Mitochondrial dysfunction and mitophagy are key pathophysiological mechanisms in sepsis-associated acute kidney injury (S-AKI). IL-37, a recently confirmed member of the IL-1 family, has been implicated in mitigating mitochondrial damage; however, its role in S-AKI remains unclear. Here, we observed elevated serum levels of IL37 in S-AKI patients compared to non-AKI patients, with IL-37 positively correlating with NGAL levels. IL-37 expression was upregulated in HK-2 cells following LPS stimulation. Treatment with recombinant human IL37 (rhIL-37) significantly reduced LPS-induced apoptosis, reactive oxygen species (ROS) overproduction, and mitochondrial membrane potential loss in HK-2 cells, while also enhancing mitophagy. Notably, IL-37-mediated mitophagy and mitochondrial protection were diminished following IL-1R8 knockdown. In a murine S-AKI model, intraperitoneal administration of rhIL-37 or transgenic expression of human IL-37 attenuated tubular injury and improved renal function. IL-37 also reduced renal ROS productions, alleviated mitochondrial damage, and promoted mitophagy. These findings suggest that IL-37 exerts renal protective effects in S-AKI by improving mitochondrial function and regulating mitophagy in an IL-1R8 receptor-dependent manner.
This study enrolled 120 patients undergoing elective abdominal or orthopedic surgery (aged 18–75 years, ASA classification I-III) and employed a prospective randomized controlled design to evaluate the effects of regional anesthesia (RA group, n = 60) versus general anesthesia (GA group, n = 60) on perioperative neuro-immune regulation. Through systematic assessment of perioperative cytokine profiles, immune cell subsets, autonomic nervous function, and clinical outcome indicators, we investigated the mechanisms underlying the role of regional anesthesia in inflammation control. The results demonstrated that at 24 h postoperatively, serum IL-6 levels in the RA group were significantly lower than those in the GA group (156.8 ± 35.7 vs 215.3 ± 41.2 pg/ml, p < 0.001), with the IL-6/IL-10 ratio reduced by 46.2% (1.89 ± 0.35 vs 3.51 ± 0.62, p < 0.001), indicating optimized pro-inflammatory/anti-inflammatory balance. Regarding immune cell function, the RA group showed a 56.9% decrease in M1/M2 ratio (0.59 ± 0.15 vs 1.37 ± 0.28, p < 0.001), maintained higher NK cell cytotoxic activity (58.3 ± 9.5% vs 38.7 ± 7.8%, p < 0.001), and exhibited a 213% increase in Treg/Th17 ratio (1.44 ± 0.28 vs 0.46 ± 0.12, p < 0.001). Autonomic nervous function assessment revealed that the RA group had 103.8% higher HRV-HF power (785.3 ± 142.6 vs 385.4 ± 98.7 ms², p < 0.001), 55.1% lower LF/HF ratio (1.28 ± 0.35 vs 2.85 ± 0.62, p < 0.001), and 77.3% elevated plasma acetylcholine levels (32.8 ± 7.5 vs 18.5 ± 5.2 pmol/ml, p < 0.001). Correlation analysis indicated that HRV-HF was positively correlated with IL-10 (r = 0.625, p < 0.001), and the LF/HF ratio was positively correlated with IL-6 (r = 0.512, p < 0.01), suggesting an association between autonomic nervous function and immune status. In terms of clinical outcomes, the RA group demonstrated lower postoperative pain scores, reduced incidence of cognitive dysfunction, and shortened hospital stay. This study suggests that regional anesthesia may improve perioperative inflammatory response by optimizing autonomic nervous balance, regulating cytokine networks, and modulating immune cell function; however, the precise mechanistic pathways require further investigation and validation.
