Adverse COVID-19 Outcomes Research Articles

Sickle Cell Disease Patients Mount Adequate Humoral but Reduced Cellular Responses to COVID-19 Vaccination

Introduction Sickle cell disease patients have an increased risk of severe and fatal coronavirus disease (COVID)-19 compared to the healthy population, even after immunization with the primary 2-dose COVID-19 mRNA vaccination schedule. We longitudinally investigated antibody and T cell responses to three mRNA COVID-19 vaccinations in sickle cell disease patients treated with hydroxyurea. Methods Serum and peripheral blood mononuclear cells (PBMC) were collected from patients with sickle cell disease prior to and 4 weeks after each vaccination and in the months ensuing. Serum was used to quantify severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific spike glycoprotein 1 immunoglobulin G (S1 IgG) concentrations against the first serum standard for COVID-19 (20/136), as provided by the National Institute for Biological Standards Control and recommended by the WHO, and to measure antibody neutralization capacity of SARS-CoV-2 wild-type and variants of concern. PBMC were stimulated with SARS-CoV-2 spike peptides to measure spike-specific CD4+ and CD8+ T cell responses by activation marker expression and cytokine production, and stained with peptide-HLA tetramers to detect spike-specific CD8+ T cells. Antibody concentrations were compared to concentrations obtained from age-matched 2-dose- and 3-dose-vaccinated, healthy individuals extracted from the PIENTER and VITAL cohort, respectively, both population-based studies conducted by the Dutch National Institute for Public Health and the Environment. T cell responses were compared to results obtained from in-house healthcare workers. Participants were excluded from further analyses when SARS-CoV-2 infected, identified as having nucleocapsid (N) IgG >14.3 BAU/ml. Results In total, 31 sickle cell disease patients, all receiving hydroxyurea, were included in the study. In 26 study participants evaluable after the 2nd dose, S1 IgG antibody concentrations correlated with antibody neutralization capacity (r=0.70; p=0.037) and were not significantly lower than in age-matched healthy individuals after the primary 2-dose schedule (p=0.86; Figure 1A) (Haggenburg et al., Blood Adv 2022). Vaccination-induced spike-specific CD4+ T cell responses were present in 10/10 sickle cell disease patients analyzed, in similar percentages compared to healthy individuals (Figure 1B). However, IL-2, IFN-γ, and/or TNF-α production by spike-specific CD4+ T cells was 1.7 fold lower than in healthy individuals (p=0.002; Figure 1B). SARS-CoV-2-specific CD8+ T cell responses were detected in 8/10 patients analyzed, which is comparable to the heterogeneous CD8+ T cell response of healthy individuals, but cytokine production by spike-specific CD8+ T cells was 3.0 fold lower (p=0.017; Figure 1B). Six and 9 months after the 2nd vaccination median S1 IgG concentration decreased from 2921 to 423 and 395 BAU/ml, respectively (Figure 1A), while 6 months after the 2nd vaccination spike-specific CD4+ and CD8+ T cell responses persisted at comparable frequencies in 5/5 and 4/5 patients, respectively (not shown). Twelve sickle cell disease patients and 16 age-matched healthy controls received a 3rd mRNA vaccination, 9 and 8 months after the 2nd vaccination, respectively. A 3rd mRNA vaccination in sickle cell disease patients led to S1 IgG concentrations not significantly lower than in 3-dose vaccinated healthy controls (Figure 1A: median 13663 BAU/ml versus 4460 BAU/ml; p=0.99). The effect of this 3rd vaccination on cellular immunity is currently investigated. Conclusion Sickle cell disease patients receiving hydroxyurea do not have an impaired antibody response to mRNA COVID-19 vaccinations compared to healthy controls. Although spike-specific CD4+ and CD8+ T cells were found in similar percentages compared to healthy controls after 2 COVID-19 vaccinations, cytokine production by CD4+ and CD8+ spike-specific T cells was significantly lower, similar as previously reported in sickle cell disease patients after influenza vaccination. Population-based studies are needed to determine whether a 3rd vaccination in sickle cell disease patients provides better protection against adverse outcomes of COVID-19 compared to the standard 2-dose schedule. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Abstract 15686: Prevalence and Effects of Deep Vein Thrombosis on Hospital Outcomes Among COVID-19 Patients

