Tixagevimab-cilgavimab (AZD7442) for the treatment of patients hospitalized with COVID-19 (DisCoVeRy): A phase 3, randomized, double-blind, placebo-controlled trial.

Dear Editor, We read with great interest the recent article by Kamboj et al., in which they described the risk of developing moderate to severe Coronavirus Disease 2019 (COVID-19) in patients with hematological malignancies receiving tixagevimab-cilgavimab (T-C) during a period in which the dominant circulating variants of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) were resistant to T-C.1 The authors highlight the ongoing need to urgently address the mAb treatment gap, particularly for immunocompromised patients. The unmet need is further highlighted by the DisCoVeRy Phase 3, adaptive, multicentre European, randomized, double-blind, superiority trial that evaluated the efficacy and safety of intravenous T-C in SARS-CoV-2 antigenic positive patients (i.e those with a high SARS-CoV-2 viral load) hospitalized with COVID-19 and followed-up to day 90. [...

Neutrophil Activation and Immune Thrombosis Profiles Persist in Convalescent COVID-19

International audiencePurpose Following a severe COVID-19 infection, a proportion of individuals develop prolonged symptoms. We investigated the immunological dysfunction that underlies the persistence of symptoms months after the resolution of acute COVID-19. Methods We analyzed cytokines, cell phenotypes, SARS-CoV-2 spike-specific and neutralizing antibodies, and whole blood gene expression profiles in convalescent severe COVID-19 patients 1, 3, and 6 months following hospital discharge. Results We observed persistent abnormalities until month 6 marked by (i) high serum levels of monocyte/macrophage and endothelial activation markers, chemotaxis, and hematopoietic cytokines; (ii) a high frequency of central memory CD4 + and effector CD8 + T cells; (iii) a decrease in anti-SARS-CoV-2 spike and neutralizing antibodies; and (iv) an upregulation of genes related to platelet, neutrophil activation, erythrocytes, myeloid cell differentiation, and RUNX1 signaling. We identified a “core gene signature” associated with a history of thrombotic events, with upregulation of a set of genes involved in neutrophil activation, platelet, hematopoiesis, and blood coagulation. Conclusion The lack of restoration of gene expression to a normal profile after up to 6 months of follow-up, even in asymptomatic patients who experienced severe COVID-19, signals the need to carefully extend their clinical follow-up and propose preventive measures

Tixagevimab-cilgavimab (AZD7442) for the treatment of patients hospitalized with COVID-19 (DisCoVeRy): A phase 3, randomized, double-blind, placebo-controlled trial

International audienc

Sotrovimab therapy elicits antiviral activities against Omicron BQ.1.1 and XBB.1.5 in sera of immunocompromised patients [letter]

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Clinical phenotypes and quality of life to define post-COVID-19 syndrome: a cluster analysis of the multinational, prospective ORCHESTRA cohortResearch in context

Summary: Background: Lack of specific definitions of clinical characteristics, disease severity, and risk and preventive factors of post-COVID-19 syndrome (PCS) severely impacts research and discovery of new preventive and therapeutics drugs. Methods: This prospective multicenter cohort study was conducted from February 2020 to June 2022 in 5 countries, enrolling SARS-CoV-2 out- and in-patients followed at 3-, 6-, and 12-month from diagnosis, with assessment of clinical and biochemical features, antibody (Ab) response, Variant of Concern (VoC), and physical and mental quality of life (QoL). Outcome of interest was identification of risk and protective factors of PCS by clinical phenotype, setting, severity of disease, treatment, and vaccination status. We used SF-36 questionnaire to assess evolution in QoL index during follow-up and unsupervised machine learning algorithms (principal component analysis, PCA) to explore symptom clusters. Severity of PCS was defined by clinical phenotype and QoL. We also used generalized linear models to analyse the impact of PCS on QoL and associated risk and preventive factors. CT registration number: NCT05097677. Findings: Among 1796 patients enrolled, 1030 (57%) suffered from at least one symptom at 12-month. PCA identified 4 clinical phenotypes: chronic fatigue-like syndrome (CFs: fatigue, headache and memory loss, 757 patients, 42%), respiratory syndrome (REs: cough and dyspnoea, 502, 23%); chronic pain syndrome (CPs: arthralgia and myalgia, 399, 22%); and neurosensorial syndrome (NSs: alteration in taste and smell, 197, 11%). Determinants of clinical phenotypes were different (all comparisons p < 0.05): being female increased risk of CPs, NSs, and CFs; chronic pulmonary diseases of REs; neurological symptoms at SARS-CoV-2 diagnosis of REs, NSs, and CFs; oxygen therapy of CFs and REs; and gastrointestinal symptoms at SARS-CoV-2 diagnosis of CFs. Early treatment of SARS-CoV-2 infection with monoclonal Ab (all clinical phenotypes), corticosteroids therapy for mild/severe cases (NSs), and SARS-CoV-2 vaccination (CPs) were less likely to be associated to PCS (all comparisons p < 0.05). Highest reduction in QoL was detected in REs and CPs (43.57 and 43.86 vs 57.32 in PCS-negative controls, p < 0.001). Female sex (p < 0.001), gastrointestinal symptoms (p = 0.034) and renal complications (p = 0.002) during the acute infection were likely to increase risk of severe PCS (QoL <50). Vaccination and early treatment with monoclonal Ab reduced the risk of severe PCS (p = 0.01 and p = 0.03, respectively). Interpretation: Our study provides new evidence suggesting that PCS can be classified by clinical phenotypes with different impact on QoL, underlying possible different pathogenic mechanisms. We identified factors associated to each clinical phenotype and to severe PCS. These results might help in designing pathogenesis studies and in selecting high-risk patients for inclusion in therapeutic and management clinical trials. Funding: The study received funding from the Horizon 2020 ORCHESTRA project, grant 101016167; from the Netherlands Organisation for Health Research and Development (ZonMw), grant 10430012010023; from Inserm, REACTing (REsearch &amp; ACtion emergING infectious diseases) consortium and the French Ministry of Health, grant PHRC 20-0424