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is primarily known as a respiratory disease. The continued study of the disease has shown that long-term COVID-19 symptoms include persisting effects of the virus on the brain when the infection is over, possibly even leading to neurodegeneration. However, the exact mechanisms of nervous system damage induced by SARS-CoV-2 are still unclear. In this study, we focused on two possibly shared pathways of SARS-CoV-2-induced neural dysfunction and neurodegeneration: protein aggregation, which is associated with impaired protein clearance, and inflammatory responses, which involve a hyper-active immune status. We observed distinct expression and distribution patterns of ten SARS-CoV-2 proteins in the two cell lines, meanwhile forming aggregation puncta and inducing pro-inflammatory responses. We found that the ER stress was induced and that the autophagy-lysosome pathway was inhibited upon viral protein expression. Boosting autophagy function attenuated protein aggregation, suggesting that modulation of autophagy might be a valid strategy for inhibiting cytotoxic effects of SARS-CoV- 2 proteins. Our study provides potential explanations of SARS-CoV-2-induced cell damage, based on shared cellular mechanisms and furthermore, suggests that modulation of proteostasis may serve as therapeutic strategies for preventing long-lasting SARS-CoV-2 cytotoxic effects.
Bedforms are widely distributed within deep-water submarine canyons, which are usually documented by vessel-mounted sensors. Yet, fine-scale geomorphology and shallow structures of bedforms in deep-water submarine canyons remain poorly documented, and understood, because of the insufficient resolution of vessel-based data. This study utilizes high-resolution autonomous underwater vehicle (AUV) dataset combined with intermediate seismic reflection profile and sediment cores to analyze bedform sets along a slope-confined submarine canyon (canyon C14) from the northern South China Sea. A train of crescent-shaped to inverted U-shaped axial steps in plan view are aligned downstream along the canyon thalweg from upper course to lower course. Based on comprehensive analysis of morphologic features, subsurface structures, flow estimates, and potential origins, these steps are likely to be cyclic steps created by supercritical turbidity currents. Sediment cores mainly comprised by silt with minor sand contents further suggesting the shallow canyon sediments probably deposited by diluted turbidity currents. Axial steps (S1-S4) with lower asymmetry and wavelengths in the upper course show an erosional truncation and horizontal to sub-horizontal reflectors draping on the lee side and stoss side, respectively, illustrating the erosional-depositional cyclic steps formed by more confined flow with higher erosion capability due to the narrow canyon (average width of 3.5 km) and steep slope gradient (average of 2.36°). Leaving transition segment, the less confined flow passing through lower course can be subject to wider canyon (average width of 5.5 km) and gently slope gradient (average of 1.2°) that increases the asymmetry and wavelengths of axial steps (S5-S7) and leave backset bed deposits on the stoss sides, probably pointing to the depositional cyclic steps with higher aggradation. Sediment filling, almost padding each cyclic step-associated scour, indicate that the previous-formed bedforms can be reworked by subsequent gravity flows deposits which mainly consist of slope failures-associated mass-transport deposits and turbidity currents deposits. Near the lower end of the canyon, reduction in flow velocity caused by further decrease of slope gradient (average of 1.05°) as the key factor leading to the shift from cyclic steps to furrows, but always under supercritical flow conditions. In this context, a sector of axial channel probably promotes the re-convergence of turbidity currents, resulting in the erosion of fine-grained cohesive deposits on the canyon floor, to form linear furrows within the axial channel. This work provides a good opportunity to investigate the fine-scale morphological features and shallow structures of bedforms in deep-water submarine canyon, and understand their evolution under the influence of canyon topography.
Immune imprinting, or original antigenic sin, challenges the control of evolving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). How the quantity and quality of pre-existing immunity modulate the recall antibody response upon re-exposure remains poorly understood. We immunized hamsters with a recombinant ancestral spike protein (S-2P) formulated with one of four distinct adjuvants to assess the impact of adjuvant-induced immunity on protective efficacy. Furthermore, we analyzed the modulatory effect of the adjuvant on the potency, breadth, and evolution of antibody responses after homologous viral challenge. We found that vaccination with Montanide ISA720-adjuvanted S-2P (S-2P:ISA720) not only induced higher initial neutralizing antibody titers and conferred stronger protection but also established a pre-existing immune state capable of cross-neutralizing the antigenically distant Omicron BA.1 variant. In contrast, aluminum hydroxide adjuvanted S-2P (S-2P:Al) elicited comparatively lower neutralizing titers and showed no cross-neutralization against BA.1. Following viral challenge, the S-2P:ISA720group exhibited significant affinity maturation toward conserved epitopes, which markedly enhanced cross-neutralization against BA.1 without increasing neutralizing titers or affinity against the homologous strain or the antigenically related Delta variant. Conversely, the S-2P:Algroup mounted a narrow, imprinting-facilitated response, characterized by boosting of strain-specific antibodies without substantial improvement in BA.1 neutralization. These findings suggest that in S-2P:ISA720-immunizedanimals, high-affinity antibodies mediate epitope masking of immunodominant sites, thereby redirecting responses toward subdominant conserved epitopes with cross-neutralizing potential. In conclusion, our study demonstrates that adjuvants can critically guide recall immune responses toward breadth and affinity maturation, offering a rational strategy for developing next-generation vaccines against SARS-CoV-2 and other variable pathogens.
