High-resolution rural poverty mapping in Pakistan with ensemble deep learning.

High resolution poverty mapping supports evidence-based policy and research, yet about half of all countries lack the survey data needed to generate useful poverty maps. To overcome this challenge, new non-traditional data sources and deep learning techniques are increasingly used to create small-area estimates of poverty in low- and middle-income countries (LMICs). Convolutional Neural Networks (CNN) trained on satellite imagery are emerging as one of the most popular and effective approaches. However, the spatial resolution of poverty estimates has remained relatively coarse, particularly in rural areas. To address this problem, we use a transfer learning approach to train three CNN models and use them in an ensemble to predict chronic poverty at 1 km2 scale in rural Sindh, Pakistan. The models are trained with spatially noisy georeferenced household survey containing poverty scores for 1.67 million anonymized households in Sindh Province and publicly available inputs, including daytime and nighttime satellite imagery and accessibility data. Results from both hold-out and k-fold validation exercises show that the ensemble provides the most reliable spatial predictions in both arid and non-arid regions, outperforming previous studies in key accuracy metrics. A third validation exercise, which involved ground-truthing of predictions from the ensemble model with original survey data of 7000 households further confirms the relative accuracy of the ensemble model predictions. This inexpensive and scalable approach could be used to improve poverty targeting in Pakistan and other low- and middle-income countries.

Urinary biomarkers to predict acute kidney damage and mortality in COVID-19.

INTRODUCTION: Acute kidney injury (AKI) is a frequent condition in patients hospitalized for COVID-19. There are only a few reports on the use of urinary biomarkers in COVID-19 and no data so far comparing the prognostic use of individual biomarkers in the prediction of adverse outcomes. MATERIALS AND METHODS: We performed a prospective mono-centric study on the value of urinary biomarkers in predicting the composite endpoint of a transfer to the intensive care unit, the need for renal replacement therapy, mechanical ventilation, and in-hospital mortality. 41 patients hospitalized for COVID-19 were enrolled in this study. Urine samples were obtained shortly after admission to assess neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), calprotectin, and vascular non-inflammatory molecule-1 (vanin-1). RESULTS: We identified calprotectin as a predictor of a severe course of the disease requiring intensive care treatment (AUC 0.728, p = 0.016). Positive and negative predictive values were 78.6% and 76.9%, respectively, using a cut-off concentration of 127.8 ng/mL. NGAL tended to predict COVID-19-associated AKI without reaching statistical significance (AUC 0.669, p = 0.053). The best parameter in the prediction of in-hospital mortality was NGAL as well (AUC 0.674, p = 0.077). KIM-1 and vanin-1 did not reach significance for any of the investigated endpoints. CONCLUSION: While KIM-1 and vanin-1 did not provide prognostic clinical information in the context of COVID-19, the present study shows that urinary calprotectin is moderately predictive of the need for intensive care unit (ICU) admission, and NGAL may be modestly predictive of AKI in COVID-19. Calprotectin and NGAL show promise as potential helpful adjuncts in the identification of patients at increased risk of poor outcomes or complications in COVID-19.

Effect of Plasma Exchange on COVID-19 Associated Excess of Von Willebrand Factor and Inflammation in Critically Ill Patients

