Characterization of Demographics and Concomittant Symptoms in Patients with Post COVID-19 Conditions or Long COVID

Objectives: Post COVID-19 conditions or long COVID continues to burden the healthcare system. With the introduction of new code in October 2021 to appropriately capture this condition (U09.9), we have enough data to understand the detailed demographic and clinical characterization of the patients with long COVID. As this new clinical entity continues to evolve, our study will provide insights for care management and planning. Method(s): We conducted a retrospective cohort study from a large deidentified database of US health insurance claims. The study population included all individuals with at least one ICD-10 code for COVID (U07.1) between June 1, 2021, and November 30, 2022. Individuals with at least one ICD-10 code for long COVID (U09.9), at least 7 days after COVID diagnosis were termed "Long COVID" patients. Index date was defined as the first long COVID diagnosis date. We also assessed the most prevalent diagnosis codes within the 30 days pre- and post-index to understand top symptoms. Result(s): A cohort of 253,145 patients (62% female patients;38% male patients) were identified. Among this cohort, 3.2% were pediatric patients aged 0 - 17 years;73.3 % aged 18 - 64 years and 23.5 % aged 65+ years. Most prevalent symptoms that increased in the 30 day pre- and post-index: Nervous system symptoms (6 fold), fatigue (7 fold), Dyspnea (4.3 fold), esophagitis (1.6 fold) chronic kidney disease (1.3 fold) among others. Conclusion(s): Our findings indicate that long COVID is more prevalent in females, with fatigue and dyspnea emerging as top symptoms. These findings are consistent with the published literature. However, we uncovered additional symptoms such as nervous system symptoms, chronic kidney disease among others. Additional analysis is planned to evaluate the association of these symptoms with sociodemographic features to understand the health inequity aspects of long COVID.Copyright © 2023

Behavioral responses of terrestrial mammals to COVID-19 lockdowns.

COVID-19 lockdowns in early 2020 reduced human mobility, providing an opportunity to disentangle its effects on animals from those of landscape modifications. Using GPS data, we compared movements and road avoidance of 2300 terrestrial mammals (43 species) during the lockdowns to the same period in 2019. Individual responses were variable with no change in average movements or road avoidance behavior, likely due to variable lockdown conditions. However, under strict lockdowns 10-day 95th percentile displacements increased by 73%, suggesting increased landscape permeability. Animals' 1-hour 95th percentile displacements declined by 12% and animals were 36% closer to roads in areas of high human footprint, indicating reduced avoidance during lockdowns. Overall, lockdowns rapidly altered some spatial behaviors, highlighting variable but substantial impacts of human mobility on wildlife worldwide.

Consistent Effects of Early Remdesivir on Symptoms and Disease Progression Across At-Risk Outpatient Subgroups: Treatment Effect Heterogeneity in PINETREE Study.

INTRODUCTION: In the PINETREE study, early remdesivir treatment reduced risk of coronavirus disease 2019 (COVID-19)-related hospitalizations or all-cause death versus placebo by 87% by day 28 in high-risk, non-hospitalized patients. Here we report results of assessment of heterogeneity of treatment effect (HTE) of early outpatient remdesivir, focusing on time from symptom onset and number of baseline risk factors (RFs). METHODS: PINETREE was a double-blind, placebo-controlled trial of non-hospitalized patients with COVID-19 who were randomized within 7 days of symptom onset and had ≥ 1 RF for disease progression (age ≥ 60 years, obesity [body mass index ≥ 30], or certain coexisting medical conditions). Patients received remdesivir intravenously (200 mg on day 1 and 100 mg on days 2 and 3) or placebo. RESULTS: In this subgroup analysis, HTE of remdesivir by time from symptom onset at treatment initiation and number of baseline RFs was not detected. Treatment with remdesivir reduced COVID-19-related hospitalizations independent of stratification by time from symptom onset to randomization. Of patients enrolled ≤ 5 days from symptom onset, 1/201 (0.5%) receiving remdesivir and 9/194 (4.6%) receiving placebo were hospitalized (hazard ratio [HR] 0.10; 95% confidence interval [CI] 0.01-0.82). Of those enrolled at > 5 days from symptom onset, 1/78 (1.3%) receiving remdesivir and 6/89 (6.7%) receiving placebo were hospitalized (HR 0.19; 95% CI 0.02-1.61). Remdesivir was also effective in reducing COVID-19-related hospitalizations when stratified by number of baseline RFs for severe disease. Of patients with ≤ 2 RFs, 0/159 (0.0%) receiving remdesivir and 4/164 (2.4%) receiving placebo were hospitalized; of those with ≥ 3 RFs, 2/120 (1.7%) receiving remdesivir and 11/119 (9.2%) receiving placebo were hospitalized (HR 0.16; 95% CI 0.04-0.73). CONCLUSIONS: In the outpatient setting, benefit of remdesivir initiated within 7 days of symptoms appeared to be consistent across patients with RFs. Therefore, it may be reasonable to broadly treat patients with remdesivir regardless of comorbidities. TRIAL REGISTRATION: ClinicalTrials.gov number NCT04501952.

