Characteristics and outcomes of older patients hospitalised for COVID-19 in the first and second wave of the pandemic in The Netherlands:the COVID-OLD study

BACKGROUND: as the coronavirus disease of 2019 (COVID-19) pandemic progressed diagnostics and treatment changed. OBJECTIVE: to investigate differences in characteristics, disease presentation and outcomes of older hospitalised COVID-19 patients between the first and second pandemic wave in The Netherlands. METHODS: this was a multicentre retrospective cohort study in 16 hospitals in The Netherlands including patients aged ≥ 70 years, hospitalised for COVID-19 in Spring 2020 (first wave) and Autumn 2020 (second wave). Data included Charlson comorbidity index (CCI), disease severity and Clinical Frailty Scale (CFS). Main outcome was in-hospital mortality. RESULTS: a total of 1,376 patients in the first wave (median age 78 years, 60% male) and 946 patients in the second wave (median age 79 years, 61% male) were included. There was no relevant difference in presence of comorbidity (median CCI 2) or frailty (median CFS 4). Patients in the second wave were admitted earlier in the disease course (median 6 versus 7 symptomatic days; P < 0.001). In-hospital mortality was lower in the second wave (38.1% first wave versus 27.0% second wave; P < 0.001). Mortality risk was 40% lower in the second wave compared with the first wave (95% confidence interval: 28–51%) after adjustment for differences in patient characteristics, comorbidity, symptomatic days until admission, disease severity and frailty. CONCLUSIONS: compared with older patients hospitalised in the first COVID-19 wave, patients in the second wave had lower in-hospital mortality, independent of risk factors for mortality. The better prognosis likely reflects earlier diagnosis, the effect of improvement in treatment and is relevant for future guidelines and treatment decisions

Interruption of CXCL13-CXCR5 Axis Increases Upper Genital Tract Pathology and Activation of NKT Cells following Chlamydial Genital Infection

Peer reviewe

TLR2, TLR4 and TLR9 genotypes and haplotypes in the susceptibility to and clinical course of Chlamydia trachomatis infections in Dutch women

Chlamydia trachomatis infections demonstrate remarkable differences in clinical course that are approximately 40% based on host genetic variation. Here, we study the single nucleotide polymorphisms (SNPs) and their haplotypes in TLR2, TLR4 and TLR9 (TLR2+2477G > A; TLR2 -16934T > A; TLR4+896A > G; TLR9-1237T > C and TLR9 +2848G > A) in relation to the susceptibility to, and severity of C. trachomatis infections. We analysed the five SNPs in a cohort of 770 Dutch Caucasian women either attending a sexually transmitted diseases outpatient clinic (n = 731) or having complaints of subfertility (n = 39). Haplotype analyses showed a trend for TLR2 haplotype I (-16934T/+2477G) to protect against the development of symptoms and tubal pathology (P-trend = 0.03) after Chlamydia infection. In the susceptibility cohort, TLR9 haplotype III (-1237C/+2848A) showed a significant decreasing trend in the development of symptoms after C. trachomatis infection (P = 0.02, OR: 0.55, 95% CI: 0.33-0.91). Logistic regression of the TLR2 haplotypes, TLR4+896A > G, and TLR9 haplotypes showed that the TLR2 haplotype combinations AG-TA and AG-TG confer risk (OR 3.4 (P = 0.01) and 1.6 (P = 0.03)), while the TLR9 haplotype combination TG-TA protects against C. trachomatis infections (OR: 0.4, P = 0.004). Our study shows that both TLR2 and TLR9 genes and SNP combinations do influence the clinical course of Chlamydia infections

Interruption of CXCL13-CXCR5 Axis Increases Upper Genital Tract Pathology and Activation of NKT Cells following Chlamydial Genital Infection

Abstract Background: Regulation of immune responses is critical for controlling inflammation and disruption of this process can lead to tissue damage. We reported that CXCL13 was induced in fallopian tube tissue following C. trachomatis infection. Here, we examined the influence of the CXCL13-CXCR5 axis in chlamydial genital infection

Disruption of the CXCL13-CXCR5 axis increased UGT pathology.

<p>GTs were harvested 49 days after infection and processed en bloc for paraffin sections. (A) Scatter plot and median of chronic inflammatory scores of BALB/c mice treated with anti-CXCL13 Ab versus an irrelevant control Ab or C56BL/6 WT mice versus <i>Cxcr5−/−</i> mice from hematoxylin and eosin stained slides. *<i>p</i><0.05, Mann-Whitney, n = 3–6 mice or 12 oviducts/group. (B) Photomicrograph of trichrome stained sections from oviducts 49 days after infection of C57BL/6 (WT) or <i>Cxcr5</i>−/− mice. Asterisk (WT) and arrows (<i>Cxcr5−/−</i>) show fibrosis and arrowhead (<i>Cxcr5−/−</i>) depicts a dilated oviduct. Sections are at 20×. (C) Fibrosis scores of C56BL/6 WT mice and <i>Cxcr5−/−</i> mice from trichrome stained slides. *<i>p</i><0.01, Mann-Whitney, n = 6 mice or 12 oviducts/group.</p

In vitro depletion of NKT cell function abrogates increased production of IFNγ and other cytokines and chemokines in <i>Cxcr5−/−</i>.

<p>Lymphocytes were isolated from spleens and treated with various conditions to deplete NKT cells to 95% purity. Cells were cultured with EB for 3 days. (A) The level of IFNγ in cell culture supernatants among groups with the indicated NKT cell depleting/blocking treatment. Each treated group was compared to its own untreated counterpart using Bonferroni's modified <i>t</i> test, *<i>p</i><0.05, **<i>p</i><0.01, n = 4 mice/group. (B) Multiple cytokines and chemokines levels were measured in supernatants from α-GalCer depleted plus anti-CD1d treated cell cultures (Depletion+blocking).</p

Lymphocytes accumulate in the oviducts of <i>Cxcr5</i>−/− mice following infection.

<p>GTs were harvested 49 days after vaginal infection with <i>C. muridarum</i> and used to isolate lymphocytes from the oviducts. (A) Representative dotplots of oviduct lymphocyte subsets stained against surface markers and intracellular cytokines. Cells were gated on CD3⁺CD4⁺ or CD3⁺CD8⁺ cells. (B) The number of lymphocyte subsets as determined in panel B, were compared between groups. Bars equal the mean ± SD. *<i>p</i><0.01 (Bonferroni's modified t test). n = 3–4 oviduct pools/group.</p