Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study.

Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

BACKGROUNDSince December 2019, an outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, and is now becoming a global threat. We aimed to delineate and compare the immunological features of severe and moderate COVID-19.METHODSIn this retrospective study, the clinical and immunological characteristics of 21 patients (17 male and 4 female) with COVID-19 were analyzed. These patients were classified as severe (11 cases) and moderate (10 cases) according to the guidelines released by the National Health Commission of China.RESULTSThe median age of severe and moderate cases was 61.0 and 52.0 years, respectively. Common clinical manifestations included fever, cough, and fatigue. Compared with moderate cases, severe cases more frequently had dyspnea, lymphopenia, and hypoalbuminemia, with higher levels of alanine aminotransferase, lactate dehydrogenase, C-reactive protein, ferritin, and D-dimer as well as markedly higher levels of IL-2R, IL-6, IL-10, and TNF-α. Absolute numbers of T lymphocytes, CD4+ T cells, and CD8+ T cells decreased in nearly all the patients, and were markedly lower in severe cases (294.0, 177.5, and 89.0 × 106/L, respectively) than moderate cases (640.5, 381.5, and 254.0 × 106/L, respectively). The expression of IFN-γ by CD4+ T cells tended to be lower in severe cases (14.1%) than in moderate cases (22.8%).CONCLUSIONThe SARS-CoV-2 infection may affect primarily T lymphocytes, particularly CD4+ and CD8+ T cells, resulting in a decrease in numbers as well as IFN-γ production by CD4+ T cells. These potential immunological markers may be of importance because of their correlation with disease severity in COVID-19.TRIAL REGISTRATIONThis is a retrospective observational study without a trial registration number.FUNDINGThis work is funded by grants from Tongji Hospital for the Pilot Scheme Project, and partly supported by the Chinese National Thirteenth Five Years Project in Science and Technology for Infectious Disease (2017ZX10202201).

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Clinical and immunological features of severe and moderate coronavirus disease 2019.

Importance The coronavirus disease 2019 (COVID-19) pandemic, due to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a worldwide sudden and substantial increase in hospitalizations for pneumonia with multiorgan disease. This review discusses current evidence regarding the pathophysiology, transmission, diagnosis, and management of COVID-19. Observations SARS-CoV-2 is spread primarily via respiratory droplets during close face-to-face contact. Infection can be spread by asymptomatic, presymptomatic, and symptomatic carriers. The average time from exposure to symptom onset is 5 days, and 97.5% of people who develop symptoms do so within 11.5 days. The most common symptoms are fever, dry cough, and shortness of breath. Radiographic and laboratory abnormalities, such as lymphopenia and elevated lactate dehydrogenase, are common, but nonspecific. Diagnosis is made by detection of SARS-CoV-2 via reverse transcription polymerase chain reaction testing, although false-negative test results may occur in up to 20% to 67% of patients; however, this is dependent on the quality and timing of testing. Manifestations of COVID-19 include asymptomatic carriers and fulminant disease characterized by sepsis and acute respiratory failure. Approximately 5% of patients with COVID-19, and 20% of those hospitalized, experience severe symptoms necessitating intensive care. More than 75% of patients hospitalized with COVID-19 require supplemental oxygen. Treatment for individuals with COVID-19 includes best practices for supportive management of acute hypoxic respiratory failure. Emerging data indicate that dexamethasone therapy reduces 28-day mortality in patients requiring supplemental oxygen compared with usual care (21.6% vs 24.6%; age-adjusted rate ratio, 0.83 [95% CI, 0.74-0.92]) and that remdesivir improves time to recovery (hospital discharge or no supplemental oxygen requirement) from 15 to 11 days. In a randomized trial of 103 patients with COVID-19, convalescent plasma did not shorten time to recovery. Ongoing trials are testing antiviral therapies, immune modulators, and anticoagulants. The case-fatality rate for COVID-19 varies markedly by age, ranging from 0.3 deaths per 1000 cases among patients aged 5 to 17 years to 304.9 deaths per 1000 cases among patients aged 85 years or older in the US. Among patients hospitalized in the intensive care unit, the case fatality is up to 40%. At least 120 SARS-CoV-2 vaccines are under development. Until an effective vaccine is available, the primary methods to reduce spread are face masks, social distancing, and contact tracing. Monoclonal antibodies and hyperimmune globulin may provide additional preventive strategies. Conclusions and Relevance As of July 1, 2020, more than 10 million people worldwide had been infected with SARS-CoV-2. Many aspects of transmission, infection, and treatment remain unclear. Advances in prevention and effective management of COVID-19 will require basic and clinical investigation and public health and clinical interventions.

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Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review.