Differences in COVID-19 vaccination coverage by occupation in England: a national linked data study

Background: Monitoring differences in COVID-19 vaccination uptake in different groups is crucial to help inform the policy response to the pandemic. A key data gap is the absence of data on uptake by occupation. This study investigates differences in vaccination rates by occupation in England, using nationwide population-level data. Methods: We calculated the proportion of people who had received three COVID-19 vaccinations (assessed on 28 February 2022) by detailed occupational categories in adults aged 18-64 and estimated adjusted ORs to examine whether these differences were driven by occupation or other factors, such as education. We also examined whether vaccination rates differed by ability to work from home. Results: Our study population included 15 456 651 adults aged 18-64 years. Vaccination rates differed markedly by occupation, being higher in health professionals (84.7%) and teaching and other educational professionals (83.6%) and lowest in people working in elementary trades and related occupations (57.6%). We found substantial differences in vaccination rates looking at finer occupational groups. Adjusting for other factors likely to be linked to occupation and vaccination, such as education, did not substantially alter the results. Vaccination rates were associated with ability to work from home, the rate being higher in occupations which can be done from home. Many occupations with low vaccination rates also involved contact with the public or with vulnerable people Conclusions: Increasing vaccination coverage in occupations with low vaccination rates is crucial to help protecting the public and control infection. Efforts should be made to increase vaccination rates in occupations that cannot be done from home and involve contact with the public.

SMALL: Open Surgery versus Minimally invasive vacuum-Assisted excision for smaLL screendetected breast cancer - a UK phase III randomised multicentre trial

Background: Mammographic screening programmes reduce breast cancer mortality, but detect many small tumours with favourable biological features which may not progress during a woman's lifetime. Screen-detected cancers are treated with standard surgery and adjuvant therapies, with associated morbidities. There is a need to reduce overtreatment of good prognosis tumours and numerous studies have evaluated the omission of radiotherapy in this context. However, there is little evidence to support surgical de-escalation, although percutaneous minimally invasive treatment approaches have been described. Vacuum-assisted excision (VAE) is in widespread use for management of benign lesions and lesions of uncertain malignant potential. SMALL (ISRCTN 12240119) is designed to determine the feasibility of using this approach for treatment of small invasive tumours detected within the UK NHS Breast Screening Programme (BSP). Method(s): SMALL is a phase III multicentre randomised trial comparing standard surgery with VAE for screendetected good prognosis cancers. The main eligibility criteria are age >=47 years, unifocal grade 1 tumours with maximum diameter 15mm, which are strongly ER/PR+ve and HER2-ve, with negative clinical/radiological axillary staging. Patients are randomised 2:1 in favour of VAE or surgery;with no axillary surgery in the VAE arm. Completeness of excision is assessed radiologically, and if excision is incomplete, patients undergo open surgery. Adjuvant radiotherapy and endocrine therapy are mandated in the VAE arm but may be omitted following surgery. Co-primary end-points are: 1. Noninferiority comparison of the requirement for a second procedure following excision 2. Single arm analysis of local recurrence (LR) at 5 years following VAE Recruitment of 800 patients will permit demonstration of 10% non-inferiority of VAE for requirement of a second procedure. This ensures sufficient patients for single arm analysis of LR rates, where expected LR free survival is 99% at 5 years, with an undesirable survival probability after VAE of 97%. To ensure that the trial as a whole only has 5% alpha, the significance level for each co-primary outcome is set at 2.5% with 90% power. The Data Monitoring Committee will monitor LR events to ensure these do not exceed 3% per year. Secondary outcome measures include time to ipsilateral recurrence, overall survival, complications, quality of life and health economic analysis. A novel feature of SMALL is the integration of a QuinteT Recruitment Intervention (QRI), which aims to optimise recruitment to the study. Recruitment challenges are identified by analysing recruiter/patient interviews and audiorecordings of trial discussions, and by review of trial screening logs, eligibility and recruitment data and study documentation. Solutions to address these are developed collaboratively, including individual/group recruiter feedback and recruitment tips documents. Result(s): SMALL opened in December 2019, but recruitment halted in 2020 for 5 months due to COVID-19. At 7st July 2022, 142 patients had been randomised from 26 centres, with a randomisation rate of approximately 45%, and a per site recruitment rate of 0.4-0.5 patients/month, approaching the feasibility recruitment target of 144 patients. Drawing from preliminary QRI findings and insights from patient representatives, a recruitment tips document has been circulated (on providing balanced information about treatments, encouraging recruiters to engage with patient preferences, and explaining randomisation). Individual recruiter feedback has commenced, with wider feedback delivered across sites via recruitment training workshops. Conclusion(s): Despite pandemic-related challenges, SMALL has an excellent recruitment rate to date and is expected to have a global impact on treatment of breast cancer within mammographic screening programmes.