Introduction: Current estimates show that, globally, there are 531 million cases and 6.3 million deaths due to COVID-19. Studies have shown that COVID-19 could lead to deep vein thrombosis (DVT) resulting in increased morbidity and mortality. In this study we sought to estimate the prevalence of DVT among COVID-19 hospitalizations as well as its effects on hospital outcomes using a large administrative database. Hypothesis: The adverse in-hospital outcomes of COVID-19 will be significantly higher among DVT hospitalizations. Methods: We conducted a retrospective analysis of the 2020 California State Inpatient Database. All hospitalizations with age 18 and above and primary diagnosis of COVID-19 were included for the study. They were classified into those with and without DVT. The main outcomes of the study were in-hospital mortality, prolonged length of stay, vasopressor use, mechanical ventilation, and ICU admission. Length of stay ≥75th percentile was grouped as prolonged length of stay. Multivariate logistic regressions with covariate adjustments were conducted to compare COVID-19 related outcomes between those with and without DVT. Results: We included a total of 94,114 primary COVID-19 hospitalizations for the analysis. Among them 1575 (1.7%) had DVT. The prevalence of mortality (27.5% versus 11.1%, P<0.001), prolonged length of stay (62.2% versus 27.8%, P<0.001), vasopressor use (7.9% versus 2.1%, P<0.001), mechanical ventilation (36.2% versus 9.7%, P<0.001), and ICU admission (35.7% versus 9.3%, P<0.001) were significantly higher among those with DVT. After adjusting for covariates, regression analysis showed that those with DVT had significantly greater odds for mortality (aOR, 2.34, 95% CI: 2.07-2.65), prolonged length of stay (aOR, 3.51, 95% CI: 3.16-3.91), vasopressor use (aOR, 4.23, 95% CI: 3.78-4.74), mechanical ventilation (aOR, 2.90, 95% CI: 2.38-3.53), and ICU admission (aOR, 4.32, 95% CI: 3.85-4.84). Conclusions: In our cohort, only few COVID-19 hospitalizations had a diagnosis of DVT. However, among those with DVT, the risk for adverse outcomes were significantly higher. Since DVT among COVID-19 is uncommon but associated with adverse hospital outcomes, healthcare providers should promptly monitor for DVT and manage it.

2D speckle-tracking echocardiography as a prognostic imaging modality for COVID-19 adverse outcomes.

2D speckle-tracking echocardiography (2D-STE) has been used to assess cardiac recovery during the COVID-19 patientfollow-ups within the pandemic. The novel role of STE in predicting adverse outcomes of COVID-19 has received attention due to its high sensitivity in identifying subclinical myocardial dysfunction. We reviewed the studies on using 2D-STE to assess COVID-19 prognosis. A literature search was conducted on PubMed and Scopus for eligible articles, 24of which discussed using prognostic 2D-STE for COVID-19 patients. 2D-STE predicts cardiovascular impairments more rapidly and precisely than conventional echocardiography. The 2D-STE technique presents an independent prognostic factor in COVID-19 infection. 2D-STE could be considered a time-efficient and accurate risk predictor of all-cause mortality in COVID-19 patients.

Impact of COVID-19 Infection on Maternal and Neonatal Outcomes: A Review of 11078 Pregnancies Reported in the Literature

Background: Pregnant women are a vulnerable group in viral outbreaks, especially in the COVID-19 pandemic. Objective: The aim of this review was to identify maternal and neonatal outcomes in available articles on pregnancies affected by COVID-19. Methods: The articles that had assessed outcomes of pregnancy and perinatal of women with COVID-19 between Oct 2019 and Aug 2020 without language limitation were considered. We searched databases, selected relevant studies and extracted data regarding maternal and neonatal outcomes from each article. Results: Data of 11078 pregnant women with COVID-19 of 23 countries were assessed from 77 articles between December 8, 2019 and Aug 18, 2020. Most pregnant women reported in their third trimester, out of which 6229 (56.22%) cases were symptomatic at the time of admission. Common onset symptoms, abnormal laboratory findings, and chest computed tomography pattern were cough (40.88%%), lymphocytopenia (43.38%), and multiple ground-glass opacities (4.42%), respectively. 51.37% of all deliveries were done through cesarean section. 158 maternal mortality and 4.2% ICU admission were reported. Vertical transmission was not reported, but its possibility was suggested in thirty-two neonates. Ten neonatal deaths, thirteen stillbirths, and nineteen abortions were reported. 60% of newborns were not breastfed. Conclusion: This review showed fewer adverse maternal and neonatal outcomes in pregnant women with COVID-19 in comparison with previous coronavirus outbreak infection in pregnancy. Limited data are available regarding the possibility of virus transmission in utero, during vaginal childbirth and breastfeeding. The effect of COVID-19 on the first and second trimesters and ongoing pregnancy outcomes in infected mothers is still questionable.

