The certification of vision impairment: A regional 21st century perspective

Certification and registration of those who are sight impaired (SI) provides commissioners, and the providers of health and social care support to those with vision loss, with quantifiable data on the extent of blindness and sight impairment within a community. In this article, we outline the results of a comprehensive review of certification/registration pathways and processes in Northern Ireland and highlight achievements to date. The Developing Eyecare Partnership (DEP) CVI Task Group established by the Health and Social Care Board (HSCB) reviewed all certification/registration processes, pathways and issues that may have contributed to regional under certification/registration. This was undertaken to ensure timely certification/registration of those who may benefit from being certified as either Severely Sight Impaired (SSI) or SI, and in so doing improving patient pathways and access to services. Activity included a review of all available epidemiological data collected in the 2-year periods before and after the introduction of the new pathway (January 1, 2018). This work has resulted in changes to the terminology used in relevant Northern Ireland legislation and other documentation concerning certification/registration. It has also resulted in the creation of more timely and efficient referral pathways and improvements in the quality of information available on certification and the process. Increased awareness of the certification process by health and social care professionals has resulted in a 22.5% increase in certifications over the 2-year period, before COVID-19. Certification rates are now comparable with those from other areas of the United Kingdom. The workings of the DEP CVI group, over a 5-year period, have increased awareness about SI and SSI Certification among patients and Health and Social Care Providers and have improved the quality of local epidemiological data on vision impairment. A patient-based evaluation of the new pathway is planned for 2020.

The impact of prone episodes on oxygenation in COVID-19 mechanically ventilated patients

Introduction: Prone positions have been used extensively to improve oxygenation in patients with acute respiratory distress syndrome (ARDS). During the COVID-19 pandemic there was widespread adoption of proning in patients with acute severe hypoxic respiratory failure. Few studies explore the use of prone positioning in mechanically ventilated COVID-19 patients. Method(s): This study was part of the REACT COVID observational study at University Hospital Southampton (UHS) [1]. Eligibility included admission to UHS with a positive COVID-19 RT-PCR between 03/2020 and 03/2022. Data was collected from all available electronic clinical data sources using semi-automated and manual data extraction. Result(s): 184 patients received invasive mechanical ventilation with documented evidence for 931 prone episodes. We performed detailed analysis for 763 prone episodes. The rest were excluded due to insufficient data. The median duration of each cycle was 16 h (IQR 15-17 h). 459 cycles were done within 7 days of intubation (early), 202 in 7-14 days (intermediate) and 102 after 14 days (late). The change in oxygenation defined as delta PaO2/ FiO2 ratio (DELTAPF) for early, intermediate, and late cycles were 2.4 +/- 5.2 kPa, 1.6 +/- 3.7 kPa and 1.4 +/- 4.0 kPa, (p = 0.03) respectively. The overall DELTAPF for all groups after a cycle was 2.1 +/- 4.7 kPa. There was an increase in PaCO2 following proning with an overall change of 0.30 +/- 1.0, however, this was not statistically significant (p = 0.30). Conclusion(s): Following proning, there was significant improvement in oxygenation. Cycles lasted for 16 h consistent with current ARDS guidelines [2]. Although the results suggest a diminishing response in those proned at later times, the DELTAPF ratio was still significant. Overall, this suggests a beneficial effect on oxygenation. However, findings cannot be translated into survival benefit. Further research including randomised controlled trials is recommended.