BACKGROUND AND AIMS Ubiquitous microthromboses in the pulmonary vasculature play a crucial role in the pathogenesis of COVID-19 associated acute respiratory distress syndrome (ARDS). Excess of von Willebrand factor (vWf) with intravascular multimer formation was identified as a key driver of this finding. Plasma exchange (PLEX) might be a therapeutic option to restore the disbalance between vWf and ADAMTS13. We report the effects of PLEX on vWf, ADAMTS13, inflammatory cytokines and parameters of ventilation. METHOD We investigated 25 patients, who were on mechanical ventilation for COVID-19 pneumonia with ARDS at two German university hospitals. All patients received PLEX as an ultima ratio measure for refractory ARDS. VWf antigen (vWf: Ag), ADAMTS13 activity, a cytokine panel mirroring the inflammatory situation and clinical parameters were assessed before and after three to six PLEX therapies with fresh frozen plasma. RESULTS Before the PLEX sequence, there was an excessive release of vWf: Ag (425.4 ± 167.5%) and mildly reduced ADAMTS13 activity (49.7 ± 23.3%). After the PLEX series, there was a significant increase of ADAMTS13 activity to 62.4 ± 17.7% (P = .029) and a significant decrease of vWf: Ag to 336.1 ± 138.2% (P = .041) resulting in a 63% improvement of the ADAMT13/vWf: Ag ratio from 14.5 ± 10.0 to 23.7 ± 14.6  (P = .024). Comparison of parameters before and after individual PLEX sessions (n = 35) revealed a mean reduction of vWf from 387.8 ± 165.1% to 213.2 ± 62.3% (P = .001) and an increase of ADAMTS13 activity from 60.4 ± 20.1% to 70.5 ± 14.0% (P = .001). Parallelly, monocyte chemotactic protein-1 and interleukin-18 decreased significantly (P = .034 each). Along the PLEX sequence lactate dehydrogenase (P = .001), C-reactive protein (P = .001), and positive end expiratory pressure (P = .01) significantly decreased accompanied by an improvement of Horovitz index (P = .001). CONCLUSION PLEX restores the disbalance between ADAMTS13 and vWf: Ag, a driver of immunothrombosis. Moreover, it reduces the inflammatory state and is associated with a benefit of ventilation parameters. These findings render a further rationale to regard PLEX as a therapeutic option in severe COVID-19.

Urinary Biomarkers to Predict Acute Kidney Damage and Mortality In COVID-19

BACKGROUND AND AIMS Acute kidney injury (AK) is a frequent condition in patients hospitalized for COVID-19. There are only few reports on the use of urinary biomarkers in COVID-19 and no data comparing the prognostic use of individual biomarkers in the prediction of adverse outcome so far. METHOD We performed a prospective monocentric study on the value of urinary biomarkers to predict the composite endpoint of a transfer to the intensive care unit (ICU), the need for renal replacement therapy (RRT), mechanical ventilation and in-hospital mortality. A total of 41 patients hospitalized for COVID-19 were enrolled in this study. Urine samples were obtained shortly after admission in order to assess neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), calprotectin and vanin-1. RESULTS We identified calprotectin as a predictor of a severe course of the disease, requiring intensive care treatment (AUC 0.728, P = .016). Positive and negative predictive values were 78.6% and 76.9%, respectively, using a cut-off concentration of 127.8 ng/mL. NGAL tended to predict COVID-19 associated AKI without reaching statistical significance (AUC 0.669, P = .053). The best parameter in the prediction of in-hospital mortality was NGAL as well (AUC 0.674, P = .077). KIM-1 and vanin-1 did not reach significance for any of the investigated endpoints. CONCLUSION While KIM-1 and vanin-1 did not provide prognostic clinical information in the context of COVID-19, this study shows that urinary calprotectin and NGAL concentrations are independent predictors of an adverse course of the disease. Calprotectin and NGAL may thereby constitute helpful adjuncts in the identification of patients at increased risk who may benefit from upcoming antiviral agents to SARS-CoV-2.

Predictors of impaired SARS-CoV-2 immunity in healthcare workers after vaccination with BNT162b2.

