. But the considerations besides indications guiding ECMO initiation under extreme pressure during the COVID-19 epidemic was not clear. We aimed to analyze the clinical characteristics and in-hospital mortality of severe critically ill COVID-19 patients supported with ECMO and without ECMO, exploring potential parameters for guiding the initiation during the COVID-19 epidemic. Methods: Observational cohort study of all the critically ill patients indicated for ECMO support from January 1 to May 1, 2020, in all 62 authorized hospitals in Wuhan, China. Results: Among the 168 patients enrolled, 74 patients actually received ECMO support and 94 not were analyzed. The in-hospital mortality of the ECMO supported patients was significantly lower than non-ECMO ones (71.6 vs. 85.1%, P = 0.033), but the role of ECMO was affected by patients' age (Logistic regression OR 0.62, P = 0.24). As for the ECMO patients, the median age was 58 (47-66) years old and 62.2% (46/74) were male. The 28-day, 60-day, and 90-day mortality of these ECMO supported patients were 32.4, 68.9, and 74.3% respectively. Patients survived to discharge were younger (49 vs. 62 years, P = 0.042), demonstrated higher lymphocyte count (886 vs. 638 cells/uL, P = 0.022), and better CO2 removal (PaCO2 immediately after ECMO initiation 39.7 vs. 46.9 mmHg, P = 0.041). Age was an independent risk factor for in-hospital mortality of the ECMO supported patients, and a cutoff age of 51 years enabled prediction of in-hospital mortality with a sensitivity of 84.3% and specificity of 55%. The surviving ECMO supported patients had longer ICU and hospital stays (26 vs. 18 days, P = 0.018; 49 vs. 29 days, P = 0.001 respectively), and ECMO procedure was widely carried out after the supplement of medical resources after February 15 (67.6%, 50/74). Conclusions: ECMO might be a benefit for severe critically ill COVID-19 patients at the early stage of epidemic, although the in-hospital mortality was still high. To initiate ECMO therapy under tremendous pressure, patients' age, lymphocyte count, and adequacy of medical resources should be fully considered.

Extracorporeal Membrane Oxygenation Therapy for Critically Ill Coronavirus Disease 2019 Patients in Wuhan, China: A Retrospective Multicenter Cohort Study.

Currently, little in-depth evidence is known about the application of extracorporeal membrane oxygenation (ECMO) therapy in coronavirus disease 2019 (COVID-19) patients. This retrospective multicenter cohort study included patients with COVID-19 at 7 designated hospitals in Wuhan, China. The patients were followed up until June 30, 2020. Univariate and multivariate logistic regression analyses were performed to identify the risk factors associated with unsuccessful ECMO weaning. Propensity score matching was used to match patients who received veno-venous ECMO with those who received invasive mechanical ventilation (IMV)-only therapy. Of 88 patients receiving ECMO therapy, 27 and 61 patients were and were not successfully weaned from ECMO, respectively. Additionally, 15, 15, and 65 patients were further weaned from IMV, discharged from hospital, or died during hospitalization, respectively. In the multivariate logistic regression analysis, a lymphocyte count ≤0.5×109/L and D-dimer concentration >4× the upper limit of normal level at ICU admission, a peak PaCO2 >60 mmHg at 24 h before ECMO initiation, and no tracheotomy performed during the ICU stay were independently associated with lower odds of ECMO weaning. In the propensity score-matched analysis, a mixed-effect Cox model detected a lower hazard ratio for 120-day all-cause mortality after ICU admission during hospitalization in the ECMO group. The presence of lymphocytopenia, higher D-dimer concentrations at ICU admission and hypercapnia before ECMO initiation could help to identify patients with a poor prognosis. Tracheotomy could facilitate weaning from ECMO. ECMO relative to IMV-only therapy was associated with improved outcomes in critically ill COVID-19 patients.

Identification of a novel coronavirus causing severe pneumonia in human: a descriptive study.

BACKGROUND: Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans. METHODS: We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed. RESULTS: Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown ß-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor. CONCLUSION: A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.

