Experiences of Counselors Who Provided Psychological Support during COVID-19 Disaster: A Qualitative Study

Background: In crisis intervention sites such as infectious disease disasters, counselors are repeatedly exposed, directly or indirectly, to the traumatic experiences of victims. Disaster counseling has a negative effect on coun-selors, which can eventually interfere with the counseling process for disaster victims. Therefore, exploring and understanding the experiences of counselors is necessary to ensure that qualitative counseling for disaster victims can be continuously and efficiently conducted. Objectives: This study investigated the experiences of counselors who participated in mental health counseling as psychological support for victims of the COVID-19 disaster in Korea. Design: This is a qualitative study. Participants: The study participants comprised 18 counselors who had mental health professional qualifications of level 2 or higher and who had provided mental health counseling for COVID-19 confirmed cases and quarantined persons. Methods: Data were collected using focus group interviews from February 21 to May 29, 2021. The duration of each interview was 60-90 min, and the data were analyzed using content analysis. Results: The final theme was "Continuing to walk this road anytime, anywhere." The par-ticipants' experiences were identified in four sub-themes: "being deployed to unprepared counseling," "encoun-tering various difficulties," "feeling full of meaning and value," and "hoping to become a better counselor." Conclusions: In order to continuously provide qualitative counseling in case of an infectious disease disaster such as COVID-19, it is important to develop a qualification and competency strengthening program through educa-tion and training to secure the crisis intervention expertise of counselors according to the characteristics of the disaster. In addition, a psychological support manual for each disaster should be prepared at the national level according to the type of disaster.

Risk factors for delirium among patients with advanced cancer in palliative care: a multicenter, patient-based registry cohort in South Korea

OBJECTIVE: Previous studies have comprehensively investigated the preva-lence and various potential risk factors for de-lirium among patients with advanced cancer ad-mitted to the acute palliative care unit (APCU). Our objective was to evaluate the comprehen-sive association between delirium and various risk factors among patients with advanced can-cer in an acute palliative care setting using a pa-tient-based multicenter registry cohort.PATIENTS AND METHODS: We performed a multicenter, patient-based registry cohort study collected in South Korea between January 1, 2019, and December 31, 2020. Delirium was identified using a medical record review based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition.RESULTS: In total, 2,124 eligible patients with advanced cancer in the APCU met the inclu-sion criteria. There were 127 out of 2,124 pa-tients (prevalence, 6.0%;95% CI, 5.0 to 7.1) with delirium during admission. Delirium in patients with advanced cancer was associated with age >70 years (OR, 1.793;95% CI, 1.246 to 2.581), male sex (OR, 1.675;95% CI, 1.131 to 2.479), no chemotherapy during hospitalization (OR, 2.019;95% CI, 1.236 to 3.298), hearing impairment (OR, 3.566;95% CI, 1.176 to 10.810), underweight (OR, 1.826;95% CI, 1.067 to 3.124), current use of opioid medication (OR, 1.942;95% CI, 1.264 to 2.982), previous history of delirium (OR, 12.497;95% CI, 6.920 to 22.568), and mental illness (OR, 2.333;95% CI, 1.251 to 4.352).CONCLUSIONS: In a large-scale multicenter patient-based registry cohort, delirium was asso-ciated with old age, male sex, no chemotherapy during hospitalization, hearing impairment, un-derweight, current use of opioid medication, and a history of delirium and mental illness. Our find-ings suggest physicians should pay attention to delirium in patients with advanced cancer admit-ted to the APCU with the above risk factors.

HostSeq: a Canadian whole genome sequencing and clinical data resource.

HostSeq was launched in April 2020 as a national initiative to integrate whole genome sequencing data from 10,000 Canadians infected with SARS-CoV-2 with clinical information related to their disease experience. The mandate of HostSeq is to support the Canadian and international research communities in their efforts to understand the risk factors for disease and associated health outcomes and support the development of interventions such as vaccines and therapeutics. HostSeq is a collaboration among 13 independent epidemiological studies of SARS-CoV-2 across five provinces in Canada. Aggregated data collected by HostSeq are made available to the public through two data portals: a phenotype portal showing summaries of major variables and their distributions, and a variant search portal enabling queries in a genomic region. Individual-level data is available to the global research community for health research through a Data Access Agreement and Data Access Compliance Office approval. Here we provide an overview of the collective project design along with summary level information for HostSeq. We highlight several statistical considerations for researchers using the HostSeq platform regarding data aggregation, sampling mechanism, covariate adjustment, and X chromosome analysis. In addition to serving as a rich data source, the diversity of study designs, sample sizes, and research objectives among the participating studies provides unique opportunities for the research community.