Breeching "The Goldilocks Zone”: Tetraplegia as a Rare Life-Altering Infective Complication of Adjuvant Breast Cancer Chemotherapy

Background: Adjuvant chemotherapy has been an integral component of breast cancer care for decades. Advances in supportive care have been made, but despite this, infective complications of therapy remain a significant toxicity concern. Case Presentation: A premenopausal patient presented to the emergency department during the third wave of the Covid-19 pandemic with sepsis after a second course of adjuvant docetaxel-cyclophosphamide chemotherapy. Overnight she developed tetraplegia. An urgent MRI cervical spine revealed a pre-vertebral, vertebral, and epidural abscess. This was treated with an emergency C4-C7 posterior cervical laminectomy and decompression. Her inpatient care involved a protracted ICU admission followed by rehabilitation. She remains tetraplegic and requires continued inpatient care over a year after presentation. Restricted pandemic-related hospital visiting has compounded the impact of her illness. Conclusion: Infective complications of adjuvant breast cancer chemotherapy remain an issue despite advances in supportive care. This case highlights the devastating, life-altering impact that these complications can have as emphasized by the inclusion of the patient's perspective. Copyright © 2022.

Increased stroke severity and mortality in patients with SARS-CoV-2 infection: An analysis from the N3C database.

BACKGROUND: Studies from early in the COVID-19 pandemic showed that patients with ischemic stroke and concurrent SARS-CoV-2 infection had increased stroke severity. We aimed to test the hypothesis that this association persisted throughout the first year of the pandemic and that a similar increase in stroke severity was present in patients with hemorrhagic stroke. METHODS: Using the National Institute of Health National COVID Cohort Collaborative (N3C) database, we identified a cohort of patients with stroke hospitalized in the United States between March 1, 2020 and February 28, 2021. We propensity score matched patients with concurrent stroke and SARS-COV-2 infection and available NIH Stroke Scale (NIHSS) scores to all other patients with stroke in a 1:3 ratio. Nearest neighbor matching with a caliper of 0.25 was used for most factors and exact matching was used for race/ethnicity and site. We modeled stroke severity as measured by admission NIHSS and the outcomes of death and length of stay. We also explored the temporal relationship between time of SARS-COV-2 diagnosis and incidence of stroke. RESULTS: Our query identified 43,295 patients hospitalized with ischemic stroke (5765 with SARS-COV-2, 37,530 without) and 18,107 patients hospitalized with hemorrhagic stroke (2114 with SARS-COV-2, 15,993 without). Analysis of our propensity matched cohort revealed that stroke patients with concurrent SARS-COV-2 had increased NIHSS (Ischemic stroke: IRR=1.43, 95% CI:1.33-1.52, p<0.001; hemorrhagic stroke: IRR=1.20, 95% CI:1.08-1.33, p<0.001), length of stay (Ischemic stroke: estimate = 1.48, 95% CI: 1.37, 1.61, p<0.001; hemorrhagic stroke: estimate = 1.25, 95% CI: 1.06, 1.47, p=0.007) and higher odds of death (Ischemic stroke: OR 2.19, 95% CI: 1.79-2.68, p<0.001; hemorrhagic stroke: OR 2.19, 95% CI: 1.79-2.68, p<0.001). We observed the highest incidence of stroke diagnosis on the same day as SARS-COV-2 diagnosis with a logarithmic decline in counts. CONCLUSION: This retrospective observational analysis suggests that stroke severity in patients with concurrent SARS-COV-2 was increased throughout the first year of the pandemic.

The effect of the pandemic on the number of examined lymph nodes following major oesophophagogastric resection

