Variation in COVID-19 disease severity at hospital admission over time and across hospitals

Abstract Background Despite the high disease burden of RSV in older adults and children, there is currently no approved vaccine. Ad26.RSV.preF, an experimental RSV vaccine, has demonstrated immunogenicity and tolerability in first-in-human clinical studies. The aim of this study was to assess the potential of the Ad26.RSV.preF vaccine to protect against RSV infection and disease in an established RSV human challenge model, used for the first time to evaluate a vaccine. Methods We conducted a randomized, double-blind, placebo-controlled, human challenge study (NCT03334695). Healthy adults received 1 × 1011 vp Ad26.RSV.preF vaccine (active) or placebo (pbo) intramuscularly. After 28 days, volunteers were challenged intranasally with a low-passage clinical strain of RSV-A (0.8 mL of Memphis 37b) and then quarantined for 12 days. Nasal washes were collected twice daily throughout quarantine, starting 2 days post-challenge (viral load [VL] by qRT-PCR and quantitative cultures). Disease severity was recorded thrice daily using symptom diary cards. Results Fifty-three volunteers (active, n = 27; pbo, n = 26) were challenged with RSV-A. Quantitative viral assessments were consistently lower in active than pbo. The primary endpoint of the study was met: the area under the curve (AUC) for RSV VL over time (via qRT-PCR) was significantly lower in active pbo (P = 0.012). Median peak VL was lower for active (0 log10 copies/mL) than pbo (5.4 log10 copies/mL). Median AUC for RSV VL over time (quantitative culture) was lower for active than pbo (0 vs. 109, P = 0.002). Disease severity was lower for active than pbo, with a median AUC total symptom score of 35 (active) vs. 167 (pbo) (P = 0.002). Overall, RSV infection (defined by qRT-PCR alone or combined with symptoms) and disease severity over time were lower in active vs. pbo. Conclusion RSV infections, VL, and RSV disease severity were consistently lower in healthy adults receiving Ad26.RSV.preF vs. placebo, demonstrating promising protection from RSV infection and disease. This was the first time that antiviral prevention was observed against RSV after active immunization. Ad26.RSV.preF warrants further evaluation in field trials for efficacy against natural RSV infections in populations considered at risk of severe RSV disease. Disclosures All Authors: No reported Disclosures.

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Complications Requiring Hospital Admission and Causes of In-Hospital Death over Time in Alcoholic and Nonalcoholic Cirrhosis Patients

Gut and Liver ◽

10.5009/gnl14363 ◽

2016 ◽

Vol 10 (1) ◽

pp. 95 ◽

Cited By ~ 10

Author(s):

Hee Yeon Kim ◽

Chang Wook Kim ◽

Jong Young Choi ◽

Chang Don Lee ◽

Sae Hwan Lee ◽

...

Keyword(s):

Hospital Admission ◽

Hospital Death ◽

Over Time

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Saliva viral load is a dynamic unifying correlate of COVID-19 severity and mortality

10.1101/2021.01.04.21249236 ◽

2021 ◽

Author(s):

Julio Silva ◽

Carolina Lucas ◽

Maria Sundaram ◽

Benjamin Israelow ◽

Patrick Wong ◽

...

Keyword(s):

Viral Load ◽

Disease Severity ◽

T Cell Subsets ◽

Temporal Association ◽

Strongly Correlated ◽

Immunological Parameters ◽

Viral Loads ◽

Patient Demographics ◽

Over Time

While several clinical and immunological parameters correlate with disease severity and mortality in SARS-CoV-2 infection, work remains in identifying unifying correlates of coronavirus disease 2019 (COVID-19) that can be used to guide clinical practice. Here, we examine saliva and nasopharyngeal (NP) viral load over time and correlate them with patient demographics, and cellular and immune profiling. We found that saliva viral load was significantly higher in those with COVID-19 risk factors; that it correlated with increasing levels of disease severity and showed a superior ability over nasopharyngeal viral load as a predictor of mortality over time (AUC=0.90). A comprehensive analysis of immune factors and cell subsets revealed strong predictors of high and low saliva viral load, which were associated with increased disease severity or better overall outcomes, respectively. Saliva viral load was positively associated with many known COVID-19 inflammatory markers such as IL-6, IL-18, IL-10, and CXCL10, as well as type 1 immune response cytokines. Higher saliva viral loads strongly correlated with the progressive depletion of platelets, lymphocytes, and effector T cell subsets including circulating follicular CD4 T cells (cTfh). Anti-spike (S) and anti-receptor binding domain (RBD) IgG levels were negatively correlated with saliva viral load showing a strong temporal association that could help distinguish severity and mortality in COVID-19. Finally, patients with fatal COVID-19 exhibited higher viral loads, which correlated with the depletion of cTfh cells, and lower production of anti-RBD and anti-S IgG levels. Together these results demonstrated that viral load – as measured by saliva but not nasopharyngeal — is a dynamic unifying correlate of disease presentation, severity, and mortality over time.