Healthcare workers are at substantially increased risk for infection with SARS-CoV-2. Successful vaccination constitutes a crucial prerequisite to protect this group during the pandemic. Since post vaccination antibody monitoring is not standard of care in all healthcare institutions, data on risk factors of impaired vaccine induced immune response are urgently required. Moreover, there are no data on cellular immune responses in humoral low responders so far. Anti-SARS-CoV-2 spike IgG was assessed after vaccination with BNT162b2 in 1386 employees of three hospitals of a German healthcare provider. Concentrations were compared to those of 45 convalescent employees. Vaccine-induced cellular immunity was measured in employees with reduced humoral response by assessment of frequencies of SARS-CoV-2-reactive CD4+ and CD8+ T cell. Anti-SARS-CoV-2 spike IgG were detected in 99.9% of 1386 healthcare workers after completed vaccination. The median antibody concentration was significantly higher after vaccination than after infection with SARS-CoV-2 (p = 0.0001). 10 subjects (0.7%) generated an IgG concentration < 100 IU/ml, and only two persons (0.1%, solid organ recipients) did not produce detectable antibodies at all. T cell responses of those subjects with submaximal or lacking humoral response were comparable to employees with maximal antibody titers. 50% of those individuals with impaired or lacking humoral immune response were on immunosuppression. Vaccination to SARS-CoV-2 with BNT162b2 is very effective in healthcare workers yielding a seroconversion rate of 99.9%. Immunosuppression is the most important risk factor of an impaired immune response. There was no case of vaccination failure without immunosuppression. Thus, post vaccination antibody monitoring is highly recommendable in those employees with immunosuppression.

Low-density lipoprotein apheresis is associated with removal of SARS-CoV-2 antibodies.

BACKGROUND: Low-density lipoprotein apheresis is not specific to lipoproteins but removes immunoglobulins as well. It remains elusive, whether protective SARS-CoV-2 antibodies after vaccination from COVID-19 are eliminated as well. METHODS: A cross-sectional case-control study on 55 patients undergoing weekly lipoprotein apheresis and 21 patients with comparable comorbidities and epidemiology not undergoing apheresis. SARS-CoV-2 IgG was assessed in all patients prior to apheresis and in 38 patients both before and after apheresis. RESULTS: SARS-CoV-2 IgG concentrations before a session of lipoprotein apheresis were comparable to control patients not undergoing apheresis(1727 IU/ml, IQR 365-2500) vs. 1652 IU/ml,(IQR408.8-2500), p = 0.78). SARS-CoV-2 IgG concentrations were reduced by lipoprotein apheresis from 1656 IU/ml(IQR 540.5-2500) prior to 1305 IU/ml (IQR 449-2500) afterwards(p < 0.0001). CONCLUSION: Lipoprotein apheresis removes SARS-CoV-2 IgG. The average elimination rate was 21.2%. In the present population of patients undergoing apheresis once weekly, however, the elimination did not lead to inferior concentrations compared to patients not undergoing lipoprotein apheresis.

Immune Response in Moderate to Critical Breakthrough COVID-19 Infection After mRNA Vaccination.

SARS-CoV-2 variants of concern (VOCs) can trigger severe endemic waves and vaccine breakthrough infections (VBI). We analyzed the cellular and humoral immune response in 8 patients infected with the alpha variant, resulting in moderate to fatal COVID-19 disease manifestation, after double mRNA-based anti-SARS-CoV-2 vaccination. In contrast to the uninfected vaccinated control cohort, the diseased individuals had no detectable high-avidity spike (S)-reactive CD4+ and CD8+ T cells against the alpha variant and wild type (WT) at disease onset, whereas a robust CD4+ T-cell response against the N- and M-proteins was generated. Furthermore, a delayed alpha S-reactive high-avidity CD4+ T-cell response was mounted during disease progression. Compared to the vaccinated control donors, these patients also had lower neutralizing antibody titers against the alpha variant at disease onset. The delayed development of alpha S-specific cellular and humoral immunity upon VBI indicates reduced immunogenicity against the S-protein of the alpha VOC, while there was a higher and earlier N- and M-reactive T-cell response. Our findings do not undermine the current vaccination strategies but underline a potential need for the inclusion of VBI patients in alternative vaccination strategies and additional antigenic targets in next-generation SARS-CoV-2 vaccines.

