Polarimetric imaging for the detection of synthetic models of SARS-CoV-2: a proof of concept

Objective To conduct a proof-of-concept study of the detection of two synthetic models of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using polarimetric imaging. Approach Two SARS-CoV-2 models were prepared as engineered lentiviruses pseudotyped with the G protein of the vesicular stomatitis virus, and with the characteristic Spike protein of SARS-CoV-2. Samples were preparations in two biofluids (saline solution and artificial saliva), in four concentrations, and deposited as 5-μL droplets on a supporting plate. The angles of maximal degree of linear polarization (DLP) of light diffusely scattered from dry residues were determined using Mueller polarimetry of 87 samples at 405 nm and 514 nm. A polarimetric camera was used for imaging several samples under 380-420 nm illumination at angles similar to those of maximal DLP. Per-pixel image analysis included quantification and combination of polarization feature descriptors in 475 samples. Main results The angles (from sample surface) of maximal DLP were 3 degrees for 405 nm and 6 degrees for 514 nm. Similar viral particles that differ only in the characteristic spike protein of the SARS-CoV-2, their corresponding negative controls, fluids, and the sample holder were discerned at 10-degree and 15-degree configurations. Significance Polarimetric imaging in the visible spectrum may help improve fast, non-contact detection and identification of viral particles, and/or other microbes such as tuberculosis, in multiple dry fluid samples simultaneously, particularly when combined with other imaging modalities. Further analysis including realistic concentrations of real SARS-CoV-2 virus particles in relevant human fluids is required. Polarimetric imaging under visible light may contribute to fast, cost-effective screening of SARS-CoV-2 and other pathogens.

Polarimetric imaging for the detection of synthetic models of SARS-CoV-2: A proof of concept.

Objective: To conduct a proof-of-concept study of the detection of two synthetic models of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using polarimetric imaging. Approach: Two SARS-CoV-2 models were prepared as engineered lentiviruses pseudotyped with the G protein of the vesicular stomatitis virus, and with the characteristic Spike protein of SARS-CoV-2. Samples were prepared in two biofluids (saline solution and artificial saliva), in four concentrations, and deposited as 5-µL droplets on a supporting plate. The angles of maximal degree of linear polarization (DLP) of light diffusely scattered from dry residues were determined using Mueller polarimetry from87 samples at 405 nm and 514 nm. A polarimetric camera was used for imaging several samples under 380-420 nm illumination at angles similar to those of maximal DLP. Per-pixel image analysis included quantification and combination of polarization feature descriptors in 475 samples. Main results: The angles (from sample surface) of maximal DLP were 3° for 405 nm and 6° for 514 nm. Similar viral particles that differed only in the characteristic spike protein of the SARS-CoV-2, their corresponding negative controls, fluids, and the sample holder were discerned at 10-degree and 15-degree configurations. Significance: Polarimetric imaging in the visible spectrum may help improve fast, non-contact detection and identification of viral particles, and/or other microbes such as tuberculosis, in multiple dry fluid samples simultaneously, particularly when combined with other imaging modalities. Further analysis including realistic concentrations of real SARS-CoV-2 viral particles in relevant human fluids is required. Polarimetric imaging under visible light may contribute to a fast, cost-effective screening of SARS-CoV-2 and other pathogens when combined with other imaging modalities.

Pembrolizumab in combination with tocilizumab in high-risk hospitalized patients with COVID-19 (COPERNICO): A randomized proof-of-concept phase II study.

OBJECTIVES: Severe COVID-19 is associated with immune dysregulation and hyperinflammation (lymphocyte exhaustion and elevated interleukin 6. Pembrolizumab (P; immune-activating anti-programmed cell death-1 antibody) plus tocilizumab (TCZ; anti- interleukin 6 receptor antibody) might interrupt the hyperinflammation and restore cellular immunocompetence. We assessed the efficacy and safety of P + TCZ + standard of care (SOC) in high-risk, hospitalized patients with COVID-19 pneumonia without mechanical ventilation. METHODS: Randomized, controlled, open-label, phase II trial in patients with severe SARS-CoV-2 infection to assess the hospitalization period to discharge. RESULTS: A total of 12 patients were randomized (P + TCZ + SOC, n = 7; SOC, n = 5). Nine (75%) were males, with a median age of 68 (41-79) years. The median time to discharge for P + TCZ + SOC and SOC was 10 and 47.5 days (P = 0.03), with zero (n = 1 patient had P-related grade 5 myositis) and two COVID-19-related deaths, respectively. CONCLUSION: The addition of P and TCZ to SOC reduced the hospitalization period, with higher and faster discharges without sequelae than SOC alone.

COVID-19 Secondary Infections in ICU Patients and Prevention Control Measures: A Preliminary Prospective Multicenter Study.