Primary liver cancer is one of the most common malignant tumors in China. The vast majority of primary liver cancer are hepatocellular carcinoma. Due to its high incidence and mortality from HCC, HCC has always been a feared type of cancer. Liver transplantation, as one of the important means to treat advanced liver cancer, has brought new hope to patients. However, as patients have been in a state of immunosuppression after liver transplantation, these patients face new problems of HCC recurrence and metastasis. A increasing number of studies have proved that blocking the PD-1/PD-L1 signaling pathway and restoring the immune killing inhibition of T cells can produce better therapeutic effects on tumors and chronic infectious diseases. As a promising treatment in the field of tumor immunotherapy, PD-1/PD-L1 inhibitors have achieved important results in liver cancer patients, but their application in liver transplantation patients is still highly controversial. This paper will introduce the mechanism of action of PD-1/PD-L1 signaling pathway and the current basic and clinical studies of PD-1/PD-L1 signaling pathway associated with immune response in HCC transplantation.
Viral hepatitis is a major worldwide public health issue, affecting hundreds of millions of people and causing substantial morbidity and mortality. The majority of the worldwide burden of viral hepatitis is caused by five biologically unrelated hepatotropic viruses: hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV), and hepatitis E virus (HEV). Metabolomics is an emerging technology that uses qualitative and quantitative analysis of easily accessible samples to provide information of the metabolic levels of biological systems and changes in metabolic and related regulatory pathways. Alterations in glucose, lipid, and amino acid levels are involved in glycolysis, the tricarboxylic acid cycle, the pentose phosphate pathway, and amino acid metabolism. These changes in metabolites and metabolic pathways are associated with the pathogenesis and medication mechanism of viral hepatitis and related diseases. Additionally, differential metabolites can be utilized as biomarkers for diagnosis, prognosis, and therapeutic responses. In this review, we present a thorough overview of developments in metabolomics for viral hepatitis.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine has been used worldwide on a large scale because of its potent ability to contain the coronavirus disease 2019 (COVID-19) pandemic, and the antibody response induced by the vaccine needs to be elucidated. Thus, we conducted a prospective trial in healthy subjects to observe the antibody response after three doses of inactivated vaccines. Our results showed that neutralizing antibody (NAb) levels were significantly higher after the booster vaccination compared to the second, a 4.9-fold increase, with the peak occurring at 28 days. The NAb level could be maintained for a longer period after the third vaccination, with higher levels still observed after 3 months. We did not observe significantly higher levels of SARS-CoV-2 spike-specific immunoglobulin G (S-IgG) and immunoglobulin M (IgM) after the third vaccination compared with the second vaccination; this was especially true for SARS-CoV-2 spike-specific immunoglobulin M (S-IgM), which was barely expressed. Notably, those who did not undergo NAb seroconversion after two doses of the vaccine produced high and long-lasting NAb after the third vaccination, confirming that they were not completely unresponsive to the vaccine. The NAb titer in younger subjects (aged 20-40 years) rose 3.4-fold compared with older subjects (aged 40-60 years) after the second vaccination, but the difference was narrowed after the third vaccination (2.8-fold increase). In addition, the levels of antibodies in older men were 3.4-fold lower than those in the older women after the third vaccination. Overall, this study elucidates the dynamic change in antibodies after three doses of vaccination, which provides a reference for the improvement of vaccination strategies.
