VASCULITIS DISEASE ACTIVITY SCORES BEFORE AND DURING THE COVID-19 PANDEMIC: A COMPARISON OF FACE-TO-FACE CLINICIAN SCORING AND PROMS COLLECTED USING REMOTE MONITORING IN A SINGLE-CENTRE COHORT

BackgroundDuring the COVID-19 pandemic, asynchronous consultations were introduced for patients with vasculitis. To assess disease activity without of face-to-face clinical reviews and blood testing, patients submitted patient reported outcome measures (PROMs) via electronic survey forms, which were subsequently triaged by clinicians.Objectives1. To investigate how patients' vasculitis disease activity was affected by the COVID-19 pandemic through retrospective comparison of clinician-assessed scores recorded pre-pandemic with intra-pandemic self-reported patient reported outcome measures (PROMs) and disease scores submitted by patients remotely.2. To assess patients' clinical outcomes, including allocation of follow-up and further management/treatment escalation during this period.3. To validate self-reported BVAS scores against an existing PROM.MethodsThis is a retrospectively study of patients with a known diagnosis of vasculitis under the care of the Nuffield Orthopaedic Centre, Oxford. For the purposes of this study, we included patients with all vasculitis diagnoses.Clinician-reported scores (Bristol Vasculitis Activity score v.3, BVAS) were recorded during in-person clinics pre-pandemic (defined as 01/01/2019-31/12/2019) [1].Patients' self-reported BVAS (SR-BVAS) and AAV-PRO (ANCA-associated vasculitis patient-reported outcomes) scores were submitted by patients via electronic forms containing the requisite questionnaires sent out during-pandemic (defined as 01/12/2020-31/03/22) [2].SR-BVAS has not been validated but was collected to allow clinical comparison to disease activity scores completed by clinicians. Response were stored and analysed in a secure database. Score comparison was performed using Wilcoxon Sign Rank testing. Clinical outcome data was collected from the local Electronic Patient Record. Data analysis was performed in Microsoft Excel and R (version 4.2.1).ResultsWe noted a significantly higher overall level of patient-reported disease activity during the pandemic than was recorded in clinics prior. In the total cohort of all vasculitis patients for whom we had data, the median BVAS increased from 2 pre-pandemic (N = 335, range 0-21) to 6 intra-pandemic (N = 143, range 0-42) (p <0.001). The overall proportion of patients with severe/active disease (defined as BVAS ≥4) increased from 27% to 36% during the pandemic period.In a smaller cohort of 64 patients for whom we had paired pre- and during-pandemic scores, increased disease activity was reported (p<0.01). Notably, the number with a BVAS consistent with severe disease increased from 7 (11%) to 19 (30%).There was a significant positive correlation between SR-BVAS and AAV-PRO (r=0.61, p< 0.001) submitted by patients during-pandemic;however, at low BVAS (≤3), the AAV-PRO ranged widely (28-87)Follow-up data was available for all 64 patients in this cohort: 8/19 (42%) with a during-pandemic SR-BVAS ≥4 were seen in clinic within 3 months (telemedicine or face-to-face).ConclusionPatients reported worsening of vasculitis disease activity during the COVID-19 pandemic. This may be attributable to impacts on well-being or access to healthcare services. We note that disease activity scores in vasculitis may be limited in their ability to capture the whole picture disease activity in the absence of clinical assessment [3]. 42% of patients with self-reported high disease activity were seen within 3 months. There was a significant positive correlation between AAV-PRO and SR-BVAS, suggesting it has some use as a PROM.References[1]Mukhtyar C, Lee R, Brown D, Carruthers D, Dasgupta B, Dubey S, et al.. Ann Rheum Dis. 2009 Dec;68(12):1827–32.[2]Malley T, Jackman J, Manderson S, Saldana Pena L, Evans E, Barrett J, et al. Ann Rheum Dis. 2021 Jun 1;80(Suppl 1):289.[3]Luqmani RA. Nephrology Dialysis Transplantation. 2015 Apr 1;30(suppl_1):i76–82.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Comparing Ankylosing Spondylitis Disease Activity during the Covid-19 Pandemic Using Patient-Reported Outcome Measures with Face-Toface Clinical Evaluation of Disease Scores Prepandemic

Background/Aims During the COVID-19 pandemic, asynchronous consultations were introduced for patients with ankylosing spondylitis (AS). To assess disease activity in the absence of face-to-face clinical review and blood testing, patients submitted patient-reported outcome measures (PROMs) via electronic survey forms which were subsequently triaged by clinicians. We compared pre-pandemic clinician-reported scores with intra-pandemic self-reported scores and assessed clinical outcomes including allocation of follow-up and further management/ treatment escalation. Methods Clinician-reported scores were obtained in-person pre-pandemic (defined as 01/01/2019-01/03/2020). Self-reported BASDAI scores were submitted by patients via electronic forms sent out duringpandemic (defined as 01/12/2020-31/03/22). The responses were stored and analysed in a secure database. These scores are analogous to disease activity scores completed by clinicians during outpatient appointments. Score comparison was performed using Wilcoxon Sign Rank testing. We used the need for a follow-up within 3 months as target for those with severe disease. Data analysis was performed in Microsoft Excel and R (version 4.2.1). Results We noted a significantly higher overall level of patient-reported disease activity during the pandemic. In the total cohort of AS patients, the median BASDAI Score collected during-pandemic increased from 5.30 (n=124, range 0-10) compared to 2.80 pre-pandemic (n=590, range 0-12) (p<0.001). The proportion of patients with severe/active disease (defined as BASDAI >4) increased from 36% pre- to 65% during pandemic. In a smaller cohort of 34 patients for whom we had both pre- and during-pandemic scores, all patient parameters worsened during the pandemic. Notably, median BASDAI increased from 2.65 to 5.62 (p<0.0001). Patients with severe AS increased from 10 (29.4%) to 21 (61.8%) intra-pandemic. Follow-up data was available for 12/21 patients with severe AS during-pandemic. 7/12 patients (58%) received a follow-up appointment within one month;11/12 (91%) were seen within three months. On subsequent clinician assessment, only 7 (58%) of patients with self-reported severe AS were felt to have active disease;treatment was escalated for 3 patients. Conclusion There was a significantly higher reported level of AS disease activity during the COVID-19 pandemic, with 62 % of patients qualifying for biologic therapy (BASDAI >4). In a focussed sample, 91% of patients with new severe disease during-pandemic were followed up within the target of 3 months. The BASDAI score is independent from clinical examination and inflammatory markers, and therefore self-reported score should reliably reflect a patient's perception of disease activity. Further work is required to determine the reason for the increased disease activity observed during pandemic, and for the disparity between clinician impression and score results.

