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Whole blood transcriptome in long-COVID patients reveals association with lung function and immune response.
Blankestijn, JM, Baalbaki, N, Bazdar, S, Beekers, I, Beijers, RJHCG, van den Bergh, JP, Bloemsma, LD, Cornelissen, MEB, Dekker, T, Duitman, JW, et al
The Journal of allergy and clinical immunology. 2024
Abstract
BACKGROUND Months after infection with severe acute respiratory syndrome coronavirus 2, at least 10% of patients still experience complaints. Long-COVID (coronavirus disease 2019) is a heterogeneous disease, and clustering efforts revealed multiple phenotypes on a clinical level. However, the molecular pathways underlying long-COVID phenotypes are still poorly understood. OBJECTIVES We sought to cluster patients according to their blood transcriptomes and uncover the pathways underlying their disease. METHODS Blood was collected from 77 patients with long-COVID from the Precision Medicine for more Oxygen (P4O2) COVID-19 study. Unsupervised hierarchical clustering was performed on the whole blood transcriptome. These clusters were analyzed for differences in clinical features, pulmonary function tests, and gene ontology term enrichment. RESULTS Clustering revealed 2 distinct clusters on a transcriptome level. Compared with cluster 2 (n = 65), patients in cluster 1 (n = 12) showed a higher rate of preexisting cardiovascular disease (58% vs 22%), higher prevalence of gastrointestinal symptoms (58% vs 29%), shorter hospital duration during severe acute respiratory syndrome coronavirus 2 infection (median, 3 vs 8 days), lower FEV1/forced vital capacity (72% vs 81%), and lower diffusion capacity of the lung for carbon monoxide (68% vs 85% predicted). Gene ontology term enrichment analysis revealed upregulation of genes involved in the antiviral innate immune response in cluster 1, whereas genes involved with the adaptive immune response were upregulated in cluster 2. CONCLUSIONS This study provides a start in uncovering the pathophysiological mechanisms underlying long-COVID. Further research is required to unravel why the immune response is different in these clusters, and to identify potential therapeutic targets to create an optimized treatment or monitoring strategy for the individual long-COVID patient.
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The effect of the urban exposome on COVID-19 health outcomes: A systematic review and meta-analysis.
Houweling, L, Maitland-Van der Zee, AH, Holtjer, JCS, Bazdar, S, Vermeulen, RCH, Downward, GS, Bloemsma, LD
Environmental research. 2024;(Pt 2):117351
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Abstract
BACKGROUND The global severity of SARS-CoV-2 illness has been associated with various urban characteristics, including exposure to ambient air pollutants. This systematic review and meta-analysis aims to synthesize findings from ecological and non-ecological studies to investigate the impact of multiple urban-related features on a variety of COVID-19 health outcomes. METHODS On December 5, 2022, PubMed was searched to identify all types of observational studies that examined one or more urban exposome characteristics in relation to various COVID-19 health outcomes such as infection severity, the need for hospitalization, ICU admission, COVID pneumonia, and mortality. RESULTS A total of 38 non-ecological and 241 ecological studies were included in this review. Non-ecological studies highlighted the significant effects of population density, urbanization, and exposure to ambient air pollutants, particularly PM2.5. The meta-analyses revealed that a 1 μg/m3 increase in PM2.5 was associated with a higher likelihood of COVID-19 hospitalization (pooled OR 1.08 (95% CI:1.02-1.14)) and death (pooled OR 1.06 (95% CI:1.03-1.09)). Ecological studies, in addition to confirming the findings of non-ecological studies, also indicated that higher exposure to nitrogen dioxide (NO2), ozone (O3), sulphur dioxide (SO2), and carbon monoxide (CO), as well as lower ambient temperature, humidity, ultraviolet (UV) radiation, and less green and blue space exposure, were associated with increased COVID-19 morbidity and mortality. CONCLUSION This systematic review has identified several key vulnerability features related to urban areas in the context of the recent COVID-19 pandemic. The findings underscore the importance of improving policies related to urban exposures and implementing measures to protect individuals from these harmful environmental stressors.
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Fatigue and symptom-based clusters in post COVID-19 patients: a multicentre, prospective, observational cohort study.
