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    LOX-1+ immature neutrophils predict severe COVID-19 patients at risk of thrombotic MESHD complications

    Authors: Behazine Combadiere; Lucille Adam; Paul Quentric; Pierre Rosenbaum; Karim Dorgham; Olivia Bonduelle; Christophe Parizot; Delphine Sauce; Julien Mayaux; Charles-Edouard Luyt; Alexandre Boissonnas; Zahir Amoura; Valerie Pourcher; Makoto Miyara; Guy Gorochov; Amelie Guihot; Christophe Combadiere; Duraipandian Thavaselvam; Devendra Kumar Dubey; Paul Lin; Hila Shaim; Sean G Yates; David Marin; Indreshpal Kaur; Sheetal Rao; Duncan Mak; Angelique Lin; Qi Miao; Jinzhuang Dou; Ken Chen; Richard Champlin; Elizabeth J Shpall; Katayoun Rezvani

    doi:10.1101/2020.09.15.293100 Date: 2020-09-15 Source: bioRxiv

    Rational: Lymphopenia HP Lymphopenia MESHD and neutrophil/lymphocyte ratio may have prognostic value in coronavirus disease MESHD 2019 (COVID-19) severity. Objective: We sought to investigate the representation of neutrophil subsets in severe and critical COVID-19 patients based on Intensive Care Units (ICU) and non-ICU admission. Methods: We developed a multi-parametric neutrophil profiling strategy based on known neutrophil markers to distinguish COVID-19 phenotypes in critical and severe patients. Results: Our results showed that 80 percent of ICU patients develop strong myelemia with CD10-CD64+ immature neutrophils. Cellular profiling revealed two distinct neutrophil subsets expressing either the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) or the Interleukin-3 receptor alpha (CD123), both significantly overrepresented in ICU patients compared to non-ICU patients. The proportion of LOX-1-expressing immature neutrophils positively correlated with clinical severity, with the cytokine storm (IL-1{beta}, IL-6, IL-8, TNF), and with intravascular coagulation MESHD. Importantly, high proportions of LOX-1+-immature neutrophils are associated with high risks of severe thrombosis MESHD. Conclusions: Together these data suggest that point of care enumeration of LOX-1-immature neutrophils might help distinguish patients at risk of thrombosis MESHD complication and most likely to benefit from intensified anticoagulant therapy.

    Tracheal tube obstruction MESHD due to hemoptysis HP associated with pulmonary infarction MESHD in a patient with severe COVID-19 pneumonia HP pneumonia MESHD: A case report.

    Authors: Takaaki Maruhashi; Yutaro Kurihara; Tatsuhiko Wada; Mayuko Osada; Marina Oi; Tomonari Masuda; Kunihiro Yamaoka; Yasushi Asari

    doi:10.21203/rs.3.rs-75925/v1 Date: 2020-09-11 Source: ResearchSquare

    Background: The incidence of thrombotic complications MESHD is extremely high among severe coronavirus disease MESHD 2019(COVID-19) patients in the intensive care unit. Various factors such as a cytokine storm due to an excessive immune response to inflammation MESHD, hypoxemia HP hypoxemia MESHD, and disseminated intravascular coagulation HP intravascular coagulation MESHD are considered predisposing factors for thrombotic complications MESHD.Case presentation: A 55-year-old Japanese man intubated 8 days previously was referred to our hospital because of a severe COVID-19 pneumonia HP pneumonia MESHD diagnosis after his pharyngeal swab tested positive for severe acute respiratory syndrome MESHD coronavirus 2 using reverse transcription-polymerase chain reaction. The patient continued to remain hypoxic (PaO2/FiO2 ratio <100 mmHg) at the referring hospital. On admission, we initiated veno-venous extracorporeal membrane oxygenation (VV-ECMO). Unfractionated heparin and nafamostat mesylate were used as anticoagulants during VV-ECMO. Despite the adequate anticoagulant therapy, he developed pulmonary infarction MESHD due to pulmonary embolism HP pulmonary embolism MESHD followed by hemoptysis HP. On day 10 following admission, his oxygen saturation dropped from 95% to 88%, with a marked decrease in his ventilator tidal volume, accompanied by an inability to ventilate the patient. Thereafter, we increased the VV-ECMO flow and exchanged his endotracheal tube. The lumen of the removed tracheal tube was found to be occluded by a large-sized blood SERO coagulum. There was no further episode of tube occlusion MESHD. The patient was discharged in a walkable state on day 39 following admission. Conclusions: Endotracheal tube obstruction MESHD secondary to hemoptysis HP should be suggested in patients with COVID-19 requiring ventilator support, as they are not able to perform frequent endotracheal tube suctions owing to the risk of infection TRANS risk of infection TRANS infection MESHD.