Evaluating the Use of Patient Reported Outcome Measures to Assess Intra-Pandemic Psoriatic Arthritis Disease Activity and Comparing Them with Pre-Pandemic Clinical Assessments

Background/Aims In our department, patient reported outcome measures (PROMs), including RAPID-3 and PSAID12, were employed during the COVID-19 pandemic in asynchronous consultations for patients with psoriatic arthritis (PsA). We compared pre-pandemic DAS28-CRP with intrapandemic PROMs to assess changes in disease activity since the pandemic. Whilst previous studies have primarily compared PsA PROMs with clinician-assessed scores (e.g. PASDAS), we compare PsA PROMs with clinicians' overall assessment of disease activity;this judgement considers PROMs, serology studies and individual patient feedback. Finally, we assess whether patients with PROMs indicating active disease were followed up appropriately. Methods Clinician-assessed scores were collected between 01/01/2019-01/03/ 2020 (''pre-pandemic''). Between 01/12/2020-31/03/2022 (''intrapandemic''), patient data from electronic surveys were analysed in a secure database for calculation of PROMs. These data, alongside blood results and patient comments, informed clinicians' triage decisions. Clinical outcome data were collected from electronic patient records;>=3 months follow-up appointment allocation was the target for patients with active disease (moderate/high disease activity). Data analysis was performed using r (version 4.2.2). Results In our pre-pandemic cohort (n=393), 79.8% of patients were in remission (per DAS28-CRP). Conversely, the intra-pandemic cohort (n=231) showed remission rates of 14.3% (per PSAID12) and 0% (RAPID-3). Indeed, 33.7% (based on PSAID12) vs 75.8% (RAPID-3) had moderate/ high disease activity. These results were validated in a paired cohort (n=38, score recorded in both windows). Disease activity worsened during the pandemic for 63.2% (PSAID12) and 97.4% (RAPID-3) of patients. PSAID-12 correlated positively with RAPID-3 (r=0.52, p<0.001), especially when RAPID-3 >=6.5 (r=0.75, p<0.001). When comparing PROMs with clinicians' assessment of PsA activity in our paired cohort, PSAID12 and RAPID-3 accurately reflected disease status in 70.6% and 58.8% of patients respectively. 3/9 and 9/27 patients with active disease, based on PSAID12 and RAPID-3 respectively, were seen within three months. Conversely, 7/10 patients who clinicians had deemed to have active disease were seen within three months. Conclusion Despite approximately 80% of patients being in pre-pandemic remission, the majority reported active intra-pandemic PsA. Whilst RAPID-3 skewed patients towards active disease, PSAID12 skewed patients towards remission/low disease activity. PSAID-12 and RAPID- 3 have been previously correlated;however, here we suggest that they could be used interchangeably in patients with high disease activity. PSAID-12 was a better predictor of clinicians' assessment of disease activity, although neither PROM correlated well with >=3 months followup appointment allocation. Although RAPID-3 and PSAID12 helped inform clinicians' decisions, neither alone sufficiently reflects patients' disease states. Remote management is practicable, but future studies should validate these findings across a larger cohort and assess the utility of different PROMs across PsA disease activity categories. Furthermore, multivariate analysis is warranted to ascertain which (combination of) variable(s) (e.g., PROMs, serology results, tender/ swollen joint count) best correlates with clinician judgement.

Arrhythmia burden in COVID-19 patients from industrial workforce evaluated by remote patient monitoring technology

Introduction: Early reports from China estimated that overall cardiac arrhythmia prevalence in patients hospitalized for COVID-19 was 17%. A higher arrhythmia incidence (44%) was observed in patients admitted to intensive care unit. The industrial workforce was affected by COVID-19 to a great extent. A noteworthy proportion also suffered from cardiac abnormalities. Objective(s): To determine the incidence of arrhythmia in patients with COVID-19 among the industrial workforce using remote patient monitoring technology. Material(s) and Method(s): This was a retrospective, observational, descriptive study of the industrial workforce from Telangana State, India. Approval of the institutional ethics committee was obtained. The need for informed consent was waived off. Patients who tested positive for COVID-19 by RTPCR and aged above 18 years were eligible. The five-day recording of lead-2 ECG on Vigo Monitoring Solution (Connect Care India Pvt. Ltd) was collected and analysed. Brady-arrhythmia during day time, second degree AV block Type-2 (Mobitz II) during the day time, complete heart block, wide QRST, non-sustained ventricular tachycardia and sinus pause were considered "clinically significant". The other sub-types were defined as "clinically non-significant". The ECGs with regular sinus rhythm were interpreted as "normal". The prevalence of clinically significant, clinically non-significant and normal heart rhythm are described here. Result(s): Out of 240 COVID-19 patients who were on-board for remote monitoring, 216 (148 male and 68 female, mean age 51+/-15 years) met the eligibility criteria and only their ECG were analysed. Among them, 18 were known diabetics, 40 were hypertensive and 31 had both comorbidities. 112 were asymptomatic and 104 were symptomatic. The burden of arrhythmia was found clinically significant in 12 (5.6%) patients, clinically non-significant in 87 (40.4%) and normal among 117 (54%) out of 216 patients. Conclusion and Recommendation: The remote patient monitoring may be utilized as a tool for early screening of significant arrhythmia which are to be addressed immediately for better clinical outcome. These devices on being integrated into COVID-19 management strategies may contribute to patient satisfaction, emergency alerts, timely management, reducing mortality rate and enhancing the safety of healthcare providers.

Lessons Learned From the COVID-19 Pandemic: Factors Affecting Decreased Incidence of Influenza

Introduction: Our goal was to identify if the cases of influenza declined in the state of Wisconsin during the COVID-19 pandemic and, if so, what factors may have been responsible for this decline. Method(s): Influenza rates during the 2018-2019 and 2020-2021 seasons were compared using data from Respiratory Virus Surveillance Reports from the Wisconsin Department of Health Services and the Centers for Disease Control and Prevention. Result(s): The number of cases and hospitalizations due to influenza decreased significantly during the 2020-2021 influenza season compared to the 2018-2019 season, although mortality rates increased during 2020-2021. Discussion(s): Reducing the burden of illnesses, hospitalizations, and deaths due to influenza on the health care system is imperative. Taking the same preventive measures used during the COVID-19 pandemic, such as wearing masks, physical distancing, and frequent handwashing, should be advised, especially for the most vulnerable patient populations.Copyright © 2023, State Medical Society of Wisconsin. All rights reserved.