Cornelissen, MEB, Bloemsma, LD, Vaes, AW, Baalbaki, N, Deng, Q, Beijers, RJHCG, Noij, LCE, Houweling, L, Bazdar, S, Spruit, MA, et al
Journal of translational medicine. 2024;(1):191
Abstract
BACKGROUND In the Netherlands, the prevalence of post COVID-19 condition is estimated at 12.7% at 90-150 days after SARS-CoV-2 infection. This study aimed to determine the occurrence of fatigue and other symptoms, to assess how many patients meet the Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) criteria, to identify symptom-based clusters within the P4O2 COVID-19 cohort and to compare these clusters with clusters in a ME/CFS cohort. METHODS In this multicentre, prospective, observational cohort in the Netherlands, 95 post COVID-19 patients aged 40-65 years were included. Data collection at 3-6 months after infection included demographics, medical history, questionnaires, and a medical examination. Follow-up assessments occurred 9-12 months later, where the same data were collected. Fatigue was determined with the Fatigue Severity Scale (FSS), a score of ≥ 4 means moderate to high fatigue. The frequency and severity of other symptoms and the percentage of patients that meet the ME/CFS criteria were assessed using the DePaul Symptom Questionnaire-2 (DSQ-2). A self-organizing map was used to visualize the clustering of patients based on severity and frequency of 79 symptoms. In a previous study, 337 Dutch ME/CFS patients were clustered based on their symptom scores. The symptom scores of post COVID-19 patients were applied to these clusters to examine whether the same or different clusters were found. RESULTS According to the FSS, fatigue was reported by 75.9% of the patients at 3-6 months after infection and by 57.1% of the patients 9-12 months later. Post-exertional malaise, sleep disturbances, pain, and neurocognitive symptoms were also frequently reported, according to the DSQ-2. Over half of the patients (52.7%) met the Fukuda criteria for ME/CFS, while fewer patients met other ME/CFS definitions. Clustering revealed specific symptom patterns and showed that post COVID-19 patients occurred in 11 of the clusters that have been observed in the ME/CFS cohort, where 2 clusters had > 10 patients. CONCLUSIONS This study shows persistent fatigue and diverse symptomatology in post COVID-19 patients, up to 12-18 months after SARS-CoV-2 infection. Clustering showed that post COVID-19 patients occurred in 11 of the clusters that have been observed in the ME/CFS cohort.
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A Systematic Review of Chest Imaging Findings in Long COVID Patients.
Bazdar, S, Kwee, AKAL, Houweling, L, de Wit-van Wijck, Y, Mohamed Hoesein, FAA, Downward, GS, Nossent, EJ, Maitland-van der Zee, AH, ,
Journal of personalized medicine. 2023;(2)
Abstract
Long COVID is the persistence of one or more COVID-19 symptoms after the initial viral infection, and there is evidence supporting its association with lung damage. In this systematic review, we provide an overview of lung imaging and its findings in long COVID patients. A PubMed search was performed on 29 September 2021, for English language studies in which lung imaging was performed in adults suffering from long COVID. Two independent researchers extracted the data. Our search identified 3130 articles, of which 31, representing the imaging findings of 342 long COVID patients, were retained. The most common imaging modality used was computed tomography (CT) (N = 249). A total of 29 different imaging findings were reported, which were broadly categorized into interstitial (fibrotic), pleural, airway, and other parenchymal abnormalities. A direct comparison between cases, in terms of residual lesions, was available for 148 patients, of whom 66 (44.6%) had normal CT findings. Although respiratory symptoms belong to the most common symptoms in long COVID patients, this is not necessarily linked to radiologically detectable lung damage. Therefore, more research is needed on the role of the various types of lung (and other organ) damage which may or may not occur in long COVID.
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Prevalence, Incidence and Ecological Determinants of Diabetic Retinopathy in Iran: Systematic Review and Meta-analysis.
Sadat Mahmoudi Nezhad, G, Razeghinejad, R, Janghorbani, M, Mohamadian, A, Hassan Jalalpour, M, Bazdar, S, Salehi, A, Molavi Vardanjani, H
Journal of ophthalmic & vision research. 2019;(3):321-335
Abstract
PURPOSE To estimate the pooled prevalence and incidence of diabetic retinopathy (DR) in Iran and to investigate their correlations with the Human Development Index (HDI), healthcare access (i.e., density of specialists and sub-specialists), and methodological issues. METHODS Electronic databases such as PubMed, Embase, Scopus, Web of Science, Google Scholar, and local databases were searched for cohort and cross-sectional studies published prior to January 2018. Prevalence and incidence rates of DR were extracted from January 2000 to December 2017 and random effects models were used to estimate pooled effect sizes. The Joanna Briggs Institute critical appraisal tool was applied for quality assessment of eligible studies. RESULTS A total of 55,445 participants across 33 studies were included. The pooled prevalence (95% CI) of DR in diabetic clinics (22 studies), eye clinics (4 studies), and general population (7 studies) was 31.8% (24.5 to 39.2), 57.8% (50.2 to 65.3), and 29.6% (22.6 to 36.5), respectively. It was 7.4% (3.9 to 10.8) for proliferative DR and 7.1% (4.9 to 9.4) for clinically significant macular edema. The heterogeneity of individual estimates of prevalence was highly significant. HDI ( P < 0.001), density of specialists ( P = 0.004), subspecialists ( P < 0.001), and sampling site ( P = 0.041) were associated with heterogeneity after the adjustment for type of DR, duration of diabetes, study year, and proportion of diabetics with controlled HbA1C. CONCLUSION Human development and healthcare access were correlated with the prevalence of DR. Data were scarce on the prevalence of DR in less developed provinces. Participant recruitment in eye clinics might overestimate the prevalence of DR.