Screening of healthcare workers for SARS-CoV-2 highlights the role of asymptomatic carriage in COVID-19 transmission

Funder: Addenbrooke's Charitable Trust, Cambridge University Hospitals; FundRef: http://dx.doi.org/10.13039/501100002927Significant differences exist in the availability of healthcare worker (HCW) SARS-CoV-2 testing between countries, and existing programmes focus on screening symptomatic rather than asymptomatic staff. Over a 3 week period (April 2020), 1032 asymptomatic HCWs were screened for SARS-CoV-2 in a large UK teaching hospital. Symptomatic staff and symptomatic household contacts were additionally tested. Real-time RT-PCR was used to detect viral RNA from a throat+nose self-swab. 3% of HCWs in the asymptomatic screening group tested positive for SARS-CoV-2. 17/30 (57%) were truly asymptomatic/pauci-symptomatic. 12/30 (40%) had experienced symptoms compatible with coronavirus disease 2019 (COVID-19)>7 days prior to testing, most self-isolating, returning well. Clusters of HCW infection were discovered on two independent wards. Viral genome sequencing showed that the majority of HCWs had the dominant lineage B∙1. Our data demonstrates the utility of comprehensive screening of HCWs with minimal or no symptoms. This approach will be critical for protecting patients and hospital staff

Complement lectin pathway activation is associated with COVID-19 disease severity, independent of MBL2 genotype subgroups

IntroductionWhile complement is a contributor to disease severity in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, all three complement pathways might be activated by the virus. Lectin pathway activation occurs through different pattern recognition molecules, including mannan binding lectin (MBL), a protein shown to interact with SARS-CoV-2 proteins. However, the exact role of lectin pathway activation and its key pattern recognition molecule MBL in COVID-19 is still not fully understood.MethodsWe therefore investigated activation of the lectin pathway in two independent cohorts of SARS-CoV-2 infected patients, while also analysing MBL protein levels and potential effects of the six major single nucleotide polymorphisms (SNPs) found in the MBL2 gene on COVID-19 severity and outcome.ResultsWe show that the lectin pathway is activated in acute COVID-19, indicated by the correlation between complement activation product levels of the MASP-1/C1-INH complex (p=0.0011) and C4d (p<0.0001) and COVID-19 severity. Despite this, genetic variations in MBL2 are not associated with susceptibility to SARS-CoV-2 infection or disease outcomes such as mortality and the development of Long COVID.ConclusionIn conclusion, activation of the MBL-LP only plays a minor role in COVID-19 pathogenesis, since no clinically meaningful, consistent associations with disease outcomes were noted

Is gingival bleeding a symptom of type 2 and 3 von Willebrand disease?

Background: Von Willebrand disease (VWD) is the most common inherent bleeding disorder. Gingival bleeding is a frequently reported symptom of VWD. However, gingival bleeding is also a leading symptom of plaque-induced gingivitis and untreated periodontal disease. In type 1 VWD gingival bleeding was not increased compared to controls. Thus, this study evaluated whether type 2 and 3 VWD determines an increased susceptibility to gingival bleeding in response to the oral biofilm. Methods: Twenty-four cases and 24 controls matched for age, sex, periodontal diagnosis, number of teeth and smoking were examined hematologically (VWF antigen, VWF activity, factor VIII activity) and periodontally (Gingival Bleeding Index [GBI]), bleeding on probing [BOP], Plaque Control Record [PCR], periodontal inflamed surface area [PISA], vertical probing attachment level). Results: BOP (VWD: 14.5±10.1%; controls: 12.3±5.3%; p = 0.542) and GBI (VWD: 10.5±9.9%; controls: 8.8±4.8%; p = 0.852) were similar for VWD and controls. Multiple regressions identified female sex, HbA1c, PCR and PISA to be associated with BOP. HbA1c and PCR were associated with GBI. Number of remaining teeth was negatively correlated with BOP and GBI. Conclusion: Type 2 and 3 VWD are not associated with a more pronounced inflammatory response to the oral biofilm in terms of BOP and GBI

Is gingival bleeding a symptom of type 2 and 3 von Willebrand disease?

<div><p>Background</p><p>Von Willebrand disease (VWD) is the most common inherent bleeding disorder. Gingival bleeding is a frequently reported symptom of VWD. However, gingival bleeding is also a leading symptom of plaque-induced gingivitis and untreated periodontal disease. In type 1 VWD gingival bleeding was not increased compared to controls. Thus, this study evaluated whether type 2 and 3 VWD determines an increased susceptibility to gingival bleeding in response to the oral biofilm.</p><p>Methods</p><p>Twenty-four cases and 24 controls matched for age, sex, periodontal diagnosis, number of teeth and smoking were examined hematologically (VWF antigen, VWF activity, factor VIII activity) and periodontally (Gingival Bleeding Index [GBI]), bleeding on probing [BOP], Plaque Control Record [PCR], periodontal inflamed surface area [PISA], vertical probing attachment level).</p><p>Results</p><p>BOP (VWD: 14.5±10.1%; controls: 12.3±5.3%; <i>p</i> = 0.542) and GBI (VWD: 10.5±9.9%; controls: 8.8±4.8%; <i>p</i> = 0.852) were similar for VWD and controls. Multiple regressions identified female sex, HbA1c, PCR and PISA to be associated with BOP. HbA1c and PCR were associated with GBI. Number of remaining teeth was negatively correlated with BOP and GBI.</p><p>Conclusion</p><p>Type 2 and 3 VWD are not associated with a more pronounced inflammatory response to the oral biofilm in terms of BOP and GBI.</p></div

Patient characteristic (chronic periodontitis: ChP).

<p>Patient characteristic (chronic periodontitis: ChP).</p

Periodontal variables (probing pocket depth: PPD; vertical probing attachment level: PAL-V).

<p>Periodontal variables (probing pocket depth: PPD; vertical probing attachment level: PAL-V).</p

Backward stepwise multiple regression analysis: Bleeding on Probing in relation to individual and periodontal variables.

<p>Backward stepwise multiple regression analysis: Bleeding on Probing in relation to individual and periodontal variables.</p

Hematologic variables.

<p>Hematologic variables.</p

Backward stepwise multiple regression analysis: Gingival Bleeding Index in relation to individual and periodontal variables.

<p>Backward stepwise multiple regression analysis: Gingival Bleeding Index in relation to individual and periodontal variables.</p