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1.
Medical Review ; 3(2):180-183, 2023.
Article in English | Scopus | ID: covidwho-20233779

ABSTRACT

Rapid developments in the coronavirus disease 2019 (COVID-19) mRNA vaccine showcased the power of lipid nanoparticle (LNP) delivery systems in fighting infectious diseases. In addition, mRNA therapeutics are also in development for cancer immunotherapy. Recently, mRNA therapy has been expanded to induce immune tolerance, the opposite of immune-boosting effects, to treat diseases involving enhanced immune responses including allergies and autoimmune diseases. mRNA LNPs have been used to treat peanut allergy by us and autoimmune experimental autoimmune encephalomyelitis by Ugur Sahin. It is expected that more and more research is going to delve into the immune tolerance field for allergies and autoimmune diseases, where effective therapies are in short supply. © 2023 the author(s), published by De Gruyter, Berlin/Boston.

2.
Medical Journal of Peking Union Medical College Hospital ; 12(1):5-8, 2021.
Article in Chinese | EMBASE | ID: covidwho-2322259

ABSTRACT

The global epidemic of coronavirus disease 2019 (COVID-19) is still growing. The response to this emerging disease should be considered with the context of its clinical characteristics and pathophysiological mechanisms. Although available therapeutic options are still very limited, current experience has suggested that the choice of clinical strategies should be based upon the disease stage and immune functions of the patients. The present article reviews the clinical characteristics of COVID-19 and current evidence of various treatment approaches. Combined with first-line experience, we summarize the current clinical strategies for COVID-19 management based on disease progress and staging.Copyright © 2021, Peking Union Medical College Hospital. All rights reserved.

3.
Infectious Diseases and Immunity ; 3(1):29-35, 2023.
Article in English | Scopus | ID: covidwho-2253708

ABSTRACT

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a tremendous burden on public health and world economies. An efficient host immune response to acute SARS-CoV-2 infection requires rapid and early activation of the innate immune system. Natural killer (NK) cells represent a critical component of the innate immunity. Here, the appearance of CD56-CD16+ NK cells and unconventional CD56dim CD16neg NK cells during the course of SARS-CoV-2 infection, and the phenotype and effector functions of NK cells during SARS-CoV-2 infection were summarized. The involvement of the dysregulated NK cells in the immunopathogenesis of the coronavirus disease 2019 (COVID-19) and clinical trials of adoptive NK cell-based therapies against COVID-19 were also discussed. © Wolters Kluwer Health, Inc. All rights reserved.

5.
Ieee Access ; 10:114374-114392, 2022.
Article in English | Web of Science | ID: covidwho-2123159

ABSTRACT

With the outbreak of COVID-19 pandemic, the problem of supply chain emergency scheduling has had a great influence on economic benefits of enterprises. The uncertainty of the COVID-19 pandemic and uncertainty of supply chain have made the problem of emergency scheduling more complicated. In this study, a multiobjective multiperiod mixed-integer programming optimization model was developed, in which two conflicting benefit factors, cost and service level were taken as the optimization target of the model. Cost and service level were normalized, and the weighted sum was taken as the objective function, which transformed the problem into a multiperiod nonlinear one. Two algorithms of Bi-level Modified Hybrid Genetic Algorithm (BMHGA) and Bi-level Hybrid Genetic Algorithm (BHGA) were designed to solve the model. Three emergency strategies have been proposed, including enabling alternative suppliers, repairing failure nodes and enabling internal suppliers' flexibility. The parameter of disruption scenario and its solution method were designed. Finally, the practicability of the proposed model and algorithm was demonstrated through application to a case study of an electronics supply chain. The results indicated that the optimal solution of two algorithms was between 2%-5%, and BMHGA could obtain a better optimal solution.