A Retrospective Study on “Effectiveness of Remote Patient Monitoring in Covid-19 patients"

Corona virus disease19 has spread over the world, affecting millions of people. It has put enormous strain on the global healthcare system. Due to frequent mutations, the pandemic is spreading rapidly. The world requires a technology that will facilitate the effective diagnosis, treatment, and discharge of COVID19 patients. A model like remote patient monitoring [RPM] makes it easier to handle Covid 19 patients. RPM helps in remotely diagnosis, treatment, as well as allowing for prompt interventions. The RPM makes use of mobile technology and IoT platforms to take clinical interventions. In this study out of 151 covid19 positive subjects 91% of them were shifted to home monitoring within 5 days of MVM monitoring with few readmissions. The study investigated the effectiveness of RPM in the Indian healthcare system, as well as the performance and usability of the Vigocare mobile application by patients and doctors. © 2022 University of Stockholm. All rights reserved.

Progression-free survival (PFS) and overall survival (OS) in advanced/recurrent (AR) mismatch repair deficient/microsatellite instability–high or proficient/stable (dMMR/MSI-H or MMRp/MSS) endometrial cancer (EC) treated with dostarlimab in the GARNET study

Background: Dostarlimab is a programmed death 1 (PD-1) inhibitor approved in the EU as a monotherapy in patients (pts) with dMMR/MSI-H AR EC that has progressed on or after platinum-based chemotherapy;and in the US as a monotherapy in pts with dMMR AR EC that has progressed on or after platinum-based chemotherapy or dMMR solid tumors that have progressed on or after prior treatment, with no satisfactory alternative treatment options. We report on PFS and OS in 2 expansion cohorts of the GARNET trial that enrolled pts with EC. Methods: GARNET is a multicenter, open-label, single-arm phase 1 study. Pts were assigned to cohort A1 (dMMR/MSI-H EC) or A2 (MMRp/MSS EC) based on local immunohistochemistry assessment. Pts received 500 mg of dostarlimab IV every 3 weeks for 4 cycles, then 1000 mg every 6 weeks until disease progression, discontinuation, or withdrawal. PFS and OS are secondary efficacy endpoints. Results: 153 pts with dMMR/MSI-H and 161 pts with MMRp/MSS EC were enrolled and treated. The efficacy-evaluable population included 143 pts with dMMR/MSI-H EC and 156 pts with MMRp/MSS EC with measurable disease at baseline and ≥6 mo of follow-up. Median follow-up was 27.6 mo for dMMR/MSI-H and 33.0 mo for MMRp/MSS EC (Table). For pts with dMMR/MSI-H EC, median PFS (mPFS) was 6.0 mo, with 3-year estimated PFS rate of 40.1%. With 37.3% of pts experiencing an event, mOS was not reached;estimated 3-year OS was >50%. For pts with MMRp/MSS EC, mPFS was 2.7 mo. mOS was 16.9 mo with 68.9% of pts experiencing an event. Safety has been previously reported. [Formula presented] Conclusions: Dostarlimab demonstrated durable antitumor activity in dMMR/MSI-H and MMRp/MSS AR EC. dMMR/MSI-H was associated with longer PFS and OS than MMRp/MSS as expected. Clinical trial identification: NCT02715284. Editorial acknowledgement: Writing and editorial support, funded by GlaxoSmithKline (Waltham, MA, USA) and coordinated by Heather Ostendorff-Bach, PhD, of GlaxoSmithKline, was provided by Shannon Morgan-Pelosi, PhD, and Jennifer Robertson, PhD, of Ashfield MedComms, an Ashfield Health company (Middletown, CT, USA). Legal entity responsible for the study: GlaxoSmithKline. Funding: GlaxoSmithKline. Disclosure: A.V. Tinker: Financial Interests, Institutional, Sponsor/Funding: AstraZeneca;Financial Interests, Personal, Other: AstraZeneca, Eisai, GlaxoSmithKline. B. Pothuri: Financial Interests, Institutional, Funding: AstraZeneca, Celsion, Clovis Oncology, Eisai, Genentech/Roche, Karyopharm, Merck, Mersana, Takeda Pharmaceuticals, Tesaro/GSK;Financial Interests, Personal, Other: Arquer Diagnostics, AstraZeneca, Atossa, Clovis Oncology, Deciphera, Elevar Therapeutics, Imab, Mersana, Tesaro/GSK, Merck, Sutro Biopharma, Tora, GOG Partners;Financial Interests, Personal, Advisory Board: Arquer Diagnostics, AstraZeneca, Atossa, Deciphera, Clovis Oncology, Eisai, Elevar Therapeutics, Imab, Merck, Mersana, Sutro Biopharma, Tesaro/GSK, Toray;Financial Interests, Personal, Leadership Role: GOG Partners, NYOB Society Secretary, SGO Clinical Practice Committee Chair, SGO COVID-19 Taskforce Co-Chair. L. Gilbert: Financial Interests, Institutional, Funding: Alkermes, AstraZeneca, Clovis, Esperas, IMV, ImmunoGen Inc, Karyopharm, Merck Sharp & Dohme, Mersana, Novocure GmbH, OncoQuest Pharmaceuticals, Pfizer, Roche, Tesaro;Financial Interests, Personal, Other: Merck, Alkermes, AstraZeneca, Eisai, Eisai-Merck, GlaxoSmithKline. R. Sabatier: Financial Interests, Institutional, Funding: AstraZeneca, Eisai;Financial Interests, Personal, Other: AstraZeneca, GlaxoSmithKline, Novartis, Pfizer, Roche;Non-Financial Interests, Personal, Other: AstraZeneca, Bristol Myers Squibb, GlaxoSmithKline, Pfizer, Roche. J. Brown: Financial Interests, Personal, Advisory Role: Caris, Clovis, Eisai, GlaxoSmithKline;Financial Interests, Personal, Funding: GlaxoSmithKline, Genentech. S. Ghamande: Financial Interests, Personal, Advisory Role: Seattle Genetics;Financial Interests, Personal, Speaker’s Bureau: GlaxoSmithKline;Financial Interests, Institutional, Funding: Abbv e, Advaxis, Bristol Myers Squibb, Clovis, Genentech, GlaxoSmithKline, Merck, Roche, Seattle Genetics, Takeda. C. Mathews: Financial