Breathing detection using thermal facial landmark with DICOM file

To limit the spread of COVID-19, thermal screening cameras were installed everywhere. These cameras observe many thermal faces. These thermal face data are generally used to monitor strange temperatures for COVID-19 screening or to maintain social distancing. Big data of Thermal face generated everywhere should be used in the more practical functions. We proposed a method to measure non-contact breathing signals using thermal face data. In addition, breathing signals data estimated from thermal face data was converted to DICOM waveform Information Object Definitions (IODs) for interoperability management of medical data. The proposed method was tested on a golden reference (chest belt) with a mean accuracy of 93.52 %. a proposed method that can extract breathing signals using thermal screening cameras that are widely available around the world and manage data as healthcare interoperability information can show important potential in the public, telemedicine field in the future. © 2022 IEEE.

Augmented reality and nonprofit marketing during the COVID-19 pandemic: AR factors that influence community participation and willingness to contribute to causes

This study used augmented reality (AR) to test the effects of perceived social presence, perceived media richness, media empathy and social capital on intentions to participate in prosocial, community-oriented behaviors in the context of the COVID-19 pandemic, which appeared to be rife with fear. Specifically, a structural model was employed to assess the hypothesized relationships based on questionnaire data from 476 respondents, who were divided into high and low fear groups. The findings revealed that perceived media richness and social presence both had a significant influence on media empathy, which in turn affected users' perceptions of social capital. Social capital predicted users' community participation intentions, which included intentions to donate. The paths from perceived social presence and perceived media richness to social capital were not significant, and media empathy did not directly influence prosocial, community participation intentions. There were no significant differences between the high and low COVID-19 fear groups. Overall, this study confirmed the importance of leveraging media richness and social presence to create media content designed to prompt users to identify with those who are negatively affected by the cause, so that media empathy will be boosted. Media empathy should be increased in a manner that leads users to feel connected to a larger community, so that perceptions of social capital will be boosted and will lead to prosocial, community participation activities and donations to the cause. © 2023 Wiley Periodicals LLC.

Working in times of COVID-19: investigating the effect of daily risk perception of COVID-19 infection on goal progress

PurposeBased on the transactional theory of stress and coping, this study aims to understand the daily impact of coronavirus disease 2019 (COVID-19) on employee goal progress. In particular, the authors explore how COVID-19 induces anxiety related to task setbacks that consequently influences one's goal progress.Design/methodology/approachA daily diary study was conducted with a total of 558 observations from 60 participants. The data were analyzed using multilevel path analysis with random slopes.FindingsThe perceived risk of COVID-19 infection was positively associated with COVID-19 task setback anxiety, which in turn improved end-of-day goal progress. Lower employee conscientiousness strengthened the relationship between perceived risk of COVID-19 infection and COVID-19 task setback anxiety, and lower supervisor bottom-line mentality strengthened the relationship between COVID-19 task setback anxiety and end-of-day goal progress.Practical implicationsAlthough COVID-19 task setback anxiety results in higher end-of-day goal progress, the authors recommend caution as the cost of coping exists. Thus, supervisors should focus on supporting the employees rather than having a bottom-line mentality.Originality/valueThis study advances stress and coping literature by examining how employees appraise and cope with COVID-19 in work context. The authors demonstrate that a perceived risk of COVID-19 induces task setbacks related to anticipatory anxiety, which in turn influences employee outcomes. In addition, the authors identify employee conscientiousness and supervisor bottom-line mentality as a boundary condition of this process.