The role of HEV infection in AP remains unclear. 1000 patients with AP and 1000 HCs were enrolled, and pancreatitis was evaluated in HEV-infected rhesus macaques. The positive rates of anti-HEV IgG, IgM, and HEV RNA in the AP patients were significantly higher than HCs. With the increase in the severity of AP, the percentage of HEV infection increased. AP patients were divided into AP- and AP + AHE groups. The percentage of severe AP in the AP + AHE group was significantly higher than in the AP- group. HEV infection was one of the main independent risk factors and had high predictive power for AP outcomes. A high level of HEV titer would prolong the recovery time and increase the risk of recurrent AP. Moreover, AP + AHE patients receiving conservative treatment showed a better prognosis. Furthermore, HEV can replicate in the pancreas of rhesus macaques. The pancreatic islet structure was damaged, the tissue was loose after 272 dpi, and a large amount of hyperemia appeared after 770 dpi. HEV infection also caused a large number of inflammatory cells in the pancreas. The pancreas and liver had a comparable viral load. HEV infection affects AP's occurrence, development, and prognosis.
Background and Aims. At present, a targeted drug has not been found for patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study assessed the effects of different therapeutic schedules on patients with COVID-19. Methods. The clinical characteristics, the prognosis of patients with western medicine (WM) treatment, and the combination of traditional Chinese medicine and western medicine (TCM-WM) treatment were retrospectively explored from January 20, 2020 to February 20, 2021. Results. 19 patients (15.20%) and 7 patients (5.60%) in the WM treatment group developed into severe type and critically ill, which were higher than 5 patients (9.43%) and 0 patients (0.00%) in the TCM-WM treatment group ( p = 0.306 and p = 0.08 ). The time from admission to severe in the WM treatment group was significantly shorter than that of the TCM-WM treatment group (7.5 vs. 11.2, p < 0.001 ). Compared with patients in the TCM-WM treatment group, the average stay time and the negative nucleic acid time of patients in the WM treatment group were both significantly longer (both p < 0.05 ). Besides, there existed no statistical difference for the safety of the two treatment options and nucleic acid test positive 14 days after discharge between the two groups. In line with the performance for severe patients, the average stay, the nucleic acid negative time, and the days of hormone therapy in the WM treatment group were all significantly longer than that of the TCM-WM treatment group (32.5 vs. 18.8, p < 0.001 ; 24.5 vs. 14.5, p < 0.001 ; 6.5 vs. 3.0, p < 0.001 ). Conclusions. TCM-WM has better performance in both the disease progression and treatment of severe patients. We recommended that timely TCM-WM should be treated with patients with COVID-19.
The prevention of the COVID-19 pandemic is highly complicated by the prevalence of asymptomatic and recurrent infection. Many previous immunological studies have focused on symptomatic and convalescent patients, while the immune responses in asymptomatic patients and re-detectable positive cases remain unclear. Here we comprehensively analyzed the peripheral T-cell receptor (TCR) repertoire of 54 COVID-19 patients in different courses, including asymptomatic, symptomatic, convalescent, and re-detectable positive cases. We identified a set of V-J gene combinations characterizing the upward immune responses through asymptomatic and symptomatic courses. Furthermore, some of these V-J combinations could be awakened in the re-detectable positive cases, which may help predict the risk of recurrent infection. Therefore, TCR repertoire examination has the potential to strengthen the clinical surveillance and the immunotherapy development for COVID-19.
Targeting the coagulation factor IX (FIX) expression in platelets has been shown to be effective in ameliorating bleeding in hemophilia B (HB) mice. To improve the therapeutic effects and evaluate the safety of this gene therapy strategy, we generated a transgenic mouse model on an HB background with FIX Padua target expressed in platelets. The transgenic mice exhibited stable expression and storage of FIX Padua in platelets. The platelet-stored FIX Padua could be released with the activation of platelets, and the proportion of platelet-stored FIX Padua in whole blood was the same as that of platelet-stored wild-type human FIX. The platelet-derived FIX Padua showed substantially increased specific activity compared with wild-type FIX. Reduced bleeding volume in the FIX Padua transgenic mice demonstrated that bleeding in the mice was improved. Levels of thrombin-antithrombin complex, fibrinogen, D-Dimer, and blood cell counts were normal in the transgenic mice, suggesting that thrombotic risk was not increased in this mouse model. However, the leakage and failure to overcome the presence of inhibitor to wild-type FIX is also observed with FIX Padua, as expected. Taken together, our results support the conclusion that targeting FIX Padua expression in platelets may be an effective and safe gene therapy strategy for HB, and could provide an ideal model to evaluate the safety of platelet-targeted gene therapy for treating hemophilia.
