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1.
Intensive Care Medicine ; 14:14, 2022.
Article in English | MEDLINE | ID: covidwho-2027451

ABSTRACT

PURPOSE: Benefit from convalescent plasma therapy for coronavirus disease 2019 (COVID-19) has been inconsistent in randomized clinical trials (RCTs) involving critically ill patients. As COVID-19 patients are immunologically heterogeneous, we hypothesized that immunologically similar COVID-19 subphenotypes may differ in their treatment responses to convalescent plasma and explain inconsistent findings between RCTs . METHODS: We tested this hypothesis in a substudy involving 1239 patients, by measuring 26 biomarkers (cytokines, chemokines, endothelial biomarkers) within the randomized, embedded, multifactorial, adaptive platform trial for community-acquired pneumonia (REMAP-CAP) that assigned 2097 critically ill COVID-19 patients to either high-titer convalescent plasma or usual care. Primary outcome was organ support free days at 21 days (OSFD-21) . RESULTS: Unsupervised analyses identified three subphenotypes/endotypes. In contrast to the more homogeneous subphenotype-2 (N = 128 patients, 10.3%;with elevated type i and type ii effector immune responses) and subphenotype-3 (N = 241, 19.5%;with exaggerated inflammation), the subphenotype-1 had variable biomarker patterns (N = 870 patients, 70.2%). Subphenotypes-2, and -3 had worse outcomes, and subphenotype-1 had better outcomes with convalescent plasma therapy compared with usual care (median (IQR). OSFD-21 in convalescent plasma vs usual care was 0 (- 1, 21) vs 10 (- 1, to 21) in subphenotype-2;1.5 (- 1, 21) vs 12 (- 1, to 21) in suphenotype-3, and 0 (- 1, 21) vs 0 (- 1, to 21) in subphenotype-1 (test for between-subphenotype differences in treatment effects p = 0.008). CONCLUSIONS: We reported three COVID-19 subphenotypes, among critically ill adults, with differential treatment effects to ABO-compatible convalescent plasma therapy. Differences in subphenotype prevalence between RCT populations probably explain inconsistent results with COVID-19 immunotherapies.

2.
8th International Conference on Higher Education Advances, HEAd 2022 ; 2022-June:521-529, 2022.
Article in English | Scopus | ID: covidwho-2025027

ABSTRACT

#DryLabsRealScience is a community of practice established to support life science educators with the provision of laboratory-based classes in the face of the COVID-19 pandemic and restricted access to facilities. Four key approaches have emerged from the innovative work shared with the network: videos, simulations, virtual/augmented reality, and datasets, with each having strengths and weaknesses. Each strategy was used pre-COVID and has a sound theoretical underpinning;here, we explore how the pandemic has forced their adaptation and highlight novel utilisation to support student learning in the laboratory environment during the challenges faced by remote and blended teaching. © HEAd 2022. All Rights Reserved.

3.
Proceedings of the National Academy of Sciences of the United States of America ; 119(39):e2204624119, 2022.
Article in English | MEDLINE | ID: covidwho-2017031

ABSTRACT

The high transmissibility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a primary driver of the COVID-19 pandemic. While existing interventions prevent severe disease, they exhibit mixed efficacy in preventing transmission, presumably due to their limited antiviral effects in the respiratory mucosa, whereas interventions targeting the sites of viral replication might more effectively limit respiratory virus transmission. Recently, intranasally administered RNA-based therapeutic interfering particles (TIPs) were reported to suppress SARS-CoV-2 replication, exhibit a high barrier to resistance, and prevent serious disease in hamsters. Since TIPs intrinsically target the tissues with the highest viral replication burden (i.e., respiratory tissues for SARS-CoV-2), we tested the potential of TIP intervention to reduce SARS-CoV-2 shedding. Here, we report that a single, postexposure TIP dose lowers SARS-CoV-2 nasal shedding, and at 5 days postinfection, infectious virus shed is below detection limits in 4 out of 5 infected animals. Furthermore, TIPs reduce shedding of Delta variant or WA-1 from infected to uninfected hamsters. Cohoused "contact" animals exposed to infected, TIP-treated animals exhibited significantly lower viral loads, reduced inflammatory cytokines, no severe lung pathology, and shortened shedding duration compared to animals cohoused with untreated infected animals. TIPs may represent an effective countermeasure to limit SARS-CoV-2 transmission.