Interests, Institutional, Research Grant: Astellas, AstraZeneca, Deciphera, Moderna, GSK, Regeneron, Seattle Genetics;Financial Interests, Personal, Advisory Board: IMAB biopharma. D. O'Malley: Financial Interests, Personal, Advisory Board: AstraZeneca, Tesaro/GSK, Immunogen, Ambry, Janssen/J&J, Abbvie, Regeneron, Amgen, Novocure, Genentech/Roche, GOGFoundation, Iovance, Eisai, Agenus, Merck, SeaGen, Novartis, Mersana, Clovis, Elevar, Takeda, Toray, INXMED, SDP Oncology (BBI), Arquer Diagnostics, Roche Diagnostics MSA, Sorrento, Corcept Therapeutics, Celsion Corp;Financial Interests, Personal, Funding: AstraZeneca, Tesaro/GSK, Immunogen, Janssen/J&J, Abbvie, Regeneron, Amgen, Novocure, Genentech/Roche, VentiRx, Array Biopharma, EMD Serono, Ergomed, Ajinomoto Inc, Ludwig Cancer Research, Stemcentrx, Inc, Cerulean Pharma, GOGFoundation, Bristol-Myers Squibb Co, Serono Inc, TRACON Pharmaceuticals, Yale University, New Mexico Cancer Care Alliance, INC Research, Inc, inVentiv Health Clinical, Iovance, PRA Intl, Eisai, Agenus, Merck, GenMab, SeaGen, Mersana, Clovis, SDP Oncology (BBI);Financial Interests, Personal, Other: Myriad Genetics, Tarveda. V. Boni: Financial Interests, Personal, Advisory Board: OncoArt, Guidepoint Global;Financial Interests, Personal, Speaker’s Bureau: Solti;Financial Interests, Personal, Other: START, Loxo, IDEAYA Biosciences;Financial Interests, Institutional, Research Grant: Sanofi, Seattle Genetics, Loxo, Novartis, CytomX Therapeutics, Pumo Biotechnology, Kura Oncology, GlaxoSmithKline, Roche/Genentech, Bristol-Myers Squibb, Menarini, Synthon, Janssen Oncology, Merck, Lilly, Merus, Pfizer, Bayer, Incyte, Merus, Zenith Epigenetics, Genmab, AstraZeneca, Seattle Genetics, Adaptimmune, Alkermes, Amgen, Array BioPharma, Boehringer Ingelheim, BioNTech AG, Boston Biomedical. A. Gravina: Financial Interests, Personal, Other: Gentili, Pfizer. S. Banerjee: Financial Interests, Personal, Advisory Board: Amgen, Genmab, Immunogen, Mersana, Merck Sereno, MSD, Roche, Tesaro, AstraZeneca, GSK, Oncxerna;Financial Interests, Personal, Invited Speaker: Clovis, Pfizer, Tesaro, AstraZeneca, GSK, Takeda, Amgen, Medscape, Research to Practice, Peerview;Financial Interests, Personal, Stocks/Shares: PerciHealth;Financial Interests, Institutional, Research Grant: AstraZeneca, GSK, Tesaro;Non-Financial Interests, Principal Investigator, Phase II clinical trial Global lead, ENGOTov60/GOG3052/RAMP201: Verastem;Non-Financial Interests, Principal Investigator, ENGOT-GYN1/ATARI phase II international trial (academic sponsored): Astrazeneca;Non-Financial Interests, Advisory Role: Epsilogen;Non-Financial Interests, Other, Member of membership committee: ESGO;Non-Financial Interests, Advisory Role, Medical advisor to UK ovarian cancer charity: Ovacome Charity;Non-Financial Interests, Other, Received research funding from UK based charity I have provided medical advice (non-remunerated): Lady GardenFoundation Charity. R. Miller: Financial Interests, Personal, Other: AZD, Clovis Oncology, Ellipses, GlaxoSmithKline, MSD, Shionogi, AZD, GlaxoSmithKline;Financial Interests, Personal, Speaker’s Bureau: AZD, Clovis Oncology, GSK, Roche. J. Pikiel: Financial Interests, Personal, Other: Amgen, Clovis Oncology, GlaxoSmithKline, Incyte, Novartis, Odonate Therapeutics, Pfizer, Regeneron, Roche. M.R. Mirza: Financial Interests, Personal, Advisory Board: AstraZeneca, Biocad, GSK, Karyopharm, Merck, Roche, Zailab;Financial Interests, Personal, Invited Speaker: AstraZeneca, GSK, Karyopharm;Financial Interests, Personal, Stocks/Shares: Karyopharm;Financial Interests, Institutional, Research Grant: GSK, AstraZeneca, ultimovacs, Apexigen;Financial Interests, Institutional, Invited Speaker: Deciphera;Non-Financial Interests, Advisory Role: Ultimovacs, Apexigen. T. Duan: Financial Interests, Personal, Full or part-time Employment: GlaxoSmithKline. G. Antony: Financial Interests, Personal, Fu l or part-time Employment: GlaxoSmithKline. S. Zildjian: Financial Interests, Personal, Full or part-time Employment: GlaxoSmithKline. E. Zografos: Financial Interests, Personal, Full or part-time Employment: GlaxoSmithKline. J. Veneris: Financial Interests, Personal, Full or part-time Employment: GlaxoSmithKline. A. Oaknin: Financial Interests, Personal, Advisory Board: AstraZeneca, Clovis Oncology, Deciphera Pharmaceuticals, Genmab, GSK, Immunogen, Mersana Therapeutics, PharmaMar, Roche, Tesaro, Merck Sharps & Dohme de España, SA, Agenus, Sutro, Corcept Therapeutics, EMD Serono, Novocure, prIME Oncology, Sattucklabs, Itheos, Eisai, F. Hoffmann-La Roche,;Financial Interests, Personal, Other, Travel and accomodation: AstraZeneca, PharmaMar, Roche;Financial Interests, Institutional, Funding: Abbvie Deutschland, Advaxis Inc., Aeterna Zentaris, Amgen, Aprea Therapeutics AB, Clovis Oncology Inc, EISAI limited LTD, F. Hoffmann –La Roche LTD, Regeneron Pharmaceuticals, Immunogen Inc, Merck, Sharp & Dohme de España SA, Millennium Pharmaceuticals Inc, PharmaMar SA, Tesaro Inc., Bristol Myers Squibb;Non-Financial Interests, Leadership Role, Executive Board member as a Co-Chair: GEICO;Non-Financial Interests, Leadership Role, Phase II Committee and Cervix Cancer Committee Representative on behalf of GEICO: GCIG;Non-Financial Interests, Officer, Chair of Gynaecological Track ESMO 2019. Scientific Track Member Gynaecological Cancers ESMO 2018, ESMO 2020, ESMO 2022. Member of Gynaecological Cancers Faculty and Subject Editor Gyn ESMO Guidelines.: ESMO;Non-Financial Interests, Member: ESMO, ASCO, GCIG, SEOM, GOG.