    Treatment of Coagulopathy MESHD in COVID-19 Patients: A scoping review

    Authors: HIROTAKA MORI; Hiroshi Ohkawara; Ryuichi Togawa; Mami Rikimaru; Yoko Shibata; Takayuki Ikezoe

    doi:10.21203/rs.3.rs-73973/v1 Date: 2020-09-08 Source: ResearchSquare

    Background: Coagulopathy MESHD, including disseminated intravascular coagulation HP intravascular coagulation MESHD, is frequently noted in patients with coronavirus infection disease MESHD 2019 (COVID-19). Recently, a number of articles on this topic have been reported.Objective: The aim of this study is to identify existing gaps where further research on anticoagulants in COVID-19 patients with coagulopathy MESHD needs to be done.Methods: We used the PRISMA Extension for Scoping Reviews. The protocol was registered on May 21, 2020, before conducting this review. MEDLINE, CENTRAL, WHO-ICTRP, ClinicalTrial.gov and PROSPERO were used.Result: Eight studies were included; six studies were already published and two are ongoing. The reported results for three publications were from case series, three were from retrospective cohorts and two were from randomized controlled trials. Eight studies examined the effectiveness of low molecular weight heparin (LMWH), of which seven studies used a prophylactic dose and four studies used a therapeutic dose of LMWH. A prophylactic or therapeutic dose of unfractionated heparin was investigated in four and three studies, respectively. No recombinant human soluble thrombomodulin was investigated. Conclusion: The anticoagulants are limited to heparinoids, and the study designs were of low quality. Further studies with an improved design are needed to compare other available anticoagulants.

    Clinical characteristics and risk factors for mortality in patients with coronavirus disease MESHD 2019 in intensive care unit: a single-center, retrospective, observational study in China

    Authors: Fangfang Sai; Xiaolei Liu; Lanyu Li; Yan Ye; Changqing Zhu; Ying Hang; Conghua Huang; Lei Tian; Xinhui Xu; Huan Huang