4.
Journal of Issues in Intercollegiate Athletics ; 14(674-693):674-693, 2021.
Article in English | CAB Abstracts | ID: covidwho-2012779

ABSTRACT

The aim of this study was to conduct a survey-based assessment of mental health symptoms among National Collegiate Athletic Association (NCAA) Division III student-athletes at a university during the COVID-19 pandemic. We sought to identify the severity of psychological distress during the fall academic semester, including a comparison of distress among gender and sport types, at a school who resumed in-person learning and preserved competition and practice sessions. A longitudinal, repeated measures design was implemented. Results indicated a significant increase in distress as the semester progressed (t(170) = 9.188, p < .001). Moreover, there was a significant difference in distress between genders at both time points (p < .001, p = .001, respectively), but only between sport types at the first data collection (p = .001). A univariate analysis of variance (ANOVA) determined a significant effect of time (p < .001), gender (p < .001), and sport (p = .008) on COVID distress as well as the interaction of gender and sport to significantly influence symptoms (p = .032). The results of this study suggest COVID-19 induced psychological distress is not stagnant and women student-athletes may be more susceptible. Colleges should consider screening student-athlete mental health to understand fluctuating, acute distress as well as symptoms that endure.

5.
Irish Journal of Medical Science ; 191(SUPPL 4):111-111, 2022.
Article in English | Web of Science | ID: covidwho-2011878
6.
Irish Journal of Medical Science ; 191(SUPPL 4):116-117, 2022.
Article in English | Web of Science | ID: covidwho-2011877
7.
Social Alternatives ; 40(4):9-14, 2021.
Article in English | Web of Science | ID: covidwho-2011163

ABSTRACT

Recruitment fraud uses the guise of a genuine job opportunity to lure potential victims into paying 'fees' directly or sending sensitive personal information (driver's licence, bank account details, passports, etc.). Those who comply can expose themselves to a range of consequences, including fraud, identity theft and money laundering. Victims of fraud more generally face challenges in accessing justice through the fraud justice network of police, consumer protection organisations and banks. However, those targeted by employment schemes are often less visible and might be more marginalised than those who experience other fraud victimisation. In 2020, the emergence of COVID-19 plunged the world into an extraordinary level of uncertainty. Millions found themselves unemployed or underemployed due to the lockdowns and physical distancing restrictions introduced to control the virus, creating a bountiful environment for offenders to effectively target potential victims of recruitment fraud and increasing the vulnerability of a larger proportion of society to such schemes. This article details the contours of recruitment fraud. The paper advocates a research agenda promoting a better understanding of fraud victimisation in this context. Ways to effectively disrupt or prevent fraud are outlined to reduce levels of victimisation and harm into the future.

8.
Frontiers in Microbiology ; 13, 2022.
Article in English | EMBASE | ID: covidwho-2005889

ABSTRACT

Early in the pandemic, in March of 2020, an outbreak of COVID-19 occurred aboard the aircraft carrier USS Theodore Roosevelt (CVN-71), during deployment in the Western Pacific. Out of the crew of 4,779 personnel, 1,331 service members were suspected or confirmed to be infected with SARS-CoV-2. The demographic, epidemiologic, and laboratory findings of service members from subsequent investigations have characterized the outbreak as widespread transmission of virus with relatively mild symptoms and asymptomatic infection among mostly young healthy adults. At the time, there was no available vaccination against COVID-19 and there was very limited knowledge regarding SARS-CoV-2 mutation, dispersal, and transmission patterns among service members in a shipboard environment. Since that time, other shipboard outbreaks from which data can be extracted have occurred, but these later shipboard outbreaks have occurred largely in settings where the majority of the crew were vaccinated, thereby limiting spread of the virus, shortening duration of the outbreaks, and minimizing evolution of the virus within those close quarters settings. On the other hand, since the outbreak on the CVN-71 occurred prior to widespread vaccination, it continued over the course of roughly two months, infecting more than 25% of the crew. In order to better understand genetic variability and potential transmission dynamics of COVID-19 in a shipboard environment of immunologically naïve, healthy individuals, we performed whole-genome sequencing and virus culture from eighteen COVID-19-positive swabs collected over the course of one week. Using the unique variants identified in those genomes, we detected seven discrete groups of individuals within the population aboard CVN-71 infected with viruses of distinct genomic signature. This is in stark contrast to a recent outbreak aboard another U.S. Navy ship with >98% vaccinated crew after a port visit in Reykjavik, Iceland, where the outbreak lasted only approximately 2 weeks and the virus was clonal. Taken together, these results demonstrate the utility of sequencing from complex clinical samples for molecular epidemiology and they also suggest that a high rate of vaccination among a population in close communities may greatly reduce spread, thereby restricting evolution of the virus.