A pneumonia outbreak associated with a new coronavirus of probable bat origin.

Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats1-4. Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans5-7. Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor-angiotensin converting enzyme II (ACE2)-as SARS-CoV.

A novel HLA class I allele, HLA-B*46:01:21, identified by sequence-based typing in a Chinese individual.

HLA-B*46:01:21 differs from HLA-B*46:01:01 by one nucleotide exchange at position 834(G>A) with no amino exchange.

Regulation Mechanism of MicroRNAs in Non-Small Cell Lung Cancer.

MicroRNAs are small non-coding RNAs with regulatory biological activity, by modulating target genes on epigenetic, transcriptional, post-transciptional and translational levels. Hundreds of reports indicated that miRNAs play important roles in non-small cell lung cancer (NSCLC). Actually, microRNAs are both regulation targets and regulators targeting effector genes. This article reviewed multifaceted role of microRNAs associated to NSCLC, not only targeting to but also targeted by tumor related genes, to help us understand microRNAs related complex regulation networks. Aberrant expressed micoRNAs and their targets were summarized; the statistical results showed that several microRNAs may play key roles by targeting multiple tumor associated targets. On the other hand, Oncogenes and tumor repressors represented by PTEN were also shown to be the most popular targets of microRNAs. Additionally, ZEB1/2 may be a featured pathway in NSCLC, with significant frequency modulated by microRNAs.

Extracorporeal membrane oxygenation for avian influenza A (H7N9) patient with acute respiratory distress syndrome: a case report and short literature review.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is performed as an acceptable life-saving bridging procedure in patients with severe acute respiratory distress syndrome (ARDS).To patients with avian influenza A (H7N9)-associated ARDS, ECMO could be adopted as a feasible therapeutic solution. We present our successful experience with ECMO utilized in a respiratory failure patient with H7N9 infection. CASE PRESENTATION: A 44 years-old female with H7N9-induced ARDS was admitted to intensive care unit (ICU) and was treated with veno-venous ECMO for six days, antiviral therapy, prolonged corticosteroid infusion and other therapies. She suffered significant hemorrhage requiring transfusion of platelets and multidrug-resistant Acinetobacter Baumannii infection during ECMO support. Bleeding and infection almost killed the patient's life. Fortunately, she was alive at last and completly recovered after 38 days of ICU stay. CONCLUSIONS: ECMO was effective in this H7N9 patient with a fatal respiratory failure. Mechanical circulatory support was the only chance for our patient with H7N9-associated ARDS to survive until respiratory function recovery. Early detection and rapid response are essential to these serious ECMO-associated complications such as hemorrhage, thrombosis and infection.

Efficacy of video-assisted thoracoscopic surgery for 29 patients with tuberculosis-destroyed lung.

BACKGROUND: Incompleteness of interlobar fissures and pleural adhesions, common in tuberculous destroyed lung (TDL), are among "technical contraindications" for video-assisted thoracoscopic surgery (VATS). The efficacy and safety of VATS in the treatment of TDL, has not yet been detailed in. OBJECTIVE: The objective of the present study is to observe the efficacy and safety of VATS in the management of TDL. METHODS: A retrospective review of anatomic lobectomy by VATS on 29 cases of TDL was performed in the Department of Thoracic Surgery of Wuhan Medical Treatment Center between October 2010 and October 2013. RESULTS: All the 29 surgeries by VATS were successfully completed. No death case was reported. Operative duration of VATS was 75~400 min, with an average of 185.4 min; intraoperative amount of bleeding ranged 50 to 2300 ml, with an average of 575.6 ml; the incidence of postoperative complication was 21.4% (6/28). Postoperative complications occurred in 6 cases, among which there were 2 cases of persistent postoperative pulmonary air leak, 2 cases of pleural effusion, one case of thoracic hemorrhage and one case of arrhythmia complicated with left heart failure. There was one patient who was converted from VATS to open thoracic surgery half-way. CONCLUSION: Our results have shown the efficacy, safety and a breakthrough in the "technical contraindications" of VATS in the management of TDL.