The incidence of secondary infections in critically ill coronavirus disease 2019 (COVID-19) patients is worrisome. We investigated whether selective digestive decontamination (SDD) added to infection control measures during an intensive care unit (ICU) stay modified these infection rates. METHODS: A retrospective observational cohort study was carried out in four ICUs in Spain. All consecutive ventilated patients with a SARS-CoV-2 infection engaged in national infection control programs between 1 March and 10 December 2020 were investigated. Patients were grouped into two cohorts according to the site of ICU admission. Secondary relevant infections were included. Infection densities corresponding to ventilator-associated pneumonia (VAP), catheter bacteremia, secondary bacteremia, and multi-resistant germs were obtained as the number of events per 1000 days of exposure and were compared between SDD and non-SDD groups using Poisson regression. Factors that had an independent association with mortality were identified using multidimensional logistic analysis. RESULTS: There were 108 patients in the SDD cohort and 157 in the non-SDD cohort. Patients in the SDD cohort showed significantly lower rates (p < 0.001) of VAP (1.9 vs. 9.3 events per 1000 ventilation days) and MDR infections (0.57 vs. 2.28 events per 1000 ICU days) and a non-significant reduction in secondary bacteremia (0.6 vs. 1.41 events per 1000 ICU days) compared with those in the non-SDD cohort. Infections caused by MDR pathogens occurred in 5 patients in the SDD cohort and 21 patients in the non-SDD cohort (p = 0.006). Differences in mortality according to SDD were not found. CONCLUSION: The implementation of SDD in infection control programs significantly reduced the incidence of VAP and MDR infections in critically ill SARS-CoV-2 infected patients.

Optical imaging spectroscopy for rapid, primary screening of SARS-CoV-2: a proof of concept.

Effective testing is essential to control the coronavirus disease 2019 (COVID-19) transmission. Here we report a-proof-of-concept study on hyperspectral image analysis in the visible and near-infrared range for primary screening at the point-of-care of SARS-CoV-2. We apply spectral feature descriptors, partial least square-discriminant analysis, and artificial intelligence to extract information from optical diffuse reflectance measurements from 5 µL fluid samples at pixel, droplet, and patient levels. We discern preparations of engineered lentiviral particles pseudotyped with the spike protein of the SARS-CoV-2 from those with the G protein of the vesicular stomatitis virus in saline solution and artificial saliva. We report a quantitative analysis of 72 samples of nasopharyngeal exudate in a range of SARS-CoV-2 viral loads, and a descriptive study of another 32 fresh human saliva samples. Sensitivity for classification of exudates was 100% with peak specificity of 87.5% for discernment from PCR-negative but symptomatic cases. Proposed technology is reagent-free, fast, and scalable, and could substantially reduce the number of molecular tests currently required for COVID-19 mass screening strategies even in resource-limited settings.

Hyperspectral image processing for the identification and quantification of lentiviral particles in fluid samples.

Optical spectroscopic techniques have been commonly used to detect the presence of biofilm-forming pathogens (bacteria and fungi) in the agro-food industry. Recently, near-infrared (NIR) spectroscopy revealed that it is also possible to detect the presence of viruses in animal and vegetal tissues. Here we report a platform based on visible and NIR (VNIR) hyperspectral imaging for non-contact, reagent free detection and quantification of laboratory-engineered viral particles in fluid samples (liquid droplets and dry residue) using both partial least square-discriminant analysis and artificial feed-forward neural networks. The detection was successfully achieved in preparations of phosphate buffered solution and artificial saliva, with an equivalent pixel volume of 4 nL and lowest concentration of 800 TU·[Formula: see text]L-1. This method constitutes an innovative approach that could be potentially used at point of care for rapid mass screening of viral infectious diseases and monitoring of the SARS-CoV-2 pandemic.

The effect of tocilizumab on cytokine release syndrome in COVID-19 patients.

BACKGROUND: This study was aimed to assess the efficacy and safety of tocilizumab (TCZ) and to investigate the factors related to the progress and mortality of patients with a secondary cytokine release syndrome caused by SARS-CoV-2. METHODS: A retrospective descriptive observational study of hospitalised patients with a positive polymerase chain reaction (PCR) result for SARS-CoV-2 and whose clinical evolution required the administration of one or more doses of TCZ was conducted. Demographic variables, clinical evolution, radiologic progress and analytical parameters were analysed on days 1, 3 and 5 after administration the first dose of TCZ. RESULTS: A total of 75 patients with a clinical history of Accurate Respiratory Distress Syndrome (ARDS) were analysed, among whom, 19 had mild ARDS (25.3%), 37 moderate ARDS (49.4%) and 19 severe ARDS (25.3%). Lymphocytopenia and high levels of PCR, D-Dimer and IL-6 were observed in almost all the patients (91.8%). Treatment with TCZ was associated with a reduction of lymphocytopenia, C-reactive protein (CRP) levels, severe ARDS cases and fever. Although a better evolution of PaO2/FiO2 was observed in patients who received two or more doses of TCZ (38/75), there was an increase in their mortality (47.4%) and ICU admission (86.8%). The 30-day mortality rate was 30.7% (20.5-42.4% CI) being hypertension, high initial D-dimer levels and ICU admission the only predictive factors found. CONCLUSION: Based on our results, treatment with TCZ was associated with a fever, swelling and ventilator support improvement. However, there is no evidence that the administration of two or more doses of TCZ was related to a mortality decrease.