Single-chirality of single-walled carbon nanotubes (SWCNTs) through chromatography and its potential biological applications

The separation of highly pure single-chirality single-walled carbon nanotubes (SWCNTs) is challenging and also in demand due to their intrinsic physical, optical, and electronic properties. The use of single-chirality and their performance characteristics makes them a selective candidate for multifunctional applications and opens a new front in nanotube development. It has previously been reported that SWCNTs can be separated in various ways by employing direct control and post-synthesis approaches. Herein, we review the separation of single-chiralities of SWCNTs on account of simplicity and time/cost effectiveness by using gel chromatography. The most recent progress in the controlled synthesis of SWCNTs is comprehensively reviewed in terms of selective-diameter, single-chirality, and specific geometric shape. The method to achieve the single-chirality of SWCNTs is also highlighted. Besides addressing COVID-19 characteristics, epidemiology, and pathology, we also review the most recent developments in nano-biosensors for the rapid and early detection of COVID-19. Furthermore, the photothermal/bioimaging response of single-chirality is reviewed in order to enhance the cytotoxicity of drugs against cancer cells over simple carbon nanotubes (CNTs). The single-chirality allows for precise imaging (due to efficient absorption and emission) of tumors/blood vessels up to ~10-fold higher by injecting a low dose. We hope this review stimulates further study on single-chirality controlled SWCNTs for practical applications. Copyright © 2023 The Royal Society of Chemistry.

Neoadjuvant cemiplimab in patients (pts) with stage II–IV (M0) cutaneous squamous cell carcinoma (CSCC): Primary analysis of a phase II study

