Background: As the COVID-19 pandemic continues to spread, early, ideally real-time, identification of SARS-CoV-2 infected individuals is pivotal in interrupting infection chains. Volatile organic compounds produced during respiratory infections can cause specific scent imprints, which can be detected by trained dogs with a high rate of precision. Methods: Eight detection dogs were trained for 1 week to detect saliva or tracheobronchial secretions of SARS-CoV-2 infected patients in a randomised, double-blinded and controlled study. Results: The dogs were able to discriminate between samples of infected (positive) and non-infected (negative) individuals with average diagnostic sensitivity of 82.63% (95% confidence interval [CI]: 82.02-83.24%) and specificity of 96.35% (95% CI: 96.31-96.39%). During the presentation of 1012 randomised samples, the dogs achieved an overall average detection rate of 94% (±3.4%) with 157 correct indications of positive, 792 correct rejections of negative, 33 incorrect indications of negative or incorrect rejections of 30 positive sample presentations. Conclusions: These preliminary findings indicate that trained detection dogs can identify respiratory secretion samples from hospitalised and clinically diseased SARS-CoV-2 infected individuals by discriminating between samples from SARS-CoV-2 infected patients and negative controls. This data may form the basis for the reliable screening method of SARS-CoV-2 infected people.

Highlights d high SARS-CoV-2 IgG but overall reduced T cell immunity in active COVID-19 patients d PD-1, Tim-3, and active caspases in T cells result in impaired T cell function d stable SARS-CoV-2 T cell repertoire yet declining humoral responses during recovery d potentially protective role of pre-existing anti-huCoV CD4 + and CD8 + T cell immunity

Background: Elucidating the role of T cell responses in COVID-19 is of utmost importance to understand the clearance of SARS-CoV-2 infection. Methods: 30 hospitalized COVID-19 patients and 60 age-and gender-matched healthy controls (HC) participated in this study. We used two comprehensive 11-colour flow cytometric panels conforming to Good Laboratory Practice and approved for clinical diagnostics. Findings: Absolute numbers of lymphocyte subsets were differentially decreased in COVID-19 patients according to clinical severity. In severe disease (SD) patients, all lymphocyte subsets were reduced, whilst in mild disease (MD) NK, NKT and gd T cells were at the level of HC. Additionally, we provide evidence of T cell activation in MD but not SD, when compared to HC. Follow up samples revealed a marked increase in effector T cells and memory subsets in convalescing but not in non-convalescing patients. Interpretation: Our data suggest that activation and expansion of innate and adaptive lymphocytes play a major role in COVID-19. Additionally, recovery is associated with formation of T cell memory as suggested by the missing formation of effector and central memory T cells in SD but not in MD. Understanding T cell-responses in the context of clinical severity might serve as foundation to overcome the lack of effective anti-viral immune response in severely affected COVID-19 patients and can offer prognostic value as biomarker for disease outcome and control.

Aims Coronavirus disease 2019 (COVID‐19) is a still growing pandemic, causing many deaths and socio‐economic damage. Elevated expression of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) entry receptor angiotensin‐converting enzyme 2 on cardiac cells of patients with heart diseases may be related to cardiovascular burden. We have thus analysed cardiovascular and inflammatory microRNAs (miRs), sensitive markers of cardiovascular damage, in critically ill, ventilated patients with COVID‐19 or influenza‐associated acute respiratory distress syndrome (Influenza‐ARDS) admitted to the intensive care unit and healthy controls. Methods and results Circulating miRs (miR‐21, miR‐126, miR‐155, miR‐208a, and miR‐499) were analysed in a discovery cohort consisting of patients with mechanically‐ventilated COVID‐19 ( n = 18) and healthy controls ( n = 15). A validation study was performed in an independent cohort of mechanically‐ventilated COVID‐19 patients ( n = 20), Influenza‐ARDS patients ( n = 13) and healthy controls ( n = 32). In both cohorts, RNA was isolated from serum and cardiovascular disease/inflammatory‐relevant miR concentrations were measured by miR‐specific TaqMan PCR analyses. In both the discovery and the validation cohort, serum concentration of miR‐21, miR‐155, miR‐208a and miR‐499 were significantly increased in COVID‐19 patients compared to healthy controls. Calculating the area under the curve using receiver operating characteristic analysis miR‐155, miR‐208a and miR‐499 showed a clear distinction between COVID‐19 and Influenza‐ARDS patients. Conclusion In this exploratory study, inflammation and cardiac myocyte‐specific miRs were upregulated in critically ill COVID‐19 patients. Importantly, miR profiles were able to differentiate between severely ill, mechanically‐ventilated Influenza‐ARDS and COVID‐19 patients, indicating a rather specific response and cardiac involvement of COVID‐19.

Purpose Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory coronavirus 2 (SARS-CoV-2) has spread around the world. Differentiation between pure viral COVID-19 pneumonia and secondary infection can be challenging. In patients with elevated C-reactive protein (CRP) on admission physicians often decide to prescribe antibiotic therapy. However, overuse of anti-infective therapy in the pandemic should be avoided to prevent increasing antimicrobial resistance. Procalcitonin (PCT) and CRP have proven useful in other lower respiratory tract infections and might help to differentiate between pure viral or secondary infection. Methods We performed a retrospective study of patients admitted with COVID-19 between 6th March and 30th October 2020. Patient background, clinical course, laboratory findings with focus on PCT and CRP levels and microbiology results were evaluated. Patients with and without secondary bacterial infection in relation to PCT and CRP were compared. Using receiver operating characteristic (ROC) analysis, the best discriminating cut-off value of PCT and CRP with the corresponding sensitivity and specificity was calculated. Results Out of 99 inpatients (52 ICU, 47 Non-ICU) with COVID-19, 32 (32%) presented with secondary bacterial infection during hospitalization. Patients with secondary bacterial infection had higher PCT (0.4 versus 0.1 ng/mL; p = 0.016) and CRP (131 versus 73 mg/L; p = 0.001) levels at admission and during the hospital stay (2.9 versus 0.1 ng/mL; p < 0.001 resp. 293 versus 94 mg/L; p < 0.001). The majority of patients on general ward had no secondary bacterial infection (93%). More than half of patients admitted to the ICU developed secondary bacterial infection (56%). ROC analysis of highest PCT resp. CRP and secondary infection yielded AUCs of 0.88 (p < 0.001) resp. 0.86 (p < 0.001) for the entire cohort. With a PCT cut-off value at 0.55 ng/mL, the sensitivity was 91% with a specificity of 81%; a CRP cut-off value at 172 mg/L yielded a sensitivity of 81% with a specificity of 76%. Conclusion PCT and CRP measurement on admission and during the course of the disease in patients with COVID-19 may be helpful in identifying secondary bacterial infections and guiding the use of antibiotic therapy.