Outcomes in Pregnant Women Hospitalized With Acute COVID-19 Infection

Introduction: There are conflicting data on COVID-19 outcomes in pregnant women. Using the AHA COVID-19 CVD Registry we evaluated COVID-19 outcomes in pregnant vs non-pregnant women with COVID-19. Method(s): Women 18-40 years old hospitalized from March 2020 to December 2021 with symptomatic COVID-19 were included (n=2,068), with 110 (5.3%) pregnant at admission. Women with unknown pregnancy status were excluded. Vaccine data were limited (2.8% of participants), therefore omitted from analysis. Baseline demographics and symptoms at presentation were compared between pregnant and non-pregnant women (Table). Rates of death, mechanical ventilation, ICU admission, hospital stay >=5 days, myocardial infarction, stroke, DVT, PE, and a composite of all outcomes were determined. Multivariable Cox regression analyses were performed, adjusting for comorbidities and prior CVD. Result(s): Pregnant women hospitalized with COVID-19 had fewer comorbidities than non-pregnant women (Table). There were no deaths in the pregnant group and 44 (2.3%) in the non-pregnant group. Fewer pregnant women were hospitalized >=5 days (29.1% vs 41.2% non-pregnant);this difference was not statistically significant after multivariable adjustment [adjusted HR (95% CI), 0.67 (0.43-1.02)]. There were no significant differences between the groups in the composite outcome [adjusted HR (95% CI), 0.72 (0.48-1.07)] or its components (Table). Conclusion(s): Pregnant women hospitalized with symptomatic COVID-19 had fewer comorbidities compared with non-pregnant women. There were fewer deaths and lower rates of hospitalization >=5 days in pregnant vs non-pregnant women which was no longer statistically significant after multivariable adjustment. The potential for residual confounding due to healthier pregnant women presenting with milder COVID-19 illness or being admitted for non-COVID-19 indications compared to non-pregnant women must be considered when interpreting these findings.

Guillain-Barre Syndrome and Parsonage-Turner Syndrome Following COVID-19 Viral Vector Vaccination