Increased circulating microparticles contribute to severe infection and adverse outcomes of COVID-19 in patients with diabetes.

Patients with diabetes infected with COVID-19 have greater mortality than those without comorbidities, but the underlying mechanisms remain unknown. This study aims to identify the mechanistic interactions between diabetes and severe COVID-19. Microparticles (MPs), the cell membrane-derived vesicles released on cell activation, are largely increased in patients with diabetes. To date, many mechanisms have been postulated for increased severity of COVID-19 in patients with underlying conditions, but the contributions of excessive MPs in patients with diabetes have been overlooked. This study characterizes plasma MPs from normal human subjects and patients with type 2 diabetes in terms of amount, cell origins, surface adhesive properties, ACE2 expression, spike protein binding capacity, and their roles in SARS-CoV-2 infection. Results showed that over 90% of plasma MPs express ACE2 that binds the spike protein of SARS-CoV-2. MPs in patients with diabetes increase 13-fold in quantity and 11-fold in adhesiveness when compared with normal subjects. Perfusion of human plasma with pseudo-typed SARS-CoV-2 virus or spike protein-bound MPs into human endothelial cell-formed microvessels-on-a chip demonstrated that MPs from patients with diabetes, not normal subjects, interact with endothelium and carry SARS-CoV-2 into cells through endocytosis, providing additional virus entry pathways and enhanced infection. Results also showed a large percentage of platelet-derived tissue factor-bearing MPs in diabetic plasma, which could contribute to thrombotic complications with SARS-CoV-2 infection. This study reveals a dual role of diabetic MPs in promoting SARS-CoV-2 entry and propagating vascular inflammation. These findings provide novel mechanistic insight into the high prevalence of COVID-19 in patients with diabetes and their propensity to develop severe vascular complications.NEW & NOTEWORTHY This study provides the first evidence that over 90% of human plasma microparticles express ACE2 that binds SARS-CoV-2 S protein with high affinity. Thus, the highly elevated adhesive circulating microparticles identified in patients with diabetes not only have greater SARS-CoV-2 binding capacity but also enable additional viral entry through virus-bound microparticle-endothelium interactions and enhanced infection. These findings reveal a novel mechanistic insight into the adverse outcomes of COVID-19 in patients with diabetes.

Associations of pre-existing comorbidities and COVID-19 in-hospital mortality: an unCoVer analyses

Abstract Background Accumulated evidence on risk factors for adverse COVID-19 outcomes revealed that old age and male sex are main associates, next to pre-existing comorbidities, as analysed from scattered single cohorts of hospitalised COVID-19 patients of accessible electronic medical records. Hence, evidence from federated analyses is called for to provide a more comprehensive and robust analyses of risk factors. Methods Using the unCoVer network, i.e., a research platform of 29 partners for the expert use of patient data as routinely gathered in real-world healthcare settings, present analyses restricted to available data of four hospitals from Spain, Slovakia, Romania and Bosnia and Herzegovina covering 8,287 hospitalised COVID-19 patients. In-hospital death after COVID-19 diagnosis was examined in relation to common pre-existing comorbidities using virtual pooling of logistic regression models adjusted for age and sex. Results Patients were on average 60.1 (± 20.9) years, 50.7% were male, almost half (43.3%) had at least one pre-existing comorbidity (17.4% having obesity, 21.9% hypertension, 18.0% diabetes and 13.7% cardiovascular diseases (CVD)), and 12.6% died during hospitalisation. Patients with comorbidities had a higher risk of mortality that was increasing with the number of comorbidities: from a virtual pooled odds ratio of 1.16 (95%CI: 0.96, 1.40) for one vs none to 1.30 (1.04, 1.64) and 2.14 (1.64, 2.79) for two and three or more comorbidities, respectively. Of the comorbidities, highest risk was seen for CVD (1.68; 1.40, 2.01), followed by hypertension (1.40; 1.19, 1.64) and diabetes (1.27; 1.07, 1.50), and the lowest for obesity (1.13; 0.94, 1.37). Conclusions By federated analyses, this study confirmed that the number of comorbidities was a strong risk factor for in-hospital death after COVID-19, in particular CVD. The unCoVer platform pursues using scattered data sources by innovative computational resources and integrated information for enhanced impact. Key messages

Prospects for studying the role of some essential and toxic trace elements in the pathogenesis of COVID-19