6.
Dili Xuebao/Acta Geographica Sinica ; 77(6):1546-1562, 2022.
Article in Chinese | Scopus | ID: covidwho-1912171

ABSTRACT

Using the data of global COVID-19 vaccine development, ordering, donation and vaccination, and through GIS and other technical methods, this paper depicts the development, circulation pattern and their dynamics of global COVID-19 vaccine. In order to provide a cognitive basis, this paper further discusses the spatial and temporal differentiation of global COVID-19 vaccination. The conclusions are as follows: (1) The global development pattern of COVID-19 vaccine is not balanced, with three cores in Western Europe, North America and Asia as a whole. Among them, the United States, China and the UK are the representative countries for the development of COVID-19 vaccine. (2) In the early stage, the global COVID-19 vaccine ordering was mainly distributed among developed countries in Western Europe and North America. Nevertheless, with the continuous expansion of the global ordering network, the ordering of COVID-19 vaccine has gradually expanded to Asian, African and Latin American countries. On the whole, the global COVID-19 vaccine ordering has formed two expansion modes, including directed expansion and non-directed expansion. (3) China and the United States are the two core countries of the global COVID-19 vaccine donation network. The United States mainly donates vaccines to Southeast Asia, South Asia, Latin America and other countries that have close relationship with the United States. China mainly donates vaccines to South Asia, Southeast Asia, West Asia and Africa. The donation of COVID-19 vaccine is mainly affected by the contact and relationship between countries, the national strategies and the need to fulfill international obligations of donor countries, but their focuses are different. (4) The development, ordering and donation pattern of global COVID-19 vaccine determines the evolution of global vaccination pattern. The vaccination process in developed countries in Western Europe and North America is ahead of most Asian, African and Latin American countries, but the gap is gradually narrowing. China's vaccination rate has jumped from a higher to the highest level, making China a representative of developing countries. © 2022, Science Press. All right reserved.

7.
Modern Pathology ; 35(SUPPL 2):16, 2022.
Article in English | EMBASE | ID: covidwho-1857688

ABSTRACT

Background: More than 20% of COVID-19 patients have gastrointestinal (GI) symptoms, among which diarrhea is the most commonly seen symptom. Studies have suggested that patients with severe disease are more likely to have abdominal manifestations. Recent studies have also implicated that coagulopathy and thromboembolic as the major pathophysiological event leading to higher mortality. Besides thrombus in larger vessels, microthrombi appears to occur systemically and plays an important role in multiple organ dysfunction. However, fewer studies have focused on microthrombosis in the GI system. Design: 13 bronchial SARS-CoV-2 PCR proven autopsy cases were included in the study. Small intestinal specimens were obtained, and processed to routine hematoxylin and eosin (H&E) and CD61 immunohistochemistry (IHC). Related clinical and laboratory data were collected from patient chats. H&E and IHC slides were reviewed by two GI pathologists to evaluate histopathology and microthrombi. The degree of microthrombosis was graded as no microthrombi, focal (1- 2 per 10x), scattered (3-5 per 10x), and diffuse (≥6 per 10x). Results: Out of 13 patients (11 males, 1 female, age range 22-89 years old), 6 had diarrhea as the initial GI symptom, while others (7 patients) did not report any GI manifestations. Sections from the small intestine showed no acute inflammation in all cases. CD61 positive microthrombi was seen in all small intestine specimens, mainly located in the microvasculature of mucosa, and occasionally submucosal tissue. Patients who had diarrhea, 4/6 (66.7%) showed diffuse (greater than 6 per 10x field) microthrombi in the small intestine. In contrast, patients without GI symptoms, only 2/7 (28.5%) had diffuse microthrombi. Data from lab tests showed the D-dimer appeared to be higher in patients with diarrhea (median, 4067, range from 867 to 10000 ng/ml) compared to patients without diarrhea (median, 2820, range from 298 to 10000 ng/ml). There was no significant difference between median levels of C-reactive protein, prothrombin time (PT) and partial thromboplastin time (aPTT) between patients with or without diarrhea. Conclusions: Our study highlights that microthrombi frequently occurs in the GI system as reported in other organs. COVID-19 patients with initial GI manifestations, may develop severe microthrombosis and progress to sever disease.