Background: Lymph node yield following oesophagogastric (OG) cancer resection remains a valuable prognosticator of overall patient survival. It is also a quality indicator of histopathological assessment and a surrogate marker of surgical technique. The Royal College of Pathologists' state a minimum lymph node yield of 15 per specimen should obtained in 100% of cases where a radical OG resection has been undertaken. It is well known that the COVID-19 pandemic placed immense strain on NHS services. This study aimed to evaluate its effect on lymph node yield reporting following major OG resection in a large volume tertiary unit. Method(s): Retrospective National OG Cancer Audit (NOGCA) metrics were collected. Histological data including total lymph node yield and positive node status were extracted from patient records. Patient data was categorised into two study periods;pre-pandemic (March 2018-Feb 2020) and pandemic (March 2020- Feb 2022) following the first UK national lockdown. Comparative analysis between the two study periods was performed and for lymph node yield >15 per specimen a X2 statistic calculated. Result(s): In the pre COVID period a total of 280 (excluding GIST) resections were performed, 75% (210) oesophagectomies v. 25% (70) gastrectomies. The median age was 69 (range 25-90, males= 189 v. females =91). In the post pandemic period a total of 188 resections were performed, 72% (135) oesophagectomies v. 28% (53) gastrectomies. The median age was 69 (38-87, males = 142 v. female= 46). Lymph node yield was available for 275 resections in pre-pandemic study period, with a median nodal yield of 20 (5-61). In the pandemic study period lymph node yield data was available for 180 patients, median 19.5 (0-69). The minimum nodal yield (>15) was obtained in 80.7% of resection specimens pre-pandemic v. 68.9% in the pandemic study period (p= 0.00382). Conclusion(s): Our study demonstrates a higher rate of inadequate nodes examined in the post pandemic study period. Despite staffing pressures, efforts should be made to improve number of nodes examined to provide robust prognostic data.

Maintaining high volume oesophagagogastric resections during the COVID-19 pandemic: A single centres experience utilising the independent sector

Background: With many resources redirected to care for the those affected by the COVID-19 pandemic, the NHS faced unprecedented pressure to maintain oesophagogastric (OG) cancer resectional services. Our institution along with many tertiary units across the country were faced with limited access to essential critical care beds. The implementation of emergency contracts between the NHS and the independent sector (IS) allowed our unit to maintain a high volume resectional service by utilising the resources of a local private hospital with HDU/ ITU provision. We began operating within the IS shortly after the first UK lockdown in March 2020, and continued through till February 2022. During this period, we continued operating at our tertiary unit (TU) albeit at a reduced capacity. This study aimed to evaluate the surgical outcomes of patients undergoing major OG resectional surgery between the two sites. Method(s): This retrospective study included all patients who underwent major OG resectional surgery (including GIST) from March 2020-February 2022. Operation type and site were identified using OPCS-4 clinical codes and combined with National OG Cancer Audit (NOGCA) data to compare basic patient demographics, length of stay, complication rates, COVID infection rates and 90-day mortality. Descriptive and statistical analysis between the two operating sites was performed. Result(s): A total of 204 major OG resections were undertaken, 44% (89) at our TU;57 oesophagectomies and 32 gastrectomies, with 56% (115) at a local IS hospital;86 oesophagectomies and 29 gastrectomies. Additionally, 13 (6.4%) open and close procedures were performed across both sites. Median patient age was similar, 69 (45-86) years at our TU v. 68 (38-85) years at the IS site. A higher proportion of ASA 3 patients (46%) were operated on at our TU. No difference in median length of stay was observed;TU= 8 (1-93) days v. IS =9 (3-69) days, this included all patients who were repatriated to the TU. Higher complication rates seemed to occur in patients operated at the IS site v. the TU though these did not reach statistical significance;18 (15.7%) patients suffered an anastomotic leak v. 9 (10.1%) respectively (p= 0.246). 21 (18.3%) v. 13 (14.6%) patients suffered a major respiratory (p=0.487) and 4 (3.5%) v. 1 (1.1%) a major cardiac (p=0.281) complication. There were no cases of COVID infection within 30 days of primary procedure at the IS site, with 2 cases within the TU cohort. Our 90-day mortality rates were similar (IS= 4.54% v. TU=5.32%), p=0.661. Conclusion(s): Our study demonstrates that resection of patients with OG cancer is feasible in an independent sector hospital if supported by critical care. It allowed a high-volume tertiary unit to continue offering potentially curative surgery to patients whose treatment options would have otherwise been limited to oncological therapy only. Long term survival data compared to non-resecting trusts is required to determine whether this approach was superior. When considering future pandemic planning, we have demonstrated the value of this model in maintaining major OG resectional services.

