Imbalance of SARS-CoV-2-specific CCR6+ and CXCR3+ CD4+ T cells and IFN-γ + CD8+ T cells in patients with Long-COVID.

Long-COVID (LC) is characterised by persistent symptoms for at least 3 months after acute infection. A dysregulation of the immune system and a persistent hyperinflammatory state may cause LC. LC patients present differences in activation and exhaustion states of innate and adaptive compartments. Different T CD4+ cell subsets can be identified by differential expression of chemokine receptors (CCR). However, changes in T cells with expression of CCRs such as CCR6 and CXCR3 and their relationship with CD8+ T cells remains unexplored in LC. Here, we performed unsupervised analysis and found CCR6+ CD4+ subpopulations enriched in COVID-19 convalescent individuals upon activation with SARS-CoV-2 peptides. SARS-CoV-2 specific CCR6+ CD4+ are decreased in LC patients, whereas CXCR3+ CCR6- and CCR4+ CCR6- CD4+ T cells are increased. LC patients showed lower IFN-γ-secreting CD8+ T cells after stimulation with SARS-CoV-2 Spike protein. This work underscores the role of CCR6 in the pathophysiology of LC.

Genitourinary tract symptoms in patients admitted with COVID-19: Exploring changes in frequency by determinants and pandemic waves.

Background: Urothelial cells exhibit increased expression of angiotensin-converting enzyme-2 receptor, which is the binding site of severe acute respiratory syndrome coronavirus 2 to cells. The frequency and distribution of genitourinary tract symptoms in patients diagnosed with coronavirus disease 2019 (COVID-19) is unknown. Objective: We explored trends in genitourinary tract symptoms by gender and each of six pandemic waves in patients admitted for COVID-19, and related them with severity, death and length of hospitalization. Design Setting and Participants: A retrospective study took place in our institution of COVID-19 admitted patients. Only patients with RT-PCR or antigen test confirmed SARS-CoV-2 infection were included. Demographic, clinical, and genitourinary symptoms were explored. Outcome Measurements and Statistical Analysis: COVID-19 patients with genitourinary tract symptoms were compared with those without. Statistical comparisons were conducted by parametric and nonparametric tests for quantitative variables, and χ 2 test for qualitative variables. Results and limitations: Out of a total of 4,661 COVID-19 patients, genitourinary symptoms were found in 21,1%. These symptoms were more frequent in patients admitted for longer than 30 days, except for urinary incontinence (UI) and erectile dysfunction (ED). Acute kidney injury (AKI) and urinary tract infections (UTI) had a higher presence in the 5th (16.7%; 12.8% respectively) and 3rd wave (13.3%; 12.6% respectively). Genitourinary symptoms were higher for those patients admitted in critical care units. Frequency of AKI, UI, UTI and acute urinary retention (AUR) were higher for patients who were finally deceased (26.2%; 3.5%; 13.6% and 3.6% respectively). Conclusions: A high frequency of genitourinary symptoms in patients admitted for COVID-19 was observed, whose frequency and distribution varied according to pandemic waves. Specific genitourinary conditions were associated with worse outcomes and poorer prognosis.

What is the added value of FeNO as T2 biomarker?

There is increasing evidence about the role of nitric oxide in type 2 (T2) immune response. Fraction of exhaled nitric oxide (FeNO) is a product of airways inflammation and it is increased in patients with asthma. Since Gustaffson published the first article about this biomarker in the 1990s, interest has continued to grow. Compared with other T2 biomarkers such as blood eosinophil count, induced sputum, or serum periostin, FeNO has some remarkable advantages, including its not invasive nature, easy repeatability, and possibility to be performed even in patients with severe airway obstruction. It is considered as an indicator of T2 inflammation and, by the same token, a useful predictor for inhaled steroid response. It is difficult to determine the utility of nitric oxide (NO) for initial asthma diagnosis. In such a heterogenous disease, a single parameter would probably not be enough to provide a complete picture. There is also an important variability among authors concerning FeNO cutoff values and the percentage of sensibility and specificity for diagnosis. Its high specificity indicates a potential role to "rule in" asthma; however, its lower sensibility could suggest a lower capacity to "rule out" this pathology. For this reason, if a diagnosis of asthma is being considered, FeNO should be considered along with other tests. FeNO has also shown its utility to detect response to steroids, adherence to treatment, and risk of exacerbation. Even though there is not enough quality of evidence to establish overall conclusions, FeNO could be an alternative procedure to diagnose or exclude asthma and also a predictive tool in asthma treated with corticosteroids.