9.
Journal of Chemical Education ; 2022.
Article in English | Web of Science | ID: covidwho-2004739

ABSTRACT

A physical chemistry lab for undergraduate students described in this report is about applying kinetic models to analyze the spread of COVID-19 in the United States and obtain the reproduction numbers. The susceptible-infectious-recovery (SIR) model and the SIR-vaccinated (SIRV) model are explained to the students and are used to analyze the COVID-19 spread data from the U.S. Centers for Disease Control and Prevention (CDC). The basic reproduction number R0 and the real-time reproduction number Rt of COVID-19 are extracted by fitting the data with the models, which explains the spreading kinetics and provides a prediction of the spreading trend in a given state. The procedure outlined here shows the differences between the SIR model and the SIRV model. The SIRV model considers the effect of vaccination, which helps explain the later stages of the ongoing pandemic. The predictive power of the models is also shown giving the students some certainty in the predictions they made for the following months.

10.
Nat Commun ; 13(1):4931, 2022.
Article in English | PubMed | ID: covidwho-2000888

ABSTRACT

Anti-SARS-CoV-2 monoclonal antibodies are mainstay COVID-19 therapeutics. Safety, antiviral, and clinical efficacy of bamlanivimab were evaluated in the randomized controlled trial ACTIV-2/A5401. Non-hospitalized adults were randomized 1:1 within 10 days of COVID-19 symptoms to bamlanivimab or blinded-placebo in two dose-cohorts (7000 mg, n = 94;700 mg, n = 223). No differences in bamlanivimab vs placebo were observed in the primary outcomes: proportion with undetectable nasopharyngeal SARS-CoV-2 RNA at days 3, 7, 14, 21, and 28 (risk ratio = 0.82-1.05 for 7000 mg [p(overall) = 0.88] and 0.81-1.21 for 700 mg [p(overall) = 0.49]), time to symptom improvement (median 21 vs 18.5 days [p = 0.97], 7000 mg;24 vs 20.5 days [p = 0.08], 700 mg), or grade 3+ adverse events. However, bamlanivimab was associated with lower day 3 nasopharyngeal viral levels and faster reductions in inflammatory markers and viral decay by modeling. This study provides evidence of faster reductions in nasopharyngeal SARS-CoV-2 RNA levels but not shorter symptom durations in non-hospitalized adults with early variants of SARS-CoV-2.

11.
Meeting Abstracts from the 70th Annual British Thyroid Association Meeting ; 2022.
Article in English | BioMed Central | ID: covidwho-1958157

