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Background & Aim: Immunological characteristics of COVID-19 show pathological hyperinflammation associated with lymphopenia and dysfunctional T cell responses. These features provide a rationale for restoring functional T cell immunity in COVID-19 patients by adoptive transfer of SARS-CoV-2 specific T cells. Methods, Results & Conclusion(s): To generate SARS-CoV-2 specific T cells, we isolated peripheral blood mononuclear cells from 7 COVID-19 recovered and 13 unexposed donors. Consequently, we stimulated cells with SARS-CoV-2 peptide mixtures covering spike, membrane and nucleocapsid proteins. Then, we culture expanded cells with IL-2 for 21 days. We assessed immunophenotypes, cytokine profiles, antigen specificity of the final cell products. Our results show that SARSCoV- 2 specific T cells could be expanded in both COVID-19 recovered and unexposed groups. Immunophenotypes were similar in both groups showing CD4+ T cell dominance, but CD8+ and CD3+CD56+ T cells were also present. Antigen specificity was determined by ELISPOT, intracellular cytokine assay, and cytotoxicity assays. One out of 14 individuals who were previously unexposed to SARS-CoV-2 failed to show antigen specificity. Moreover, ex-vivo expanded SARS-CoV-2 specific T cells mainly consisted of central and effector memory subsets with reduced alloreactivity against HLA-unmatched cells suggesting the possibility for the development of third-party partial HLA-matching products. In conclusion, our findings show that SARSCoV- 2 specific T cell can be readily expanded from both COVID-19 and unexposed individuals and can therefore be manufactured as a biopharmaceutical product to treat severe COVID-19 patients.Copyright © 2023 International Society for Cell & Gene Therapy
ABSTRACT
Real-estate prices have soared since the start of the COVID-19 pandemic amid historically low mortgage rates and limited supply. The external shock observed in the real-estate market through relief measures may trigger changes in optimal conservation portfolios. The objective of this research is to identify the impacts of the real-estate market shock triggered by the pandemic through low-interest rates and limited real-estate supply on risk-diversification strategies for land conservation investment and to understand the implications of these impacts. We use a case study involving biodiversity conservation in the central and southern Appalachian region of the US by comparing modern portfolio theory (MPT) outputs using future conservation cost predictions with and without the shock. We find that the financial burden to fund the same level of risk-diversifying conservation benefits increases due to the shock and increases at an increasing rate as the return on investment (ROI) objective rises. This finding is alarming since higher conservation costs triggered by the shock decrease the cost-effectiveness of risk diversification, and this effect exacerbates with the goal of achieving higher ROI. Spatial diversification strategies with and without the shock offer risk-diversification information to help conservation organizations determine effective investment strategies.
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Air pollution, especially the continual increase in atmospheric particulate matter (PM), is a global environmental challenge. To reduce the PM concentration, a remarkable amount of machine learning-based research has been proposed. However, increasing the accuracy of the predictions and providing clear interpretations of the predictions are challenging. In particular, no studies have addressed models that predict and interpret PM before and during the COVID-19 pandemic. In this paper, we present a two-step predictive and explainable model to obtain insights into reducing PM. We first use attentive multi-task learning to predict the air quality of cities. To accurately predict the concentration of particles with sizes of similar to 10 mu m or similar to 2.5 mu m (PM10 and PM2.5, respectively), we demonstrate a performance difference between single-task and multi-task learning, as well as among the state-of-the art methods. The proposed attentive model with multi-task learning outperformed the others in terms of accuracy performance. We then used Shapley additive explanations, a representative explainable artificial intelligence framework, to interpret and determine the significance of features for predicting PM10 and PM2.5. We demonstrated the superiority of the proposed approach in predicting and explaining both PM10 and PM2.5 concentrations, and observed a statistically significant difference in air pollution before and during the COVID-19 pandemic.