The appearance and magnitude of the immune response and the related factors correlated with SARS-CoV-2 vaccination need to be defined. Here, we enrolled a prospective cohort of 52 participants who received two doses of inactivated vaccines (BBIBP-CorV). Their serial plasma samples (n = 260) over 2 months were collected at five timepoints. We measured antibody responses (NAb, S-IgG and S-IgM) and routine blood parameter. NAb seroconversion occurred in 90.7% of vaccinated individuals and four typical NAb kinetic curves were observed. All of the participants who seroconverted after the first dose were females and had relatively high prevaccine estradiol levels. Moreover, those without seroconversion tended to have lower lymphocyte counts and higher serum SAA levels than those who experienced seroconversion. The NAb titers in young vaccine recipients had a significantly higher peak than those in elderly recipients. S-IgG and S-IgM dynamics were accompanied by similar trends in NAb. Here, we gained insight into the dynamic changes in NAbs and preliminarily explored the prevaccine blood parameters related to the kinetic subclasses, providing a reference for vaccination strategies.
Background Corticoid therapy has been recommended in the treatment of critically ill patients with COVID-19, yet its efficacy is currently still under evaluation. We investigated the effect of corticosteroid treatment on 90-day mortality and SARS-CoV-2 RNA clearance in severe patients with COVID-19. Methods 294 critically ill patients with COVID-19 were recruited between December 30, 2019 and February 19, 2020. Logistic regression, Cox proportional-hazards model and marginal structural modeling (MSM) were applied to evaluate the associations between corticosteroid use and corresponding outcome variables. Results Out of the 294 critically ill patients affected by COVID-19, 183 (62.2%) received corticosteroids, with methylprednisolone as the most frequently administered corticosteroid (175 accounting for 96%). Of those treated with corticosteroids, 69.4% received corticosteroid prior to ICU admission. When adjustments and subgroup analysis were not performed, no significant associations between corticosteroids use and 90-day mortality or SARS-CoV-2 RNA clearance were found. However, when stratified analysis based on corticosteroid initiation time was performed, there was a significant correlation between corticosteroid use (≤ 3 day after ICU admission) and 90-day mortality (logistic regression adjusted for baseline: OR 4.49, 95% CI 1.17–17.25, p = 0.025; Cox adjusted for baseline and time varying variables: HR 3.89, 95% CI 1.94–7.82, p < 0.001; MSM adjusted for baseline and time-dependent variants: OR 2.32, 95% CI 1.16–4.65, p = 0.017). No association was found between corticosteroid use and SARS-CoV-2 RNA clearance even after stratification by initiation time of corticosteroids and adjustments for confounding factors (corticosteroids use ≤ 3 days initiation vs no corticosteroids use) using MSM were performed. Conclusions Early initiation of corticosteroid use (≤ 3 days after ICU admission) was associated with an increased 90-day mortality. Early use of methylprednisolone in the ICU is therefore not recommended in patients with severe COVID-19.
The interaction between existing chronic liver diseases caused by hepatitis B virus (HBV) infection and COVID‐19 has not been studied. We analysed 70 COVID‐19 cases combined with HBV infection (CHI) to determine the epidemiological, clinical characteristics, treatment and outcome. We investigated clinical presentation, imaging and laboratory parameters of COVID‐19 patients of seven hospitals from Jan 20 to March 20, 2020. Multivariate analysis was used to analyse risk factors for progression of patients with COVID‐19 combined with HBV infection. Compared with COVID‐19 without HBV infection (WHI) group, patients with dual infection had a higher proportion of severe/critically ill disease (32.86% vs. 15.27%, P = .000), higher levels of alanine aminotransferase (ALT), aspartate transaminase (AST) and activated partial thromboplastin (APTT) [50(28‐69)vs 21(14‐30), P = .000; 40(25‐54) vs 23(18‐30), P = .000; 34.0(27.2‐38.7) vs 37.2(31.1‐41.4), P = .031]. The utilization rates of Arbidol and immunoglobulin were significantly higher than those in the co‐infected group [48.57% vs. 35.64%, P < .05; 21.43% vs. 8.18%, P < .001], while the utilization rate of chloroquine phosphate was lower (1.43% vs 14.00%, P < .05) in the co‐infected patients group. Age and c‐reactive protein (CRP) level were independent risk factors for recovery of patients with COVID‐19 combined with HBV infection. The original characteristics of COVID‐19 cases combined with HBV infection were higher rate of liver injury, coagulation disorders, severe/critical tendency and increased susceptibility. The elderly and patients with higher level of CRP were more likely to experience a severe outcome of COVID‐19.
