Targeting Senescent Alveolar Epithelial Cells Using Engineered Mesenchymal Stem Cell-Derived Extracellular Vesicles To Treat Pulmonary Fibrosis.

Type 2 alveolar epithelial cell (AEC2) senescence is crucial to the pathogenesis of pulmonary fibrosis (PF). The nicotinamide adenine dinucleotide (NAD+)-consuming enzyme cluster of differentiation 38 (CD38) is a marker of senescent cells and is highly expressed in AEC2s of patients with PF, thus rendering it a potential treatment target. Umbilical cord mesenchymal stem cell (MSC)-derived extracellular vesicles (MSC-EVs) have emerged as a cell-free treatment with clinical application prospects in antiaging and antifibrosis treatments. Herein, we constructed CD38 antigen receptor membrane-modified MSC-EVs (CD38-ARM-MSC-EVs) by transfecting MSCs with a lentivirus loaded with a CD38 antigen receptor-CD8 transmembrane fragment fusion plasmid to target AEC2s and alleviate PF. Compared with MSC-EVs, the CD38-ARM-MSC-EVs engineered in this study showed a higher expression of the CD38 antigen receptor and antifibrotic miRNAs and targeted senescent AEC2s cells highly expressing CD38 in vitro and in naturally aged mouse models after intraperitoneal administration. CD38-ARM-MSC-EVs effectively restored the NAD+ levels, reversed the epithelial-mesenchymal transition phenotype, and rejuvenated senescent A549 cells in vitro, thereby mitigating multiple age-associated phenotypes and alleviating PF in aged mice. Thus, this study provides a technology to engineer MSC-EVs and support our CD38-ARM-MSC-EVs to be developed as promising agents with high clinical potential against PF.

Procoagulant Properties of Mesenchymal Stem Cells and Extracellular Vesicles: A Novel Aspect of Thrombosis Pathogenesis.

Mesenchymal stem cells (MSCs) are multipotent cells that can differentiate into various cell types and secrete extracellular vesicles (EVs) that transport bioactive molecules and mediate intercellular communication. MSCs and MSC-derived EVs (MSC-EVs) have shown promising therapeutic effects in several diseases. However, their procoagulant activity and thrombogenic risk may limit their clinical safety. In this review, we summarize current knowledge on procoagulant molecules expressed on the surface of MSCs and MSC-EVs, such as tissue factor and phosphatidylserine. Moreover, we discuss how these molecules interact with the coagulation system and contribute to thrombus formation through different mechanisms. Additionally, various confounding factors, such as cell dose, tissue source, passage number, and culture conditions of MSCs and subpopulations of MSC-EVs, affect the expression of procoagulant molecules and procoagulant activity of MSCs and MSC-EVs. Therefore, herein, we summarize several strategies to reduce the surface procoagulant activity of MSCs and MSC-EVs, thereby aiming to improve their safety profile for clinical use.

Targeting cytohesin-1 suppresses acute myeloid leukemia progression and overcomes resistance to ABT-199.

Adhesion molecules play essential roles in the homeostatic regulation and malignant transformation of hematopoietic cells. The dysregulated expression of adhesion molecules in leukemic cells accelerates disease progression and the development of drug resistance. Thus, targeting adhesion molecules represents an attractive anti-leukemic therapeutic strategy. In this study, we investigated the prognostic role and functional significance of cytohesin-1 (CYTH1) in acute myeloid leukemia (AML). Analysis of AML patient data from the GEPIA and BloodSpot databases revealed that CYTH1 was significantly overexpressed in AML and independently correlated with prognosis. Functional assays using AML cell lines and an AML xenograft mouse model confirmed that CYTH1 depletion significantly inhibited the adhesion, migration, homing, and engraftment of leukemic cells, delaying disease progression and prolonging animal survival. The CYTH1 inhibitor SecinH3 exerted in vitro and in vivo anti-leukemic effects by disrupting leukemic adhesion and survival programs. In line with the CYTH1 knockdown results, targeting CYTH1 by SecinH3 suppressed integrin-associated adhesion signaling by reducing ITGB2 expression. SecinH3 treatment efficiently induced the apoptosis and inhibited the growth of a panel of AML cell lines (MOLM-13, MV4-11 and THP-1) with mixed-lineage leukemia gene rearrangement, partly by reducing the expression of the anti-apoptotic protein MCL1. Moreover, we showed that SecinH3 synergized with the BCL2-selective inhibitor ABT-199 (venetoclax) to inhibit the proliferation and promote the apoptosis of ABT-199-resistant leukemic cells. Taken together, our results not only shed light on the role of CYTH1 in cell-adhesion-mediated leukemogenesis but also propose a novel combination treatment strategy for AML.