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Critically ill patients with COVID-19 pneumonia in the intensive care unit (ICU) may develop neurological complications of their central nervous system (CNS) or peripheral nervous system (PNS) that may arise directly from the COVID-19 virus, indirectly as a complication of the COVID-19-related hospitalization, or by mechanisms that have not yet been elucidated. These include encephalopathy, delirium, ischemic stroke, intracranial hemorrhage, peripheral nerve injury, and critical illness myopathy. As the evidence of neurological complications in COVID-19 patients accumulate, we aim to provide a concise review on optimal management strategies of these complications. For the purpose of our review, we are excluding patients in the ICU who develop new neurological symptoms and are found to have otherwise asymptomatic SARS-CoV-2 PCR positivity. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.
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Neurological complications of COVID-19 contribute significantly to mortality in the intensive care unit (ICU). Preventive therapy, though discussed in literature, is limited for COVID-19 neurological manifestations and treatment algorithms continue to rely on evidence from previous pandemics. Thus, in this chapter we evaluate current in vitro, in vitro, histopathological studies to ascertain the most likely mechanisms of SARS-CoV-2 central nervous system entry. From this understanding, we determine probable mechanisms for neurological compilations observed in COVID-19 as relevant to the clinician. SARS-CoV-2 infection of nasal epithelium and the respiratory tract may allow for a systemic inflammatory response that results in neuroinflammation. While most neurological complications are inflammatory in etiology, rarely, SARS-CoV-2 may enter into the central nervous system and mediate neuronal damage. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.
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To prevent and curb viral outbreaks, such as COVID-19, it is important to increase vaccination coverage while resolving vaccine hesitancy and refusal. To understand why COVID-19 vaccination coverage had rapidly increased in Japan, we analyzed Twitter posts (tweets) to track the evolution of people's stance on vaccination and clarify the factors of why people decide to vaccinate. We collected all Japanese tweets related to vaccines over a five-month period and classified the vaccination stances of users who posted those tweets by using a deep neural network we designed. Examining diachronic changes in the users' stances on this large-scale vaccine dataset, we found that a certain number of neutral users changed to a pro-vaccine stance while very few changed to an anti-vaccine stance in Japan. Investigation of their information-sharing behaviors revealed what types of users and external sites were referred to when they changed their stances. These findings will help increase coverage of booster doses and future vaccinations. © 2022 IEEE.
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This study aims to explore differences found both at the surface level and at the interactional level between online and offline writing tutorials at a university located in Seoul, Korea. To date, tutors' online interactions with tutees have not been examined as much as the offline ones, despite the surge of online teaching since the global outbreak of COVID-19. In order to examine how online and offline conditions affect tutor-tutee interactions, this study audio-recorded a total of 16 online and offline writing tutorials conducted by four different Korean writing tutors. Each tutor met two tutees twice— meeting one online and the other offline at first, and then the other way around for the second. Additionally, the tutees' writings, including their first and revised drafts, were collected to better understand the tutor-tutee interactions. The surface-level comparison reveals that backchannels and overlaps hinder the communication in online tutorials and that tutees have limited access to the shared text because of technical limitations inherent to online communication. The interactional-level comparison shows that more collaborations occur during the offline tutorials than during the online counterpart. Based on these findings, this study argues for further technical development in the area of online courses, and suggests that both tutors and tutees need training and experience in order to efficiently communicate online. © 2023 KASELL All rights reserved.
