A scoping review of regulatory T cell dynamics in convalescent COVID-19 patients - Implications for Long COVID?

BackgroundRecovery from coronavirus disease 2019 (COVID-19) can be impaired by the persistence of symptoms or new-onset health complications, commonly referred to as Long COVID. In a subset of patients, Long COVID is associated with immune system perturbations of unknown etiology, which could be related to compromised immunoregulatory mechanisms. ObjectiveThe aim of this scoping review was to investigate if regulatory T cell (Treg) dysregulation is observable beyond the acute illness and if it might be involved in Long COVID immunopathology. DesignA systematic search of studies investigating Tregs during COVID-19 convalescence was conducted on MEDLINE (via Pubmed) and Web of Science. ResultsThe literature search yielded 17 relevant studies, of which three included a distinct cohort of patients with Long COVID. The reviewed studies suggest that the Treg population of COVID-19 patients can reconstitute quantitatively and functionally during recovery. However, the comparison between recovered and seronegative controls revealed that an infection-induced dysregulation of the Treg compartment can be sustained for at least several months. The small number of studies investigating Tregs in Long COVID allowed no firm conclusions to be drawn about their involvement in the syndromes etiology. Yet, even almost one year post-infection Long COVID patients exhibit significantly altered proportions of Tregs within the CD4+ T cell population. ConclusionsPersistent alterations in cell frequency in Long COVID patients indicate that Treg dysregulation might be linked to immune system-associated sequelae. Future studies should aim to address the association of Treg adaptations with different symptom clusters and blood parameters beyond the sole quantification of cell frequencies while adhering to consensualized phenotyping strategies.

Establishment of an evaluation panel for the decentralized technical evaluation of the sensitivity of 31 rapid detection tests for SARS-CoV-2 diagnostics

BackgroundThe detection of SARS-CoV-2 with rapid diagnostic tests has become an important tool to identify infected people and break infection chains. These rapid diagnostic tests are usually based on antigen detection in a lateral flow approach. Aims & MethodsWhile for PCR diagnostics the validation of a PCR assay is well established, for antigen tests e.g. rapid diagnostic tests there is no common validation strategy. Here we present the establishment of a panel of 50 pooled clinical specimens that cover a SARS-CoV-2 concentration range from approximately 1.1 x 109 to 420 genome copies per mL of specimen. The panel was used to evaluate 31 rapid diagnostic tests in up to 6 laboratories. ResultsOur results show that there is significant variation in the detection limits and the clinical sensitivity of different rapid diagnostic tests. We conclude that the best rapid diagnostic tests can be applied to reliably identify infectious individuals who are presenting with SARS-CoV-2 loads correlated to 106 genome copies per mL of specimen. Infected individuals displaying SARS-CoV-2 genome loads corresponding to less than 106 genome copies per mL will be identified by only some rapid diagnostics tests, while many tests miss these viral loads to a large extent. ConclusionsSensitive RDTs can be applied to identify infectious individuals with high viral loads, but not to identify infected individuals.

Comparative sensitivity evaluation for 122 CE-marked SARS-CoV-2 antigen rapid tests

ObjectiveIndependent evaluation of the sensitivity of CE-marked SARS-CoV-2 antigen rapid diagnostic tests (Ag RDT) offered in Germany. MethodThe sensitivity of 122 Ag RDT was adressed using a common evaluation panel. Minimum sensitivity of 75% for panel members with CT<25 was used for differentiation of devices eligible for reimbursement in in the German healthcare system. ResultsThe sensitivity of different SARS-CoV-2 Ag RDT varied over a wide range. The sensitivity limit of 75% for panel members with CT <25 was met by 96 of the 122 tests evaluated; 26 tests exhibited lower sensitivity, few of which were completely failing. Some devices exhibited high sensitivity, e.g. 100% for CT<30. ConclusionThis comparative evaluation succeeded to distinguish less sensitive from better performing Ag RDT. Most of the Ag RDT evaluated appear to be suitable for fast identification of acute infections associated with high viral loads. Market access of SARS-CoV-2 Ag RDT should be based on minimal requirements for sensitivity and specificity.

The Boussinesq Debate: Reversibility, Instability, and Free Will.

In 1877, a young mathematician named Joseph Boussinesq presented a mémoire to the Académie des sciences which demonstrated that some differential equations may have more than one solution. Boussinesq linked this fact to indeterminism and to a possible solution to the free will versus determinism debate. Boussinesq's main interest was to reconcile his philosophical and religious views with science by showing that matter and motion do not suffice to explain all there is in the world. His argument received mixed criticism that addressed both his philosophical views and the scientific content of his work, pointing to the physical "realisticness" of multiple solutions. While Boussinesq proved to be able to face the philosophical criticism, the scientific objections became a serious problem, thus slowly moving the focus of the debate from the philosophical plane to the scientific one. This change of perspective implied a wide discussion on topics such as instability, the sensitivity to initial conditions, and the conservation of energy. The Boussinesq debate is an example of a philosophically motivated debate that transforms into a scientific one, an example of the influence of philosophy on the development of science.

Disease progression and recurrence in women treated for vulvovaginal intraepithelial neoplasia / 부인종양

OBJECTIVE: The malignant potential of intraepithelial neoplasia of the vulva and vagina after treatment is not well defined. Our objective was to examine risk factors for recurrence and invasive disease. METHODS: Four hundred sixty-four women with biopsy proven high-grade intraepithelial neoplasia of the vulva and vagina were identified in the electronic databases of four colposcopy clinics. Inclusion criteria were a follow-up of more than one year, no history of invasive cancer and no invasive cancer within the first year after initial treatment. We investigated the potential factors associated with recurrence and progression using a logistic regression analysis to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Of the 411 eligible patients, 123 patients (29.9%) recurred later than one year after initial treatment and 24 patients (5.8%) progressed to invasive disease. According to multivariate analyses, the risk factors associated with recurrence were multifocality (OR, 3.33; 95% CI, 2.02 to 5.51), immunosuppression (OR, 2.51; 95% CI, 1.09 to 5.81), excision as initial treatment (vs. laser evaporation; OR, 1.79; 95% CI, 1.11 to 2.91) and smoking (OR, 1.61; 95% CI, 1.02 to 2.55). Risk factors for progression to invasive disease were immunosuppression (OR, 4.00; 95% CI, 1.30 to 12.25), multifocality (OR, 3.05; 95% CI, 1.25 to 7.43) and smoking (OR, 2.97; 95% CI, 1.16 to 7.60), but not treatment modality. CONCLUSION: Laser evaporation combined with extensive biopsy is at least as efficacious as initial treatment of intraepithelial neoplasia with excision. Smoking is a risk factor for both recurrence and progression to invasive disease. Hence, smoking cessation should be advised and maintaining a long follow-up period due to late relapses is necessary.