Case Diagnosis: Patient is a 63-year-old male with Guillain-Barre Syndrome and Parsonage-Turner Syndrome following COVID-19 Vaccination Case Description or Program Description: Eight days after receiving a viral vector COVID-19 vaccination, the patient developed low back and left thigh pain with severe right shoulder pain developing the following day. He denied recent viral illnesses, gastrointestinal symptoms, or prior right shoulder pain. Pain, weakness, and sensory changes gradually involved all four extremities. He was hospitalized and Guillain-Barre Syndrome (GBS) was confirmed by lumbar puncture. He tested negative for Campylobacter jejuni. Cervical and lumbar spine MRIs showed mild degenerative changes without stenosis or neuroforaminal impingement. Right shoulder MRI showed no abnormality. He responded to a 5-day course of IVIG. His extremity pain gradually resolved but right shoulder weakness remained. Electrodiagnostic testing six months after symptom onset showed evidence of GBS in recovery. Right shoulder girdle muscles were not tested during the first EMG. After stays at an LTAC and SNF, the patient was admitted to IPR. While at IPR, he reported debilitating right shoulder weakness and limited ROM. On exam, significant atrophy of the right deltoid, infraspinatus, and supraspinatus muscles was observed. A repeat electrodiagnostic study showed evidence of a right Parsonage-Turner syndrome (PTS) in addition to the GBS in recovery. Setting(s): Inpatient Rehabilitation (IPR) Assessment/Results: Patient's presentation and EMG findings pointed to a concurrent occurrence of PTS and GBS after his COVID-19 vaccination. A right shoulder ultrasound-guided glenohumeral joint corticosteroid injection improved his shoulder ROM. The patient was discharged home with outpatient therapy after four weeks of IPR. Discussion (relevance): Rare instances of GBS and Parsonage-Turner Syndrome have been reported after a COVID-19 vaccination. This appears to be the first reported case where GBS and PTS have both occurred in a patient soon after receiving a COVID-19 vaccination. Conclusion(s): Concurrent PTS and GBS can develop after COVID-19 vaccine administration.

SARS-CoV-2 Antibody Seroprevalence in Jakarta, Indonesia

The SARS-CoV-2 transmission dynamics in low- and middle-income countries remain poorly understood. This study aimed to estimate the SARS-CoV-2 antibodies seroprevalence in Jakarta, Indonesia, and to increase knowledge of SARS-CoV-2 transmission in urban settings. A population-based serosurvey among individuals aged one year or older was conducted in Jakarta. Employing a multistage sampling design, samples were stratified by district, slum and non-slum residency, sex, and age group. Blood samples were tested for IgG against three different SARS-CoV-2 antigens. Seroprevalence was estimated after applying sample weights and adjusting for cluster characteristics. In March 2021, this study collected 4,919 respondents. The weighted estimate of seroprevalence was 44.5% (95% CI = 42.5-46.5). Seroprevalence was highest among adults aged 30-49 years, with higher seroprevalence in women and the overweight/obese group. Respondents residing in slum areas were 1.3-fold more likely to be seropositive than non-slum residents. It was estimated that 4,717,000 of Jakarta's 10.6 million residents had prior SARS-CoV-2 infection. This suggests that approximately 10 infections were undiagnosed/underreported for every reported case. About one year after the first COVID-19 case was confirmed, close to half of Jakarta's residents have been infected by SARS-CoV-2.

SMALL: Open surgery versus minimally invasive vacuum-assisted excision for small screen-detected breast cancers

Background: Mammographic screening programmes reduce breast cancer mortality but detect many small tumours with favourable biology which may not progress. These are treated with surgery and adjuvant therapies, but associated morbidities mean there is a need to reduce overtreatment. Minimally invasive treatments such as vacuum-assisted excision (VAE) have been described but there is no prospective randomised evidence to support their routine use. SMALL (ISRCTN 12240119) is designed to establish the feasibility of using VAE to treat small tumours detected within the UK NHS Breast Screening Programme (BSP). Methods: Phase III multicenter randomized trial comparing surgery with VAE for screen-detected good prognosis cancers. Eligibility criteria are age ≥47 years, unifocal grade 1 tumors (maximum diameter 15mm), strongly ER/PR+ve and HER2-ve, with negative axillary staging. Patients are randomized 2:1 to VAE or surgery, with no axillary surgery in the VAE arm. Excision is assessed radiologically, and if incomplete, patients undergo surgery. Adjuvant radiotherapy and endocrine therapy are mandated in the VAE arm. Coprimary end-points are: (1) Non-inferiority comparison of the requirement for a second procedure. (2) Single-arm analysis of local recurrence (LR) at 5 years after VAE. Recruitment of 800 patients will permit demonstration of 10% non-inferiority of VAE for requirement of a second procedure, ensuring sufficient patients for single arm analysis of LR rates, where expected LR free survival is 99% at 5 years, with an undesirable survival probability after VAE of 97%. The DMC will monitor LR events to ensure these do not exceed 3% per year. Secondary outcome measures include time to ipsilateral recurrence, overall survival, complications, quality of life and health economic analysis. A QuinteT Recruitment Intervention (QRI) is integrated throughout SMALL to optimize recruitment and informed consent. Recruitment challenges are identified by analyzing recruiter/ patient interviews, audio-recordings of trial discussions, and by review of screening, eligibility and recruitment data and study documentation. Solutions are developed collaboratively, including recruiter feedback and recruitment tips documents. Results: SMALL opened in December 2019, but recruitment halted for 5 months due to COVID-19. At 11th February 2022, 91 patients had been recruited from 22 centers, with an approached/consented ration of 50%. Drawing from preliminary QRI findings, a recruitment tips document has been circulated (on discussing SMALL, providing balanced information on treatment options and explaining randomization). Individual recruiter feedback has commenced, with wider feedback planned shortly. Conclusion: Despite pandemic-related challenges, SMALL has excellent recruitment to date and is expected to have a global impact on treatment of screen-detected breast cancer.