THE IMPACT of TELEMEDICINE CONSULTATIONS for RHEUMATOID ARTHRITIS, GIANT CELL ARTERITIS, OSTEOARTHRITIS and CRYSTAL ARTHRITIS during COVID19 PANDEMIC

Background: Rheumatology departments across the UK have adapted to the COVID-19 pandemic, implementing novel methods of working via remote consultations. Objectives: We wanted to explore the rates of telemedicine consultations for patients with Rheumatoid Arthritis (RA), Giant cell arteritis (GCA), Osteoarthritis (OA), and Crystal arthritis (CA). We also wanted to check how effective the tele-medicine consultations had been in terms of avoiding the need for a face-to-face appointment. Methods: No telemedicine consultations took place before the COVID-19 pandemic in patients diagnosed with GCA, RA, CA and OA. We assessed the number of telemedicine consultations (telephone or videocall) using data from the departmental database covering September 2020 to December 2021. We analysed the rates of face-to-face versus telemedicine appointments for both new referrals and follow-up consultations. The statistical analysis was conducted using chi-square test. Results: There were 20,648 patients assessed in our department from September 2020 to December 2021. In total 1786 face-to-face and 2079 telemedi-cine consultations were conducted for GCA (18%), RA (66%), OA (13%) and CA (3%). The highest percentage of telemedicine consultations versus face-to-face for new referrals were observed for OA (30% Vs 70%) followed by RA (14% Vs 86%), CA (12% Vs 88%) and GCA (2% Vs 98%) (Table 1). Combining all these conditions, 68% of clinicians felt the telemedicine appointment avoided a face-to-face appointment. However, 33% of clinicians seeing new patients with RA did not feel the telemedicine appointment avoided a face-to-face appointment. In contrast, follow-up appointments were mainly conducted by telemedicine when compared with face-to-face;RA (65% Vs 35%), GCA (53%Vs 47%), OA (51% Vs 49%) and CA (61% Vs 39%). For the follow-ups, an overall majority of 90% of telemedicine consultations avoided the need for a face-to-face appointment, particularly observed for patients with CA and GCA (98% and 93% respectively). We noted that patients with RA were more likely than GCA to have a telemedicine follow-up (p value<0.00001). Conclusion: Telemedicine appointments for new referrals and follow-up patients with Rheumatological diagnoses has been a new development because of COVID-19 pandemic. Our analysis shows that most of our new RA, GCA, OA, and CA referrals are still being seen face-to-face but most follow-up appointments are telemedicine consultations. In most cases, clinicians felt that telemed-icine consultations avoided the need for a face-to-face appointment.

A REDUCTION in NEW REFERRALS for RHEUMATOID ARTHRITIS, OSTEOARTHRITIS and CRYSTAL ARTHRITIS COMPARED to GCA during COVID19 PANDEMIC

Background: The COVID-19 pandemic has had profound effects on the Rheumatology department;we wanted to see if consequently referrals for Rheumatoid arthritis (RA), Crystal Arthritis (CA), Osteoarthritis (OA) and Giant cell arteritis (GCA) were affected. A greater understanding of the impact may enable adequate number of clinics and resources to be made available where needed. Objectives: To evaluate the impact of COVID-19 pandemic on volume of new referrals to the Rheumatology department for RA, CA, OA and GCA. Methods: A retrospective analysis of data was conducted from the period of January 2016 to December 2021. The Rheumatology department database was closely analysed and information about new referrals for GCA, RA, OA and CA were evaluated. Statistical analysis was conducted using t-test to compare the mean value pre and during the COVID19 outbreak (2020). Results: From 2016 to 2021 a total number of 9998 new patients were referred to the Rheumatology department. There were 2768 new referrals for GCA (15%), RA (34%), OA (40%) and CA (11%) made during this period. In 2020, there was a signifcant decrease in OA, RA and CA referrals (p value 0.000004, 0.00017, 0.0042 respectively) but an insignifcant decrease in GCA referrals (p value 0.243). Conclusion: During COVID19 pandemic in 2020 there was a signifcant reduction in the number of new referrals for RA, OA, and CA in contrast to GCA where the referrals have been constant. This may be due to the detrimental consequences of untreated GCA with regards to risk of sight loss. However, with less RA referrals, this may result in a delayed diagnosis with an impact on the disease course.

Preparation of surface-functionalized electrospun PVA nanowebs for potential remedy for SARS-CoV-2

Infections with coronaviruses remain a burden that is negatively affecting human life. The use of metal oxides to prevent and control the spread of severe acute respiratory syndrome coronavirus (SARS-CoV-2) has been widely studied. However, the use of metal oxides in masks to enhance the performances of barrier face coverings in trapping and neutralizing SARS-CoV-2 remained unexplored. In the present study, we explore the possibility of developing surface functional PVA/ZnO electrospun nanowebs to be used as a component of multilayer barrier face coverings. Polyvinyl alcohol (PVA) and zinc acetate (ZnA) nanowebs were electrospun as precursor samples. After calcination at 400 degrees centigrade under a controlled atmosphere of nitrogen gas, product nanowebs containing ZnO (PVA/ZnO) were obtained. The presence of ZnO was determined using an attenuated total reflectance Fourier Transform Infrared (FT-IR) spectrometer. This study inspired the possibility of developing surface-functional materials to produce enhanced performance masks against the spread of SARS-CoV-2.