Radiotheranostics in advanced prostate cancer: Current and future directions.

The discovery of small molecules that target the extracellular domain of prostate-specific membrane antigen (PSMA) has led to advancements in diagnostic imaging and the development of precision radiopharmaceutical therapies. In this review, we present the available existing data and highlight the key ongoing clinical evaluations of PSMA-based imaging in the management of primary, biochemically recurrent, and metastatic prostate cancer. We also discuss clinical studies that explore the use of PSMA-based radiopharmaceutical therapy (RPT) in metastatic prostate cancer and forthcoming trials that investigate PSMA RPT in earlier disease states. Multidisciplinary collaboration in clinical trial design and therapeutic administration is critical to the continued progress of this evolving radiotheranostics field.

Management Strategy for Prostate Imaging Reporting and Data System Category 3 Lesions.

PURPOSE OF REVIEW: Prostate Imaging Reporting and Data System (PI-RADS) category 3 lesions present a clinical dilemma due to their uncertain nature, which complicates the development of a definitive management strategy. These lesions have an incidence rate of approximately 22-32%, with clinically significant prostate cancer (csPCa) accounting for about 10-30%. Therefore, a thorough evaluation is warranted. RECENT FINDINGS: This review highlights the need for radiology peer review, including the confirmation of dynamic contrast-enhanced (DCE) compliance, as the initial step. Additional MRI models such as VERDICT or Tofts need to be verified. Current evidence shows that imaging and clinical indicators can be used for risk stratification of PI-RADS 3 lesions. For low-risk lesions, a safety net monitoring approach involving annual repeat MRI can be employed. In contrast, lesions deemed potentially risky based on prostate-specific antigen density (PSAD), 68 Ga-PSMA PET/CT, MPS, Proclarix, or AI/machine learning models should undergo biopsy. It is recommended to establish a multidisciplinary team that takes into account factors such as age, PSAD, prostate, and lesion size, as well as previous biopsy pathological findings. Combining expert opinions, clinical-imaging indicators, and emerging methods will contribute to the development of management strategies for PI-RADS 3 lesions.

SARS-CoV-2 Omicron BA.5.2-infection and COVID-19 in persons with chronic myeloid leukaemia.

OBJECTIVE: A SARS-CoV-2 Omicron (BA.5.2) epidemic began in China in December, 2022 following stopping the zero COVID policy. METHODS: We studied features of the epidemic in 1,121 persons with chronic myeloid leukaemia (CML). RESULTS: 1103 (98%) were in chronic, 10 in accelerated and 8 in acute phases. 834 (74%) became infected almost all of whom met criteria for COVID-19. The most common symptoms were fever (91%), cough (90%) and fatigue (82%). 42 infected persons were asymptomatic. Most people quarantined at home and self-medicated. 22 were hospitalized for COVID-19. At admission 5 had mild, 14, moderate and 3, severe/critical disease according to World Health Organization (WHO) criteria. 5 received respiratory assistance, 3 were admitted to the intensive care unit (ICU) and 1 in accelerated phase died from COVID-19. Co-variates associated with a risk of COVID-19 in SARS-CoV-2-infected subjects include age ≥ 65 years, higher education level and imatinib therapy. CONCLUSION: In conclusion, most SARS-CoV-2 Omicron BA.5.2 infections in persons with CML resulted in COVID-19 most of which cases are mild with only 1 death.

The predictive impact of dual somatostatin receptor/fluorodeoxyglucose (FDG) positron emission tomography (PET) in metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs): review of literature and a single institution experience.