UX design research for improving student experience in online laboratories

The COVID-19 pandemic forced educators and students to transition to online instruction. This change brought the importance of user interfaces into stark relief for engineering lab classes, compelling educators to consider how the design of online courses and virtual laboratory experiences either served or worked against student learning. In summer 2020, we began educational and user experience (UX) research with the online laboratory experiences in an electrical engineering lab classroom at the University of Georgia's College of Engineering. The NSF-funded project work draws on ready-to-use remote labs for electronics applied to several courses. It seeks to explore the faculty and student perspective on online experimentation in engineering curricula. However, the UX thrust of the project rounds out a holistic view of the online learning ecosystem and might specifically uncover barriers or factors of success related to the implementation of online labs. This project highlighted the importance of UX design in delivering science curriculum via virtual laboratory exercises with the specific conclusion that deficits in perspicuity in the UX create an obstacle to learning for engineering students. © American Society for Engineering Education, 2022.

Oxygen indices in COVID-19 mechanically ventilated patients with acute hypoxic respiratory failure: A cohort study

Introduction: Hypoxic respiratory failure, a hallmark of severe COVID-19, often requires oxygen therapy.1 Mechanical ventilation carries a high mortality.2 We evaluate trends in oxygen indices (PaO2/FiO2 ratio, CaO2, O2ER) in COVID-19 patients throughout an intensive care admission and correlation with clinical outcomes. Objectives: To establish the trends in oxygen indices in mechanically ventilated adult COVID-19 patients throughout an intensive care admission. Methods: We performed a retrospective observational cohort study in a UK university hospital (ethics through REACT COVID-193), including all adult COVID-19 patients requiring mechanical ventilation between 01/03/20 and 31/ 03/21. We collected baseline characteristics, clinical outcomes and oxygen parameters. Results: 184 patients met inclusion criteria, providing 34592 blood gas data points over 30-days. The median age was 59.5 (IQR 51, 67), and median BMI 30 (IQR 25.8, 35.5). The majority were men (62.5%) of white ethnicity (70.1%). Median mechanical ventilation duration was 15-days (IQR 8, 25) and 133 patients (72.3%) survived 30-days. Oxygen indices are presented in Table 1. Non-survivors exhibited lower oxygen extraction;there was an averaged mean difference in O2ER of -0.06 (95% CI -0.09, -0.03) across days one to seven and -0.09 (95% CI -0.10, -0.07) across days one to 30. While both survivors and non-survivors had sub-physiological CaO2 (which trended down throughout their ICU admission), non-survivors tended to exhibit higher values;there is an averaged mean difference of 0.23 (95% CI 0.13, 0.34) across day one to day seven and 0.28 (95% CI 0.21, 0.35) across days one to 30. Conclusions: As a novel cause of respiratory failure, COVID-19 offers a unique opportunity to study a homogenous cohort. In mechanically ventilated adult COVID-19 patients, oxygen indices are abnormal. Despite having similar CaO2 values, oxygen extraction differs significantly between survivors and non-survivors, suggesting COVID-19 causes impaired oxygen utilisation. Urgent further evaluation is warranted.

Experience with over 10,000 sleep telemedicine visits for diagnosis and treatment of OSAS

