Access to Post-Acute Care after Covid-19 and Non-Covid-19 Sepsis Hospitalization

INTRODUCTION: The COVID-19 pandemic disrupted access and delivery of routine continuing care for sepsis recovery, including provision of postacute services like skilled nursing facility (SNF) discharge, home healthcare (HH), and outpatient follow up. We hypothesized pandemic-related precautions and care disturbances would disparately impact postacute care for adults with sepsis due to COVID-19 vs non-COVID-19 pneumonia. METHOD(S): ENCOMPASS is an ongoing hybrid trial to test implementation of a multidisciplinary postsepsis transitional care program at 8 diverse hospitals (NCT04495946). In the current study, we analyzed community-dwelling trial participants (i.e., adults with clinically defined sepsis) enrolled July 2020-Nov 2021 with discharge diagnoses of COVID-19 (ICD10 U07.1) or non-COVID-19 pneumonia (ICD10 J13-18). Using EHR data, we examined discharge care setting (SNF or inpatient rehab, HH, or home with self care) and outpatient follow up within 14 days (in-person, virtual, or none) as primary and secondary outcomes. For each outcome, we fit multinomial regression models adjusted for patient (age, insurance), clinical (comorbidity burden, organ failure, length of stay) and community factors (rurality by zip code). RESULT(S): Among 410 participants with COVID-19 (n=151) or non-COVID-19 (n=259) pneumonia (median, at enrollment: age=70, CCI=5, SOFA score=4), 52 (13%) died in hospital and 18 (4%) discharged to hospice. of remaining patients, 134 (39%) were discharged to home with self care, 118 (35%) to HH, and 88 (26%) to SNF or inpatient rehab. Survivors with vs without COVID-19 had similar adjusted odds of discharge to HH (OR=1.17 95%CI=0.65-2.10) and SNF or inpatient rehab (OR=1.60 95%CI=0.81-3.14) compared to home. Outpatient visit completion was similar for COVID-19 and non-COVID-19 survivors (26% vs 30%, p=0.43), but patients with vs without COVID-19 had higher odds of virtual (OR=4.76 95%CI=2.11-10.75) compared to no completed follow-up. CONCLUSION(S): In an ongoing postsepsis care trial, COVID-19 and non-COVID-19 survivors had similar provision of postacute services. COVID-19 was associated with increased virtual outpatient follow up, highlighting the value of telehealth to reduce exposure risk while maintaining close follow up of patients recovering from serious illness during the pandemic.

Post-Hospital Recovery Experiences for Sepsis Survivors during the Covid-19 Pandemic

INTRODUCTION: Prior data indicate that sepsis survivors face persistent health challenges and fail to receive adequate support after hospital discharge. Delivery of high-quality transition care may be exacerbated by the COVID-19 pandemic. We assessed patient reported satisfaction with transitional care and health outcome status for survivors of respiratory sepsis (due to COVID-19 and non-COVID-19 pneumonia) during the pandemic. METHOD(S): We enrolled patients (or surrogate caregivers) from both usual care and intervention arms of ENCOMPASS, an ongoing clinical trial evaluating the effectiveness of a multicomponent sepsis transition program. Individuals who consented to participate completed health related quality of life (HRQoL;EQ-5D-5L) and other outcomes measures (Mini-MOCA, IES-6, mMRC) 3 months after hospital discharge and responded to questions about post-discharge support. Interviews were conducted via telephone. Data were collected in REDCap (Research Electronic Data Capture) and analyzed with SAS. RESULT(S): Among 18 participants (14 patients, 4 caregivers [non-overlapping]), 56% were female, median patient age was 67 years, median Charlson index was 4, median SOFA was 4, and 2 patients were recovering from COVID-19. Most reported being satisfied/very satisfied with their transitional care (15, 83%) and were able to get all of the healthcare services needed during the pandemic (14, 78%). Many participants reported persistent problems at 3 months after discharge (mobility [17, 94%], self-care [17, 94%], usual activities [18, 100%], pain or discomfort [17, 94%], and anxiety or depression [15, 83%]), independent of coexisting chronic disease burden. The median EQ-5D visual analog scale was 65 (IQR=40-80). 12 (86%) patients reported persistent dyspnea, 2 (14%) had cognitive impairment by mini-MOCA, and 3 (21%) had symptoms of post-traumatic stress by IES-6. CONCLUSION(S): Sepsis survivors experience multidimensional HRQoL problems 3 months after discharge. Despite concerns about the provision of transitional support during the pandemic, most patients in this small study were satisfied with the transitional support received. Our findings reinforce the need for high-quality transitional support that addresses the new or worsening health problems experienced after sepsis.