Treatment with radiolabelled somatostatin analogs, a form of peptide receptor radionuclide therapy (PRRT), has changed the management of patients with advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs). There is a subgroup of patients who have suboptimal benefit and rapidly progress on PRRT, indicating that accurate prognostic and predictive markers are urgently needed. Currently, most of the literature concentrate on the prognostic impact of the dual positron emission tomography (PET) scan with very few information regarding the predictive value. We report a case series and review the literature to summarizes the predictive value of combined somatostatin receptor (SSTR) and fluorodeoxyglucose (FDG) PET in metastatic GEP-NETs. We conducted a review of the literature for data published from 2010 to 2021 in MEDLINE, Embase, the National Institutes of Health trial registry, Cochrane CENTRAL, and published proceedings from major gastrointestinal and neuroendocrine cancer meetings. Our main criteria included all published prospective and retrospective data in which the predictive value of dual PET scans using SSTR and FDG was correlated with PRRT response in patients with metastatic GEP-NETs. We summarized clinical outcomes including progression-free survival (PFS), overall survival (OS), and post-therapy complications associated with PRRT according to FDG avidity. We excluded studies that did not include FDG PET scan, GEP patients, studies with no clear predictive value of the FDG PET scan, and studies that did not report a direct correlation between FDG avidity and primary outcome. Additionally, we summarized our institutional experience in eight patients who progressed during or within the first year of PRRT treatment. Our search identified 1306 articles; most of them showed only the prognostic value of Integrated SSTR/FDG PET imaging biomarker in GEP-NETs. Only three studies (n=75 patients) met our inclusion criteria and retrospectively investigated the predictive value of dual SSTR and FDG imaging in subjects being considered for PRRT. The results confirmed that FDG avidity correlates with advanced NET grades. Lesions that are both SSTR and FDG avid had early disease progression. In one study, at multivariate analysis, FDG PET results were independently predictive of lower PFS for PRRT. In our case series, there were eight patients with metastatic well-differentiated GEP-NETs (grades 2 and 3) who progressed within one year of PRRT. Seven of them had positive FDG PET scan at the time of progression. In conclusion, Dual SSTR/FDG PET imaging has a potential predictive impact for PRRT in GEP-NETs. It permits the capturing of the disease complexity and aggressiveness, which correlates with PRRT response. Therefore, prospective future trials should validate the predictive value of dual SSTRs/FDG PET for better PRRT stratification.

CD151 and prostate cancer progression: A review of current literature.

Prostate cancer morbidity and mortality are increasing globally and in China, and the rate of metastasis is also rising, limiting the therapeutic effect and clinical prognosis of prostate cancer. CD151 is considered to be the first promoter of tumor metastasis in the tetraspanin superfamily. Previous research has linked CD151 to the progression of a number of malignancies, including prostate cancer. However, a recent study found that CD151 can inhibit the progression of prostate cancer. As a result, this paper examines existing research on CD151 and prostate cancer progression in order to clarify the relationship and provide a possible reference for future studies.

Seeking bridge symptoms of anxiety, depression, and sleep disturbance among the elderly during the lockdown of the COVID-19 pandemic-A network approach.

Background: Besides physical changes, elderly adults are prone to have mental disorders such as anxiety, depression, and sleep disturbance, and the pandemic of COVID-19 worsened the situation. However, internal relationships and co-occurrence of psychopathologies were scarcely examined. Therefore, in the current study, through network analysis, we inspected relationships among symptoms of depression, anxiety, and sleep disturbance and identified key symptoms that espoused the disease. Methods: We asked 1,302 elderly adults to fill in Patient Health Questionnaire-2 (depressive symptoms), the Generalized Anxiety Disorder-2 (anxiety symptoms), and the Youth Self-rating Insomnia Scale (sleep disturbance) and then constructed three networks for elderly adults, male elderly, and female elderly. Via network analysis, we accomplished four goals. First, we identified symptom with the highest centrality (i.e., strength) index for each network; then, we found the strongest correlation (i.e., edges) in each network; thirdly, we confirmed specific nodes that could bridge anxiety, depression, and sleep disturbance; the last was to compare networks based on genders. Network stability and accuracy tests were performed. Results: Networks of elderly adults, male elderly, and female elderly were stable, accurate, and intelligible. Among all networks, "Nervousness"- "Excessive worry" (GAD-1- GAD-2) had the strongest correlation, and "Nervousness" (GAD-1) had the highest strength and bridge strength value. When we made a comparison between female elderly's and male elderly's networks, except for the significant difference in the mean value of "Difficulty initiating sleep" (YSIS-3), the findings showed that the two networks were similar. Network stability and accuracy proved to be reliable. Conclusions: In networks of anxiety, depression, and sleep disturbance, anxiety played a conspicuous role in comorbidity, which could be a target for practical intervention and prevention.