Importance Coronavirus disease 2019 (COVID-19) has resulted in considerable morbidity and mortality worldwide since December 2019. However, information on cardiac injury in patients affected by COVID-19 is limited. Objective To explore the association between cardiac injury and mortality in patients with COVID-19. Design, Setting, and Participants This cohort study was conducted from January 20, 2020, to February 10, 2020, in a single center at Renmin Hospital of Wuhan University, Wuhan, China; the final date of follow-up was February 15, 2020. All consecutive inpatients with laboratory-confirmed COVID-19 were included in this study. Main Outcomes and Measures Clinical laboratory, radiological, and treatment data were collected and analyzed. Outcomes of patients with and without cardiac injury were compared. The association between cardiac injury and mortality was analyzed. Results A total of 416 hospitalized patients with COVID-19 were included in the final analysis; the median age was 64 years (range, 21-95 years), and 211 (50.7%) were female. Common symptoms included fever (334 patients [80.3%]), cough (144 [34.6%]), and shortness of breath (117 [28.1%]). A total of 82 patients (19.7%) had cardiac injury, and compared with patients without cardiac injury, these patients were older (median [range] age, 74 [34-95] vs 60 [21-90] years;P  Conclusions and Relevance Cardiac injury is a common condition among hospitalized patients with COVID-19 in Wuhan, China, and it is associated with higher risk of in-hospital mortality.

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Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China.

Pathological findings of COVID-19 associated with acute respiratory distress syndrome.

A Klebsiella pneumoniae bacteriophage (vB_KpnM_IME346) was isolated from a hospital sewage sample. This bacteriophage specifically infects a clinical K. pneumoniae strain with a K63 capsular polysaccharide structure. The phage genome was evaluated by next-generation sequencing, which revealed a linear double-stranded DNA genome consisting of 49,482 base pairs with a G+C content of 49.1%. The latent period of vB_KpnM_IME346 was shown to be 20 min, and the burst size was 25-30 pfu (plaque-forming units)/infected cell. Transmission electron microscopy and phylogenetic analysis showed that the JD001-like phage belongs to the genus Jedunavirus of the family Myoviridae. The newly isolated vB_KpnM_IME346 shows infectivity in the clinical host K. pneumoniae KP576 strain, indicating that it is a promising alternative to antibacterial agents for removing K. pneumoniae from patients. 

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Characterization and Genomic Analysis of Bacteriophage vB_KpnM_IME346 Targeting Clinical Klebsiella pneumoniae Strain of the K63 Capsular Type

Few studies have reported Legionella sainthelensi infection. This infection primarily presents with respiratory manifestations. Here, we report an immunocompromised patient with cavitary pneumonia caused by L. sainthelensi who mainly had abdominal symptoms. The timely administration of moxifloxacin provided clinical improvement and resolution of symptoms. To our knowledge, this is one of the rare cases of L. sainthelensi infection presenting uniquely with abdominal distension and liver function impairment but without obvious respiratory symptoms. 

Legionella sainthelensi Pneumonia with Abdominal Symptoms as Prominent Manifestations

Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease characterized by chronic, progressive, and fibrotic lung injury. Although remarkable progress has been made toward understanding the pathogenesis of PF, finding more effective treatments for this fatal disease remains a challenge. In this study, we describe an innovative macrophage-based approach to deliver anti-fibrotic protein to the lung and inhibit PF in a mouse model of bleomycin (BLM)-induced lung injury. We engineered macrophages to continuously secrete three types of proteins: interleukin-10, which prevents inflammation; TGFRcFc, a soluble truncated TGF-βR2 that blocks TGF-β; and CD147, which induces matrix metalloproteinases (MMPs) and causes collagen degradation. Infusing these engineered macrophages into the lungs of BLM-induced PF mouse models in an optimal pattern significantly ameliorated PF in mice. Specifically, the most effective therapeutic outcome was achieved by infusing IL-10-secreting macrophages on day 1, followed by TGFRcFc-secreting macrophages on day 7 and CD147-secreting macrophages on day 14 into the same mice after BLM treatment. Our data suggest that macrophage-based delivery of anti-fibrotic proteins to the lungs is a promising therapy for fibrotic lung disorders. 

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/btm2.10555

Changqing Bai

Papers

Pathological findings of COVID-19 associated with acute respiratory distress syndrome.

Characterization and Genomic Analysis of Bacteriophage vB_KpnM_IME346 Targeting Clinical Klebsiella pneumoniae Strain of the K63 Capsular Type

Legionella sainthelensi Pneumonia with Abdominal Symptoms as Prominent Manifestations

Macrophage‐based delivery of anti‐fibrotic proteins alleviates bleomycin‐induced pulmonary fibrosis in mice