8.
Modern Pathology ; 35(SUPPL 2):2-3, 2022.
Article in English | EMBASE | ID: covidwho-1857027

ABSTRACT

Background: SARS-CoV-2 causes diffuse alveolar damage, lymphocyte infiltration in the lungs and a cytokine storm. In this study we examined inflammatory cell infiltrates in the lungs of patients with COVID-19. Design: Eighteen COVID-19 autopsy cases (COVID group), 9 non-COVID cases with diffuse alveolar damage (DAD, non-COVID group), and eleven controls without lung diseases were included. Immunostainings for CD3, CD4, CD8, CD68 and broad-spectrum keratins were performed. Results: The average age of COVID-19 patients was 64.4±2.1 years. The most common co-morbidities were hypertension (12/17, 70.6%), diabetes mellitus (9/17, 52.9%) and chronic kidney disease (3/17, 17.6%). The survival duration of 17 patients with available clinical information was 21.2 ± 3.4 days (range 7-53 days) after onset of symptoms. Patients younger than 67 years old (namely young patients thereafter, N=9) survived 26.4 ± 5.9 days after onset of symptoms, which was significantly longer than those greater than 67 years old (namely older patients thereafter, 15.2 ± 1.4 days, N=8, P<0.05). The younger patients had significantly lower platelet counts (107.7 ± 33.2 x 109/L, N=8) than the older ones (224.6 ± 42.4 x 109/L, N=8, P<0.05). Conversely, the younger patients had much higher absolute lymphocyte counts (1.5 ± 0.4 x 109/L, N=7) than the older ones (0.7 ± 0.1 x 109/L, N=8, P<0.05). Interestingly, the patients with low platelet counts (<100 x 109/L) survived longer than those with higher platelet counts (P<0.05). Patients with high troponin levels (>0.2 ng/ml) had shorter survival duration after onset of symptoms (16.8 ± 1.9 days) than those with low troponin levels (30.8 ± 8.0 days, P<0.05). Patients with macrophages >130/HPF, CD3+ T cells >145/HPF, CD8+ T cells <30/HPF and CD8+/CD4+ ratio<1 had a shorter survival time compared to those with macrophages <130/HPF, CD3+ T cells <145/HPF, CD8+ T cells >30/HPF and CD8+/CD4+ ratio>1, respectively. Conclusions: Patients' age > 67 years, blood troponin levels >0.2 ng/ml, platelet count >100 x 109/L, lung macrophages >130/HPF, CD3+ T cells >145/HPF, CD8+ T cells <30/HPF, and CD8/CD4 ratio <1 were associated with shorter survival duration after onset of symptoms.

9.
Modern Pathology ; 35(SUPPL 2):2, 2022.
Article in English | EMBASE | ID: covidwho-1857026

ABSTRACT

Background: Hospital autopsy rates have been steadily dropping over the past 50 years in the United States. It is unclear whether concerns of potential risks of exposure to SARS-CoV-2 through aerosols generated during dissection of lungs, infusion of formalin into lungs, and during opening skulls with an oscillating saw affect the overall autopsy rate. Design: Autopsy rate was calculated during a period from March 2019 to February 2020 (before COVID-19 pandemic in Rhode Island) and that from March 2020 to February 2021 (COVID-19 pandemic period). Death and autopsy numbers were also analyzed. Results: Autopsy rate over a year before the COVID-19 pandemic (between March 2019 and February 2020) was 8.4% (117/1391), whereas it was 9.1% (136/1492) during the COVID-19 pandemic (March 2020-February 2021). The difference was not statistically significant. During the COVID-19 pandemic between October 2020 and April 2021, the autopsy rate for non-COVID patients was 11%, whereas it was 8.6% in patients with COVID-19. The autopsy rate was slightly lower in COVID-19 patients, but the difference was not statistically significant. The death number and the percentage of death of patients with COVID-19 among all deaths reached a peak in December 2020, whereas the death number in non-COVID patients was relatively stable. The autopsy number also reached the peak in December 2020 and January 2021. From October 2020 to February 2021, the total autopsy number increased by 38-200%, when compared with one year ago (October 2019 to February 2020). The autopsy rate also increased from 7.9% before COVID-19 (from October 2019 to February 2020) to 10.7% during the same months of the COVID-19 pandemic, but the increase did not have the statistical significance. Conclusions: The COVID-19 pandemic did not affect the overall autopsy rate, but it increased the number of autopsy cases.