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Semiconducting single-walled carbon nanotubes (SWCNTs) with tailored corona phases (CPs), or surface-adsorbed molecules, have emerged as a promising interface for sensing applications. The adsorption of an analyte can be specifically transduced as a modulation of their band-gap near-infrared (nIR) photoluminescence (PL). One such CP ideal for this purpose is single-stranded DNA (ssDNA), where subsequent sequence-dependent hybridization can result in PL emission wavelength shifts. Due to ssDNA adsorption to the SWCNT surface, the resultant noncanonical hybridization and its effect on SWCNT photophysical properties are not well understood. In this work, we study 20- and 21-mer DNA and RNA hybridization on the complementary ssDNA-SWCNT CP in the context of nucleic acid sensing for SARS-CoV-2 sequences as model analytes. We found that the van't Hoff transition enthalpy of hybridization on SWCNT CP was −11.9 kJ mol-1, much lower than that of hybridization in solution (−707 kJ mol-1). We used SWCNT solvatochromism to calculate the solvent-exposed surface area to indicate successful hybridization. We found that having a 30-mer anchor region in addition to the complementary region significantly improved PL response sensitivity and selectivity, with a (GT)15 anchor preferred for RNA targets. Coincubation of ssDNA-SWCNTs with an analyte at 37 °C resulted in faster hybridization kinetics without sacrificing specificity. Other methods aimed to improve CP rearrangement kinetics such as bath sonication and surfactant additions were ineffective. We also determined that the target sequence choice is important as secondary structure formation in the target is negatively correlated with hybridization. Best-performing CPs showed detection limits of 11 and 13 nM for DNA and RNA targets, respectively. Finally, we simulated sensing conditions using the saliva environment, showing sensor compatibility in biofluids. In total, this work elucidates key design features and processing to enable sequence-specific hybridization on ssDNA-SWCNT CPs. © 2022 American Chemical Society.
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With the advent of COVID-19, new virtual social activities arose. These activities include virtual studying, which is studying while joining a video conference. Virtual studying is different from most virtual activities in that users try to minimize unnecessary interactions while sharing their presence through video streaming. Here, video streaming that runs in the background can cause problems such as invasion of privacy and excessive self-awareness. In this paper, we aim to investigate whether a new video conferencing interface that reduces video explicitness but detects important actions can mitigate the problems of video streaming and still deliver users' presence in virtual studying. To this end, we designed a research prototype in three versions: blurred video version, small video version, and no video version. All versions were provided with an activity recognizer that detects absence, leaning, and using a smartphone. To evaluate the feasibility of the design, we conducted a user study where four virtual studying teams used all three versions of the prototype and participated in an interview. Our study explored the effects of new design strategies for virtual studying, which is a new virtual activity that focuses on sharing presence. © 2022 Owner/Author.
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Engaging diverse groups of older adults is essential to addressing health disparities. In this presentation, we will describe how we used our research team's networks and knowledge of the target population to engage key stakeholders in our KAP project. We will address our partnerships with clergy, NGO staff and administrators, housing authorities, colleagues at Puerto Rican universities, and older adults who serve as informal community and institutional gatekeepers. We will discuss how these partnerships facilitated our ability to identify and access study sites and participants;conduct telephone and in-person interviews;ensure data quality through training and monitoring;and, assure safety through adherence to COVID-19 protocols. Finally, we will describe key cultural and ethical issues of conducting research with older adults through community partnerships during a pandemic. The presentation has implications for developing beneficial partnerships with local community leaders and enhancing the representation of diverse groups of older adults in research.
ABSTRACT
Semiconducting single-walled carbon nanotubes (SWCNTs) with tailored corona phases (CPs), or surface adsorbed molecules, have emerged as a promising interface for sensing applications. The adsorption of an analyte can be specifically transduced as a modulation of their band-gap near infrared (nIR) photoluminescence (PL). One such CP ideal for this purpose is single-stranded DNA (ssDNA), where subsequent sequence-dependent hybridization can result in PL emission wavelength shifts. Due to ssDNA adsorption to the SWCNT surface, the resultant noncanonical hybridization and its effect on SWCNT photophysical properties are not well understood. In this work, we study 20-and 21-mer DNA and RNA hybridization on the complementary ssDNA-SWCNT CP in the context of nucleic acid sensing for SARS-CoV-2 sequences as model analytes. We found that the van't Hoff transition enthalpy of hybridization on SWCNT CP was -11.9 kJ mol-1, much lower than that of hybridization in solution (-707 kJ mol-1). We used SWCNT solvatochromism to calculate the solvent-exposed surface area to indicate successful hybridization. We found that having a 30-mer anchor region in addition to the complementary region significantly improved PL response sensitivity and selectivity, with a (GT)15 anchor preferred for RNA targets. Coincubation of ssDNA-SWCNTs with an analyte at 37 degrees C resulted in faster hybridization kinetics without sacrificing specificity. Other methods aimed to improve CP rearrangement kinetics such as bath sonication and surfactant additions were ineffective. We also determined that the target sequence choice is important as secondary structure formation in the target is negatively correlated with hybridization. Best performing CPs showed detection limits of 11 and 13 nM for DNA and RNA targets, respectively. Finally, we simulated sensing conditions using the saliva environment, showing sensor compatibility in biofluids. In total, this work elucidates key design features and processing to enable sequence-specific hybridization on ssDNA-SWCNT CPs.