Background: CSCC is highly immune-responsive;a prior pilot study demonstrated a high rate of pathologic complete response (pCR) or major pathologic response (MPR, ≤10% viable tumor), using cemiplimab anti-programmed death 1 (PD-1) therapy in the neoadjuvant setting. Here, we present the primary analysis of a confirmatory, open-label, multicenter, Phase 2, single-arm trial of neoadjuvant cemiplimab in pts with resectable Stage II–IV (M0) CSCC. Methods: Pts received cemiplimab 350 mg IV q3W for up to 4 doses before surgery. The primary endpoint was pCR rate per independent central pathologic review (ICPR). Key secondary endpoints included MPR rate per ICPR, objective response rate (ORR;complete response [CR] + partial response [PR]) per RECIST v1.1, investigator-assessed pCR and MPR, safety and tolerability. Results: At data cutoff date of 01 Dec 2021, 79 pts were enrolled (67 male;median age 73.0 yrs [range, 66.0–81.0];ECOG performance status 0 (n=60) and 1 (n=19) with stage II (n=5), III (n=38), or IV(M0) (n =36) disease;62 pts received all 4 doses (median number of doses given (Q1:Q3), 4 (4:4);70 pts underwent surgery. The study met its primary endpoint: pCR was observed in 40 (50.6%) pts (95% confidence interval [CI], 39.1–62.1%). MPR was observed in an additional 10 (12.7%) pts (95% CI, 6.2–22.0%). ORR was 68.4% (95% CI, 56.9–78.4) (5 CR, 49 PR, 16 stable disease, 8 progressive disease (PD), 1 non evaluable. Reasons 9 pts did not have surgery: 3 responders declined surgery, 2 lost to follow-up or noncompliance, 2 had inoperable PD, 2 due to AE. Fourteen (17.7%) pts experienced Grade ≥3 AE. Four pts died due to AEs: 1 exacerbation of cardiac failure, 2 myocardial infarctions, and 1 COVID-19 pneumonia. The most common AEs regardless of attribution (all grades) were fatigue (30.4%), rash maculo-papular (13.9%), diarrhea (13.9%) and nausea (13.9%). Conclusions: The pCR + MPR of 63.3% by ICPR in pts with Stage II–IV (M0) CSCC is the highest observed in a multicenter anti-PD-1 neoadjuvant monotherapy study for any solid tumor type. The safety profile of neoadjuvant cemiplimab is consistent with previous anti-PD-1 monotherapy experience. Ongoing follow-up will describe disease-free survival. Clinical trial identification: NCT04154943. Editorial acknowledgement: Medical writing support was provided by John G Facciponte, PhD, of Prime, Knutsford, UK, funded by Regeneron Pharmaceuticals, Inc., and Sanofi. Legal entity responsible for the study: Regeneron Pharmaceuticals, Inc., and Sanofi. Funding: Regeneron Pharmaceuticals, Inc., and Sanofi. Disclosure: N. Gross: Financial Interests, Personal, Research Grant: Regeneron Pharmaceuticals, Inc.;Financial Interests, Personal, Advisory Board: PDS Biotechnology, Shattuck Labs and Genzyme;Financial Interests, Personal, Advisory Role: PDS Biotechnology, Shattuck Labs and Genzyme. D.M. Miller: Financial Interests, Personal, Advisory Role: Castle Biosciences, EMD Serono, Merck KGaA, Merck Sharpe & Dome, Pfizer, Regeneron, Sanofi Genzyme;Financial Interests, Personal, Ownership Interest: Checkpoint Therapeutics;Financial Interests, Personal, Research Grant: Kartos Therapeutics, NeoImmune Tech, Inc., Regeneron Pharmaceuticals, Inc. N. Khushanlani: Financial Interests, Personal, Research Grant: Regeneron Pharmaceuticals, Inc., Bristol Myers Squibb, HUYA Bioscience International, Merck, Novartis, GlaxoSmithKline, Celgene, Amgen;Financial Interests, Personal, Advisory Board: EMD Serono, Regeneron Pharmaceuticals, Inc., Genentech, AstraZeneca (data safety monitoring committee), Merck, Array Biopharma, Jounce Therapeutics, Immunocore, Bristol Myers Squibb, HUYA Bioscience International;Financial Interests, Personal, Other, honoraria: Sanofi;Financial Interests, Personal, Stocks/Shares: Bellicum Pharmaceuticals, Mazor Robotics, Amarin, Transenetrix. V. Divi: Financial Interests, Institutional, Research Grant: Genentech. E.S. Ruiz: Financial Interests, Personal, Advisory Board: Genentech, Leo Pharmaceuticals, Regeneron Pharmaceuticals, Inc., Sanofi;Financial Int rests, Personal, Advisory Role, consulting fees: Genentech, Leo Pharmaceuticals, Regeneron Pharmaceuticals, Inc., Sanofi;Financial Interests, Personal, Member of the Board of Directors: Checkpoint Therapeutics. E.J. Lipson: Financial Interests, Personal, Other, Advisory board and consulting fees: Bristol Myers-Squibb, Eisai, Genentech, Immunocore, Instil Bio, MacroGenics, Merck, Natera, Nektar Therapeutics, Odonate Therapeutics, OncoSec, Pfizer, Rain Therapeutics, Regeneron, Sanofi;Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, Merck, Regeneron. F. Meier: Financial Interests, Personal, Other, Travel support, speaker’s fees or advisor’s honoraria: Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre, Roche and Sanofi;Financial Interests, Personal, Research Grant: Novartis and Roche. P.L. Swiecicki: Financial Interests, Institutional, Research Grant: Ascentage Pharma, Pfizer;Financial Interests, Personal, Advisory Board: Prelude Therapeutics, Elevar Therapeutics, Regeneron Pharmaceuticals. J.L. Atlas: Financial Interests, Personal, Advisory Role: Regeneron Pharmaceuticals, Inc., Sanofi, and Bristol Myers Squibb. J.L. Geiger: Financial Interests, Institutional, Research Grant: Alkermes, Debio, Merck, Regeneron Pharmaceuticals, Inc., and Roche/Genentech;Financial Interests, Personal, Advisory Role: Exelixis, Merck and Regeneron Pharmaceuticals, Inc. A. Hauschild: Financial Interests, Personal and Institutional, Other, Institutional grants, speaker’s honoraria and consultancy fees: Amgen, Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre, Provectus and Roche;Financial Interests, Institutional, Other, Institutional grants and consultancy fees: EMD Serono, Philogen and Regeneron Pharmaceuticals, Inc.;Financial Interests, Personal, Advisory Role: OncoSec Medical. J.H. Choe: Financial Interests, Personal, Advisory Role: Exelixis, Coherus Biosciences, Regeneron Pharmaceuticals, Inc. B.G.M. Hughes: Financial Interests, Personal, Advisory Role: AstraZeneca, Bristol Myers Squibb, Eisai, Merck Sharp & Dohme, Pfizer and Roche;Financial Interests, Institutional, Research Grant: Amgen. S. Yoo: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.;Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. K. Fenech: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.;Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. M.D. Mathias: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.;Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. H. Han: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.;Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. M.G. Fury: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.;Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. D. Rischin: Financial Interests, Institutional, Research Grant: Regeneron Pharmaceuticals, Inc., Genentech, Sanofi, Kura Oncology, Roche, Merck Sharp & Dohme, Merck KGaA, Bristol Myers Squibb, GlaxoSmithKline, ALX Oncology;Financial Interests, Personal, Advisory Role: Merck Sharp & Dohme, Regeneron Pharmaceuticals, Inc., Sanofi, GlaxoSmithKline, Bristol Myers Squibb;Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme, Regeneron Pharmaceuticals, Inc., Sanofi, GlaxoSmithKline, Bristol Myers Squibb. All other authors have declared no conflicts of interest.