Despite the development and implementation of vaccines in various countries of the world, COVID-19 remains a significant medical and social problem. This is directly related to the characteristic feature of SARS-CoV-2 to form new strains, which reduces the effectiveness of vaccination. In connection with the foregoing, the priority in the prevention of COVID-19 is to improve and maintain the normal functioning of the human immune system. Recently, more and more scientists have noted the significant role of micronutrients in ensuring immune function. However, most research focuses on micronutrients such as zinc, selenium, iron and copper, while it is known that the balance of micronutrients depends on all its constituents. Consequently, any change in the content of one mineral substance can affect the level of others, leading to an imbalance of trace elements in the body. The aim of this work was to analyze literature data on less studied microelements in the context of the COVID-19 pandemic, both essential and toxic, that can affect the state of the immune system and, as a result, the incidence and risk of complications and adverse outcomes in COVID-19. An analysis of the literature on the effect of manganese, chromium, iodine, cadmium, mercury, lead, arsenic and lithium on human antiviral protection, including in the case of a disease caused by SARS-CoV-2, showed that the determination of the microelement status, taking into account the above microelements and, with necessary, the appointment of preparations containing minerals is promising for the purpose of prevention and as an additional therapy for COVID-19.

Individual-level factors associated with COVID-19 vaccine acceptance among U.S. patients with cancer

IntroductionVaccine hesitancy in the wake of the COVID-19 pandemic is a major public health concern in the US. Cancer patients are especially vulnerable to adverse COVID-19 outcomes and require targeted prevention efforts against COVID-19. MethodsWe used longitudinal survey data from patients seen at Moffitt Cancer Center to identify attitudes, beliefs, and sociodemographic factors associated with COVID-19 vaccination acceptance among cancer patients. Patients with confirmed invasive cancer diagnosis through Cancer Registry data were asked about vaccine acceptance through the question “Now that a COVID-19 vaccine is available, are you likely to get it?” and dichotomized into high accepters (already received it, would get it when available) and low accepters (waiting for a doctor to recommend it, waiting until more people received it, not likely to get it). ResultsMost patients (86.8% of 5,814) were high accepters of the COVID-19 vaccine. High accepters had more confidence in the effectiveness and safety of the vaccine than low accepters. Multivariable logistic regression showed older individuals (70–89 vs.18–49: OR:2.57, 95% CI:1.33–4.86), those with greater perceived severity of COVID-19 infection (very serious vs. not at all serious: OR:2.55, 95% CI:1.76–3.70), practicing more risk mitigation behaviors (per one standard deviation OR:1.75, 95% CI:1.57–1.95), and history of receiving the flu shot versus not (OR:6.56, 95% CI:5.25–8.20) had higher odds of vaccine acceptance. Individuals living with more than one other person (vs. alone: OR: 0.53, 95% CI: 0.35, 0.79) and those who were more socioeconomically disadvantaged (per 10 percentile points: OR: 0.89, 95 %CI: 0.85, 0.93) had lower odds of reporting vaccine acceptance. ConclusionMost patients with cancer have or would receive the COVID-19 vaccine. Those who are less likely to accept the vaccine have more concerns regarding effectiveness and side effects, are younger, more socioeconomically disadvantaged, and have lower perceptions of COVID-19 severity.

COVID-19, Endothelium and the Cardiometabolic Patient: A Possible Role for Capillary Leak Syndrome.

Capillary leak syndrome is an under-diagnosed condition leading to serious hypoalbuminemia with diffuse edema, pulmonary edema, severe hypotension, and possibly death. Sepsis leading to hemophagocytic lymphohistiocytosis (HLH) is a major risk factor; however, capillary hyper-permeability is the core underlying pathophysiological mechanism. Endothelial dysfunction plays a major role in cardiometabolic disease through insulin resistance, lipotoxicity, and, eventually, oxidative stress and chronic inflammation. We review the literature concerning the aforementioned mechanisms as well-established risk factors for adverse COVID-19 outcomes. We especially focus on data regarding the underlying endothelial effects of SARS-CoV-2 infection, including direct damage and increased vascular leakage through a hyper-inflammatory cascade and diminished nitric oxide bioavailability. Interestingly, an increased incidence of hypoalbuminemia has been observed in patients with severe COVID-19, especially those with underlying cardiometabolic disease. Importantly, low albumin levels present a strong, positive association with poor disease outcomes. Therefore, in this review article, we highlight the important role of cardiovascular risk factors on endothelium integrity and the possible link of endothelial damage in the hypoalbuminemia-associated adverse prognosis of COVID-19 patients.