10.
Annals of Behavioral Medicine ; 56(SUPP 1):S683-S683, 2022.
Article in English | Web of Science | ID: covidwho-1849189
11.
Educational Technology and Society ; 25(1):142-154, 2022.
Article in English | Scopus | ID: covidwho-1728221

ABSTRACT

With the outbreak of COVID-19, more online learning has been adopted for distance learning. However, the effectiveness of online learning for those students engaged in it for the first time has not been discussed. This study aims to investigate perceived ineffectiveness of online learning and its antecedents related to cognitive and affective factors. Internet self-efficacy (ISE) and Self-efficacy of interacting with learning content (SEILC) were hypothesized to have a correlation with perceived ineffectiveness of online learning (PIOL) mediated by participants’ Internet cognitive fatigue (ICF) and mind-unwandered, while ICF was hypothesized to have a correlation with mind-unwandered. Data of 251 students collected from high schools in China during the lockdown period of COVID-19 were subjected to confirmatory factor analysis via AMOS. Results indicated that participants’ ISE and SEILC were positively related to mind-unwandered, but negatively related to ICF during online learning, while ICF was positively associated with PIOL. On the other hand, mind-unwandered was negatively associated with PIOL. Furthermore, students’ ISE and SEILC indirectly affected their PIOL mediated by ICF. Findings suggest that an enhancement of learners’ ISE and SEILC could have reduced the level of PIOL the first time that online learners experienced under the COVID-19 lockdown to promote their learning effectiveness. This understanding will be useful in case of another pandemic outbreak. © 2022, Educational Technology and Society. All rights reserved.

12.
2020 IEEE Nuclear Science Symposium and Medical Imaging Conference, NSS/MIC 2020 ; 2020.
Article in English | Scopus | ID: covidwho-1706502

ABSTRACT

Computed tomography (CT) of COVID-19 manifests a relatively global effect through the whole lungs, like peripheral ground glass, consolidation, reticular pattern, nodules etc. This characteristic effect renders the difficulties in differentiating COVID-19 from the normal body or other lung diseases by CT. This work presents a novel method to relieve the difficulties by reducing the global effect through the 3D whole lung volume into 2D-like domain. The hypothesis is that the lung tissue shares the similar anatomic structure within a small lung sub-volume for normal subjects. Therefore, the anatomic land-markers along the z-axis, denoted as Lung Marks are used to eliminate axial variable. Our experiments indicated that 30 Lung Marks are sufficient to eliminate the axial variable. The method computes texture measures from each 2D-like volumetric data and maps the measures on to the corresponding Lung Mark, resulting in a profile along the z-axis. The difference of the profiles between two different abnormalities is the proposed sensitive merit to differentiate COVID-19 cases from others in CT images. 48 COVID-19 cases and 48 normal screening cases were used to test the effectiveness of the proposed sensitive merit. Intensity and gradient based texture descriptors were computed from each axial cross image at the corresponding Lung Mark along the z-axis. Euclidean, Jaccard and Dice distances are calculated to generate the profiles of the proposed sensitive merit. Consistent results are observed across texture descriptor types and distance types in the texture measure between the normal and COVID-19 subjects. Uneven Profiles demonstrate the variation along the z-axis. With Lung Mark, the variation of texture descriptor has been reduced prominently. The Gradient based descriptor is more sensitive. Individual Haralick features analysis shows the 2nd and 10th dimensions are most distinguishable. © 2020 IEEE

13.
Journal of Marine Science and Engineering ; 10(2), 2022.
Article in English | Scopus | ID: covidwho-1686855

ABSTRACT

The global outbreak of Corona Virus Disease 2019 (COVID-19) has led to an extreme increase in the use of disposable masks. If the used disposable masks are not appropriately disposed of, they will enter the natural environment and lead to environmental pollution. In order to understand the impacts of disposable masks after being disposed of into the natural environment, aging experiments with simulated natural conditions were performed on the outer, inner, and middle layers of the masks to verify the aging characteristics of disposable masks. We analyzed the mechanical behavior, surface morphology, and Fourier Transform Infrared Spectroscopy (FT-IR) spectra of disposable masks treated with different levels of UV irradiation to understand the possible changes in the masks under UV. Results showed that the elongation at break, tensile strength, and maximum force of all three polypropylene (PP) mask layers decreased after UV irradiation, indicating chemical bond breakage. In the process of photoaging, each layer of the disposable masks showed a different degree of microscopic surface changes after UV irradiation, and these changes gradually intensified with the extension of UV exposure time. FT-IR results showed that functional groups, such as hydroxyl and carbonyl groups increased in each layer after UV irradiation. The results of this study support that, although the different layers of the disposable masks are all made of PP, they age differently in the environment. With the ever-increasing number of disposable masks in the environment, we need to further study the aging and degradation of disposable masks to better understand their potential impacts on the environment in the future. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