Introduction: Since March 2020 BlueSleep has completed over 10,000 telemedicine consultations for diagnosis and treatment of sleep apnea exclusively by real-time telemedicine consultations using HIPAA-compliant video conferencing. Materials and Methods: This is a retrospective chart review of all virtual consultations performed between March 13, 2020 and December 31, 2021 at the BlueSleep center. This period coincided with the lockdown in New York City because of the COVID19 Pandemic. 10,171 telemedicine consultations were performed both for new and existing patients. No patients under the age of 18 were evaluated. The median patient age was 40 years old;2,412 males, 1,098 females. Diagnosis of sleep apnea was performed with disposable single-night or multi-night Home Sleep Tests (HST) with WatchaptOne (Itamar Medical) or Nightowl (Ectosense). Patients were given instructions for HSTs via asynchronous videos. HST data was transmitted to a portal for scoring and interpretation. Follow-up visit was by telemedicine, and treatment options including oral appliance therapy and CPAP were discussed. Surgical options were not available during the lockdown. If oral appliance therapy was chosen by the patient, a virtual visit with a dental professional was scheduled before sending a home impression kit. Home impressions were guided in real time with a dental professional. Dental impressions were submitted to the dental labs for fabrication of Mandibular Advancement Devices (MAD), and sent to the patient for a virtual home delivery by the dental professionals. A follow-up virtual visit was scheduled after the 4-week titration period, and depending on subjective results of decreased snoring and decreased daytime sleepiness, the patient was then instructed to repeat a HST for efficacy evaluation. If the patient chose CPAP, CPAP was shipped to the home, and a follow-up visit was scheduled for a virtual set-up visit, followed by compliance visits. All patients were scheduled for continuous telemedicine follow-up visits. Results: 10,171 visits were completed including first and follow-up visits. A total of 289 single-night and 2,275 multi-night HSTs were performed. 2,348 patients were diagnosed with OSA. 36% with mild OSA, 41% of patients with moderate OSA, and 23% with severe OSA. 1,163 had no OSA. 53% of patients were treated with OAT, 20% with CPAP. 271 patients were treated for primary snoring. 256 patients were treated for insomnia. 31 patients were diagnosed with Narcolepsy, and 636 patients were diagnosed with "other". Conclusions: A fully virtual model for diagnosis and treatment for obstructive sleep apnea and other sleep disorders is feasible and desirable. Telemedicine allows greater convenience (less time lost from work), and availability (greater geographic availability), and is a lower cost option. Acknowledgements: We wish to thank the entire BlueSleep staff that has helped make our service to patients available during the Covid 19 Pandemic.

“I Didn't Know Before that You Can Get Birth Control this Way”: Developing a Tool to Teach Young People About Telehealth for Contraception

Purpose: The COVID-19 pandemic has led to widespread expansion of telehealth services for adolescent and young adult patients, including contraceptive care. However, many young people lack awareness of telehealth services or how to use them. Our aim was to develop and conduct formative testing of an educational tool to increase young people’s knowledge of telehealth for contraception. Methods: We developed a youth-friendly visual tool on how to access contraception through video and phone visits and online birth control platforms. In July 2021, we recruited 35 young people aged 18-25 of all gender identities in California through social media and outreach at community colleges to inform tool development. Participants completed pre and post surveys after reviewing the tool, and we measured changes in telehealth knowledge using McNemar’s statistical testing. We also conducted semi-structured interviews to understand the survey responses, their perceptions of the educational tool, and their experiences and challenges using telehealth for contraception. We used a modified form of grounded theory to analyze the interview data. Results: Participants included diverse sexual orientations, with 51% straight, 26% bisexual and 18% gay/lesbian or queer. 80% were sexually active and 63% wanted birth control. Most of the participants (86%) identified as a woman, 11% man, and 3% genderqueer/gender non-binary. Participants largely identified as Latinx (57%), with 14% Asian, 14% White, 11% Mideastern, and 9% Black. Telehealth knowledge increased universally after viewing the educational tool. The percentage who knew what telehealth is increased from 60% to 100% (p< 0.001), and knowledge of how to get contraception without going to a clinic in person increased from 37% to 97% (p< 0.001). After viewing the telehealth information, most participants correctly identified which contraceptive methods are available through telemedicine visits, including the pill (100%), patch (100%), vaginal ring (86%), and emergency contraception (86%). Acceptability was high, with all participants agreeing that the tool was useful, taught them new things, and that they would share the information with friends. One participant commented, “I liked seeing what methods you can get through telehealth.” The interview data revealed areas where participants need additional education about telehealth for contraception. Many participants shared concerns about the cost and insurance coverage of telehealth services, confidentiality, and the safety and legitimacy of online birth control prescription companies. Many were unsure how to find a health center that offers telemedicine visits. Most participants wanted to know more about birth control methods available through telehealth, such as their effectiveness and how to use them. Conclusions: This youth-friendly tool helped to improve young people’s knowledge of telehealth for contraception. The next stage will involve community advisory board review and testing a revised version with a larger and more representative sample to ensure acceptability and effectiveness among all young people. As the use of telehealth continues to grow, educational materials are necessary to help address the low levels of telehealth knowledge and barriers to health care among young people. Sources of Support: The JPB Foundation, The William and Flora Hewlett Foundation.