Opportunistic Infections in COVID-19: A Systematic Review and Meta-Analysis

The prevalence, incidence, and characteristics of bacterial infections in patients infected with severe acute respiratory syndrome coronavirus 2 are not well understood and have been raised as an important knowledge gap. Therefore, our study focused on the most common opportunistic infections/secondary infections/superinfections in coronavirus disease 2019 (COVID-19) patients.This systematic review and meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Eligible studies were identified using PubMed/Medline since inception to June 25, 2021. Studies meeting the inclusion criteria were selected. Statistical analysis was conducted in Review Manager 5.4.1. A random-effect model was used when heterogeneity was seen to pool the studies, and the result was reported as inverse variance and the corresponding 95% confidence interval.We screened 701 articles comprising 22 cohort studies which were included for analysis. The pooled prevalence of opportunistic infections/secondary infections/superinfections was 16% in COVID-19 patients. The highest prevalence of secondary infections was observed among viruses at 33%, followed by bacteria at 16%, fungi at 6%, and 25% among the miscellaneous group/wrong outcome.Opportunistic infections are more prevalent in critically ill patients. The isolated pathogens included Epstein-Barr virus, Pseudomonas aeruginosa, Escherichia coli, Acinetobacter baumannii, Hemophilus influenza, and invasive pulmonary aspergillosis. Large-scale studies are required to better identify opportunistic/secondary/superinfections in COVID-19 patients.

Association between Sleep Quality and Mental Health among Patients at a Post-COVID-19 Recovery Clinic.

A growing body of research documents the persistence of physical and neuropsychiatric symptoms following the resolution of acute COVID-19 infection. To the best of our knowledge, no published study has examined the interaction between insomnia and mental health. Accordingly, we proposed to examine new diagnoses of insomnia, and referrals to pulmonary and sleep medicine clinics for treatment of sleep disorders, in patients presenting to one post-acute COVID-19 recovery clinic. Additionally, we aimed to examine the relationship between poor sleep quality, depression, anxiety, and post-traumatic stress. Patients presented to the clinic on average 2 months following COVID-19 infection; 51.9% (n = 41) were hospitalized, 11.4% (n = 9) were in the intensive care unit, 2.5% (n = 2) were on a mechanical ventilator, and 38.0% (n = 30) were discharged on oxygen. The most commonly reported symptom was fatigue (88%, n = 70), with worse sleep following a COVID-19 infection reported in 50.6% (n = 40). The mean PSQI score was 9.7 (82.3%, n = 65 with poor sleep quality). The mean GAD-7 score was 8.3 (22.8%, n = 14 with severe depression). The mean PHQ-9 was 10.1 (17.8%, n = 18 with severe anxiety). The mean IES-6 was 2.1 (54.4%, n = 43 with post-traumatic stress). Poor sleep quality was significantly associated with increased severity of depression, anxiety, and post-traumatic stress. Future work should follow patients longitudinally to examine if sleep, fatigue, and mental health symptoms improve over time.

Item-level analysis of mental health symptom trajectories during the COVID-19 pandemic in the UK: Associations with age, sex and pre-existing psychiatric conditions.

BACKGROUND: There is widespread concern regarding how the COVID-19 pandemic has affected mental health. Emerging meta-analyses suggest that the impact on anxiety/depression may have been transient, but much of the included literature has major methodological limitations. Addressing this topic rigorously requires longitudinal data of sufficient scope and scale, controlling for contextual variables, with baseline data immediately pre-pandemic. AIMS: To analyse self-report of symptom frequency from two largely UK-based longitudinal cohorts: Cohort 1 (N = 10,475, two time-points: winter pre-pandemic to UK first winter resurgence), and Cohort 2 (N = 10,391, two time-points, peak first wave to UK first winter resurgence). METHOD: Multinomial logistic regression applied at the item level identified sub-populations with greater probability of change in mental health symptoms. Permutation analyses characterised changes in symptom frequency distributions. Cross group differences in symptom stability were evaluated via entropy of response transitions. RESULTS: Anxiety was the most affected aspect of mental health. The profiles of change in mood symptoms was less favourable for females and older adults. Those with pre-existing psychiatric diagnoses showed substantially higher probability of very frequent symptoms pre-pandemic and elevated risk of transitioning to the highest levels of symptoms during the pandemic. Elevated mental health symptoms were evident across intra-COVID timepoints in Cohort 2. CONCLUSIONS: These findings suggest that mental health has been negatively affected by the pandemic, including in a sustained fashion beyond the first UK lockdown into the first winter resurgence. Women, and older adults, were more affected relative to their own baselines. Those with diagnoses of psychiatric conditions were more likely to experience transition to the highest levels of symptom frequency.

When virtual becomes reality: short term impressions of a two-week virtual urology sub-internship program

INTRODUCTION: The COVID-19 pandemic disrupted medical student education and posed a unique challenge for educators, especially for surgical clerkships. In response to COVID-19 rotation restrictions, we implemented a virtual urologic surgery sub-internship program and evaluated medical student impressions of the experience. MATERIALS AND METHODS: A two-week urology curriculum was created with content delivered by interactive videoconferencing. The curriculum included synchronous and individual learning with live patient clinical experiences in the outpatient clinic and operating room, lectures, departmental conferences, a suture lab, self-reflective writing exercises, and an oral presentation. Student impressions were assessed with an exit survey. Descriptive statistics were utilized to evaluate the 5-point Likert scale responses. RESULTS: A total of 40 students applied, and 18 were selected for 1 of 5 two-week rotation blocks. All students successfully passed the rotation. Of the 18 students who participated, 16 (88.9%) completed the exit survey. The overall experience was rated as "strongly positive" by 14 of 16 (87.5%) students. The learning experience was rated as 4.75 (0.45) (average (SD)). The rotation positively impacted our virtual students' plan to apply to this residency program (mean 4.81 (0.54)). All students reported they would recommend this rotation to a fellow student, and feedback regarding the self-reflection activities was positive. CONCLUSIONS: We successfully implemented a two-week virtual urology sub-internship rotation with a wide variety of clinical and educational experiences. The rotation was well received by our medical students. This is a unique experience in urology that can easily be implemented by other surgical sub-specialty programs in the future.