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Longitudinal profiling of the lung microbiome in the AERIS study demonstrates repeatability of bacterial and eosinophilic COPD exacerbations

Thorax ◽

10.1136/thoraxjnl-2017-210408 ◽

2018 ◽

Vol 73 (5) ◽

pp. 422-430 ◽

Cited By ~ 62

Author(s):

David Mayhew ◽

Nathalie Devos ◽

Christophe Lambert ◽

James R Brown ◽

Stuart C Clarke ◽

...

Keyword(s):

Disease Severity ◽

High Throughput Sequencing ◽

Respiratory Infections ◽

Markov Chain Model ◽

Chain Model ◽

Copd Exacerbations ◽

Lung Microbiome ◽

Registration Number ◽

The Stability ◽

Over Time

BackgroundAlterations in the composition of the lung microbiome associated with adverse clinical outcomes, known as dysbiosis, have been implicated with disease severity and exacerbations in COPD.ObjectiveTo characterise longitudinal changes in the lung microbiome in the AERIS study (Acute Exacerbation and Respiratory InfectionS in COPD) and their relationship with associated COPD outcomes.MethodsWe surveyed 584 sputum samples from 101 patients with COPD to analyse the lung microbiome at both stable and exacerbation time points over 1 year using high-throughput sequencing of the 16S ribosomal RNA gene. We incorporated additional lung microbiology, blood markers and in-depth clinical assessments to classify COPD phenotypes.ResultsThe stability of the lung microbiome over time was more likely to be decreased in exacerbations and within individuals with higher exacerbation frequencies. Analysis of exacerbation phenotypes using a Markov chain model revealed that bacterial and eosinophilic exacerbations were more likely to be repeated in subsequent exacerbations within a subject, whereas viral exacerbations were not more likely to be repeated. We also confirmed the association of bacterial genera, including Haemophilus and Moraxella, with disease severity, exacerbation events and bronchiectasis.ConclusionsSubtypes of COPD have distinct bacterial compositions and stabilities over time. Some exacerbation subtypes have non-random probabilities of repeating those subtypes in the future. This study provides insights pertaining to the identification of bacterial targets in the lung and biomarkers to classify COPD subtypes and to determine appropriate treatments for the patient.Trial registration numberResults, NCT01360398.

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Quantitative Electromyography

Clinical Neurophysiology ◽

10.1093/med/9780190259631.003.0025 ◽

2016 ◽

pp. 437-464

Author(s):

Benn E. Smith

Keyword(s):

Disease Severity ◽

Normative Data ◽

Neuromuscular Diseases ◽

Accurate Assessment ◽

Quantitative Electromyography ◽

Quantitative Emg ◽

Over Time

Semi-quantitative EMG methods are in common use in clinical electromyography laboratories but have a number of drawbacks and limitations, including examiner bias in MUP analysis and challenges distinguishing between MUP categories of normal and neurogenic and normal and myopathic waveforms. An array of formal MUP quantitation methods has been developed in recent decades, which seek to address many of the shortcomings of semiquantitative EMG. The advantages of quantitative EMG (QEMG) include: (1) making measurements of MUP recordings consisting of numerical values derived from precise measurements, (2) generating normative data and allowing comparisons with data from patients with suspected neuromuscular diseases, (3) allowing for reproducible results that can be compared at different times by different examiners and in different labs, and (4) allowing accurate assessment of improvement or deterioration in disease severity over time.

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Disease severity declines over time after a wild boar population has been affected by classical swine fever—Legend or actual epidemiological process?

Preventive Veterinary Medicine ◽

10.1016/j.prevetmed.2012.01.024 ◽

2012 ◽

Vol 106 (2) ◽

pp. 185-195 ◽

Cited By ~ 13

Author(s):

M. Lange ◽

S. Kramer-Schadt ◽

S. Blome ◽

M. Beer ◽

H.-H. Thulke

Keyword(s):

Wild Boar ◽

Disease Severity ◽

Classical Swine Fever ◽

Wild Boar Population ◽

Over Time

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1409. Genomic Variation Among Respiratory Syncytial Viruses

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1591 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S712-S712

Author(s):

Christopher S Anderson ◽

Yun Zhang ◽

Anthony Corbett ◽

Chin-Yi Chu ◽

Lu Wang ◽

...