14.
Chinese Journal of Disease Control and Prevention ; 25(4):416-420, 2021.
Article in Chinese | Scopus | ID: covidwho-1566856

ABSTRACT

Objective To explore the epidemiological characteristics of confirmed cases of coronavirus diseases 2019 (COVID-19) in Puyang, Henan Province, so as to provide basis for diseases control and preventive. Methods The epidemiological data of 17 cases of COVID-19 in Puyang were collected, and the time, regional and population distribution characteristics of COVID-19 were described and analyzed by drawing disease sequence diagram and case relationship diagram. Results Among the 17 cases, 7 were male (41.2%);the median age was 36 years old with age ranged from 12 to 66 years. A total of 4 clustered outbreaks occurred, involving 12 cases (70.6%), all of which were family recurrent cases. The median incubation period was 6.5 days, the shortest 3 days and the longest 13 days. The onset time of a second-generation case was 11 days earlier than that of the indicator case. The median time between onset and treatment was 4 days, the shortest was 0 days and the longest was 12 days. Of the 17 cases, 6 had a sojourning history in Hubei Province within 14 days, and 1 had a history of overseas tourism. The other cases were all local infections, 8 of them were close contacts of the confirmed cases, and 2 of them were from unknown sources. Among the close contacts, the cases involved in the family clustering epidemic were transmitted through close contact and respiratory tract. After detailed investigation and inquiry, it was inferred that the transmission route was the staircase droplet transmission. Conclusion In Puyang City, most of the cases were from Hubei Province, and was dominated by family clustering epidemic. There was a possibility of infection in the incubation period. © 2021, Publication Centre of Anhui Medical University. All rights reserved.

15.
Zhonghua Nei Ke Za Zhi ; 59(8): 577-579, 2020 Aug 01.
Article in Chinese | MEDLINE | ID: covidwho-1555227

Subject(s)
COVID-19 , Cities , Humans , SARS-CoV-2
16.
Rhode Island Medicine ; 104(10):21-25, 2021.
Article in English | MEDLINE | ID: covidwho-1539268

ABSTRACT

Autopsy training is required for board certification by the American Board of Pathology and may be affected by autopsy rate. It is unclear whether the COVID-19 pandemic has affected autopsy education and rate. Prior to the pandemic, our autopsy gross organ review lectures at the Brown University pathology residency program were in-person and used a detective style to discover the pathological lesions followed by an integrated discussion of anatomic and clinical pathology. During the COVID-19 pandemic, these lectures became remote and there was a noticeable impact on the involvement and responsiveness of the audience compared to in-person teaching. Certain qualities of face-to-face teaching can be difficult to be reproduced through virtual teaching, including the detective style to look for pathological lesions and the ability to palpate lesions from gross specimens. Our results showed that the autopsy case number increased during the COVID-19 pandemic, but the overall autopsy rate did not significantly change.

17.
30th ACM International Conference on Information and Knowledge Management, CIKM 2021 ; : 4383-4392, 2021.
Article in English | Scopus | ID: covidwho-1528566

ABSTRACT

The outbreak of the COVID-19 pandemic has largely influenced the world and our normal daily lives. To combat this pandemic efficiently, governments usually need to coordinate essential resources across multiple regions and adjust intervention polices at the right time, which all call for accurate and robust forecasting of future epidemic trends. However, designing such a forecasting system is non-trivial, since we need to handle all kinds of locations at different administrative levels, which include pretty different epidemic-evolving patterns. Moreover, there are dynamic and volatile correlations of pandemic conditions among these locations, which further enlarge the difficulty in forecasting. With these challenges in mind, we develop a novel spatialoral forecasting framework. First, to accommodate all kinds of locations at different administrative levels, we propose a unified hierarchical view, which mimics the aggregation procedure of pandemic statistics. Then, this view motivates us to facilitate joint learning across administrative levels and inspires us to design the cross-level consistency loss as an extra regularization to stabilize model training. Besides, to capture those dynamic and volatile spatial correlations, we design a customized spatial module with adaptive edge gates, which can both reinforce effective messages and disable irrelevant ones. We put this framework into production to help the battle against COVID-19 in the United States. A comprehensive online evaluation across three months demonstrates that our projections are the most competitive ones among all results produced by dozens of international group and even surpass the official ensemble in many cases. We also visualize our unique edge gates to understand the evolvement of spatial correlations and present intuitive case studies. Besides, we open source our implementation at https://github.com/dolphin-zs/HierST to facilitate future research towards better epidemic modeling. © 2021 ACM.