Background: Since the end of 2019, coronavirus disease-2019 (COVID-19) outbreak spreads around the world. We aimed to share the details of critically ill patients with COVID-19 in China. Methods: As of February 15, 2020, 112 consecutive critically ill patients with COVID-19 in Hubei province, China were included. Epidemiologic data, clinical features, treatments and outcomes were collected. The primary outcome was 28-day mortality. Findings: Among the 112 critically ill patients, the median (IQR) age was 66 (56.0-76.0) years; 77 were male (68.7%). Lymphopenia (92%), acute respiratory distress syndrome(ARDS)(90.2%) and septic shock (51.8%) were remarkable. Most critically ill patients required mechanical ventilation (92.8%). Neuromuscular blocker (41.1%), prone ventilation (22.3%) and extracorporeal membrane oxygenation (ECMO) (12.5%) were often needed. Severely hypoxemia was common in the early stage, and subsequently hypercapnia occurred, in the end pulmonary fibrosis, and pulmonary hypertension became remarkable. Secondary infection was common (30.3%). Case-fatality rate in hospitalized COVID-19 patients was 2.2% and the 28-day mortality of critically ill patients was 46.4%. Leading causes of death was multi-organ failure induced by ARDS (75.8%). High APACHE II score was independent associated with death in multivariable analysis. High viral load were observed in non-survivors. Interpretations: Mortality of critically ill patients with COVID-19 was high. Lymphopenia, ARDS and septic shock were notable in the clinical course of critical illness. Ventilation support and hemodynamic support were usually needed. Multi-organ failure induced by ARDS was the main death cause. Funding Statement: This work was supported by the National Natural Science Foundation (81701941). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: This case series was approved by the institutional ethics board of the three medical centers. Oral consent was obtained from patients.
This single-center case series describes the demographics, symptoms, laboratory and imaging findings, treatment, and clinical course of 138 patients hospitalized with 2019 novel coronavirus (2019-nCoV)-infected pneumonia (NCIP) in Wuhan, China, highlighting presumed human-to-human hospital-associated transmission in many cases. Importance In December 2019, novel coronavirus (2019-nCoV)-infected pneumonia (NCIP) occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of affected patients is limited. Objective To describe the epidemiological and clinical characteristics of NCIP. Design, Setting, and Participants Retrospective, single-center case series of the 138 consecutive hospitalized patients with confirmed NCIP at Zhongnan Hospital of Wuhan University in Wuhan, China, from January 1 to January 28, 2020; final date of follow-up was February 3, 2020. Exposures Documented NCIP. Main Outcomes and Measures Epidemiological, demographic, clinical, laboratory, radiological, and treatment data were collected and analyzed. Outcomes of critically ill patients and noncritically ill patients were compared. Presumed hospital-related transmission was suspected if a cluster of health professionals or hospitalized patients in the same wards became infected and a possible source of infection could be tracked. Results Of 138 hospitalized patients with NCIP, the median age was 56 years (interquartile range, 42-68; range, 22-92 years) and 75 (54.3%) were men. Hospital-associated transmission was suspected as the presumed mechanism of infection for affected health professionals (40 [29%]) and hospitalized patients (17 [12.3%]). Common symptoms included fever (136 [98.6%]), fatigue (96 [69.6%]), and dry cough (82 [59.4%]). Lymphopenia (lymphocyte count, 0.8 x 10(9)/L [interquartile range {IQR}, 0.6-1.1]) occurred in 97 patients (70.3%), prolonged prothrombin time (13.0 seconds [IQR, 12.3-13.7]) in 80 patients (58%), and elevated lactate dehydrogenase (261 U/L [IQR, 182-403]) in 55 