ABSTRACT

Background: We present the case of a male patient with a diagnosis of TSH-secreting pituitary adenoma (TSHoma) who became infected with SARS-CoV-2 and developed a post-COVID-19 thyroiditis with resultant confusing changes in his thyroid function tests (TFTs). Case Presentation: The patient presented with an incidental finding of elevated Free T4 and inappropriately normal TSH, confirmed on multiple analytical platforms. A TRH test showed a flat TSH response, and an MRI pituitary showed a 2.4 cm macroadenoma. Somatostatin analogue treatment was commenced pending surgery, with rapid normalization of TFTs. The patient then became symptomatic of headache, pyrexia, dysgeusia and anosmia lasting two weeks, at a time when the first wave of the COVID-19 pandemic was affecting Ireland. The patient had been a close contact of two confirmed COVID-19 cases. He did not have a SARS-CoV2 PCR test at the time but later tested positive for COVID-19 spike and nucleocapsid antigen IgG antibodies (vaccine naïve), indicating previous exposure to SARS-CoV-2. Two months after this illness, the patient’s TFTs showed a pattern typical of primary hyperthyroidism with grossly elevated FT4 and fully suppressed TSH (with co-existent thyrotoxicosis symptoms), followed by a pattern of primary hypothyroidism with a low FT4 and high TSH – a pattern consistent with subacute thyroiditis post-viral illness. TRAb was negative. The patient’s TFTs later showed high normal TSH and normal FT4 while continuing lanreotide therapy. He is currently euthyroid and awaiting pituitary surgery which was delayed due to the COVID-19 emergency. Conclusion: To our knowledge, this is the first case of post-COVID-19 thyroiditis in a patient with underlying TSHoma. The case highlights the importance of considering an alternative or new diagnosis in the setting of rapidly changing patterns in thyroid function tests, and for close clinical and biochemical follow-up in these situations. The patient gave written consent to this publication. SARS-CoV-2 = Severe Acute Respiratory Syndrome Coronavirus 2 TFT = Thyroid Function Test FT4 = Free Thyroxine TSH = Thyroid-Stimulating Hormone TRH = Thyrotropin-Releasing Hormone MRI = Magnetic Resonance Imaging TRAB = TSH Receptor Antibodies Anti-TPO Ab = Anti-Thyroid Peroxidase Antibodies

12.
LANCET ; 399(10342):2212-2225, 2022.
Article in English | Web of Science | ID: covidwho-1935221

ABSTRACT

Background Vaccination of children and young people against SARS-CoV-2 is recommended in some countries. Scarce data have been published on immune responses induced by COVID-19 vaccines in people younger than 18 years compared with the same data that are available in adults. Methods COV006 is a phase 2, single-blind, randomised, controlled trial of ChAdOx1 nCoV-19 (AZD1222) in children and adolescents at four trial sites in the UK. Healthy participants aged 6-17 years, who did not have a history of chronic respiratory conditions, laboratory-confirmed COVID-19, or previously received capsular group B meningococcal vaccine (the control), were randomly assigned to four groups (4:1:4:1) to receive two intramuscular doses of 5 x 10(1)degrees viral particles of ChAdOx1 nCoV-19 or control, 28 days or 84 days apart. Participants, clinical investigators, and the laboratory team were masked to treatment allocation. Study groups were stratified by age, and participants aged 12-17 years were enrolled before those aged 6-11 years. Due to the restrictions in the use of ChAdOx1 nCoV-19 in people younger than 30 years that were introduced during the study, only participants aged 12-17 years who were randomly assigned to the 28-day interval group had received their vaccinations at the intended interval (day 28). The remaining participants received their second dose at day 112. The primary outcome was assessment of safety and tolerability in the safety population, which included all participants who received at least one dose of the study drug. The secondary outcome was immunogenicity, which was assessed in participants who were seronegative to the nucleocapsid protein at baseline and received both prime and boost vaccine. This study is registered with ISRCTN (15638344). Findings Between Feb 15 and April 2, 2021, 262 participants (150 [57%] participants aged 12-17 years and 112 [43%] aged 6-11 years;due to the change in the UK vaccination policy, the study terminated recruitment of the younger age group before the planned number of participants had been enrolled) were randomly assigned to receive vaccination with two doses of either ChAdOx1 nCoV-19 (n=211 [n=105 at day 28 and n=106 at day 84]) or control (n=51 [n=26 at day 28 and n=25 at day 84]). One participant in the ChAdOx1 nCoV-19 day 28 group in the younger age bracket withdrew their consent before receiving a first dose. Of the participants who received ChAdOx1 nCoV-19, 169 (80%) of 210 participants reported at least one solicited local or systemic adverse event up to 7 days following the first dose, and 146 (76%) of 193 participants following the second dose. No serious adverse events related to ChAdOx1 nCoV-19 administration were recorded by the data cutoff date on Oct 28, 2021. Of the participants who received at least one dose of ChAdOx1 nCoV-19, there were 128 unsolicited adverse events up to 28 days after vaccination reported by 83 (40%) of 210 participants. One participant aged 6-11 years receiving ChAdOx1 nCoV-19 reported a grade 4 fever of 40.2 degrees C on day 1 following first vaccination, which resolved within 24 h. Pain and tenderness were the most common local solicited adverse events for all the ChAdOx1 nCoV-19 and capsular group B meningococcal groups following both doses. Of the 242 participants with available serostatus data, 14 (6%) were seropositive at baseline. Serostatus data were not available for 20 (8%) of 262 participants. Among seronegative participants who received ChAdOx1 nCoV-19, anti-SARS-CoV-2 IgG and pseudoneutralising antibody titres at day 28 after the second dose were higher in participants aged 12-17 years with a longer interval between doses (geometric means of 73 371 arbitrary units [AU]/mL [95% CI 58 685-91 733] and 299 half-maximal inhibitory concentration [IC 50;95% CI 230-390]) compared with those aged 12-17 years who received their vaccines 28 days apart (43 280 AU/mL [95% CI 35 852-52 246] and 150 IC 50 [95% CI 116-194]). Humoral responses were higher in those aged 6-11 years than in those aged 12-17 years receiving their second dose at the same 112-day interval (geometric mean ratios 1.48 [95% CI 1.07-2.07] for anti-SARS-CoV-2 IgG and 2.96 [1.89-4.62] for pseudoneutralising antibody titres). Cellular responses peaked after a first dose of ChAdOx1 nCoV-19 across all age and interval groups and remained above baseline after a second vaccination. Interpretation ChAdOx1 nCoV-19 is well tolerated and immunogenic in children aged 6-17 years, inducing concentrations of antibody that are similar to those associated with high efficacy in phase 3 studies in adults. No safety concerns were raised in this trial. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd.