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Introduction: Coronavirus Disease 2019 has prompted widespread school closures and physical distancing measures. Concerns regarding COVID-19 school closures often increase stress levels in parents. Objective(s): This study examined whether higher levels of parental concerns were associated with children's problematic behaviors and other factors during COVID-19-related primary school closures. Method(s): Participants were 217 parents who responded to a webbased questionnaire covering parental concerns, subjective stress, and depression;children's sleep patterns, behavioral problems, and changes in activity level after COVID-19;previously received mental health services;and media usage during the online-only class period from community center in Suwon city. Result(s): The number of parental concerns was associated with children's behavioral problem index (BPI) score (Pearson correlation 0.211, p < 0.01), sleep problems (0.183, p < 0.01), increased smartphone usage (0.166, p < 0.05), increased TV usage (0.187, p < 0.01), parents' subjective stress levels (0.168, p < 0.05), and parental depression (0.200, p < 0.01). In families with children who previously received mental health services, the children reportedly suffered from more sleep and behavioral problems but not increased media usage, and parents noted more stress and depression. Parental concerns are related to family factors such as change of caregiver, no available caregiver, decreased household income, and recent adverse life events. Economically vulnerable people also reported higher rates of reported caregiver burden during COVID-19-related primary school closures, thus will require the potential heightened mental health needs. Conclusion(s): Ongoing monitoring of mental health at risky group and multiple support systems should be considered for parents having difficulty in caring their children.
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With the outbreak of the covid-19 pandemic in recent years, Video Stream Analytics technology quickly became a hot topic of discussion across technology forums. As it has appeared, in the pandemic situation in recent years, the use of masks when interacting with the community is a must, that's why the research works on mask identification today and more. receiving more and more attention. Understanding the situation, the team conducted facial recognition analysis inside the video to determine if the people appearing in the video were wearing masks. to then apply the trained model into practice. After a period of research, the team has also successfully built a mask recognition system that can generate images and can display the results as real-time video. Especially, the model is trained successful using systemml machine learning system. This is considered a positive result with real-time masked face recognition analysis. © 2022 IEEE.
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In March 2020, the United States responded to the COVID-19 pandemic. With this response of quarantining, social distancing, and other precautions, a need to ensure that access to healthcare occurred. Technology in the form of telemedicine and virtual visits addresses this need. Patients can use telemedicine and virtual healthcare services to improve convenience, improve access, and reduce other healthcare and pharmacy service barriers. The continuation and expansion of telemedicine and virtual visits in the practice of pharmacy provide more equitable access to healthcare and offer solutions to health disparities concerning language barriers and cultural differences, provided practitioners utilize effective communication. Copyright © 2022, Jobson Publishing Corporation. All rights reserved.
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Background: Chronic diseases contribute to 74% of annual global deaths. The coronavirus disease (COVID-19) pandemic further aggravated the burden of chronic diseases. The reasons for this adverse impact must be elucidated to develop an appropriate response.Current Concepts: COVID-19 increases the burden of chronic disease in three ways. First, chronic disease comorbidities are associated with a higher severity and fatality rate in patients with COVID-19. Second, the post COVID-19 condition results in chronic health problems. Lastly, a disruption in the system for chronic disease screening and care was observed during the COVID-19 pandemic.Discussion and Conclusion: Strong efforts are needed to mitigate the impact of the COVID-19 pandemic on chronic diseases, and to re-establish an effective system for chronic disease management.