patients (39.9%). Chest computed tomographic scans showed bilateral patchy shadows or ground glass opacity in the lungs of all patients. Most patients received antiviral therapy (oseltamivir, 124 [89.9%]), and many received antibacterial therapy (moxifloxacin, 89 [64.4%]; ceftriaxone, 34 [24.6%]; azithromycin, 25 [18.1%]) and glucocorticoid therapy (62 [44.9%]). Thirty-six patients (26.1%) were transferred to the intensive care unit (ICU) because of complications, including acute respiratory distress syndrome (22 [61.1%]), arrhythmia (16 [44.4%]), and shock (11 [30.6%]). The median time from first symptom to dyspnea was 5.0 days, to hospital admission was 7.0 days, and to ARDS was 8.0 days. Patients treated in the ICU (n = 36), compared with patients not treated in the ICU (n = 102), were older (median age, 66 years vs 51 years), were more likely to have underlying comorbidities (26 [72.2%] vs 38 [37.3%]), and were more likely to have dyspnea (23 [63.9%] vs 20 [19.6%]), and anorexia (24 [66.7%] vs 31 [30.4%]). Of the 36 cases in the ICU, 4 (11.1%) received high-flow oxygen therapy, 15 (41.7%) received noninvasive ventilation, and 17 (47.2%) received invasive ventilation (4 were switched to extracorporeal membrane oxygenation). As of February 3, 47 patients (34.1%) were discharged and 6 died (overall mortality, 4.3%), but the remaining patients are still hospitalized. Among those discharged alive (n = 47), the median hospital stay was 10 days (IQR, 7.0-14.0). Conclusions and Relevance In this single-center case series of 138 hospitalized patients with confirmed NCIP in Wuhan, China, presumed hospital-related transmission of 2019-nCoV was suspected in 41% of patients, 26% of patients received ICU care, and mortality was 4.3%. Question What are the clinical characteristics of hospitalized patients with 2019 novel coronavirus (2019-nCoV)-infected pneumonia (NCIP) in Wuhan, China? Findings In this single-center case series involving 138 patients with NCIP, 26% of patients required admission to the intensive care unit and 4.3% died. Presumed human-to-human hospital-associated transmission of 2019-nCoV was suspected in 41% of patients. Meaning In this case series in Wuhan, China, NCIP was frequently associated with presumed hospital-related transmission, 26% of patients required intensive care unit treatment, and mortality was 4.3%.
ABSTRACT Introduction: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging zoonosis infected by virus (SFTSV) in central and eastern China, which is associated with high mortality. However, limited clinical data have been reported about this critical illness. Patients and Methods: Retrospective cohort study in intensive care unit (ICU) patients with SFTSV infection admitted in 2014 to 2019. Diagnosis was confirmed using reverse transcription polymerase chain reaction on serum samples. Results: One hundred sixteen patients with SFTSV infection were included (mean age 63 ± 9 years, 59 [51.3%] males). Non-survivors (43.1%) were older, and had lower Glasgow Coma Score, higher Acute Physiology and Chronic Health Evaluation II, and sequential organ failure assessment score at ICU admission. In addition, non-survivors had more severe respiratory failure (PaO2/FiO2: 208 ± 14 mm Hg vs. 297 ± 15 mm Hg), more frequent shock (25[50%] vs. 7[10.6%]), and required more frequently mechanical ventilation (78% vs. 19.7%; P < 0.001) and vasopressor support (56% vs. 9.1%; P < 0.001). Non-survivors experienced more obvious monocyte loss. After adjustment for potential confounding factors, older age, elevated lactate level, and elevated creatinine level were the independent risk factors for death. Conclusion: We provided knowledge about the clinical characteristics of SFTS admitted in ICU. Older age, elevated lactate level, and elevated creatinine level may be useful for identifying patients with poor outcome and intensive medical intervention can be provided for patients as soon as possible to reduce mortality.