COVID-19 pandemic and chronic liver disease (cld)

Background: CLD patients may experience substantial burden and disruption of life associated with COVID-19 pandemic. The aim was to assess the impact of COVID-19 pandemic on CLD patients. Methods: CLD patients from our Global Liver and Global NASH Registries (GLR/GNR) were invited to complete a COVID-19 survey with 23 items starting March 2020. Questions included whether patients had been infected with COVID-19, characteristics of the illness for those who had been infected, and various aspects of pandemicrelated disruptions of life regardless of being diagnosed with COVID-19. Results: Out of 10,500 GLR/GNR enrollees, 2500 from 7 countries completed the survey: 20% chronic hepatitis B (CHB), 14% chronic hepatitis C (CHC), and 66% non-alcoholic fatty liver disease (NAFLD), mean (SD) age 49±13 years, 53% male. Of all survey completers, 9.3% had had COVID-19. Of those infected, 86% were diagnosed by laboratory test, 93% had least one symptom, 75% received treatment for their symptoms. The mean duration of illness was 12.5±10.5 days, 64% reported receiving antiviral treatment, 19% were hospitalized, 13% needed oxygen support, no one required mechanical ventilation. Of patients regardless of COVID-19 diagnosis, 11.3% reported that the pandemic had an impact on their liver disease with 73% reporting delays in follow-up care. The Life Disruption Event Perception (LDEP) questionnaire confirmed that 81% of COVID-19-infected patients vs. 69% patients without COVID-19 (p=0.0001) experienced worsening in at least one aspect of their life (Figure). Self-assessed health scores were lower in patients with COVID-19: 6.7±2.2 vs. 7.4±2.2 (on a 1-10 scale with 10 indicating perfect health) (p<0.0001) despite having reported similar scores before the pandemic (8.5±1.4 vs. 8.4±1.6, p=0.59). The highest proportion of exercise and social impairments were reported from Turkey and Mexico, respectively. In multivariate analysis, after adjustment for country of enrollment, liver disease etiology and severity, age, sex, BMI, diabetes, history of psychiatric comorbidities, having had COVID-19 was found to be independently associated with lower self-assessed health scores (β=-0.71±0.14, p<0.0001). Conclusion: CLD patients experience substantial burden of COVID-19 pandemic on their daily lives regardless of whether they had been infected. However, self-reported health scores were lower in CLD patients with COVID-19 infection in comparison to those who did not have it.

A characterization of the psychosocial impact of COVID-19 lockdown in post-bariatric surgery patients

Introduction: The lockdown caused by COVID-19 has an extreme impact on most people's lives. Notwithstanding, some individuals are more predisposed to experience deterioration in their psychological status and/or inaccessibility to adequate treatment and, consequently, they should be devoted with greater attention. Namely, for example, post-bariatric surgery patients who need continuous monitoring about eating behavior and psychological distress. Particularly in medium/long term post-surgery (≥ 36 months), a period of increased susceptibility to weight regain. The present study goals are to characterize the psychosocial impact of COVID-19 lockdown for post-bariatric patients and identify its associations with disordered eating behavior and psychological distress. Methods: Twenty-four post-bariatric surgery (M=42.88 months post-surgery, DP=4.73) women (M=50.92 years, DP=12.81) responded to an online questionnaire and a telephone-interview assessing the perceived impact of the lockdown, psychosocial, psychological, and eating behavior aspects during the first lockdown period. Results: Fourteen (58.3%) of the participants inquired reported perceived weight gain during the lockdown, thirteen (54.1%) reported limited access to social support, and twelve (50%) reported limited access to health care. Positive associations were found between the global psychosocial impact experienced during lockdown and difficulties in dealing with emotionally activating situations (rs=.45, p=.027) and stress symptoms (rs=.44, p=.030). Negative associations were found between co-habiting with more persons during lockdown and difficulties in dealing with emotionally activating situations (rs=-.49, p=.015), fear of getting fat (rs=-.48, p=.019), fear of losing control over eating (rs=-.56, p=.005), and disordered eating psychopathology (rs=-.47, p=.022). Conclusion: As clinical implications, the present findings highlighted the need to monitor post-bariatric surgery patients, facilitate health care access, and promote social support during lockdown periods.