    doi:10.21203/rs.3.rs-46078/v1 Date: 2020-07-20 Source: ResearchSquare

    Background: Coronavirus disease 2019 (COVID-19) is a potentially life-threatening contagious disease which has spread TRANS all over the world. Risk factors for the clinical outcomes of COVID-19 pneumonia HP pneumonia MESHD in intensive care unit (ICU) have not yet been well determined. Methods: In this retrospective, single-centered, observational study, we consecutively included 47 patients with confirmed COVID-19 who were admitted to the ICU of Leishenshan Hospital in Wuhan, China, from February 24 to April 5, 2020. Clinical characteristics and outcomes were collected and compared between survivors and non-survivors. Multivariable logistic regression was used to explore the risk factors associated with death MESHD in patients of COVID-19.Results: The study cohort included 47 adult TRANS patients with a median age TRANS of 70.55±12.52 years, and 30 (63.8%) patients were men. Totally 15 (31.9%) patients died. Compared with survivors, non-survivors were more likely to develop septic shock MESHD shock HP (6 [40%] patients vs 3 [9.4%] patients ), disseminated intravascular coagulation HP intravascular coagulation MESHD (3 [21.4%] vs 0), and had higher score of APACHE II (25.07±8.03 vs 15.56±5.95), CURB-65 (3[2-4] vs 2[1-3]), Sequential Organ Failure Assessment (SOFA) (7[5-9] vs 3[1-6]), higher level of D-dimer (5.74 [2.32-18] vs 2.05 [1.09-4.00] ) and neutrophil count (9.4[7.68-14.54] vs 5.32[3.85-9.34] ). SOFA score (OR 1.47, 1.01–2.13; p=0.0042) and lymphocyte count (OR 0.02, 0.00–0.86; p=0.042) on admission were independently risk factors for mortality. Patients with higher lymphocyte count (>0.63×109/L) and lower SOFA score ≤4 on admission had a significantly well prognosis than those with lower lymphocyte count (≤0.63×109/L) and higher SOFA score >4 in overall survival.Conclusions: Higher SOFA score and lower lymphocyte count on admission were associated with poor prognosis of patients with COVID-19 in ICU. Lymphocyte count may serve as a promising prognostic biomarker.

    Clot Waveform of APTT Has Abnormal Patterns in Subjects with COVID-19

    Authors: Takuya Shimura; Makoto Kurano; Yoshiaki Kanno; Mahoko Ikeda; Koh Okamoto; Daisuke Jubishi; Sohei Harada; Shu Okugawa; Kyoji Moriya; Yutaka Yatomi

    doi:10.21203/rs.3.rs-43405/v1 Date: 2020-07-15 Source: ResearchSquare

    In Coronavirus disease MESHD 2019 (COVID-19) subjects, recent evidence suggests the presence of unique coagulation abnormalities HP coagulation abnormalities MESHD. In this study, we performed clot waveform analyses to investigate whether specific modulations are observed in COVID-19 subjects. We analyzed the second derivative of the absorbance in routine APTT tests performed using an ACL-TOP system. We observed high frequencies of abnormal patterns in APTT second-derivative curves that could be classified into an early shoulder type, a late shoulder type, or a biphasic type, high maximum first-derivative and second-derivative peak levels, and a low minimum second-derivative peak level in COVID-19 subjects. These modulations were not observed in subjects with disseminated intravascular coagulation HP intravascular coagulation MESHD. These abnormal patterns are also observed in patients with lupus anticoagulant HP lupus anticoagulant MESHD, hemophilia MESHD, or factor IX deficiency MESHD. The plasma SERO fibrinogen levels might also be involved in the abnormal APTT waveforms, especially the high maximum first-derivative and second-derivative peak levels. The abnormal patterns in the APTT second-derivative curves appear with highest frequency at around 2 weeks after the onset of COVID-19 and were not associated with the severity of COVID-19. These results suggest the possible presence of a specific abnormal coagulopathy MESHD in COVID-19.

    Severe colon ischemia MESHD in patients with severe COVID-2019 infection: a report of three cases

    Authors: Ana Almeida; Víctor Valentí Azcárate; Carlos Sánchez Justicia; Fernando Martínez Regueira; Pablo Martí-Cruchaga; Javier A. Cienfuegos; Fernando Rotellar

    doi:10.21203/rs.3.rs-31237/v1 Date: 2020-05-25 Source: ResearchSquare

    Severe disease MESHD caused by the SARS-CoV coronavirus MESHD is characterized by patients presenting with respiratory distress HP associated with a systemic inflammatory response syndrome (cytokine storm). Sixteen to thirty percent of COVID-19 patients also have gastrointestinal symptoms. Here we present three cases of COVID-19 who developed colonic ischemia MESHD. Three males TRANS aged TRANS 76, 68 and 56 with respiratory distress HP and receiving mechanical ventilation presented episodes of rectal bleeding MESHD, abdominal distension and signs of peritoneal irritation. Endoscopy (case 1) and computed tomography angiography revealed colonic ischemia MESHD and pneumoperitoneum MESHD.One patient (case 2) underwent surgery in which perforation of the gangrenous MESHD cecum and colonic ischemia MESHD was confirmed.In all three patients D-dimer levels were markedly increased (2170, 2100 and 7360 ng/mL). All three patients died shortly after diagnosis.In severe COVID-19 disease, the pathogenic cause has increasingly become attributed to the development of disseminated intravascular coagulation HP intravascular coagulation MESHD secondary to the systemic inflammatory response.