RISK AND PROTECTIVE FACTORS ASSOCIATED WITH MENTAL HEALTH DIFFICULTIES FOR CHILDREN WITH ADHD OVER THE COVID-19 PANDEMIC: A LONGITUDINAL STUDY

Background: A growing number of studies have reported both positive and negative outcomes associated with COVID-19 in children with attention-deficit/hyperactivity disorder (ADHD) and their families. However, very few longitudinal studies have examined outcomes over multiple time points over the pandemic. Objectives: To examine COVID-19-related mental health (MH) impacts for children with ADHD and their families over a 12-month period over the pandemic. Methods: The parents of 213 Australian children (5-17 years) with ADHD were recruited in May 2020 when COVID-19 restrictions were in place. Parents completed surveys at repeated time points assessing MH (CoRonavIruS Health Impact Survey [CRISIS] - mood states subscale) and predictors. Latent profile analyses were used to examine the patterns of MH difficulties over the pandemic using the first four waves of data collected from May to August 2020, and the fifth wave of data collected in May-July 2021. Numerous baseline predictors of MH patterns were examined. Findings: Using the first four waves of data, three groups were identified comprising: (1) children with unchanging (36%), (2) increasing resolved (30%) and (3) increasing persistent (34%) MH difficulties. The most robust predictor of increasing persistent MH difficulties was stress related to COVID-19 (e.g. stress associated with restrictions related to COVID-19). Analyses are being updated to include our fifth wave of data collection (May-July 2021) (70% retention rate). Conclusion: A subgroup of children with ADHD appears to be struggling with MH, which is related to the stress associated with COVID-19 restrictions.

The acute phase response identifies cancer patients with adverse outcomes from SARS-CoV-2 infection as quantified by the OnCovid Inflammatory Score