CLL-VR: A UK study of vaccine responses in patients with B-cell chronic lymphocytic leukaemia

B-cell chronic lymphocytic leukaemia (CLL) is associated with immune suppression and patients are at increased risk following SARS-CoV-2 infection. The Chronic Lymphocytic Leukaemia-Vaccine Response (CLL-VR) study was designed to assess immune responses following the introduction of Covid-19 vaccination in UK. Five hundred patients with CLL were recruited nationally through NHS and charity communications. Phlebotomy blood samples were taken from local patients ( n = 100) and dried blood spot samples were collected via post from participants across the UK ( n = 400). Ninety-six age-matched control subjects were also recruited locally. Samples were taken at 2-3 weeks following the first, second and third primary vaccine doses. Antibody and cellular responses against spike protein, and neutralising antibody titre to delta and omicron variant, were measured. Total serum immunoglobulin level was also determined. Responses were analysed according to clinical history, serum immunoglobulin level and vaccine type received. Donors with a clinical or serological history of prior natural infection were excluded from the analysis. Twenty percent (70/353) of participants developed a measurable antibody response after the first vaccination and this increased to 67% (323/486) following the second dose and 80% (202/254) after a third dose. The response rate in healthy controls plateaued at 100% after only two doses. The magnitude of the antibody response was also 3.7-fold lower following the second vaccine compared to controls ( n = 244;490 vs. 1821 U/ml, p < 0.0001) but increased markedly to 3114 U/ ml after third dose ( n = 51). No difference was observed in relation to the initial vaccine platform received. Multivariate analysis on 486 participants showed that BTKi therapy, history of recurrent infection and low serum antibody levels of IgA or IgM were independent prognostic markers for poor antibody response. Among participants with a detectable antibody response, a marked reduction in the ability to neutralise the delta and omicron variants of concern was noted compared to healthy controls following both the second and third dose of vaccine. Cellular responses were assessed following the second vaccine by IFN-g ELISPOT ( n = 91). Patients who had received the ChAdOx1 vaccine had similar levels to controls ( p = 0.39), while those who had received BNT162b2 had lower levels ( p < 0.0001). Five patients with poor spike-specific antibody responses to vaccination subsequently developed breakthrough infection with SARS-CoV-2 delta variant. Antibody responses and neutralisation remained poor following recovery from infection although T-cell responses were strong and only one patient required hospital admission. CLL-VR is the largest vaccine study conducted in patients with CLL and reveals diminished but comparable antibody responses to both the ChAdOx1 and BNT162b2 vaccines with some improvement following third primary dose of mRNA vaccine. In contrast T-cell responses following second dose are greater in those who received ChAdOx1 platform. Low neutralising activity against the delta and omicron variants highlights an ongoing risk for this vulnerable population despite repeated vaccination and reveals the need for alternative approaches to protection including prophylactic monoclonal antibody therapy..

Antibody responses after first and second Covid-19 vaccination in patients with chronic lymphocytic leukaemia.