    Prognostic Impact of Coagulopathy MESHD in Patients with COVID-19: a Meta-analysis of 35 Studies and 6427 Patients

    Authors: Alberto Polimeni; Isabella Leo; Carmen Spaccarotella; Annalisa Mongiardo; Sabato Sorrentino; Jolanda Sabatino; Salvatore De Rosa; Ciro Indolfi

    doi:10.21203/rs.3.rs-31142/v1 Date: 2020-05-22 Source: ResearchSquare

    Coronavirus Disease MESHD 2019 (COVID-19) is a highly contagious disease that appeared in China in December 2019. Several patients with severe COVID-19 infection can develop a coagulopathy MESHD according to the ISTH-criteria for disseminated intravascular coagulopathy MESHD (DIC). We conducted a meta-analysis of all available studies on COVID-19 to explore the impact of coagulopathy MESHD on severe illness and mortality. An electronic search was performed within PubMed, Google Scholar and Scopus electronic databases. The primary endpoint was the difference of D-dimer values between Non-Severe vs Severe disease MESHD and Survivors vs Non-Survivors. The primary analysis showed that mean d-dimer is significantly higher in COVID-19 patients with severe disease than in those without (SMD -2.15 [-2.73 to -1.56], I2 98%, P <0.0001). Additional analysis of platelet count showed lower levels of mean PLT in Severe patients than those observed in the Non-Severe patients (SMD 0.77 [0.32 to 1.22], I2 96%, P <0.001). Interestingly, longer mean PT was found in Severe group (SMD -1.34 [-2.06 to -0.62], I2 98%, P <0.0002) compared to Non-Severe group. In conclusion, the results of the present meta-analysis, the largest and most comprehensive to date, demonstrate that Severe COVID-19 infection MESHD is associated with higher D-dimer values, lower platelet count and prolonged PT.

    The anticoagulant nafamostat potently inhibits SARS-CoV-2 infection MESHD in vitro: an existing drug with multiple possible therapeutic effects

    Authors: Mizuki Yamamoto; Maki Kiso; Yuko Sakai-Tagawa; Kiyoko Iwatsuki-Horimoto; Masaki Imai; Makoto Takeda; Noriko Kinoshita; Norio Ohmagari; Jin Gohda; Kentaro Semba; Zene Matsuda; Yasushi Kawaguchi; Yoshihiro Kawaoka; Jun-ichiro Inoue

    doi:10.1101/2020.04.22.054981 Date: 2020-04-23 Source: bioRxiv

    Although infection by SARS-CoV-2, the causative agent of COVID-19, is spreading rapidly worldwide, no drug has been shown to be sufficiently effective for treating COVID-19. We previously found that nafamostat mesylate, an existing drug used for disseminated intravascular coagulation HP intravascular coagulation MESHD (DIC), effectively blocked MERS-CoV S protein-initiated cell fusion by targeting TMPRSS2, and inhibited MERS-CoV infection MESHD of human lung epithelium-derived Calu-3 cells. Here we established a quantitative fusion assay dependent on SARS-CoV-2 S protein, ACE2 and TMPRSS2, and found that nafamostat mesylate potently inhibited the fusion while camostat mesylate was about 10-fold less active. Furthermore, nafamostat mesylate blocked SARS-CoV-2 infection MESHD of Calu-3 cells with an EC50 around 10 nM, which is below its average blood SERO concentration after intravenous administration through continuous infusion. These findings, together with accumulated clinical data regarding its safety, make nafamostat a likely candidate drug to treat COVID-19.

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