Early nutritional screening, appropriate first line advice and prescribed oral nutrition support across organisational boundaries. New oral nutrition support pathway striving for seamless delivery of care from Hospital into Community Care

In the UK, approximately 3 million people are malnourished or at risk of malnutrition. Malnutrition is a major public health issue with costs the NHS over £19 billion per year in England alone. We know 93% of malnutrition happens in peoples own homes, 5% in care homes and 2% in hospital. It is also understood that 30% of inpatients are at higher risk of becoming malnourished in hospital. 1 As many departments, demand for dietetic services has outweighed capacity, in part due to improved rates of nutritional risk screening across the organisation. The Trust uses an internal validated nutritional screening tool but community partners largely use MUST (Malnutrition Universal Screening Tool). Within our Dietetic team, we identified a number of treatment strategies needed to ensure timely care, patient empowerment and patient safety with a focus on improved nutrition to help recovery across organisational boundaries from the acute admission and into primary care. Patients who are identified as malnourished or at very high risk of malnutrition, have specialist requirements should have immediate referral to a dietitian. Oral nutritional supplements are now prescribed appropriately whilst in hospital and post discharge in line with national and local guidelines. 4 Communication between different healthcare professionals and settings is essential for the seamless delivery of care2 and hospital teams discharging patients with an identified risk of malnutrition should communicate this in writing to primary care teams3. As a team, we decided to encompass nutrition and dysphagia scores as an inpatient on discharge letters. This was be achieved by working closely with the pharmacy, Speech and Language, catering, nursing and medical teams to develop and implement a clear process for all adult inpatients to improve ward based nutritional care and appropriate prescribing, based on their individual risk of malnutrition. We have developed and implemented a discharge process that provides patients with a nutrition pack (malnutrition pathway leaflets, cover letter +/- Care Homes information) +/- nutritional supplements on discharge. The process was developed with local CCGs, GPs, PCN Pharmacists and community dietetic services. Outcomes measured include;appropriate prescribing, access to snacks and supplements, clinical outcomes including length of stay (LOS), readmission rates and timely access to first line advice. Baseline audit information revealed only 8% of inpatients received the a first line nutrition leaflet, this has increased to 13% just 6 weeks post implementation, patient first line snacks has increased to 5 different categories as choice available has increased. Oral nutritional support (ONS) is now solely prescribed using the agreed ONS pathway. Early indications suggest a direct improvement in patient care and choice. References 1. Brothern A, Simmonds N, Stroud M.2010. Malnutrition Matters: Meeting Quality Standards in Nutritional Care. A report on behalf BAPEN Quality Group 2. ‘A Guide to Managing Adult Malnutrition in the Community’ Last accessed from: on 02.07.2021 3. ‘Pathway for using ONS in the Management of Malnutrition’ Last accessed from:https://www.malnutritionpathway.co.uk/library/ons_pathway.pdf on 29.06.2021 4. ‘Nutritional considerations for primary care teams managing patients with or recovering from COVID-19’ BDA and optimising nutritional prescribing last accessed :. 02.07.21