We sought to determine parameters of the acute phase response, a feature of innate immunity activated by infectious noxae and cancer, deranged by Covid-19 and establish oncological indices' prognostic potential for patients with concomitant cancer and Covid-19. Between 27/02 and 23/06/2020, OnCovid retrospectively accrued 1,318 consecutive referrals of patients with cancer and Covid-19 aged 18 from the U.K., Spain, Italy, Belgium, and Germany. Patients with myeloma, leukemia, or insufficient data were excluded. The neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), prognostic nutritional index (PNI), modified Glasgow prognostic score (mGPS), and prognostic index (PI) were evaluated for their prognostic potential, with the NLR, PLR, and PNI risk stratifications dichotomized around median values and the pre-established risk categorizations from literature utilized for the mGPS and PI. 1,071 eligible patients were randomly assorted into a training set (TS, n=529) and validation set (VS, n=542) matched for age (67.9±13.3 TS, 68.5±13.5 VS), presence of 1 comorbidity (52.1% TS, 49.8% VS), development of 1 Covid-19 complication (27% TS, 25.9% VS), and active malignancy at Covid-19 diagnosis (66.7% TS, 61.6% VS). Among all 1,071 patients, deceased patients tended to categorize into poor risk groups for the NLR, PNI, mGPS, and PI (P<0.0001) with a return to pre-Covid-19 diagnosis NLR, PNI, and mGPS categorizations following recovery (P<0.01). In the TS, higher mortality rates were associated with NLR>6 (44.6% vs 28%, P<0.0001), PNI<40 (46.6% vs 20.9%, P<0.0001), mGPS (50.6% for mGPS2 vs 30.4% and 11.4% for mGPS1 and 0, P<0.0001), and PI (50% for PI2 vs 40% for PI1 and 9.1% for PI0, P<0.0001). Findings were confirmed in the VS (P<0.001 for all comparisons). Patients in poor risk categories had shorter median overall survival [OS], (NLR>6 30 days 95%CI 1-63, PNI<40 23 days 95%CI 10-35, mGPS2 20 days 95%CI 8-32, PI2 23 days 95%CI 1-56) compared to patients in good risk categories, for whom median OS was not reached (P<0.001 for all comparisons). The PLR was not associated with survival. Analyses of survival in the VS confirmed the NLR (P<0.0001), PNI (P<0.0001), PI (P<0.01), and mGPS (P<0.001) as predictors of survival. In a multivariable Cox regression model including all inflammatory indices and pre-established prognostic factors for severe Covid-19 including sex, age, comorbid burden, malignancy status, and receipt of anti-cancer therapy at Covid-19 diagnosis, the PNI was the only factor to emerge with a significant hazard ratio [HR] in both TS and VS analysis (TS HR 1.97, 95%CI 1.19-3.26, P=0.008;VS HR 2.48, 95%CI 1.47- 4.20, P=0.001). We conclude that systemic inflammation drives mortality from Covid-19 through hypoalbuminemia and lymphocytopenia as measured by the PNI and propose the PNI as the OnCovid Inflammatory Score (OIS) in this context.

COVID-19 Infection of HSCT Recipients Is Associated with High Mortality but No Detectable Cytokine Storm at Presentation