18.
Journal of the American Society of Nephrology ; 32:104, 2021.
Article in English | EMBASE | ID: covidwho-1489428

ABSTRACT

Introduction: Cytokine storm syndrome (CSS) is a common and severe cause of mortality among critically ill COVID-19 patients. BPTs, especially continuous renal replacement therapy (CRRT), may work by removing cytokines and blocking the cascade of inflammation and thus preventing the progression of CSS. However, the efficacy of Blood purification therapies (BPTs) in patients with complications of CSS but without AKI(Acute kidney injury) is still controversial. Case Description: We report the case of a 66-year-old female who had severe COVID-19 without AKI. After admission, the patient's condition progressed rapidly to severe respiratory failure and heart failure, and she had been treated with venousvenous extracorporeal membrane oxygenation (VV-ECMO). Meanwhile, the level of interleukin-6 (IL-6) increased rapidly and reached 304.8 pg/ml. Although there was no kidney impairment in our patient, CRRT was initiated to reduce the levels of cytokines in circulation, while the decrease in IL-6 in serum and dialysate was not significant. Oxiris-CRRT was then introduced and there was a significant decline in serum levels of IL-6 after 3 Oxiris-CRRT sessions. However, when we stopped Oxiris-CRRT after the third treatment, the serum levels of IL-6 were elevated again 12 hours after the suspension of Oxiris-CRRT Subsequently. Therefore, the patient received 6 additional Oxiris-CRRT sessions until the serum IL-6 levels of 2.67 pg/ml. After 144 days of hospitalization, including 2 CRRT sessions, 9 Oxiris-CRRT sessions and 2 therapeutic plasma exchange (TPE) sessions, she completely recovered (shown in Fig. 1). Discussion: In our patient, BPTs, especially Oxiris-CRRT, showed unique superiority and application value in the clearance of excess plasma cytokines, promoting a smooth recovery, which suggests that even if AKI does not occur, it is beneficial to use BPTs to prevent the progression of CSS in COVID-19 patients.

19.
R I Med J (2013) ; 104(8):11-14, 2021.
Article in English | PubMed | ID: covidwho-1439157

ABSTRACT

Coronavirus disease 2019 (COVID-19) may cause a hypercoagulability state and thrombotic complications. Multiorgan infarctions in young patients are very rare. Here we report a 35-year-old male patient with COVID-19 complicated by multiorgan infarctions. The patient had a past medical history of uncontrolled insulin-dependent diabetes mellitus and was admitted to the intensive care unit with progressive hypoxia in the setting of SARS-CoV-2 infection. The patient received prophylactic anticoagulant during the entire hospital course. During the hospitalization, the patient developed hypoxic respiratory arrest, diffuse anoxic brain injury and brain herniation. Postmortem examination demonstrated multiple infarctions and thromboses involving the heart, bilateral lungs, kidneys, and spleen. In conclusion, multiple organ infarctions may occur in young patients with COVID-19 despite prophylactic anticoagulation therapy.