13.
Neurology ; 98(18 SUPPL), 2022.
Article in English | EMBASE | ID: covidwho-1925241

ABSTRACT

Objective: We sought to determine the emotional impact, stress, and burden of the COVID-19 pandemic on movement disorders patients. Background: The COVID-19 pandemic has caused stress for the whole population, as it is the only major incidence of a widespread infectious illness that most have experienced in their lifetime. The impact of COVID-19 on patients with chronic neurodegenerative disease, including movement disorders, is largely unknown. Design/Methods: Over 4 months (May to August 2021), subjects were asked to fill out a subjective questionnaire that asked whether neurological symptoms, relationships, mental health care, finances, or healthcare delays worsened during the COVID-19 pandemic, as well as the Pandemic Emotional Impact Scale (PEIS). The PEIS is a validated scale designed to measure the emotional impact of a worldwide pandemic. The scale has 16 questions, each of which is scored on a scale of 1 to 5, 5 being the worst. The two-sample t-test was used to obtain p-values at α=0.05. Results: The cohort had a mean age of 68.0 ± 10.5 years, with 54% males and 46% females. 62% of subjects had diagnoses of PD, and 38% had either ET, ataxia, or dystonia. The average disease duration for the cohort was 8.80 ± 9.47 years. The mean PEIS score for the cohort was 32.52 ± 12.61 (range 16-80). Higher (worse) PEIS scores were significantly associated with “personal financial loss” (p=0.0077), “worsening neurological symptoms” (p=0.0006), “strained relationships” (p=0.0021), “friends/family experiencing financial loss” (p=0.0006), “friends/family hospitalized” (p=0.0178), “delay in healthcare” (p < 0.0001), and “masks impacting health” (p = 0.0064). Conclusions: Although the emotional burden of COVID-19 was reasonably low in this cohort, patients were affected by financial burden, strained relationships, delays in healthcare, and mask wearing. The mental health and emotional burden of movement disorder patients should be carefully addressed.