The transplantation of rapamycin-treated senescent human mesenchymal stem cells with enhanced proangiogenic activity promotes neovascularization and ischemic limb salvage in mice.

Few therapies can reverse the proangiogenic activity of senescent mesenchymal stromal/stem cells (MSCs). In this study, we investigated the effects of rapamycin on the proangiogenic ability of senescent human umbilical cord MSCs (UCMSCs). An in vitro replicative senescent cell model was established in cultured UCMSCs. We found that late passage (P25 or later) UCMSCs (LP-UCMSCs) exhibited impaired proangiogenic abilities. Treatment of P25 UCMSCs with rapamycin (900 nM) reversed the senescent phenotype and notably enhanced the proangiogenic activity of senescent UCMSCs. In a nude mouse model of hindlimb ischemia, intramuscular injection of rapamycin-treated P25 UCMSCs into the ischemic limb significantly promoted neovascularization and ischemic limb salvage. We further analyzed the changes in the expression of angiogenesis-associated genes in rapamycin-primed MSCs and found higher expression of several genes related to angiogenesis, such as VEGFR2 and CTGF/CCN2, in primed cells than in unprimed MSCs. Taken together, our data demonstrate that rapamycin is a potential drug to restore the proangiogenic activity of senescent MSCs, which is of importance in treating ischemic diseases and tissue engineering.

COVID-19 in China and the US: Differences in Hospital Admission Co-Variates and Outcomes.

(1) Background: Although there are extensive data on admission co-variates and outcomes of persons with coronavirus infectious disease-2019 (COVID-19) at diverse geographic sites, there are few, if any, subject-level comparisons between sites in regions and countries. We investigated differences in hospital admission co-variates and outcomes of hospitalized people with COVID-19 between Wuhan City, China and the New York City region, USA. (2) Methods: We retrospectively analyzed clinical data on 1859 hospitalized subjects with COVID-19 in Wuhan City, China, from 20 January to 4 April 2020. Data on 5700 hospitalized subjects with COVID-19 in the New York City region, USA, from 1 March to 4 April 2020 were extracted from an article by Richardson et al. Hospital admission co-variates (epidemiological, demographic, and laboratory co-variates) and outcomes (rate of intensive care unit [ICU] admission, invasive mechanical ventilation [IMV], major organ failure and death, and length of hospital stay) were compared between the cohorts. (3) Results: Wuhan subjects were younger, more likely female, less likely to have co-morbidities and fever, more likely to have a blood lymphocyte concentration > 1 × 109/L, and less likely to have abnormal liver and cardiac function tests compared with New York subjects. There were outcomes data on all Wuhan subjects and 2634 New York subjects. Wuhan subjects had higher blood nadir median lymphocyte concentrations and longer hospitalizations, and were less likely to receive IMV, ICU hospitalization, and interventions for kidney failure. Amongst subjects not receiving IMV, those in Wuhan were less likely to die compared with New York subjects. In contrast, risk of death was similar in subjects receiving IMV at both sites. (4) Conclusions: We found different hospital admission co-variates and outcomes between hospitalized persons with COVID-19 between Wuhan City and the New York region, which should be useful developing a comprehensive global understanding of the SARS-CoV-2 pandemic and COVID-19.

Quality in MR reporting of the prostate ­ improving acquisition, the role of AI and future perspectives

The high quality of MRI reporting of the prostate is the most critical component of the service provided by a radiologist. Prostate MRI structured reporting with PI-RADS v. 2.1 has been proven to improve consistency, quality, guideline-based care in the management of prostate cancer. There is room for improved accuracy of prostate mpMRI reporting, particularly as PI-RADS core criteria are subjective for radiologists. The application of artificial intelligence may support radiologists in interpreting MRI scans. This review addresses the quality of prostate multiparametric MRI (mpMRI) structured reporting (include improvements in acquisition using artificial intelligence) in terms of size of prostate gland, imaging quality, lesion location, lesion size, TNM staging, sector map, and discusses the future prospects of quality in MR reporting.

Demographic, signs and symptoms, imaging characteristics of 2126 patients with COVID-19 pneumonia in the whole quarantine of Wuhan, China.