Keyword(s):

Protein Structure ◽

Disease Severity ◽

Genomic Variation ◽

Structure Variation ◽

Time Period ◽

Nasal Swabs ◽

Rsv Infection ◽

Respiratory Syncytial Viruses ◽

Syncytial Virus ◽

Over Time

Abstract Background Respiratory Syncytial Virus (RSV) can be easily classified into two subtypes (A and B) based on the nucleic acid sequence of their genome. Phylogenic approaches have shown that within both subtypes separate lineages of viruses exist and new lineages continue to emerge. The role these genomic variations play in disease severity during RSV infection is largely unknown. Methods Next-generation viral RNA sequencing was performed on archived frozen nasal swabs of children infected with RSV in Rochester, NY between 1977-1998. Genomic variation was compared across year-of-isolation, age of host, and inpatient/outpatient status of host. Local RSV genomic variation was compared to variation of publicly available sequences isolated from hosts residing in other parts of the world. Results A and B subtypes demonstrated significant differences in the genetic sequence and primary-protein structure over time. G-protein was the most variable in both subtypes, but they differed in the number of unique genotypes detected. We found a significant association with disease severity (inpatient/outpatient status) and RSV phylogenetic topology, although the magnitude of the association differed by subtype. Variation in the primary protein structure of RSV viral proteins was also significantly associated with disease severity, but depended on which viral protein, and which subtype, was investigated. Lastly, local RSV genomic and protein-structure variation was similar to what was seen globally during this time period. Conclusion Overall, both subtypes demonstrated significant genetic change over time and these changes were associated with disease severity. These results suggest that the genetic variability of RSV may affect RSV disease in humans. Disclosures All Authors: No reported disclosures

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Course and Survival of COVID-19 Patients with Comorbidities in Relation to the Trace Element Status at Hospital Admission

Nutrients ◽

10.3390/nu13103304 ◽

2021 ◽

Vol 13 (10) ◽

pp. 3304

Author(s):

Gijs Du Du Laing ◽

Mirko Petrovic ◽

Carl Lachat ◽

Marthe De De Boevre ◽

Georg J. Klingenberg ◽

...

Keyword(s):

Hospital Admission ◽

Trace Element ◽

Disease Severity ◽

Clinical Care ◽

Severe Disease ◽

Therapeutic Interventions ◽

Zn Deficiency ◽

Disease Course ◽

Entire Study ◽

Risk Of Cancer

Selenium (Se) and zinc (Zn) are essential trace elements needed for appropriate immune system responses, cell signalling and anti-viral defence. A cross-sectional observational study was conducted at two hospitals in Ghent, Belgium, to investigate whether Se and/or Zn deficiency upon hospital admission correlates to disease severity and mortality risk in COVID-19 patients with or without co-morbidities. Trace element concentrations along with additional biomarkers were determined in serum or plasma and associated to disease severity and outcome. An insufficient Se and/or Zn status upon hospital admission was associated with a higher mortality rate and a more severe disease course in the entire study group, especially in the senior population. In comparison to healthy European adults, the patients displayed strongly depressed total Se (mean ± SD: 59.2 ± 20.6 vs. 84.4 ± 23.4 µg L−1) and SELENOP (mean ± SD: 2.2 ± 1.9 vs. 4.3 ± 1.0 mg L−1) concentrations at hospital admission. Particularly strong associations were observed for death risk of cancer, diabetes and chronic cardiac disease patients with low Se status, and of diabetes and obese patients with Zn deficiency. A composite biomarker based on serum or plasma Se, SELENOP and Zn at hospital admission proved to be a reliable tool to predict severe COVID-19 course and death, or mild disease course. We conclude that trace element assessment at hospital admission may contribute to a better stratification of patients with COVID-19 and other similar infectious diseases, support clinical care, therapeutic interventions and adjuvant supplementation needs, and may prove of particular relevance for patients with relevant comorbidities.

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Variation in hospital admission in febrile children evaluated at the Emergency Department (ED) in Europe: PERFORM, a multicentre prospective observational study

PLoS ONE ◽

10.1371/journal.pone.0244810 ◽

2021 ◽

Vol 16 (1) ◽

pp. e0244810

Author(s):

Dorine M. Borensztajn ◽

Nienke N. Hagedoorn ◽

Irene Rivero Calle ◽

Ian K. Maconochie ◽

Ulrich von Both ◽

...