Introduction The clinical manifestations of COVID-19 infection in recipients of allogeneic hematopoietic stem cell transplantation (HSCT) have been reported in multiple retrospective cohorts of patients, but there have been no prospective studies to date. Previous studies report that HSCT recipients are at higher risk, with cumulative incidence of death between 17-35%. Although an excessive pro-inflammatory viral response has been documented in the general population, its role in the immune incompetent HSCT setting has not been documented. We present a combined prospective and retrospective national study run through the UK IMPACT trial network to characterize the clinical and immunological features of COVID-19 infection in 96 adult and pediatric recipients of HSCT in the United Kingdom. Methods HSCT recipients of any age and transplanted for any indication, with an RT-PCR-proven COVID-19 infection, were eligible for this study. Patients within 72 hours of COVID-19 diagnosis, who had not received cytokine-targeted treatment, were recruited to a prospective cohort. All other patients were eligible for a retrospective cohort. Prospective patients provided blood samples within 72 hours of COVID-19 diagnosis, and again within 72 hours of clinical deterioration (defined as requirement for oxygen administration) if applicable. Follow-up data were collected on patients 30 and 100 days after COVID-19 diagnosis. Results 100 patients were recruited from 16 sites across the UK between May 2020-June 2021, comprising 12 in a prospective cohort and 88 recruited retrospectively. 96 patients were evaluable, as 4 proved ineligible post-registration. Patients were diagnosed with COVID-19 at a median of 11 months after HSCT. Patient/HSCT characteristics are shown Table 1. The most common symptoms associated with the onset of COVID-19 were fever in 8 prospective (73%) and 35 (41%) retrospective patients, followed by cough in 5 (45%) prospective and 35 (41%) retrospective patients and dyspnea in 4 (36%) prospective and 16 (19%) retrospective patients. 8 (73%) prospective and 40 (47%) retrospective patients were actively immunosuppressed at the time of COVID-19 infection. 16% of the patients had moderate/severe disease at baseline. At day 30 (±2 days) after COVID-19 diagnosis, 2 prospective and 8 retrospective patients continued to demonstrate SARS-CoV-2 positivity on respiratory PCR testing. The median time to viral clearance was 40 (IQR 17-78) days for the prospective and 34 (IQR 15-70) days for the retrospective cohort. Prolonged (more than 14 days) neutropenia was reported in 4 (5%) patients in the retrospective cohort, prolonged thrombocytopenia in 2 (18%) prospective and 11 (13%) retrospective patients. 1 retrospective patient developed secondary hemophagocytic lymphohistiocytosis, and graft rejection was reported in 1 (1%) retrospective patient, within 30 days of COVID-19 diagnosis. In the prospective cohort, 3 (27%) patients died, all by day 30, and all due to COVID-19. In the retrospective cohort, 13 (17%) patients died by day 30, rising to 18 (21%) by day 100, 61% of deaths were attributed to COVID-19. Lower baseline platelets (p=0.013, Mann-Whitney U test), lymphocytes (p=0.012), albumin (p=0.028), and higher baseline CRP (p=0.007), were seen in patients who died following COVID-19 diagnosis. Additionally, exploratory univariate logistic regression of the retrospective cohort found mortality at day 100 to be associated with increased age at diagnosis (OR 1.04, 95% CI 1.01-1.08, p=0.04), and no requirement compared with requirement for invasive ventilation (OR 0.02, 95% CI 0.00-0.16, p=0.001). The 11 prospective patients showed normal levels of interleukin (IL)-2, -4, -10, interferon gamma and tumor necrosis factor alpha at COVID-19 presentation. IL-6 was minimally raised (up to 127 pg/ml, nv<50) in 3/11 pts at presentation. Respiratory deterioration was not associated with detectable cytokine storm. Conclusion Our study confirms a significant mortality rate in patients affected by COVID-19 post HSCT and confirms age as well s requirement for invasive ventilation to be independent risk factors associated with death at day 100. Baseline laboratory data at disease presentation can identify patients at higher risk of COVID-19 related death. In the prospective cohort of our study, pathophysiology of the viral disease did not seem related to cytokine storm-mediated inflammation. [Formula presented] Disclosures: Protheroe: Jazz Pharmaceuticals: Honoraria;Astellas: Honoraria;Kite Gilead: Honoraria. Peggs: Autolus: Consultancy, Current equity holder in publicly-traded company. Craddock: Novartis Pharmaceuticals: Other: Advisory Board;Celgene/BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding. Nicholson: BMS/Celgene: Consultancy;Kite, a Gilead Company: Other: Conference fees, Speakers Bureau;Novartis: Consultancy, Other: Conference fees;Pfizer: Consultancy. Amrolia: ADC Therapeutics: Other: Named inventor on a patent which is being transferred to ADCT.;Autolus: Patents & Royalties.

Urban-rural differences in COVID-19 exposures and outcomes in the South: a preliminary analysis of South Carolina

As the COVID-19 pandemic moved beyond the initial heavily impacted and urbanized Northeast region of the United States, hotspots of cases in other urban areas ensued across the country in early 2020. In South Carolina, the spatial and temporal patterns were different, initially concentrating in small towns within metro counties, then diffusing to centralized urban areas and rural areas. When mitigation restrictions were relaxed, hotspots reappeared in the major cities. This paper examines the county-scale spatial and temporal patterns of confirmed cases of COVID-19 for South Carolina from March 1st - September 5th, 2020. We first describe the initial diffusion of the new confirmed cases per week across the state, which remained under 2,000 cases until Memorial Day weekend (epi week 23) then dramatically increased, peaking in mid-July (epi week 29), and slowly declining thereafter. Second, we found significant differences in cases and deaths between urban and rural counties, partially related to the timing of the number of confirmed cases and deaths and the implementation of state and local mitigations. Third, we found that the case rates and mortality rates positively correlated with pre-existing social vulnerability. There was also a negative correlation between mortality rates and county resilience patterns, as expected, suggesting that counties with higher levels of inherent resilience had fewer deaths per 100,000 population.