14.
European Journal of Clinical Pharmacology ; 78(SUPPL 1):S68-S69, 2022.
Article in English | Web of Science | ID: covidwho-1913146
15.
Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research ; 25(7):S300-S300, 2022.
Article in English | EuropePMC | ID: covidwho-1905229
16.
Topics in Antiviral Medicine ; 30(1 SUPPL):173, 2022.
Article in English | EMBASE | ID: covidwho-1880928

ABSTRACT

Background: The discovery and development of SARS-CoV-2 therapies remains a priority. SAB-185 is a Transchromosomic, bovine-derived, fully human polyclonal immunoglobulin product for SARS-CoV-2 being studied in ACTIV-2, randomized controlled platform trial evaluating the safety and efficacy of investigational agents for non-hospitalized adults with mild-moderate COVID-19 Methods: This Phase II trial was a superiority comparison of SAB-185 vs. placebo. Participants with confirmed SAR-CoV-2 infection received intravenous infusion of SAB-185 (3,840 Units/kg) or placebo. Primary outcome measures were proportion of participants with SARS-CoV-2 RNA < lower limit of quantification (LLoQ) in nasopharyngeal (NP) swab, time to improvement in targeted symptoms for 2 consecutive days after Day 0, and safety through Day 28. Secondary outcomes included quantitative NP RNA levels and all-cause hospitalizations and deaths. Antiviral or clinical efficacy and safety criteria for graduation to Phase III were pre-specified. Results: From April to August 2021, randomized participants from 42 sites in the US received SAB-185 (N=107) or placebo (N=106). Median age was 38 years (quartiles: 30,48), 54% female, >98% cis-gender, 7% Black/African-American, 50% Hispanic, and 11% were classified as high-risk for COVID-19 progression, with median 4 days (3,6) from symptom onset. Day 0 NP SARS-CoV-2 RNA levels were similar between SAB-185 and placebo: 4.80 vs 4.80 log10 copies/ml. No differences were observed in the proportion with NP SARS-CoV-2 RNA< lower limit of quantification (LLoQ) in nasopharyngeal (NP) swab, time to improvement in targeted symptoms for 2 consecutive days after Day 0, and safety through Day 28. Secondary outcomes included quantitative NP RNA levels and all-cause hospitalizations and deaths. Antiviral or clinical efficacy and safety criteria for graduation to phase 3 were pre-specified. Conclusion: SAB-185 was safe in this Phase II study. While no significant differences to placebo were seen in symptom duration and proportion of participants with NP SARS-CoV-2 RNA< lower limit of quantification (LLoQ) in nasopharyngeal (NP) swab, time to improvement in targeted symptoms for 2 consecutive days after Day 0, and safety through Day 28. Secondary outcomes included quantitative NP RNA levels and all-cause hospitalizations and deaths. Antiviral or clinical efficacy and safety criteria for graduation to phase 3 were pre-specified.

17.
Topics in Antiviral Medicine ; 30(1 SUPPL):41, 2022.
Article in English | EMBASE | ID: covidwho-1880388

ABSTRACT

Background: Camostat, a serine protease inhibitor, prevents activation of the SARS-CoV-2 spike protein and blocks SARS-CoV-2 infection in vitro. We studied the safety and antiviral and clinical efficacy of orally administered camostat in non-hospitalized adults with mild-moderate COVID-19. Methods: ACTIV-2/A5401 is a platform trial to evaluate therapies for non-hospitalized adults with mild-moderate COVID-19. In a Phase II portion of the study, participants were enrolled within 10 days of COVID-19 related symptom onset and randomized to camostat 200 mg orally every 6 hours for 7 days or the pooled placebo group. Objectives were to evaluate the safety and efficacy of camostat to reduce the duration of COVID-19 symptoms and increase the proportion of participants with SARS-CoV-2 RNA below the lower limit of quantification (LLoQ) from nasopharyngeal (NP) swabs on days 3, 7, and 14. Participants completed a study diary from day 0 to day 28 scoring COVID-19 symptoms as absent, mild, moderate, or severe. Results: Of the 224 participants enrolled from 54 US sites, 215 participants (108 camostat, 107 placebo) initiated study intervention and formed the modified intent-to-treat population. Fifty-four percent were female, >99% cis-gender, 85% White, 9% Black, and 51% Latinx. Median age was 37 years;47% reported ≤5 days of symptoms at study entry and 26% met the protocol definition of higher risk of progression to severe COVID-19. Most frequent symptoms on day 0 were cough (86%), fatigue (85%), nasal obstruction/congestion (71%) and body/muscle aches (71%). There was no significant difference between camostat and placebo arms in grade 3 or higher adverse events (7.4% vs. 6.5%, respectively). Median (Q1, Q3) time to symptom improvement was 9 days for both camostat (5, 20) and placebo (6, 19). There were no significant differences in the proportion of participants with NP SARS-CoV-2 RNA<="" div=""> Conclusion: Camostat was well-tolerated. Despite compelling in vitro data, camostat did not show evidence of antiviral or clinical efficacy in ACTIV-2/A5401. This highlights the critical importance of randomized controlled trials in the evaluation of therapies for COVID-19.