Investigating links between air pollution, COVID-19 and lower respiratory infectious diseases – A review

Background/aim Hundreds of air pollution and COVID-19 papers have been published in a short time varying widely in quality. The Greater London Authority commissioned a comprehensive overview of the most credible evidence for the links between air pollution and COVID-19 and other lung infections. Methods Building on the Brunekreef et al (2021) review, a literature search was performed from November 2020 – May 2021, classifying the evidence by exposure, the potential mechanism and the health outcome. Studies on hospital admissions for lower respiratory infections were reviewed from 2011 Results Long-term exposure increased the risk of hospitalization in people already infected with COVID-19 in two good-quality cohort studies with individual data, perhaps due to respiratory and cardiovascular disease from air pollution increasing vulnerability to COVID-19 adverse outcomes. Mortality results were conflicting. Inconsistent results were found for long-term exposure and COVID-19 cases in ecological studies. Studies on short-term exposure were unclear and hard to evaluate. Several studies demonstrated that inhaled pollutant increased expression of the ACE2 receptor and other host susceptibility genes in both alveolar epithelial cells and macrophages. Susceptibility to infection by SARS-CoV-2 can be inferred from these results but only one study used SARS-CoV-2 directly. Several studies from 2011-2021 showed a link between air pollution and hospital admissions for lung infections although the studies were spread across different age groups and disease definitions. Particulate matter does not appear to play any important part in transporting COVID-19 in the environment, as had been suggested by some earlier studies. Conclusions The publication of cohort studies with individual data in this time period is an important step forward. Results are suggestive for long-term exposure and hospital admissions for COVID-19 and some toxicological effects are plausible but further research will be necessary to strengthen these emerging findings. Keywords Air pollution, COVID-19, lower respiratory infections.

Approaches to Vaccination of Patients with Diabetes Mellitus and Obesity in the Current Epidemiological Situation

Relevance. To date, there is ample evidence that diabetes mellitus (DM) and obesity are predictors of a severe course and adverse outcome of COVID-19. The SARS-CoV-2 virus is known to have deleterious effects on the pancreas, exacerbating insulin resistance The SARS-CoV-2 virus is known to have deleterious effects on the pancreas, exacerbating insulin resistance. Long-term data have been accumulated regarding pneumococcal infection and influenza, both of which are severe in patients with diabetes and obesity. The aim is to analyze scientific publications on the problems of vaccinating patients with diabetes and obesity against SARS-CoV-2, pneumococcal infection, and influenza. Conclusions. Vaccination against COVID-19 in patients with DM and obesity is an effective preventive measure. Experience with vaccination against COVID-19 using the following vaccines: Moderna mRNA-1273, Pfizer BioNTech, BNT162b2, AstraZeneca COVID-19 vaccine AZD1222, SII Covishield, SK Bioscience, Sputnik V showed similar safety and efficacy profiles among obese and DM patients and those at risk. Researchers in numerous publications have emphasized the importance of routine vaccination for people living with diabetes amid a pandemic of a new coronavirus infection. Researchers in numerous publications have emphasized the importance of routine vaccination for people living with diabetes in the face of a new coronavirus pandemic. Analysis of the literature reviewed in this review suggests that vaccination against SARS-CoV-2, especially for those at risk, will be an intensive area of research in the coming years and that vaccination against coronavirus infection is likely to be routine for people with diabetes and obesity.

Obesity and COVID-19 Outcomes in a Primarily Black Population

Background: Studies have noted higher COVID-19 mortality with more severe obesity in populations that included a small percentage of Black patients. Methods: We retrospectively analyzed COVID-19 outcomes associated with obesity in our largely African American patient population. A total of 1101 symptomatic patients with a positive COVID-19 laboratory test March 5 to June 3, 2020, were categorized into weight groups based on body mass index (BMI). Of these patients, 679 (61.7%) were Black. A total of 355 (32.2%) patients had overweight and 516 (46.9%) had obesity. Results: BMI was an independent risk factor for intubation and an independent predictor for ICU length of stay and intubation days. An unexpected observation was favorable outcomes in mild obesity compared with normal weight and more severe obesity, likely a result of older age and higher Charlson comorbidity index in patients with normal BMI compared with patients with mild obesity. Conclusions: In a diverse primarily Black population, comorbidities were a concern for adverse COVID-19 outcomes and COVID-19 outcomes were significantly worse with moderate and severe obesity.

Decrease in COVID-19 adverse outcomes in adults during the Delta and Omicron SARS-CoV-2 waves, after vaccination in Mexico.