B-cell chronic lymphocytic leukaemia (CLL) is associated with immunosuppression and patients are at increased clinical risk following SARS-CoV-2 infection. Covid-19 vaccines offer the potential for protection against severe infection but relatively little is known regarding the profile of the antibody response following first or second vaccination. We studied spike-specific antibody responses following first and/or second Covid-19 vaccination in 299 patients with CLL compared with healthy donors. 286 patients underwent extended interval (10-12 week) vaccination. 154 patients received the BNT162b2 mRNA vaccine and 145 patients received ChAdOx1. Blood samples were taken either by venepuncture or as dried blood spots on filter paper. Spike-specific antibody responses were detectable in 34% of patients with CLL after one vaccine (n = 267) compared to 94% in healthy donors with antibody titres 104-fold lower in the patient group. Antibody responses increased to 75% after second vaccine (n = 55), compared to 100% in healthy donors, although titres remained lower. Multivariate analysis showed that current treatment with BTK inhibitors or IgA deficiency were independently associated with failure to generate an antibody response after the second vaccine. This work supports the need for optimisation of vaccination strategy in patients with CLL including the potential utility of booster vaccines.

A New Measure of Market Inefficiency

Financial crises, such as the Great Financial Crisis of 2007-2009 and the COVID-19 Crisis of 2020-2021, lead to high volatility in financial markets and highlight the importance of the debate on the Efficient Markets Hypothesis, a corollary of which is that in an efficient market it should not be possible to systematically make excess returns. In this paper, we discuss a new empirical measure-Excess Trading Returns-that distinguishes between market and trading returns and that can be used to measure inefficiency. We define an Inefficiency Matrix that can provide a complete, empirical characterization of the inefficiencies inherent in a market. We illustrate its use in the context of empirical data from a pair of model markets, where information asymmetries can be clearly understood, and discuss the challenges of applying it to market data from commercial exchanges.

Determinants of lung health in a vulnerable population burdened by air pollution during the COVID-19 pandemic

Rationale. Jefferson County Alabama, became a U.S. Southeastern cornerstone of industrial mining for coal, iron, and limestone in the 1800's. Coal-fired power plants deposit heavy metals into the air, soil, and water. Residents living in close proximity to these plants are increasingly stricken with lung diseases such as COPD and asthma. Many reside in an area the Environmental Protection Agency (EPA) has requested to be placed on the National Priorities List (NPL). This site has been named the Superfund Research Center (SRC) by the National Institutes of Health (NIH). Air pollution from PM2.5 carrying heavy metals such as cadmium and arsenic have left a legacy of obstructive lung disease in the SRC site. Methods. The American Lung Association “State of the Air” 2020 report, finds parts of Jefferson County remains among the worst in the nation for year-round particle pollution. The Alabama Department of Public Health (ADPH) COVID-19 dashboard was used to identify the number of cases and associated deaths per county in the first four months of the pandemic. The Jefferson County Department of Health, Community Health Equity Report was used to identify demographic and life expectancy reported data. Results. Although African Americans are 29% of the population in Alabama, 45% of the deaths due to COVID-19 are in the African American population, many living within the SRC site. Subjects younger than 50 years of age showed evidence of COPD as compared to those living outside the SRC site. Subjects living in the SRC site also exhibit higher levels of cadmium in their blood than those living outside the site, even if they were nonsmokers. Prior to the pandemic, subjects living within the SRC site had a life expectancy of 60-70 years while other areas with white populations had a life expectancy of 80-90 years. Conclusion. Residents in the SRC are experiencing a cascade of effects that place their lung health at stake. Combine a vulnerable population with varying lung diseases, in a heavily polluted area, with a new onset COVID-19 infection, and an already difficult situation, with pollution induced COPD becomes dire, underscoring the environmental disadvantage the residents face. COVID- 19 has laid bare the disparities in lung health in populations suffering from environmental exposures to toxic air pollution in Jefferson County. Continued efforts in air pollution regulation and continued research and evaluation of the impacts of long-term exposure to air pollution on lung health is the ongoing focus.