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Background: In an interim analysis of Asian pts with uHCC in the observational REFINE study of regorafenib (NCT03289273), treatment-emergent adverse events (TEAEs) were consistent with those reported in the global, phase 3 RESORCE trial. Here, we present the final analysis of Asian pts with uHCC in REFINE. Method(s): REFINE is an international, prospective, multicenter study that enrolled pts with uHCC for whom a decision to treat with regorafenib was made by the treating physician prior to enrollment, according to the local health authority approved label. The primary objective is safety, including the incidences of TEAEs and dose modifications due to TEAEs (NCI-CTCAE v4.03). Secondary endpoints include overall survival, progression-free survival, and treatment duration. Result(s): Of the 1005 evaluable pts, 557 (55%) were from Asia (Korea [31%], Japan [26%], Taiwan [24%], China [18%], Thailand [1%]) and 82% were male. At baseline, median age was 65 years (range 21-94) and the most common HCC etiology in Asian pts was hepatitis B (60%) and in non-Asian pts was alcohol use (36%;Table). More Asian pts (71%) had received prior transarterial chemoembolization vs non-Asian pts (42%). The initial daily regorafenib dose was 160/120/80/40 mg in 51%/12%/35%/3% of Asian pts and 42%/9%/45%/4% of non-Asian pts. The median treatment duration was 3.7 months (range 0-34.4) in Asian pts and 3.6 months (range 0-38.9) in non-Asian pts. The most common TEAEs in Asian pts were hand-foot skin reaction (40%), diarrhea (27%), and decreased appetite (17%). TEAEs led to dose modification in 44% of Asian pts. [Formula presented]. Conclusion(s): These final data from REFINE confirm the safety and effectiveness of regorafenib in Asian pts with uHCC from a broad population in real-world practice. Final analyses from REFINE are ongoing and will be presented at the conference. Clinical trial identification: NCT03289273. Editorial acknowledgement: Editorial assistance in the preparation of this manuscript was provided by Matthew Reynolds of OPEN Health Communications (London, UK), with financial support from Bayer. Legal entity responsible for the study: Bayer. Funding(s): Bayer. Disclosure: Y.J. Kim: Financial Interests, Personal, Advisory Role: Bayer, Bristol Myers Squibb, Samil, PharmaKing, Celltrion, Bukwang;Financial Interests, Personal, Invited Speaker: Roche, AbbVie, Eisai, Ipsen, Boston Scientific, Bristol Myers Squibb, BTG, Bayer, MSD, Gilead Sciences, Novo Nordisk, Green Cross Cell, Boehringer Ingelheim, AstraZeneca;Financial Interests, Personal, Funding: BTG, Bayer, Boston Scientific, AstraZeneca, Gilead Sciences, Samjin, BL&H. M. Kurosaki: Financial Interests, Personal, Speaker's Bureau: Gilead Sciences, AbbVie, Eisai, Chugai, Lilly, Takeda. H.Y. Lim: Financial Interests, Personal, Advisory Role: Bayer, Eisai, Roche, Ipsen. M. Ikeda: Financial Interests, Personal, Advisory Board: AstraZeneca, Chugai, Eli Lilly Japan, Eisai, Nihon Servier, Novartis, Ono, Takeda, GlaxoSmithKline;Financial Interests, Personal, Invited Speaker: AstraZeneca, Bayer, Bristol Myers Squibb, Chugai, Eli Lilly Japan, Eisai, Nihon Servier, Novartis, Taiho, Yakult, Teijin Pharma, AbbVie, Abbott Japan, Fujifilm Toyama Chemical, Incyte Biosciences Japan, ASLAN, Chugai, Nihon Servier, Takeda;Financial Interests, Institutional, Invited Speaker: Bayer, Bristol Myers Squibb, Eisai, AstraZeneca, Eli