18.
Topics in Antiviral Medicine ; 30(1 SUPPL):246, 2022.
Article in English | EMBASE | ID: covidwho-1880203

ABSTRACT

Background: Randomized COVID-19 trials provide opportunities to describe post-acute sequelae of SARS-CoV-2 (PASC)-related symptom burden longitudinally and assess the impact of early use of antivirals on PASC prevalence. Methods: ACTIV-2 evaluates safety and efficacy of investigational agents for non-hospitalized adults with mild to moderate COVID-19 in a Phase II/III trial. In Phase II, participants were randomized within 10 days of symptom onset and a positive SARS-CoV-2 virologic test to receive bamlanivimab (BAM) or placebo as a single infusion at 7000mg (n=94) or 700mg (n=225). In a subsequent single-arm open-label study, 1059 participants received 700mg BAM. Participants completed a 13-symptom daily diary from enrollment through Day 28. A long-term (LT) diary (14 additional symptoms) introduced after the study was underway was completed by a subset of individuals every 12 weeks. We report Week 24 findings. Results: Between Aug 2020 to Feb 2021 605 participants enrolled and completed LT diary at Week 24 [Phase II: 7000mg vs. placebo (n=25);700mg vs. placebo (n=68);single-arm open-label cohort: 700mg (n=512)]. Median age was 50 years, 51% female sex, 99% identified as cis-gender, 5% Black/African American, and 35% Hispanic/Latino. At enrollment, 53% reported ≥1 high-risk comorbidity and 0.3% were vaccinated against COVID-19. By Week 24, 14% (87/605) had not returned to their pre-COVID-19 health by self-report, with 57% (50/87) reporting ≥3 PASC symptoms. The most common symptoms were fatigue (45% of 87), smell disorder (36%), breathing difficulties (30%), taste disorders (25%), musculoskeletal pain (26%) or weakness (23%), and cognitive complaints: difficulty concentrating/thinking (30%), difficulty reasoning and solving problems (21%), memory loss (25%) and insomnia (23%). Most reported symptoms as "mild". Participants who reported acute viral illness symptoms between Days 22-28 were more likely to report PASC symptoms at Week 24 than those who did not report symptoms at Days 22-28 [51% (164/320) vs. 27% (76/285);p<0.0001]. Conclusion: In outpatients with mild to moderate COVID-19, 14% had not returned to pre-COVID-19 health by 24 weeks post infection, with generally mild but multiple symptoms. Presence of acute viral illness symptoms at 3-4 weeks was associated with an increased risk of PASC symptoms months later. Larger placebo-controlled studies within ACTIV-2 will assess the potential for early antiviral therapies to mitigate or prevent PASC.