Eating behaviors and weight outcomes in post-bariatric surgery patients during the COVID-19 pandemic: A three-year longitudinal study

Introduction: The lockdown imposed by many countries to curb the COVID-19 epidemic had an unprecedented impact on the general population's lives. Recent studies suggest that eating habits are one of the areas particularly affected by stay-at-home orders. Individuals that received bariatric surgery for weight loss may represent a particularly susceptible population to the adverse effects of the COVID-19 lockdown for its potential impact on eating, psychological and, weight loss outcomes. This study seeks to investigate the incremental impact of COVID-19 lockdown on bariatric surgery outcomes. Methods: The present investigation uses data from an ongoing longitudinal study of bariatric patients assessed before surgery (T0), 1.5 (T1), and 3 years after surgery (T2). Two independent groups were compared: the COVID-19-Group (n=35) - T0 and T1 assessment were conducted before the pandemic started, but T2 assessment was conducted at the end of the mandatory COVID-19 lockdown;and the NonCOVID-19-Group (n=66) - who completed the pre-surgery, 1.5-, and 3-year assessment before the epidemic began. Assessment included self-report measures for disordered eating, negative urgency, depression, anxiety, stress, and weight outcomes. General Linear Models for repeated measures were used. Results: General Linear Models for repeated measures showed that the COVID-19-Group presented significantly higher weight concern (F=8.403, p=.005, η2p=.094), grazing behavior (F=7.166, p=.009, η2p=.076), and negative urgency (F=4.522, p=.036, η2p=.05) than the NonCOVID-19-Group. The COVID-19-Group also showed less weight loss (F=4.029, p=.05, η2p=.04) and greater weight regain at T2, with more COVID-19-Group participants experiencing excessive weight regain (20% vs 4.5%).Conclusions: These results show evidence for the impact of the coronavirus outbreak on eating-related psychopathology and weight outcomes in post-bariatric surgery patients, making specialized and systematic care an urgent matter for this population.

The Magnitude and Functionality of SARS-CoV-2 Reactive Cellular and Humoral Immunity in Transplant Population Is Similar to the General Population Despite Immunosuppression.

BACKGROUND: The ability of transplant (Tx) patients to generate a protective antiviral response under immunosuppression is pivotal in COVID-19 infection. However, analysis of immunity against SARS-CoV-2 is currently lacking. METHODS: Here, we analyzed T cell immunity directed against SARS-CoV-2 spike-, membrane-, and nucleocapsid-protein by flow cytometry and spike-specific neutralizing antibodies in 10 Tx in comparison to 26 nonimmunosuppressed (non-Tx) COVID-19 patients. RESULTS: Tx patients (7 renal, 1 lung, and 2 combined pancreas-kidney Txs) were recruited in this study during the acute phase of COVID-19 with a median time after SARS-CoV-2-positivity of 3 and 4 d for non-Tx and Tx patients, respectively. Despite immunosuppression, we detected antiviral CD4+ T cell-response in 90% of Tx patients. SARS-CoV-2-reactive CD4+ T cells produced multiple proinflammatory cytokines, indicating their potential protective capacity. Neutralizing antibody titers did not differ between groups. SARS-CoV-2-reactive CD8+ T cells targeting membrane- and spike-protein were lower in Tx patients, albeit without statistical significance. However, frequencies of anti-nucleocapsid-protein-reactive, and anti-SARS-CoV-2 polyfunctional CD8+ T cells, were similar between patient cohorts. Tx patients showed features of a prematurely aged adaptive immune system, but equal frequencies of SARS-CoV-2-reactive memory T cells. CONCLUSIONS: In conclusion, a polyfunctional T cell immunity directed against SARS-CoV-2 proteins as well as neutralizing antibodies can be generated in Tx patients despite immunosuppression. In comparison to nonimmunosuppressed patients, no differences in humoral and cellular antiviral-immunity were found. Our data presenting the ability to generate SARS-CoV-2-specific immunity in immunosuppressed patients have implications for the handling of SARS-CoV-2-infected Tx patients and raise hopes for effective vaccination in this cohort.