Lilly Japan, Chugai Pharmaceutical, Merck Serono, MSD, Ono, Yakult, Novartis, Takeda, J-Pharma, Pfizer, Chiome Bioscience, Nihon Servier, Delta-Fly Pharma, Syneos Health, Merus.N.V. M. Kudo: Financial Interests, Personal, Invited Speaker: Eisai, Chugai, Eli Liiy, Bayer, Takeda, MSD;Financial Interests, Institutional, Research Grant: Otsuka, Sumitomo Dainippon Pharma, EA Pharma, Taiho, Eisai, AbbVie, Gilead Sciences, Takeda, GE Healthcare, Chugai. Y. Huang: Financial Interests, Personal, Advisory Role: Eisai, Bayer, BMS, Ono, Gilead, Lilly, AbbVie, Roche;Financial Interests, Personal, Invited Speaker: Eisai, Bayer, BMS, Ono, Gilead, Lilly, AbbVie, Roche;Financial Inte ests, Personal, Speaker's Bureau: Eisai, Bayer, BMS, Ono, Gilead, Lilly, AbbVie, Roche;Financial Interests, Institutional, Funding: Gilead. N. Kato: Financial Interests, Personal, Invited Speaker: Gilead Sciences Inc., AbbVie G.K., Ohtsuka Pharmaceutical Co., Ltd., Bayer Yakuhin Ltd., Chugai Pharmaceutical Co., Ltd., AstraZeneca K.K., Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Co., Ltd., Zeria Pharmaceutical Co., Ltd., Olympus Corporation, Eisai Co., Ltd., Aska Pharmaceutical Co., Ltd., Tsumura & Co., Mochida Pharmaceutical Co., Ltd., Miyarisan Pharmaceutical Co., Ltd., Covidien Japan Inc., Eli Lilly Japan K.K., Nobelpharma Co., Ltd., Kowa Company, Ltd., Incyte Biosciences Japan GK, Yakult Honsha Co.,Ltd., Olympus Marketing, Inc., Taisho Pharmaceutical Co.,Ltd., Janssen Pharmaceutical K.K.;Financial Interests, Institutional, Research Grant: AbbVie G.K., Ohtsuka Pharmaceutical Co., Ltd., Bayer Yakuhin Ltd., Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Sumitomo Dainippon Pharma Co., Ltd., Shionogi & Co., Ltd., Eisai Co., Ltd., Tsumura & Co., Nippon Kayaku Co., Ltd., JIMRO Co., Ltd., Kowa Company, Ltd. C. Hsu: Financial Interests, Personal, Speaker's Bureau: Bristol Myers Squibb, Ono Pharmaceutical, Merck Sharp & Dohme, Roche, Eisai;Financial Interests, Institutional, Funding: Ono Pharmaceutical, AstraZeneca, MSD, Merck Serono, Taiho Pharmaceutical, Bristol Myers Squibb, BeiGene, NuCana BioMed, Johnson & Johnson, Roche/Genentech, BeiGene;Financial Interests, Personal, Advisory Role: Ono Pharmaceutical, MSD, Bristol Myers Squibb, Merck Serono, Roche/Genentech. B. Chewaskulyong: Financial Interests, Personal, Advisory Role: Pfizer, STADA;Financial Interests, Personal, Invited Speaker: AstraZeneca, Pfizer, DKSH, Janssen, BMS, MSD, Roche, TAIHO;Financial Interests, Personal, Speaker's Bureau: AstraZeneca, Pfizer, DKSH, Janssen, BMS, MSD, Roche, TAIHO;Financial Interests, Institutional, Funding: Bayer. J. Khan: Financial Interests, Institutional, Full or part-time Employment: Bayer. K. Ozgurdal: Financial Interests, Institutional, Full or part-time Employment: Bayer;Financial Interests, Personal, Stocks/Shares: Bayer. All other authors have declared no conflicts of interest. Copyright © 2022
ABSTRACT
Background: Hemorrhage, coagulopathy and thrombosis (HECTOR) are reported complications of coronavirus disease 2019 (COVID-19) however, more information is needed on the prevalence of these complications and their associated outcomes in intensive care unit (ICU) settings. Aim(s): To determine the prevalence and outcomes of HECTOR complications in ICU patients with COVID-19. Method(s): Observational cohort study spanning 229 ICUs across 32 countries. Patients >=16 years admitted for severe COVID-19 from 1st January 2020, through 