Plant and bird communities at Phoenix valley

南投縣鹿谷鄉鳳凰谷地區植物茂盛, 野生鳥類眾多。本研究係就鳳凰谷地區生育地環 境概況、植物組成、野鳥種類及季節性變化, 飼養鳥籠之植栽, 生蛋月份及死亡率等 進行調查與探討。所得結果摘述如下: 1.鳳凰谷地區的維管束植物, 初步調查共計116 科376 種。以大戟科與樟科、菊科最 多。 2.本地區樹姿優美而能適應低海拔之鄉土植物, 在喬木有烏心石、南投黃肉楠、瓊楠 、五掌楠、牛樟、香桂、鳳凰山茶、大頭茶、重陽木、烏 、青剛櫟、九丁榕、青楓 、黃蓮木、黃杞、鵝掌柴、烏皮九芎等; 灌木有華八仙、野牡丹、山煙草、硃砂根、 通草、銳葉柃木、小葉桑、燈稱花、密毛冬青、水雞油、通條樹、十大功勞、台灣莢 等; 草木則有普剌特草、油點草、倒地蜈蚣、五節芒等。 3.鳳凰谷地區的野生鳥類, 初步調查共計有21科57種。以畫眉科與鶇科最多。其中以 大冠 、藍腹鷴、翡翠、五色鳥、巨嘴鴉、紅山椒鳥、紅嘴黑鴨、紫嘯鶇、鉛色水鶇 、白鶺鴒等10種較具特色。 4.由於冬候鳥加入以及高海拔鳥類往低海拔移棲避寒覓食, 鳳凰谷地區鳥類從九月到 第二年四月種類最多, 從五月起鳥類開始減少, 到七、八月種類最少。 5.野生鳥類從四月起開始有築巢行為, 一直到七月還可發現; 飼養鳥類在鳥籠中二月 底即有築巢行為, 一直延續到八月底。飼養鳥類從三月上旬還可以發現生蛋行為, 其 中以三、四、五、六四個月最多。 6.本地區可提供野生鳥類花蜜、果實或種子等食物的植物有冇骨消、監膚木、百香果 、木瓜、九丁榕、月橘、土蜜樹、蓮霧、小葉桑、構樹、桃、山黃麻、茄苳、樟樹、 朴樹、長果縣鉤子、番石榴、硃砂根、紅果苔、五節芒、龍葵、姑婆芋、長梗紫麻、 山櫻等

COVID-19 outcomes in patients with inflammatory rheumatic and musculoskeletal diseases treated with rituximab: a cohort study

International audienceBackground: Various observations have suggested that the course of COVID-19 might be less favourable in patients with inflammatory rheumatic and musculoskeletal diseases receiving rituximab compared with those not receiving rituximab. We aimed to investigate whether treatment with rituximab is associated with severe COVID-19 outcomes in patients with inflammatory rheumatic and musculoskeletal diseases.Methods: In this cohort study, we analysed data from the French RMD COVID-19 cohort, which included patients aged 18 years or older with inflammatory rheumatic and musculoskeletal diseases and highly suspected or confirmed COVID-19. The primary endpoint was the severity of COVID-19 in patients treated with rituximab (rituximab group) compared with patients who did not receive rituximab (no rituximab group). Severe disease was defined as that requiring admission to an intensive care unit or leading to death. Secondary objectives were to analyse deaths and duration of hospital stay. The inverse probability of treatment weighting propensity score method was used to adjust for potential confounding factors (age, sex, arterial hypertension, diabetes, smoking status, body-mass index, interstitial lung disease, cardiovascular diseases, cancer, corticosteroid use, chronic renal failure, and the underlying disease [rheumatoid arthritis vs others]). Odds ratios and hazard ratios and their 95% CIs were calculated as effect size, by dividing the two population mean differences by their SD. This study is registered with ClinicalTrials.gov, NCT04353609.Findings: Between April 15, 2020, and Nov 20, 2020, data were collected for 1090 patients (mean age 55·2 years [SD 16·4]); 734 (67%) were female and 356 (33%) were male. Of the 1090 patients, 137 (13%) developed severe COVID-19 and 89 (8%) died. After adjusting for potential confounding factors, severe disease was observed more frequently (effect size 3·26, 95% CI 1·66-6·40, p=0·0006) and the duration of hospital stay was markedly longer (0·62, 0·46-0·85, p=0·0024) in the 63 patients in the rituximab group than in the 1027 patients in the no rituximab group. 13 (21%) of 63 patients in the rituximab group died compared with 76 (7%) of 1027 patients in the no rituximab group, but the adjusted risk of death was not significantly increased in the rituximab group (effect size 1·32, 95% CI 0·55-3·19, p=0·53).Interpretation: Rituximab therapy is associated with more severe COVID-19. Rituximab will have to be prescribed with particular caution in patients with inflammatory rheumatic and musculoskeletal diseases