Haemostatic differences between SARS-CoV-2 PCR-positive and negative patients at the time of hospital admission.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with thrombosis. We conducted a cohort study of consecutive patients, suspected of SARS-CoV-2 infection presented to the emergency department. We investigated haemostatic differences between SARS-CoV-2 PCR positive and negative patients, with dedicated coagulation analysis. The 519 included patients had a median age of 66 years, and 52.5% of the patients were male. Twenty-six percent of the patients were PCR-positive for SARS-CoV-2.PCR positive patients had increased levels of fibrinogen and (active) von Willebrand Factor (VWF) and decreased levels of protein C and α2-macroglobulin compared to the PCR negative patients. In addition, we found acquired activated protein C resistance in PCR positive patients. Furthermore, we found that elevated levels of factor VIII and VWF and decreased levels of ADAMTS-13 were associated with an increased incidence of thrombosis in PCR positive patients. In conclusion, we found that PCR positive patients had a pronounced prothrombotic phenotype, mainly due to an increase of endothelial activation upon admission to the hospital. These findings show that coagulation tests may be considered useful to discriminate severe cases of COVID-19 at risk for thrombosis.

Low prevalence of SARS-CoV-2 in plasma of COVID-19 patients presenting to the emergency department.

Correct and reliable identification of SARS-CoV-2 in COVID-19 suspected patients is essential for diagnosis. Respiratory samples should always be tested with real-time PCR for SARS-CoV-2. In addition, blood samples have been tested, but without consistent results and therefore the added value of this sample type is unknown. The aim of this study was to determine the prevalence of SARS-CoV-2 by real-time PCR in blood samples obtained from PCR-proven COVID-19 patients and in addition to elaborate on the potential use of blood for diagnostics. In this single center study, blood samples drawn from patients at the emergency department with proven COVID-19 infection based on a positive SARS-CoV-2 PCR in respiratory samples were tested for the presence of SARS-CoV-2. Samples from 118 patients were selected, of which 102 could be included in the study (median age was 65 (IQR 10), 65.7 % men). In six (5.9 %) of the tested samples, SARS-CoV-2 was identified by real-time PCR. In conclusion, SARS-CoV-2 can be detected by real-time PCR in plasma samples from patients with proven COVID-19, but only in a minority of the patients. Plasma should therefore not be used as primary sample in an acute phase setting to identify SARS-CoV-2 infection. These findings are important to complete the knowledge on possible sample types to test to diagnose COVID-19.

Toll-Like Receptors (TLRs) Expression in Contracted Capsules Compared to Uncontracted Capsules.

INTRODUCTION: The etiology of capsular contracture after surgical implantation of breast implants remains unclear, but an important role is seen for the immune system. Toll-like receptors are immune receptors recognizing both pathogen-associated molecular patterns and damage-associated molecular patterns. The former are present on bacteria such as Staphylococcus epidermidis (bacteria earlier associated with capsular contracture), and the latter are released after (mechanical) stress. The aim of this study was to investigate the expression of TLRs 1-10 in relation to capsular contracture. MATERIALS AND METHODS: Fifty consecutive breast capsules were collected during implant removal or replacement. The extent of capsular contracture was scored according to the Baker score. A sample specimen (0.5 cm3) was obtained from all tissues. cDNA was synthesized from isolated mRNA from the collected specimens. PCR analyses were conducted to test for cDNA presence and to quantify concentration. TLR1-10 expression was measured for each of the Baker scores separately and compared to all Baker scores. RESULTS: Expression of all TLRs in all Baker scores was seen. TLR2 and TLR6 were more often present in contracted samples (Baker 3 or 4) compared to uncontracted samples (Baker 1 or 2) [Baker 2 vs. 3 (p = 0.034) and Baker 2 vs. 3 (p = 0.003), respectively]. None of the TLRs displayed a significantly higher expression in contracted capsules compared to uncontracted capsules. CONCLUSION: This study shows that TLR2 and TLR6 are more often expressed in contracted capsules compared to non-contracted capsules however not in higher concentrations. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Waddlia chondrophila and Chlamydia trachomatis antibodies in screening infertile women for tubal pathology.

Since Waddlia chondrophila is closely related to Chlamydia trachomatis, we hypothesise that W. chondrophila may also be associated with tubal factor infertility (TFI) in women, a major complication of chronic C. trachomatis infection. Five hundred twenty serum samples were tested for anti-Waddlia antibodies by ELISA. Among the 520 investigated women, a total number of 142 (27.3%) has had laparoscopic diagnosis performed, and were either classified TFI positive or negative. Presence of high titres of W. chondrophila antibodies was linked to TFI (p < 0.0001; OR: 7.5; 95% CI: 3.3-17). Moreover, antibody positivity to both W. chondrophila and C. trachomatis-MOMP was strongly associated with TFI (p < 0.0001; OR: 21; 95% CI: 3.8-12E1). This association was much stronger than the statistical association of C. trachomatis-MOMP antibodies only (p < 0.0001; OR: 7.1; 95% CI: 3.7-14), suggesting that co-infection with W. chondrophila and C. trachomatis may lead to more severe reproductive sequelae and immune responses than single infection with either Chlamydiales members.

Serogroup distribution of urogenital Chlamydia trachomatis in urban ethnic groups in The Netherlands.