The impact of the COVID-19 on the screening of breast and cervical cancer in Korea

Background: The COVID-19 pandemic has affected use of healthcare services, especially disrupting individual participation in cancer screening programs. The National Cancer Screening Program (NCSP) of Korea provides screening services for six common cancers - stomach, liver, colorectum, breast, cervix, and lung. As complete national lockdown measures were not implemented, the NCSP continued operation during the three major COVID-19 waves in Korea, which allowed us to assess the changes in health-seeking behavior. We examined the cancer screening rates for breast and cervical cancers among NCSP participants in different geographic regions and by age group, in association with the COVID-19 pandemic. Methods: From the National Health Insurance Service database, we obtained information on the number of eligible population and NCSP participants from January 2019 to December 2020. The target group for biennial mammography screening is women aged 40 years and over, and that for biennial pap smear is women aged 20 years and over. We compared monthly screening rates for breast and cervical cancer between 2020 vs 2019 and described them as a percentage change. Results: The overall cancer screening rate has decreased in both cancers in 2020 compared with that of 2019: breast (55.8% vs 63.8%), cervical (52.2% vs 57.8%). Screening rates for both cancers declined in all age groups in March and December of 2020, which corresponds to the first and third COVID-19 wave. The month of March 2020 had the sharpest drop in screening rates, by 57.9% for breast cancer and 43.7% for cervical cancer compared with March 2019. In June 2020, screening rates for both cancers rebounded compared with 2019 (breast, +29.2%;cervical, +26.3%), which remained higher compared with the same months in 2019 until November 2020. By December 2020, screening rates for both cancers have dropped, compared with December 2019 (breast, -19.5%;cervical, -21.0%). For breast cancer, the screening rate decreased in all age groups, and the largest decline was observed in women aged 80 years and over. Although the cervical cancer screening rate has been steadily increasing since 2010, it decreased in all age groups in 2020 compared with that of 2019, with the exception of the 20-29 age group. Considering social distancing measures that were implemented nationwide during each COVID-19 wave, we observed a similar pattern of cancer screening rates in major cities. Conclusions: It was observed that after the two major COVID-19 waves, mammography and pap smear rates declined compared with that of 2019. The largest decline in cancer screening rates was seen in elderly women. The pattern of screening rate changes was comparable according to geographic region. In contrast to reports showing a deficit in cancer screening in other countries, our results suggest a substantial recovery in cancer screening in Korea. Additional analyses are needed to assess the effect of the 6-month extension of NCSP.

Colorectal and gastric cancer screening rates in Korea during the COVID-19 pandemic

Background: The COVID-19 pandemic has disrupted healthcare delivery, which is widely discussed as the distraction effect. This study aimed to estimate the distraction effect of the COVID-19 pandemic in Korea by analyzing colorectal and gastric cancer screening rates in the years 2019 and 2020. Methods: Information of eligible population who had colorectal and gastric cancer screening provided by the National Cancer Screening Program in the years 2019 and 2020 was collected. Participation rates were analyzed by age group, sex, geographic region, and calendar month. Percentage change was calculated by dividing the percentage point difference by the screening rate of the reference period (2019). Results: Overall, the colorectal and gastric cancer screening rates had decreased in 2020, compared to the reference period. For colorectal cancer, the screening rate decreased from 68.3% in 2019 (5,886,319 participants/14,526,424 eligible population) to 54.6% in 2020 (5,135,218/9,410,525) For gastric cancer, the screening rates decreased from 61.9% in 2019 (7,194,489/11,625,627) to 54.6% in 2020 (6,244,491/11,439,246). In March, during the first wave, the screening rates declined sharply (percentage change: colorectal, 56.6%;gastric, 57.3%). Although the screening rates had rebounded aftermath, they declined again in December, during the third wave (percentage change: colorectal, 17.0%;gastric, 13.8%). According to specific-age group, we found a substantial decline in screening rates for older adults aged 80∼84, and those over 85 (percentage change: colorectal, 19.0% & 23.0%;gastric, 17.4% & 25.1% respectively). Conclusion: During the COVID-19 pandemic, the screening rates for both colorectal and gastric cancer decreased. There was a substantial decline during the first and the third waves of the epidemic, in March and in December. The older adults group showed the highest reduction in screening rates. However, comparing the screening rate by region and sex, we did not find a significant difference. Delayed cancer diagnosis or excess death due to distraction effect of the COVID-19 pandemic has not yet been detected in Korea, therefore, further studies are needed.