Mexico, one of the countries severely affected by COVID-19, accumulated more than 5. 1 all-cause excess deaths/1,000 inhabitants and 2.5 COVID-19 confirmed deaths/1,000 inhabitants, in 2 years. In this scenario of high SARS-CoV-2 circulation, we analyzed the effectiveness of the country's vaccination strategy that used 7 different vaccines from around the world, and focused on vaccinating the oldest population first. We analyzed the national dataset published by Mexican health authorities, as a retrospective cohort, separating cases, hospitalizations, deaths and excess deaths by wave and age group. We explored if the vaccination strategy was effective to limit severe COVID-19 during the active outbreaks caused by Delta and Omicron variants. Vaccination of the eldest third of the population reduced COVID-19 hospitalizations, deaths and excess deaths by 46–55% in the third wave driven by Delta SARS-CoV-2. These adverse outcomes dropped 74–85% by the fourth wave driven by Omicron, when all adults had access to vaccines. Vaccine access for the pregnant resulted in 85–90% decrease in COVID-19 fatalities in pregnant individuals and 80% decrease in infants 0 years old by the Omicron wave. In contrast, in the rest of the pediatric population that did not access vaccination before the period analyzed, COVID-19 hospitalizations increased >40% during the Delta and Omicron waves. Our analysis suggests that the vaccination strategy in Mexico has been successful to limit population mortality and decrease severe COVID-19, but children in Mexico still need access to SARS-CoV-2 vaccines to limit severe COVID-19, in particular those 1–4 years old.

Inflammation and immunity connect hypertension with adverse COVID-19 outcomes.

Objectives: To explore the connection of hypertension and severe COVID-19 outcomes. Methods: A total of 68 observational studies recording mortality and/or general severity of COVID-19 were pooled for meta-analyses of the relationship of severe COVID-19 outcomes with hypertension as well as systolic and diastolic blood pressure. Genome-wide cross-trait meta-analysis (GWCTM) was performed to explore the genes linking between hypertension and COVID-19 severity. Results: The results of meta-analysis with the random effect model indicated that pooled risk ratios of hypertension on mortality and severity of COVID-19 were 1.80 [95% confidence interval (CI) 1.54–2.1] and 1.78 (95% confidence interval 1.56–2.04), respectively, although the apparent heterogeneity of the included studies was detected. In subgroup analysis, cohorts of severe and mild patients of COVID-19 assessed in Europe had a significant pooled weighted mean difference of 6.61 mmHg (95% CI 3.66–9.55) with no heterogeneity found (p = 0.26). The genes in the shared signature of hypertension and the COVID-19 severity were mostly expressed in lungs. Analysis of molecular networks commonly affected both by hypertension and by severe COVID-19 highlighted CCR1/CCR5 and IL10RB signaling, as well as Th1 and Th2 activation pathways, and also a potential for a shared regulation with multiple sclerosis. Conclusion: Hypertension is significantly associated with the severe course of COVID-19. Genetic variants within inflammation- and immunity-related genes may affect their expression in lungs and confer liability to both elevated blood pressure and to severe COVID-19.

Cystatin C is associated with adverse COVID-19 outcomes in diverse populations

COVID-19 has highly variable clinical courses. The search for prognostic host factors for COVID-19 outcome is a priority. We performed logistic regression for ICU admission against a polygenic score (PGS) for Cystatin C (CyC) production in patients with COVID-19. We analyzed the predictive value of longitudinal plasma CyC levels in an independent cohort of patients hospitalized with COVID-19. In four cohorts spanning European and African ancestry populations, we identified a significant association between CyC-production PGS and odds of critical illness (n cases=2,319), with the strongest association captured in the UKB cohort (OR 2.13, 95% CI 1.58-2.87, p=7.12e-7). Plasma proteomics from an independent cohort of hospitalized COVID-19 patients (n cases = 131) demonstrated that CyC production was associated with COVID-specific mortality (p=0.0007). Our findings suggest that CyC may be useful for stratification of patients and it has functional role in the host response to COVID-19.