19.
Journal of Clinical Urology ; 15(1):88, 2022.
Article in English | EMBASE | ID: covidwho-1869009

ABSTRACT

Introduction: The COVID-19 pandemic has changed many care pathways. We have analysed the treatment of patients with ureteric colic during the pandemic compared to an equivalent period before it began. Methods: Patients with acute ureteric colic were identified from acute CTKUBs requested in the emergency department from 1 September to 31 December 2020 ('pandemic cohort') and compared to the same timeframe in 2019 ('pre-pandemic cohort'), supplemented by clinical notes review. Results: There were 92 patients in the pandemic cohort, and 107 in the pre-pandemic cohort. Full results are detailed in Table 4. The rates of conservative management (64% vs 76%), temporising stent insertion (11% vs 14%) and emergency nephrostomy insertion (1% vs 1%) was similar in both cohorts (p > 0.05). However, more primary treatment was provided during the pandemic (25% vs 10%) mainly as extracorporeal shockwave therapy (ESWL, 21% vs 7%;p < 0.05). The pandemic cohort also had a shorter time to intervention (17 vs 39 days), driven by more rapid ESWL (4 vs 12 days) and to confirmation of stone passage (44 vs 91 days) (p < 0.05 for all three parameters), whereas the time to salvage ureteroscopy for failed conservative management was equivalent (35 vs 45 days, p > 0.05). Fifteen percent of the pandemic and 30% of the prepandemic cohort were lost to follow-up (p < 0.05). Conclusion: During COVID, reduced elective activity, particularly ESWL for renal stones, created capacity for urgent intervention such that the proportion of patients who had acute ESWL tripled (21% vs 7%) and were treated in one-third of the time (4 vs 12 days). Accordingly, the time to confirmation of stone passage was more than halved during the pandemic (44 vs 91 days). In accordance with recommendations from NICE, TISU, and GIRFT, these data confirm the importance of ringfencing urgent ESWL slots as we emerge from the pandemic.

20.
British Journal of Haematology ; 197(SUPPL 1):124-126, 2022.
Article in English | EMBASE | ID: covidwho-1861241

ABSTRACT

International Myeloma Working group (IMWG) diagnostic criteria for myeloma (MM) requires the presence of ≥10% clonal plasma cells alongside a MM defining event-traditionally a CRAB feature (hypercalcaemia, renal impairment, anaemia, bone disease). In 2014, three biomarkers were added (≥60% plasma cells in the marrow, light chain ratio ≥100 and ≥2 focal lesions on MRI), each associated with around an 80% probability of developing CRAB features within 2 years. These biomarkers are the SLiM criteria and the recommendation is that such patients are treated. In March 2020 UK Myeloma Forum issued guidance for MM therapy during the Covid-19 pandemic, recommending patients who fulfil the SLiM part only of the SLiM/CRAB (SLiM positive) or who only have anaemia should be monitored. There is a lack of real-world data available to validate the recommendation to treat based on SLiM criteria. The impact of not treating these patients during the Covid-19 pandemic remains unknown. We conducted a retrospective analysis of the outcomes of SLiM positive patients at Nottingham University Hospitals (NUH) NHS Trust who underwent observation rather than treatment during the Covid-19 pandemic. SLiM positive patients were detected via the MM MDT min from 1st April 2020-30 Nov 2021. Time to progression (TTP) was defined as the time from diagnosis of SLiM positive MM until the time systemic therapy was initiated (day 1 cycle 1). Decision to treat was based on development of CRAB features, worsening of SLiM criteria and patient choice. 22 SLiM positive patients were identified. Patient characteristics and outcomes for the entire cohort and for those who did and did not progress are shown in Table 1. No patients were R-ISS stage III and 1q gain was the only high-risk cytogenetic abnormality detected. This may suggest higher risk patients are more likely to present with CRAB features and less likely to be SLiM positive. The median follow-up was 12 months. Forty-one percent of patients progressed to require therapy in keeping with the IMWG data suggesting 80% of SLiM positive patients will progress over a 2-year period. The median TTP was not reached. For those patients who did progress, the median TTP was 3.8 months. Reasons for progression are shown in Table 1. Overall survival (OS) was 100% hence no suggestion thus far that observation of SLiM positive patients during the Covid-19 pandemic increased MM-related mortality. The majority who remained under observation were SLiM positive on WBMRI alone. In contrast, the majority who did progress had been SLiM positive on SFLC ratio, marrow infiltrate or a combination of features. We acknowledge the small numbers and relatively short follow-up of this study. Results thus far are in keeping with the IMWG finding that SLiM positive patients have around an 80% chance of progression at 2 years. There is a suggestion that patients who present with SLiM criteria only may have genomically lower risk disease. OS has not been affected thus far by monitoring SLiM patients. Our results also suggest that patients SLiM positive due to SFLC ratio or BM infiltration are more likely to require early intervention than those positive on WBMRI. We recommend a future multicentre UK wide analysis of the outcome of SLiM positive patients during Covid-19. Results would help counsel UK MM patients regarding when to offer treatment and potentially help develop a UK-based biomarker model to predict risk of progression..

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