20.
Blood ; 136:25-26, 2020.
Article in English | EMBASE | ID: covidwho-1344053

ABSTRACT

Introduction To further improve efficacy and duration of response of CAR-T therapy for Relapsed/Refractory Multiple Myeloma (R/R MM), we have designed a dual FasT CAR-T targeting both B cell maturation antigen (BCMA), a well-established MM target, and CD19, which is expressed on MM cells and their progenitors. Here we report early results from the first-in-human multicenter clinical study (NCT04236011;NCT04182581) to determine safety, pharmacokinetics (PK) and efficacy of BCMA-CD19-directed FasT CAR-T (GC012F) in patients with R/R MM. Methods The BCMA-CD19 dual CAR was constructed by linking BCMA and CD19 scFv, joined by a CD8 hinge, transmembrane domain, co-stimulatory domain and CD3z. Peripheral blood (PB) mononuclear cells were obtained by leukapheresis, T cells were isolated and CAR-T cells were manufactured (FasT CAR platform). From September 2019 to April 2020, we enrolled 16 heavily pretreated R/R MM patients (Age range 27-71), with a median of 5 prior lines of therapies (range 2-7), 93.8% (15/16) of these patients were high risk as defined by mSMART criteria, 5 had extramedullary disease. 4 out of 16 patients had received prior anti CD38 therapy, 93.8% (15/16) patients had received prior IMiD, all patients received at least 1 prior PI and corticosteroids with 3 patients being primary refractory to last therapy. Prior to CAR-T infusion patients received a conditioning regimen over 3 days of 30 mg/m2/d fludarabine and 300 mg/m2/d cyclophosphamide. CAR-T cells were administered in a single infusion at 3 dose levels 1x105/Kg (DL1) (1 patients), 2x105/Kg (DL2) (9 patients) and 3x105/Kg (DL3) (6 patients). Results As of July 17th 2020, all 16 patients were evaluable for response assessment, 15 out of 16 patients responded to treatment (ORR 93.8%) in all dose levels with the earliest response observed at day 28. Best response to date is MRD- CR/sCR in 9/16 patients (56.3%). In DL3 100% (6/6) of patients achieved sCR, 3 at data cut off had been confirmed by PET-CT. In all response evaluable patients, 78.6% (11/14) were MRD- by flow at month 1, and 100% at month 3 (11/11) and 6 (10/10) (sensitivity by flow cytometry measured at 10-4 in 7 patients, and at 10-6 in 9 patients tested by EuroFlow with at least 1.08x107 cells analyzed). At data cut off, the median follow up time was 7.3 months, the longest follow up was 10 months post infusion. CAR-T PK in PB was monitored by qPCR and flow cytometry. The CAR-T median proliferation peak was reached on Day10 (Day8-Day14), and the median peak copy number was 140,982 (16,011-374,346) copies /ug DNA. GC012F showed an acceptable safety profile with 14 out of 16 patients experiencing a cytokine release syndrome (CRS) grade 1-2 (n=14, 87.5%) and 2 grade 3 (n=2, 12.5%). The median duration of CRS was 4 days (1-8 days). No neurotoxicity of any grade was observed. One patient (DL2) presented with fever and died shortly after Day 78 of unknown cause during the COVID-19 Pandemic. Two patients had progression of extramedullary disease while achieving MRD negativity at month 1 and 3, respectively. At landmark analysis at 6 months, all patients in DL3 had achieved and maintained MRD- sCR including patients heavily pretreated including Daratumumab - among them 83.3% (5/6) patients in DL3 had high risk features according to mSMART criteria, and 5 out of 6 patients in DL3 were assessed by 10-6 Euroflow for MRD. The study is still enrolling patients and we will continue to be monitoring safety and efficacy including duration of response. Conclusion The data of BCMA-CD19 dual FasT CAR-T showed an early and high response rate with 93.8% ORR to date with a promising early high MRD-sCR rate in the highest dose level DL3 (100%) which was sustained with a median duration of follow up of 7.3 months at cut off. The data shows very promising activity of the BCMA-CD19 dual FasT CAR-T with a favorable safety profile in R/R MM patients. 93.8% (15/16) of the treated patients exhibited high risk features - a specifically difficult to treat patient population which remains a high unmet medical need in Mul iple Myeloma. This data indicates that BCMA-CD19 dual FasT CAR-T (GC012F) may present an effective new treatment option for patients with R/R MM including those with high-risk features who failed multiple prior therapies including anti-CD38. The study is still ongoing and enrolling patients, we will update the results as they become available. Disclosures: Zhao: Gracell Biotechnologies Ltd: Current Employment. Han: Gracell Biotechnologies Co., Ltd.: Current Employment. Chen: Gracell Biotechnologies Ltd: Current Employment. Xu: Gracell Biotechnologies Ltd: Current Employment. Zhang: Gracell Biotechnologies Ltd: Current Employment. He: Gracell Biotechnologies Co., Ltd.: Current Employment. Shi: Gracell Biotechnologies Ltd: Current Employment. Han: Gracell Biotechnologies Co., Ltd.: Current Employment. Ye: Gracell Biotechnologies Co., Ltd.: Current Employment. Wang: Gracell Biotechnologies Ltd: Current Employment. Liu: Gracell Biotechnologies Co., Ltd.: Current Employment. Shen: Gracell Biotechnologies Ltd: Current Employment. Cao: Gracell Biotechnologies Ltd: Current Employment. Sersch: Gracell Biotechnologies Co., Ltd.: Current Employment.

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