OBJECTIVE: The accurate knowledge of demographic, signs and symptoms, imaging characteristics of coronavirus disease 2019 (COVID-19) is essential for the accurate management of these patients. However, the claims between the previous papers are not always consistent and may even contradict each other, for example, some claims the virus infects more men than women in Wuhan. In this large-scale cohort study, we aimed to update the demographic, signs and symptoms, imaging characteristics of patients with COVID-19 in the whole quarantine of Wuhan, China. METHODS: A cohort of 2126 patients with a diagnosis of COVID-19 pneumonia (confirmed by real-time reverse transcriptase-polymerase chain reaction, RT-PCR) who were admitted to one hospital in Wuhan were retrospectively enrolled. Data were collected between January 13, 2020, and April 8, 2020, the end of Wuhan quarantine. Demographic, signs and symptoms, imaging characteristics were analyzed. CT imaging characteristics associated with respiratory failure or death were identified. RESULTS: Of the 2126 patients with COVID-19, 1051 (49.44%) were men and 1075 (50.56%) were women, 1933 (90.92%) have fever and 1328 (62.46%) have dry cough. The mean age was 57.43 years of age (range 1-95). The CT imaging findings were bilateral pneumonia (1883[88.57%]), unilateral pneumonia (243[11.43%]), ground-glass opacity (GGO) or consolidation (1175[55.27%]), pleural effusion (69[3.25%]). Patients with respiratory failure or death were more likely to have pleural effusion on CT than patients without respiratory failure or death (p < 0.05). CONCLUSION: Men and women have been infected by SARS-CoV-2 in roughly equal numbers. Fever and cough are the most prevalent symptoms at disease onset in patients. Other prevalent symptoms include fatigue, and sputum production. COVID-19 patients with bilateral pneumonia and pleural effusion are more likely to develop respiratory failure or death.

Extracellular vesicles deposit PCNA to rejuvenate aged bone marrow-derived mesenchymal stem cells and slow age-related degeneration.

Stem cell senescence increases alongside the progressive functional declines that characterize aging. The effects of extracellular vesicles (EVs) are now attracting intense interest in the context of aging and age-related diseases. Here, we demonstrate that neonatal umbilical cord (UC) is a source of EVs derived from mesenchymal stem cells (MSC-EVs). These UC-produced MSC-EVs (UC-EVs) contain abundant anti-aging signals and rejuvenate senescing adult bone marrow-derived MSCs (AB-MSCs). UC-EV-rejuvenated AB-MSCs exhibited alleviated aging phenotypes and increased self-renewal capacity and telomere length. Mechanistically, UC-EVs rejuvenate AB-MSCs at least partially by transferring proliferating cell nuclear antigen (PCNA) into recipient AB-MSCs. When tested in therapeutic context, UC-EV-triggered rejuvenation enhanced the regenerative capacities of AB-MSCs in bone formation, wound healing, and angiogenesis. Intravenously injected UC-EVs conferred anti-aging phenotypes including decreased bone and kidney degeneration in aged mice. Our findings reveal that UC-EVs are of high translational value in anti-aging intervention.

Venetoclax Combined with Hypomethylating Agents for Treatment-Naïve B/Myeloid Mixed Phenotype Acute Leukemia.

Mixed phenotype acute leukemia (MPAL) is a rare hematological malignancy that lacks consensus on optimal management. We report for the first time two cases of treatment-naïve B/myeloid MPAL patients treated with a novel chemo-free regimen using venetoclax combined with hypomethylating agents, which successfully induced complete remission with tolerable toxicities.

Water-stable and finasteride-loaded polyvinyl alcohol nanofibrous particles with sustained drug release for improved prostatic artery embolization - In vitro and in vivo evaluation.