The impact of a dedicated department clinical research team and formal residency research curriculum

INTRODUCTION AND OBJECTIVE: Our objective was to assess the impact of a dedicated clinical research team and a formal residency research curriculum implementation on the number of publications, journal impact factor, resident initiated clinical trials and patient enrollment. METHODS: Data was collected three years prior to the creation of a department clinical research division and implementation of the research curriculum in residency (2014, 2015, 2016) as well as four years post-implementation (2017, 2018, 2019, 2020). The clinical research division and formal residency research curriculum was established in 2017. The number of publications with a resident author, journal's impact factor, number of resident initiated trials, and number of patients recruited were collected. Additionally, the total impact factor and average impact factor per article were calculated for each year. RESULTS: Prior to implementation (2014, 2015, and 2016) of the research curriculum and the creation of a clinical research division, there were 8, 8, 9 resident publications respectively, with an average of 8.33 resident publications per year. The total impact score was calculated as 16.15, 8.48, and 19.01 as well as the average impact per article, 2.02, 1.06, and 2.11 for the respective years. The number of resident initiated trials were 0 with 0 patient enrollments prior to implementation. The data four years after implementation (2017, 2018, 2019,2020) was calculated for the post-implementation impact and the average resident publications were 10, 7, 10, and 14 respectively, with an average of 10.25 resident publications per year. The total impact factor for those years was 18.77, 22.65, 25.79, and 34.32 with an average impact per article of 1.88, 3.24, 2.58, and 2.45. The number of resident initiated trials was 2, 6, 8, and 10 with a total patient enrollment of 40, 162, 261, and 204 in the respective postimplementation years. CONCLUSIONS: The clinical demands of a Urology resident are time consuming. With the implementation of a dedicated clinical research team and formal resident research curriculum, the number of resident publications per year and article impact factor increased. Additionally, the number of resident initiated clinical trials and patient enrollment grew significantly. The year 2020 had the highest number of resident trials and patient enrollment despite the COVID-19 pandemic. This data suggests a focused research curriculum and dedicated clinical research team can significantly increase resident research output, impact, and initiated trials.

When virtual becomes reality: Development and implementation of a virtual urologic sub-internship program for fourth year medical students

INTRODUCTION AND OBJECTIVE: The COVID-19 pandemic has resulted in a disruption and disturbance in medical education and the training of our future physicians. This pandemic posed a unique challenge for educators, especially in the surgical clerkship learning environment where a large proportion of teaching occurs in the operating room. It has required medical educators to become creative in their training efforts of medical students. These changes prompted the development of a virtual urology sub-internship rotation our institution for visiting fourth year medical students. The purpose of this study was to implement a virtual urologic surgery sub-internship program and evaluate medical student impressions of the experience. METHODS: A two-week urology curriculum was created with content delivered by two-way, interactive videoconferencing. The curriculum included synchronous and individual learning with live patient clinical experiences in the outpatient clinic and operating room, faculty lectures, and departmental conferences. The students also completed self-reflective writing exercises and a grand rounds presentation. Student impressions of the rotation were assessed with an anonymous exit survey. Descriptive statistics were utilized to evaluate the 5-point Likert Scale responses, with 5 being “strongly positive” and 1 “strongly negative”. RESULTS: A total of 40 students applied for the rotation and 18 were selected for 1 of 5 two-week rotation blocks. All students successfully completed the rotation and received a Pass. Of the 18 students who participated in the virtual rotation, 16 (88.9%) completed the exit survey. The overall experience was rated as “strongly positive” by 14 of 16 (87.5%) students. The learning experience was rated as 4.75±0.45 (average±SD). The rotation positively impacted our virtual students' plan to apply to this residency program (4.81±0.54). All students reported they would recommend this rotation to a fellow student. All feedback regarding the self-reflection activities was positive. CONCLUSIONS: We successfully implemented a two-week virtual urologic sub-internship rotation with a wide variety of clinical and educational experiences. This is a unique experience in surgery that can easily be implemented by other urology or surgical subspeciality programs in the future.

ACUTE PULMONARY HISTOPLASMOSIS: A DIAGNOSTIC DILEMMA DURING COVID-19 PANDEMIC

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: Acute histoplasmosis is usually a concern in immunocompromised individuals. In immunocompetent patients, histoplasmosis is generally mild or asymptomatic unless there is inhalation of a large inoculum. Below, we present a case of severe acute pulmonary histoplasmosis in an otherwise healthy, immunocompetent person and discuss the diagnostic challenges it presented during the COVID-19 pandemic. CASE PRESENTATION: A 30-year-old non-smoking Caucasian man with hypertension presented to our hospital with 1 week duration of headache, dyspnea, productive cough and high fever. He was admitted with a provisional diagnosis of COVID-19 pneumonia and started on dexamethasone and empiric antibiotics. He had elevated inflammatory markers. Chest x-ray showed diffuse bilateral interstitial and alveolar opacities. CT chest demonstrated numerous clustered ground glass nodular opacities bilaterally with mediastinal and hilar adenopathy. Subsequently, RT-PCR for SARS-CoV2 returned negative. The patient continued to deteriorate clinically over the next few days. Repeat imaging showed diffuse micronodules with mediastinal adenopathy. Upon further questioning, the patient recalled demolishing a chimney at his parents' house in Michigan 2 weeks prior to admission. The differential diagnosis was broadened to include acute hypersensitivity pneumonitis and fungal infection. BAL, transbronchial biopsies and EBUS-TBNA was performed while escalating steroids. The lung biopsy confirmed Histoplasma. Urine Histoplasma antigen returned positive. The patient was treated with itraconazole with an overlap of steroids for 2 weeks upon discharge. He was readmitted within a week with worsening hypoxia and worsening infiltrates on lung imaging. He was then treated with liposomal amphotericin with gradual clinical improvement. Follow-up 1 month post discharge revealed complete clinical and radiologic resolution. DISCUSSION: Viral pneumonia and acute pulmonary histoplasmosis have overlapping clinical and radiologic features which can make diagnosis challenging. COVID-19 pneumonia typically presents with peripheral ground glass opacities with or without superimposed consolidations. Invasive fungal pneumonia can have a similar appearance on CT usually with additional findings of hilar and mediastinal adenopathy. CONCLUSIONS: This case highlights the challenges involved in diagnosing acute pulmonary histoplasmosis in an immunocompetent individual in the midst of the pandemic. Clinicians should always maintain a wide differential diagnosis to avoid diagnostic delay. REFERENCE #1: Staffolani, S., Buonfrate, D., Angheben, A., Gobbi, F., Giorli, G., Guerriero, M., Barchiesi, F. (2018). Acute histoplasmosis in immunocompetent travelers: A systematic review of literature. BMC Infectious Diseases, 18(1). doi:10.1186/s12879-018-3476-z REFERENCE #2: Duzgun, S. A., Durhan, G., Demirkazik, F. B., Akpinar, M. G., & Ariyurek, O. M. (2020). COVID-19 pneumonia: the great radiological mimicker. Insights into imaging, 11(1), 118. https://doi.org/10.1186/s13244-020-00933-z REFERENCE #3: Klein, M., Khan, M., Salinas, J. L., & Sanchez, R. (2019). Disseminated pulmonary histoplasmosis in immunocompetent patients: A common epidemiological exposure. BMJ Case Reports, 12(3). doi:10.1136/bcr-2018-227994 DISCLOSURES: No relevant relationships by Joseph Arguinchona, source=Web Response No relevant relationships by Michael Kaster, source=Web Response No relevant relationships by Muazzam Mirza, source=Web Response No relevant relationships by Anusha Pinjala, source=Web Response no disclosure on file for Venketraman Sahasranaman;

