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BMC Health Serv Res ; 22(1): 166, 2022 Feb 09.
Article in English | MEDLINE | ID: covidwho-1779644


BACKGROUND: The COVID-19 pandemic has a huge impact on healthcare provided. The nationwide pathology registry of the Netherlands, PALGA, offers an outstanding opportunity to measure this impact for diseases in which pathology examinations are involved. METHODS: Pathology specimen numbers in 2020 were compared with specimen numbers in 2019 for 5 periods of 4 weeks, representing two lockdowns and the periods in between, taking into account localization, procedure and benign versus malignant diagnosis. RESULTS: The largest decrease was seen during the first lockdown (spring 2020), when numbers of pathology reports declined up to 88% and almost all specimen types were affected. Afterwards each specimen type showed its own dynamics with a decrease during the second lockdown for some, while for others numbers remained relatively low during the whole year. Generally, for most tissue types resections, cytology and malignant diagnoses showed less decrease than biopsies and benign diagnoses. A significant but small catch-up (up to 17%) was seen for benign cervical cytology, benign resections of the lower gastro-intestinal tract, malignant skin resections and gallbladder resections. CONCLUSION: The COVID-19 pandemic has had a significant effect on pathology diagnostics in 2020. This effect was most pronounced during the first lockdown, diverse for different anatomical sites and for cytology compared with histology. The data presented here can help to assess the consequences on (public) health and provide a starting point in the discussion on how to make the best choices in times of scarce healthcare resources, considering the impact of both benign and malignant disease on quality of life.

COVID-19 , Communicable Disease Control , Humans , Netherlands/epidemiology , Pandemics , Quality of Life , SARS-CoV-2
PUBMED; 2020.
Preprint in English | PUBMED | ID: ppcovidwho-292827


The recent outbreak of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has led to a worldwide pandemic. One week after initial symptoms develop, a subset of patients progresses to severe disease, with high mortality and limited treatment options. To design novel interventions aimed at preventing spread of the virus and reducing progression to severe disease, detailed knowledge of the cell types and regulating factors driving cellular entry is urgently needed. Here we assess the expression patterns in genes required for COVID-19 entry into cells and replication, and their regulation by genetic, epigenetic and environmental factors, throughout the respiratory tract using samples collected from the upper (nasal) and lower airways (bronchi). Matched samples from the upper and lower airways show a clear increased expression of these genes in the nose compared to the bronchi and parenchyma. Cellular deconvolution indicates a clear association of these genes with the proportion of secretory epithelial cells. Smoking status was found to increase the majority of COVID-19 related genes including ACE2 and TMPRSS2 but only in the lower airways, which was associated with a significant increase in the predicted proportion of goblet cells in bronchial samples of current smokers. Both acute and second hand smoke were found to increase ACE2 expression in the bronchus. Inhaled corticosteroids decrease ACE2 expression in the lower airways. No significant effect of genetics on ACE2 expression was observed, but a strong association of DNA- methylation with ACE2 and TMPRSS2- mRNA expression was identified in the bronchus.

American Journal of Respiratory and Critical Care Medicine ; 203(9):2, 2021.
Article in English | Web of Science | ID: covidwho-1407093
American Journal of Respiratory and Critical Care Medicine ; 203(9), 2021.
Article in English | EMBASE | ID: covidwho-1277568


RATIONALE: The genes that influence the pathophysiology of COVID-19 have yet to be identified. Association analysis has found genetic loci for COVID-191. We used integrative genomics (IG) to combine gene expression and proteomic information with COVID-19 susceptibility loci in order to identify candidate genes for this disease. METHODS: For these analyses we used the COVID-19 Host Genetics Initiative genome-wide association (GWA) meta-analysis version 4 (COVID-19 positive versus COVID-19 negative), the Lung eQTL study2 (n=1,038), eQTLGen3 study (n=31,784) and the INTERVAL4 study (n=3,301). We conducted two IG methods (Bayesian Colocalization [coloc] and Summary Based Mendelian Randomization) to link gene and protein expression in lung and blood tissues with COVID-19 susceptibility loci. We identified the most consistently colocalized gene and conducted a Mendelian Randomization (MR) to assess the causal association of its protein ('exposure') with COVID-19 susceptibility ('outcomes'). Significant MR was set as P<0.05. RESULTS: The expression of 6 genes in lung and 12 in blood colocalized with COVID-19 susceptibility loci. SMR results demonstrated that the expression levels of 6 genes in lung tissue and 5 in blood were associated with COVID-19. Out of the candidate genes identified, two (ABO and SLC6A20) were within previously identified loci (Figure 1). Based on the SMR we found that the expression of SLC6A20 in lung was associated with a higher risk of COVID-19. Novel discovered associations included ERMP1, FCER1G, and CA11, genes which have been previously linked with respiratory diseases (i.e.: asthma) and host immune responses (i.e.: neutrophil and eosinophil counts). COVID-19 susceptibility also colocalized with plasma protein levels of ABO. Based on MR, ABO demonstrated a significant causal association (P = 2.10 × 10-5) with the risk of COVID-19 with increased levels of this protein in plasma associated with an increased risk of COVID-19. The top variant in the MR test (rs505922) was in complete linkage disequilibrium with the variant responsible for the blood O genotype, conferring reduced risk. CONCLUSIONS: This multi-omics approach led to the discovery of novel genes associated with COVID-19. We found that the ABO protein is a causal risk factor for COVID-19, with blood group O being protective against COVID-19. REFERENCES: 1. Ellinghaus, D. et al. N. Engl. J. Med. (2020). 2. Hao, K. et al. PLoS Genet. (2012). 3. Ṽsa, U. et al. bioRxiv. (2018). 4. Sun, B. B. et al. Nature. (2018) .