Predictive performance and clinical application of COV50, a urinary proteomic biomarker in early COVID-19 infection: a prospective multicentre cohort study

BackgroundThe SARS-CoV-2 pandemic is a worldwide challenge. The CRIT-CoV-U pilot study generated a urinary proteomic biomarker consisting of 50 peptides (COV50), which predicted death and disease progression from SARS-CoV-2. After the interim analysis presented for the German Government, here, we aimed to analyse the full dataset to consolidate the findings and propose potential clinical applications of this biomarker.MethodsCRIT-CoV-U was a prospective multicentre cohort study. In eight European countries (Austria, France, Germany, Greece, North Macedonia, Poland, Spain, and Sweden), 1012 adults with PCR-confirmed COVID-19 were followed up for death and progression along the 8-point WHO scale. Capillary electrophoresis coupled with mass spectrometry was used for urinary proteomic profiling. Statistical methods included logistic regression and receiver operating characteristic curve analysis with a comparison of the area under curve (AUC) between nested models. Hospitalisation costs were derived from the care facility corresponding with the Markov chain probability of reaching WHO scores ranging from 3 to 8 and flat-rate hospitalisation costs adjusted for the gross per capita domestic product of each country.FindingsFrom June 30 to Nov 19, 2020, 228 participants were recruited, and from April 30, 2020, to April 14, 2021, 784 participants were recruited, resulting in a total of 1012 participants. The entry WHO scores were 1–3 in 445 (44%) participants, 4–5 in 529 (52%) participants, and 6 in 38 (4%) participants; and of all participants, 119 died and 271 had disease progression. The odds ratio (OR) associated with COV50 in all 1012 participants for death was 2·44 (95% CI 2·05–2·92) unadjusted and 1·67 (1·34–2·07) when adjusted for sex, age, BMI, comorbidities, and baseline WHO score; and for disease progression, the OR was 1·79 (1·60–2·01) when unadjusted and 1·63 (1·41–1·91) when adjusted (p<0·0001 for all). The predictive accuracy of the optimised COV50 thresholds was 74·4% (71·6–77·1%) for mortality (threshold 0·47) and 67·4% (64·4–70·3%) for disease progression (threshold 0·04). When adjusted for covariables and the baseline WHO score, these thresholds improved AUCs from 0·835 to 0·853 (p=0·033) for death and from 0·697 to 0·730 (p=0·0008) for progression. Of 196 participants who received ambulatory care, 194 (99%) did not reach the 0·04 threshold. The cost reductions associated with 1 day less hospitalisation per 1000 participants were million Euro (M€) 0·887 (5–95% percentile interval 0·730–1·039) in participants at a low risk (COV50 <0·04) and M€2·098 (1·839-2·365) in participants at a high risk (COV50 ≥0·04).InterpretationThe urinary proteomic COV50 marker might be predictive of adverse COVID-19 outcomes. Even in people with mild-to-moderate PCR-confirmed infections (WHO scores 1–4), the 0·04 COV50 threshold justifies earlier drug treatment, thereby potentially reducing the number of days in hospital and associated costs.FundingGerman Federal Ministry of Health.

A population-based approach to assessing diabetes management during COVID-19: insights from population data in Ontario, Canada.

ObjectiveDiabetes management requires ongoing monitoring of diabetes care from primary care, specialist care and laboratory testing. COVID-19 led to changes in access to in-person care. The purpose of this research was to assess changes in the management of diabetes during the COVID-19 pandemic using population-linked datasets and population segmentation.&#x0D; ApproachWe identified over 1.4 Million Ontarians with diabetes (approximately 10% of the population) with valid health insurance as of April 1, 2019 and April 1, 2020. We measured 11 indicators of diabetes management including laboratory testing for HbA1c and LDL (highlighted in this abstract). With screening indicators, we examined changes in the proportion of the population up-to-date with screening at the end of each fiscal year (March 31, 2020 and March 31, 2021) overall and according to population segments created using linked health data from primary care, home care, long term care and hospitals.&#x0D; ResultsOverall screening rates that required laboratory testing for HbA1c and LDL fell substantially from 54% to 40% and 68% to 59% overall. Comparing across population segments, residents in Long Term Care facilities had the smallest changes in screening rates; individuals with low, medium and high complexity chronic conditions and end-of-life conditions had the largest changes; maternity, cancer, mental health and frail populations were in the middle. Differences according the primary care enrolment models (capitation vs fee-for-service) were relatively minor but patients who were not rostered to a primary care physician had the largest reductions in laboratory screening. Results for all 11 indicators will be shared in the presentation.&#x0D; ConclusionCOVID-19 was associated with substantial reductions in laboratory-based diabetes screening. Poor diabetes management is one of the strongest risk-factors for adverse outcomes in COVID-19. Rates of diabetes management declined most for at risk patient populations amplifying the need to differentially connect with patients to ensure ongoing care during the pandemic.

Use of technology by people with dementia and informal carers during COVID-19: A cross-country comparison.