Rapid implementation of triaging system for assessment of breast referrals from primary care centres during the COVID-19 pandemic.

OBJECTIVE: The aim of this study was to establish a triaging system for assessment of breast referrals from primary care to ensure safe and effective breast services without compromising breast cancer management. BACKGROUND: COVID-19 was officially declared a global pandemic on 11 March 2020, and with no effective treatment available, preventing spread has been paramount. Previously, all referrals from primary care were seen in the rapid-access breast clinic (RABC). Clinic appointments exposed patients and healthcare professionals to risk. METHOD: Initial triage during the lockdown was in line with national governing body guidance, rejected low risk referrals and streamed remaining patients through a telephone consultation to RABC or discharge. A modified triage pathway streamed all patients through virtual triage to RABC, telephone clinic or discharge with advice and guidance categories. Demographics, reasons for referral and outcomes data were collected and presented as median with range and frequency with percentages. RESULTS: Initial triage (23 March-23 April 2020) found fewer referrals with a higher percentage of breast cancer diagnoses. Modified triage (22 June-17 July 2020) resulted in a 35.1% (99/282) reduction in RABC attendance. Overall cancer detection rate remained similar at 4.2% of all referrals pre-COVID (18/429) and 4.3% (12/282) during modified triage. After six months follow-up of patients not seen in RABC during the modified triage pathway, 18 patients were re-referred to RABC and none were diagnosed with cancer. CONCLUSION: A modified triage pathway has the potential to improve triage efficiency and prevent unnecessary visits during the COVID-19 pandemic. Further refinement of pathway is feasible in collaboration with primary care.

Changes in surgical practice by surgical residents and consultants during covid-19 pandemic: A cross-sectional survey

Objective: During the COVID-19 pandemic, surgical practice is greatly changed. This study was done to see what changes have been made in the surgical practice by the surgical consultants and residents in various surgical disciplines. Study Design: Cross-sectional study. Place and Duration of Study: The Children's Hospital, and the Institute of Child Health, Lahore. It was conducted during May 2020. Materials and Methods: A Survey form was developed on the 'Google Forms' application and distributed to surgical consultants and residents. The submission was received online during May 2020. The collected data were entered and analyzed using SPSS V.23. Qualitative data were presented as frequencies and percentages. Quantitative data were presented as mean and standard deviation. Results: Overall, 272 consultants and residents from 45 teaching hospitals from Pakistan and around the world participated in the survey. Among the participants, 100 (36.8%) were surgical consultants and 172 (63.2%) were surgical residents. About 42% of participants were not performing elective surgeries during this pandemic of COVID-19 but almost all participants were performing emergency surgeries (93%). Over 60% of the respondents admitted that their practice is either reduced to more than 50% or completely shut down during this pandemic. Over 80% stated that their training activities were compromised due to the pandemic. Conclusion: COVID-19 pandemic has greatly affected surgical practice both in the public and corporate sectors. Elective surgeries are affected the most in addition to the suspension of training activities of the residents.

Ambulatory day case oncoplastic and reconstructive breast surgery during the peak of COVID 19 pandemic

Background: The World Health Organization (WHO) declared a novel coronavirus disease 2019 (COVID 19) pandemic on the 11 March 20. In response to this, the United Kingdom (UK) Association of Breast Surgeons (ABS) released guidelines on breast cancer management during the pandemic on the 15 March 20. The UK was in lockdown on the 23 March 20. Whilst the UK breast units adapted to deliver safe cancer services, many limited and some stopped all oncoplastic and reconstructive breast surgery (OPRBS). With careful stratification and prioritisation of cases, coupled with our existing successful integrated ambulatory day case surgery pathway, our unit continued to perform OPRBS safely and we present the outcomes of our OPRBS during the pandemic. Materials and Methods: OPRBS performed between 11 March 20 and 31 July 20 were included in this study. All OPRBS cases were supported by our multidisciplinary team. Surgeons and patients followed hospital’s COVID 19 precautions policy. Primary outcome measured was COVID 19 exposure before or after surgery. Secondary outcomes measured were 30 days surgical complications and delay in adjuvant treatment. Results: A total of 117 patients (120 breasts) had breast cancer related surgeries during the study period. Ten patients (12 breasts), that is 10% underwent immediate OPRBS following breast conserving surgery or mastectomy were included in the study analysis. All OPRBS were planned for ambulatory day case surgery (ADCS). Patients' age ranged was from 35 to 63 years. There were 6 pre-pectoral implant based reconstructions, 4 partial breast reconstruction with chest wall perforator flaps, 1 therapeutic mammoplasty, and 1 central BCS with nipple reconstruction. None contracted COVID 19 before or after surgery, 2 patient developed minor complications with no delay in adjuvant treatment. Six patients were discharged on the day of surgery, and 4 patients were discharged within 23 hours of admission as part of our unit's integrated ADCS (<23 hours stay) pathway. Conclusions: With an established integrated ambulatory day case surgery pathway, and careful stratification and adherence to COVID 19 precautions, oncoplastic and reconstructive breast surgery can be delivered safely and effectively during the peak of the pandemic. Our model can be extrapolated to the reshaping and resuming of oncoplastic and reconstructive breast surgery in the era of COVID 19.