Keyword(s):

Emergency Department ◽

Hospital Admission ◽

Disease Severity ◽

Severe Disease ◽

Patient Characteristics ◽

Care Utilization ◽

Upper Respiratory Tract ◽

Admission Rates ◽

Patient Groups ◽

Tract Infections

Objectives Hospitalisation is frequently used as a marker of disease severity in observational Emergency Department (ED) studies. The comparison of ED admission rates is complex in potentially being influenced by the characteristics of the region, ED, physician and patient. We aimed to study variation in ED admission rates of febrile children, to assess whether variation could be explained by disease severity and to identify patient groups with large variation, in order to use this to reduce unnecessary health care utilization that is often due to practice variation. Design MOFICHE (Management and Outcome of Fever in children in Europe, part of the PERFORM study, www.perform2020.org), is a prospective cohort study using routinely collected data on febrile children regarding patient characteristics (age, referral, vital signs and clinical alarming signs), diagnostic tests, therapy, diagnosis and hospital admission. Setting and participants Data were collected on febrile children aged 0–18 years presenting to 12 European EDs (2017–2018). Main outcome measures We compared admission rates between EDs by using standardised admission rates after adjusting for patient characteristics and initiated tests at the ED, where standardised rates >1 demonstrate higher admission rates than expected and rates <1 indicate lower rates than expected based on the ED patient population. Results We included 38,120 children. Of those, 9.695 (25.4%) were admitted to a general ward (range EDs 5.1–54.5%). Adjusted standardised admission rates ranged between 0.6 and 1.5. The largest variation was seen in short admission rates (0.1–5.0), PICU admission rates (0.2–2.2), upper respiratory tract infections (0.4–1.7) and fever without focus (0.5–2.7). Variation was small in sepsis/meningitis (0.9–1.1). Conclusions Large variation exists in admission rates of febrile children evaluated at European EDs, however, this variation is largely reduced after correcting for patient characteristics and therefore overall admission rates seem to adequately reflect disease severity or a potential for a severe disease course. However, for certain patient groups variation remains high even after adjusting for patient characteristics.

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Neutralizing antibody responses over time in demographically and clinically diverse individuals recovered from SARS-CoV-2 infection in the United States and Peru: A cohort study

PLoS Medicine ◽

10.1371/journal.pmed.1003868 ◽

2021 ◽

Vol 18 (12) ◽

pp. e1003868

Author(s):

Shelly Karuna ◽

Shuying Sue Li ◽

Shannon Grant ◽

Stephen R. Walsh ◽

Ian Frank ◽

...

Keyword(s):

United States ◽

Disease Severity ◽

Disease Onset ◽

Clinical Manifestations ◽

The United States ◽

Immune Defense ◽

Severe Illness ◽

Pseudotyped Virus ◽

Wide Range ◽

Over Time

Background People infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) experience a wide range of clinical manifestations, from asymptomatic and mild illness to severe illness and death, influenced by age and a variety of comorbidities. Neutralizing antibodies (nAbs) are thought to be a primary immune defense against the virus. Large, diverse, well-characterized cohorts of convalescent individuals provide standardized values to benchmark nAb responses to past SARS-CoV-2 infection and define potentially protective levels of immunity. Methods and findings This analysis comprises an observational cohort of 329 HIV–seronegative adults in the United States (n = 167) and Peru (n = 162) convalescing from SARS-CoV-2 infection from May through October 2020. The mean age was 48 years (range 18 to 86), 54% of the cohort overall was Hispanic, and 34% identified as White. nAb titers were measured in serum by SARS-CoV-2.D614G Spike-pseudotyped virus infection of 293T/ACE2 cells. Multiple linear regression was applied to define associations between nAb titers and demographic variables, disease severity and time from infection or disease onset, and comorbidities within and across US and Peruvian cohorts over time. nAb titers peaked 28 to 42 days post-diagnosis and were higher in participants with a history of severe Coronavirus Disease 2019 (COVID-19) illness (p < 0.001). Diabetes, age >55 years, male sex assigned at birth, and, in some cases, body mass index were also independently associated with higher nAb titers, whereas hypertension was independently associated with lower nAb titers. nAb titers did not differ by race, underlying pulmonary disease or smoking. Two months post-enrollment, nAb ID50 (ID80) titers declined 3.5 (2.8)-fold overall. Study limitations in this observational, convalescent cohort include survivorship bias and missing early viral loads and acute immune responses to correlate with the convalescent responses we observed. Conclusions In summary, in our cohort, nAb titers after SARS-CoV-2 infection peaked approximately 1 month post-diagnosis and varied by age, sex assigned at birth, disease severity, and underlying comorbidities. Our data show great heterogeneity in nAb responses among people with recent COVID-19, highlighting the challenges of interpreting natural history studies and gauging responses to vaccines and therapeutics among people with recent infection. Our observations illuminate potential correlations of demographic and clinical characteristics with nAb responses, a key element for protection from COVID-19, thus informing development and implementation of preventative and therapeutic strategies globally. Trial registration ClinicalTrials.gov NCT04403880.

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