Considering the adverse outcomes of COVID-19, it is essential to provide adequate support and care for people with dementia and informal carers. Technology can reduce the distress associated with social distancing rules and the decreased access to in-person services. This study aimed to explore the use of technology and its perceived effects across different settings and countries. The sample was composed of 127 informal carers and 15 people with dementia from the UK, Italy, Australia and Poland. Semi-structured interviews explored participants' experiences of using technology and their perceived effects. Transcripts were analysed by researchers in each country using an inductive approach. Three overarching themes were developed: (1) Technology kept us alive during COVID-19; (2) Remote care was anything but easy; (3) Perceived technology limitations. Many similarities emerged between countries supporting the role of technology for being socially engaged, having a routine, and staying active. However, the benefits of technology for health and psychosocial care were more limited. Across countries, barriers to the access and use of technology included lack of digital literacy, dementia severity, and lack of appropriate digital environments. Help and supervision from carers were also necessary and sometimes perceived as an additional burden. Technology can effectively reduce the shrinking world that may be amplified by the pandemic, thus preserving people with dementia's social skills and maintaining family connections. However, for more extensive and well-adapted use of technology in dementia care, actions should be taken to overcome the barriers to the access and use of technology by older and vulnerable people globally.

The effects of hypertension on the prognosis of coronavirus disease 2019: a systematic review and meta-analysis on the interactions with age and antihypertensive treatment.

Hypertension and angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) have been reported to be associated with the prognosis of COVID-19, but the findings remain controversial. Here, we conducted a systematic review to summarize the current evidence. We retrieved all the studies by MEDLINE via PubMed, CENTRAL, and Embase using the MeSH terms until 30 April 2021. A fixed or random effect model was applied to calculate pooled adjusted odds ratio (AOR) with 95% confidence interval (CI). Interactive analysis was performed to identify the interaction effect of hypertension and age on in-hospital mortality. In total, 86 articles with 18 775 387 COVID-19 patients from 18 countries were included in this study. The pooled analysis showed that the COVID-19 patients with hypertension had increased risks of in-hospital mortality and other adverse outcomes, compared with those without hypertension, with an AOR (95% CI) of 1.36 (1.28-1.45) and 1.32 (1.24-1.41), respectively. The results were mostly repeated in countries with more than three independent studies. Furthermore, the effect of hypertension on in-hospital mortality is more evident in younger and older COVID-19 patients than in 60-69-year-old patients. ACEI/ARBs did not significantly affect the mortality and adverse outcomes of COVID-19 patients, compared with those receiving other antihypertensive treatments. Hypertension is significantly associated with an increased risk of in-hospital mortality and adverse outcomes in COVID-19. The effect of hypertension on in-hospital mortality among consecutive age groups followed a U-shaped curve. ACEI/ARB treatments do not increase in-hospital mortality and other poor outcomes of COVID-19 patients with hypertension.

The Role of Lymphocyte Subsets, PD-1, and FAS (CD95) in COVID-19 Cancer Patients.

Lymphocytes are the main orchestrators that regulate the immune response in SARS-COV-2 infection. The exhaustion of T lymphocytes is a contributing factor to lymphopenia, which is responsible for the COVID-19 adverse outcome. However, it is still not demonstrated on a large scale, including cancer patients. Peripheral blood samples were obtained from 83 SARS-CoV2 infected cancer patients, and 29 COVID-19 infected noncancer patients compared to 28 age-matched healthy controls. Lymphocyte subsets were assessed for CD3, CD4, CD8, CD56, PD-1, and CD95 using flow cytometry. The data were correlated to the patients' clinical features, COVID-19 severity and outcomes. Lymphopenia, and decreased CD4+ T cells and CD8+ T cells were significantly observed in COVID-19 cancer and noncancer patients compared to the control group (p < 0.001, for all). There was a significantly increased expression of CD95 and PD-1 on the NK cells, CD4+ T cells, and CD8+ T cells in COVID-19 cancer and noncancer patients in comparison to the control group. The increased expression of CD95 on CD8+ T cells, as well as the increased expression of PD-1 on CD8+ T cells and NK cells are significantly associated with the severity of COVID-19 infection in cancer patients. The increased expression of CD95 and PD-1 on the CD4+ T cells, CD8+ T cells, and NK cells was observed significantly in nonsurviving patients and those who were admitted to the intensive care unit in COVID-19 cancer and noncancer patients. The increased expression of PD-1 and CD95 could be possible prognostic factors for COVID-19 severity and adverse outcomes in COVID-19 cancer and noncancer patients.