31st December 2021 were included. Patient characteristics and clinical data were collected. Survival analysis estimated the instantaneous impact of HECTOR complications on ICU-mortality and discharge. Result(s): HECTOR complications occurred in 1,735 (14%) of 11,972 study-eligible patients. Acute thrombosis occurred in 1,249 (10%) patients, including 712 (57%) with pulmonary embolism, 413 (33%) with myocardial infarction, 93 (7.4%) with deep vein thrombosis, and 49 (3.9%) with ischemic stroke. Hemorrhagic complications were reported in 582 (4.9%) patients, including 276 (48%) with gastrointestinal hemorrhage, 83 (14%) with hemorrhagic stroke, and 77 (13%) with pulmonary hemorrhage. Disseminated intravascular coagulation occurred in 11 (0.09%) patients. Univariate analysis identified diabetes, hypertension, cardiac and kidney disease and ECMO as statistically-significant risk factors for HECTOR complications. Patients with versus without HECTOR complications suffered higher ICU-mortality at 28 days (25%vs.13%, p < 0.001), 90 days (32%vs.15%, p < 0.0001) and overall (44%vs.36%, p < 0.001). Among ICU survivors, the ICU stay was longer (median days 19vs.12, p < 0.001). ICU mortality was similar between patients with and without HECTOR complications (HR = 1.01, 95%CI 0.92-1.12, p = 0.783) where an increased hazard of ICU mortality with hemorrhage (HR = 1.26, 1.09-1.45, p = 0.002) was balanced by a reduced hazard of thrombosis (HR = 0.88, 0.79-0.99, p = 0.03). Kaplan-Meier curves are presented in the Figure. Conclusion(s): HECTOR events are frequent complications of severe COVID-19 in ICU patients. Hemorrhagic, but not thrombotic complications are associated with increased ICU-mortality.
ABSTRACT
Background & Aim: Background. Immunological characteristics of COVID-19 show pathological hyperinflammation associated with lymphopenia and dysfunctional T cell responses. These features provide a rationale for restoring functional T cell immunity in COVID-19 patients by adoptive transfer of SARS-CoV-2 specific T cells. Methods, Results & Conclusion: Methods. To generate SARS-CoV-2 specific T cells, we isolated peripheral blood mononuclear cells from 7 COVID-19 recovered and 13 unexposed donors. Consequently, we stimulated cells with SARS-CoV-2 peptide mixtures covering spike, membrane and nucleocapsid proteins. Then, we culture expanded cells with IL-2 for 21 days. We assessed immunophenotypes, cytokine profiles, antigen specificity of the final cell products. Results. Our results show that SARS-CoV-2 specific T cells could be expanded in both COVID-19 recovered and unexposed groups. Immunophenotypes were similar in both groups showing CD4+ T cell dominance, but CD8+ and CD3+CD56+ T cells were also present. Antigen specificity was determined by ELISPOT, intracellular cytokine assay, and cytotoxicity assays. One out of 14 individuals who were previously unexposed to SARS-CoV-2 failed to show antigen specificity. Moreover, ex-vivo expanded SARS-CoV-2 specific T cells mainly consisted of central and effector memory subsets with reduced alloreactivity against HLA-unmatched cells suggesting the possibility for the development of third-party partial HLA-matching products. Conclusion. In conclusion, our findings show that SARS-CoV-2 specific T cell can be readily expanded from both COVID-19 and unexposed individuals and can therefore be manufactured as a biopharmaceutical product to treat severe COVID-19 patients.