The prevalence of Chlamydia trachomatis varies between ethnic groups in The Netherlands. It is, however, unknown whether this is associated with specific serogroups. The objective of this study was to determine whether serogroup distribution is associated with ethnic origin in the region of The Hague, The Netherlands. Serogroups of 370 microbiologically confirmed C. trachomatis-positive samples were analysed. The samples were obtained from 247 women and 123 men between January and October 2008, of self-reported Dutch Caucasian, Dutch Antillean, Surinamese, N. African/Turkish or other descent. We observed a difference in serogroup distribution comparing Dutch Caucasian women to Dutch Antillean women (χ2 for distribution P = 0·035). Serogroup C was more common in Dutch Antillean women, whereas serogroup B was less common (P = 0·03). This difference was not observed for Dutch Antillean men. The observed difference in distribution of C. trachomatis serogroups between ethnic groups is relevant for further transmission studies.

Chlamydia trachomatis infections and subfertility: opportunities to translate host pathogen genomic data into public health.

Chlamydia trachomatis (CT) infections in women can result in tubal pathology (TP). Worldwide 10-15% of all couples are subfertile, meaning they did not get pregnant after 1 year. Part of the routine subfertility diagnostics is the Chlamydia Antibody Test (CAT) to decide for laparoscopy or not in order to diagnose TP. The CAT positive and negative predictive value is such that many unneeded laparoscopies are done and many TP cases are missed. Addition of host genetic markers related to infection susceptibility and severity could potentially improve the clinical management of couples who suffer from subfertility. In the present study, the potential translational and clinical value of adding diagnostic host genetic marker profiles on the basis of infection and inflammation to the current clinical management of subfertility was investigated. This review provides an overview of the current state of the art of host genetic markers in relation to CT infection, proposes a new clinical diagnostic approach, and investigates how the Learning-Adapting-Leveling model (LAL, a public health genomic (PHG) model) can be of value and provide insight to see whether these host genetic markers can be translated into public health. This review shows that the preliminary basis of adding host genetic marker profiles to the current diagnostic procedures of subfertility is present but has to be further developed before implementation into health care can be achieved. CT infection is an example in the field of PHG with potential diagnostic to be taken up in the future in the field of subfertility diagnosis with a time line for integration to be dependent on enhanced participation of many stakeholders in the field of PHG which could be advanced through the LAL model.

Detection of Chlamydia trachomatis and Neisseria gonorrhoeae in an STI population: performances of the Presto CT-NG assay, the Lightmix Kit 480 HT CT/NG and the COBAS Amplicor with urine specimens and urethral/cervicovaginal samples.

OBJECTIVES: This study assessed the performances of the Presto CT-NG assay, the Lightmix Kit 480 HT CT/NG and the COBAS Amplicor for Chlamydia trachomatis and Neisseria gonorrhoeae detection. DESIGN: A cross-sectional study design. SETTING: Izore, Centre for Diagnosing Infectious Diseases in Friesland, the Netherlands, tested samples sent from regional sexually transmitted infection (STI) outpatient clinics and regional hospitals from the province Friesland, the Netherlands. PARTICIPANTS: Samples were collected from 292 men and 835 women. These samples included 560 urine samples and 567 urethral/cervicovaginal samples. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measure is C trachomatis infection. No secondary outcome measures are available. RESULTS: The sensitivity, specificity, positive predicative value (PPV) and negative predictive value (NPV) for C trachomatis detection in urine samples using the Presto CT-NG assay were 100%, 99.8%, 98.1% and 100%, respectively; for the Lightmix Kit 480 HT CT/NG: 94.2%, 99.8%, 96.1% and 99.4%, respectively; for the COBAS Amplicor: 92.3%, 99.6%, 96% and 99.2%, respectively. The sensitivity, specificity, PPV and NPV for C trachomatis detection in urethral/cervicovaginal swabs using the Presto CT-NG assay and the COBAS Amplicor were 100%, 99.8%, 97.7% and 100%, respectively; for the Lightmix Kit 480 HT CT/NG: 100%, 99.6%, 97.7% and 100%, respectively. Calculations for N gonorrhoeae could not be made due to a low prevalence. CONCLUSIONS: All three assays had a high sensitivity, specificity, PPV and NPV for C trachomatis, with best performance for the Presto CT-NG assay.

Lymphogranuloma venereum variant L2b-specific polymerase chain reaction: insertion used to close an epidemiological gap.

The management of the ongoing lymphogranuloma venereum epidemic in industrialized Western countries caused by Chlamydia trachomatis variant L2b still needs improvements in diagnosis, therapy and prevention. We therefore developed the first rapid C. trachomatis variant L2b-specific polymerase chain reaction to circumvent laborious ompA gene sequencing.

Significantly higher serologic responses of Chlamydia trachomatis B group serovars versus C and I serogroups.

Chlamydia trachomatis serovars are divided into three serogroups, namely serogroup B, serogroup I (Intermediate) and serogroup C, and subsequently into 19 different serovars. Worldwide, serogroup B is the most prevalent followed by serogroup I. Clear differences have been observed in the duration of infection and growth kinetics between serovars from different serogroups in murine and cell culture models. Reasons for these observed differences are bacterial and host related, and are not well understood. The aim of this study was to determine the differences in immunoglobulin (Ig) G responses between the three serogroups in a group of patients infected with different serovars. Serovars were assessed from 235 C. trachomatispositive patients and quantitative IgG responses were determined. Analyses of variance were used to compare the IgG responses between the three serogroups. Of the serovars, 46% were B group (with serovar E the most prevalent: 35.3%), 39.6% were I group and 14.3% were C group. A highly significant difference in serologic response was shown when comparing the mean IgG concentrations (AU/mL) of patients having serovars in the most prevalent serogroup compared to the other serogroups: B = 135, C = 46 and I = 60 (B vs. C and B vs. I, P < 0.001). In conclusion, the most prevalent serovars generate the highest serologic responses.