The mediating effects of co-worker relationship between job affirmation expectation and job order request based on medical workers

This study empirically examines how medical workers associate co-work relationship, job affirmation expectation, and job order request. Co-work relationship measures collaboration and trust among co-workers. Job affirmation expectation measures the belief that diligent work is rewarded. Job order request measures how demanding the work is. We document that medical worker perceptions of job order request are negatively related with affirmation expectations and co-work relationship. This association varies across worker characteristics: this relationship is stronger among single workers relative to married workers. When dealing with a demanding work environment, single workers think more negatively about the organizational system and compensation expectation. These findings are important because they document how the effects of a demanding work place may be mitigated. Expanding co-worker collaboration programs can help mitigate the negative effects of demanding work environments. Given the challenges of the current COVID-19 pandemic, this study highlights how demanding medical work environments can be improved. © 2021, Badebio Biotechnololgy Ltd. All rights reserved.

Spatio-Temporal Split Learning for Privacy-Preserving Medical Platforms: Case Studies with COVID-19 CT, X-Ray, and Cholesterol Data

Machine learning requires a large volume of sample data, especially when it is used in high-accuracy medical applications. However, patient records are one of the most sensitive private information that is not usually shared among institutes. This paper presents spatio-temporal split learning, a distributed deep neural network framework, which is a turning point in allowing collaboration among privacy-sensitive organizations. Our spatio-temporal split learning presents how distributed machine learning can be efficiently conducted with minimal privacy concerns. The proposed split learning consists of a number of clients and a centralized server. Each client has only has one hidden layer, which acts as the privacy-preserving layer, and the centralized server comprises the other hidden layers and the output layer. Since the centralized server does not need to access the training data and trains the deep neural network with parameters received from the privacy-preserving layer, privacy of original data is guaranteed. We have coined the term, spatio-temporal split learning, as multiple clients are spatially distributed to cover diverse datasets from different participants, and we can temporally split the learning process, detaching the privacy preserving layer from the rest of the learning process to minimize privacy breaches. This paper shows how we can analyze the medical data whilst ensuring privacy using our proposed multi-site spatio-temporal split learning algorithm on Coronavirus Disease-19 (COVID-19) chest Computed Tomography (CT) scans, MUsculoskeletal RAdiographs (MURA) X-ray images, and cholesterol levels. Author

Supercomputer-Based Ensemble Docking Drug Discovery Pipeline with Application to Covid-19.

We present a supercomputer-driven pipeline for in silico drug discovery using enhanced sampling molecular dynamics (MD) and ensemble docking. Ensemble docking makes use of MD results by docking compound databases into representative protein binding-site conformations, thus taking into account the dynamic properties of the binding sites. We also describe preliminary results obtained for 24 systems involving eight proteins of the proteome of SARS-CoV-2. The MD involves temperature replica exchange enhanced sampling, making use of massively parallel supercomputing to quickly sample the configurational space of protein drug targets. Using the Summit supercomputer at the Oak Ridge National Laboratory, more than 1 ms of enhanced sampling MD can be generated per day. We have ensemble docked repurposing databases to 10 configurations of each of the 24 SARS-CoV-2 systems using AutoDock Vina. Comparison to experiment demonstrates remarkably high hit rates for the top scoring tranches of compounds identified by our ensemble approach. We also demonstrate that, using Autodock-GPU on Summit, it is possible to perform exhaustive docking of one billion compounds in under 24 h. Finally, we discuss preliminary results and planned improvements to the pipeline, including the use of quantum mechanical (QM), machine learning, and artificial intelligence (AI) methods to cluster MD trajectories and rescore docking poses.