Prostatic artery embolization (PAE) has been a well-established treatment for benign prostatic hyperplasia (BPH). To enhance the therapeutic efficacy, a strategy is to use embolic agent preloaded with 5α-reductase inhibitors for localized drug delivery. In this study, finasteride (FNS) was encapsulated into the polyvinyl alcohol (PVA) nanofibers via co-electrospinning technique, followed by heat treatment and cryogenic grinding to convert them into nanofibrous particles as a drug-loaded embolic agent. The FNS was found to be distributed uniformly in PVA nanofibers, and the processed FNS/PVA nanofibrous particles were 272 µm in mean particle size. Besides, the studies on the composition, thermal properties, swelling ratio, and water stability of the nanofibers and drug showed that the FNS remained its crystalline state in PVA nanofibers. The heat treatment increased the crystallinity of nanofibers and rendered them water stability. Both FNS and PVA possessed excellent thermal stability at high temperature (150 °C). In addition, in vitro drug release studies suggested the FNS followed a favorable sustained release up to 744 h. Furthermore, the cell viability and hemocompatibility assays indicated the nanofibers possessed excellent cytocompatibility and with no evidence of hemolysis. More importantly, the in vivo PAE procedures on beagles demonstrated the crosslinked FNS/PVA nanofibrous particles exhibited higher embolization efficacy with more obvious prostate volume (PV) reduction compared to crosslinked PVA nanofibrous particles after embolization for 1, 3, and 6 months (P < 0.05). Therefore, such drug-loaded PVA nanofibrous particles combined physical embolization and localized medical therapy together, which offer great potential to be used as an effective embolic agent for BPH therapy.

Cancer increases risk of in-hospital death from COVID-19 in persons <65 years and those not in complete remission.

The impact of cancer on outcome of persons with coronavirus disease 2019 (COVID-19) after infection with acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is controversial. We studied 1859 subjects with COVID-19 from seven centers in Wuhan, China, 65 of whom had cancer. We found having cancer was an independent risk factor for in-hospital death from COVID-19 in persons <65 years (hazard ratio [HR] = 2.45, 95% confidence interval [CI], 1.04, 5.76; P = 0.041) but not in those ≥65 years (HR = 1.12 [0.56, 2.24]; P = 0.740). It was also more common in those not in complete remission. Risks of in-hospital death were similar in subjects with solid cancers and those with hematological cancers. These data may help predict outcomes of persons with cancer and COVID-19.

Hematological features of persons with COVID-19.

We studied admission and dynamic demographic, hematological and biochemical co-variates in 1449 hospitalized subjects with coronavirus infectious disease-2019 (COVID-19) in five hospitals in Wuhan, Hubei province, China. We identified two admission co-variates: age (Odds Ratio [OR] = 1.18, 95% Confidence Interval [CI] [1.02, 1.36]; P = 0.026) and baseline D-dimer (OR = 3.18 [1.48, 6.82]; P = 0.003) correlated with an increased risk of death in persons with COVID-19. We also found dynamic changes in four co-variates, Δ fibrinogen (OR = 6.45 [1.31, 31.69]; P = 0.022), Δ platelets (OR = 0.95 [0.90-0.99]; P = 0.029), Δ C-reactive protein (CRP) (OR = 1.09 [1.01, 1.18]; P = 0.037), and Δ lactate dehydrogenase (LDH) (OR = 1.03 [1.01, 1.06]; P = 0.007) correlated with an increased risk of death. The potential risk factors of old age, high baseline D-dimer, and dynamic co-variates of fibrinogen, platelets, CRP, and LDH could help clinicians to identify and treat subjects with poor prognosis.

Risk factors for death in 1859 subjects with COVID-19.

We studied 1859 subjects with confirmed COVID-19 from seven centers in Wuhan 1651 of whom recovered and 208 died. We interrogated diverse covariates for correlations with risk of death from COVID-19. In multi-variable Cox regression analyses increased hazards of in-hospital death were associated with several admission covariates: (1) older age (HR = 1.04; 95% Confidence Interval [CI], 1.03, 1.06 per year increase; P < 0.001); (2) smoking (HR = 1.84 [1.17, 2.92]; P = 0.009); (3) admission temperature per °C increase (HR = 1.32 [1.07, 1.64]; P = 0.009); (4) Log10 neutrophil-to-lymphocyte ratio (NLR; HR = 3.30 [2.10, 5.19]; P < 0.001); (5) platelets per 10 E + 9/L decrease (HR = 0.996 [0.994, 0.998]; P = 0.001); (6) activated partial thromboplastin (aPTT) per second increase (HR = 1.04 [1.02, 1.05]; P < 0.001); (7) Log10 D-dimer per mg/l increase (HR = 3.00 [2.17, 4.16]; P < 0.001); and (8) Log10 serum creatinine per µmol/L increase (HR = 4.55 [2.72, 7.62]; P < 0.001). In piecewise linear regression analyses Log10NLR the interval from ≥0.4 to ≤1.0 was significantly associated with an increased risk of death. Our data identify covariates associated with risk of in hospital death in persons with COVID-19.