Electronic Sensors to Detect SARS-CoV-2 Viruses in Real Time

Sensors with 60 nm gap junctions coated with aptamers that bind with S1 and S2 spiking proteins of the SARS-CoV-2 virus were developed. Sensor impedance changes with virus enabling rapid (∼1 min), point-of-care detection. Exosomes and other nanoparticles in the saliva produce false positive signals but do not bind with aptamers and are easily removed to achieve 6% false positivity rates. A positive sensor voltage is used to attract negatively charged SARS-CoV-2 viruses to the junction and reduce sensor false negativity rates to below 7%. The limit of detection of the sensor is 1000 viruses and can be altered by changing the sensor's lateral dimensions and its transduction noise level. © 2001-2012 IEEE.

Electronic Sensors to Detect SARS-CoV-2 Viruses in Real Time

Sensors with 60 nm gap junctions coated with aptamers that bind with S1 and S2 spiking proteins of the SARS-CoV-2 virus were developed. Sensor impedance changes with virus enabling rapid (~1 min), point-of-care detection. Exosomes and other nanoparticles in the saliva produce false positive signals but do not bind with aptamers and are easily removed to achieve 6% false positivity rates. A positive sensor voltage is used to attract negatively charged SARS-CoV-2 viruses to the junction and reduce sensor false negativity rates to below 7%. The limit of detection of the sensor is ~1000 viruses and can be altered by changing the sensor’s lateral dimensions and its transduction noise level. IEEE

Plasma Neutrophil Extracellular Trap Levels Correlate with Acute Respiratory Distress Syndrome Disease Severity

Rationale: Acute Respiratory Distress Syndrome (ARDS) is characterized by acute onset of hypoxic respiratory failure, which can be complicated by multi-organ dysfunction and death. ARDS results from inflammatory alveolar injury precipitated by direct or indirect lung injury. Neutrophils play a central role in the pathology of ARDS and release neutrophil extracellular traps (NETs) to trap and kill pathogens. Dysregulated NET formation, however, can cause inflammatory tissue damage and exacerbate acute lung injury as in COVID-19 associated ARDS. Whether detection of plasma NETs predicts outcomes in non-COVID-19 associated ARDs remains unknown. We hypothesized that plasma NET levels correlate directly with disease severity and mortality in non-COVID-19 ARDS patients. Methods: We obtained previously collected plasma samples from patients (n=200) with moderate to severe ARDS enrolled in the Re-evaluation of Systemic Early Neuromuscular Blockade (ROSE) trial at three different time points (admission, 24 hours, and 48 hours after admission) complete with clinical outcome data through 28 days after admission. We also examined age- and gender-matched healthy donor plasma (n=20). We assayed cell-free DNA levels via fluorescence and MPO-DNA complexes as a surrogate for NETs in each plasma sample. Clinical outcomes from ROSE trial participants were correlated with the quantification of NETs. We also assessed NET formation by neutrophils isolated from healthy adults following incubation with ARDS patient and healthy donor plasma samples using live cell imaging and confocal microscopy. Results: We demonstrated elevated plasma markers of NETs (cell-free DNA and MPO-DNA complexes) in ARDS plasma compared to healthy donor plasma. Deceased study participants demonstrated higher plasma NET levels on admission and at 48 hours as compared to ARDS survivors (admission: p = 0.0045 and 48 hours: p = 0.0050). Increased plasma NETs on admission, at 24 hours, and 48 hours also correlated with illness severity. Furthermore, ARDS plasma samples induced NET formation in vitro in neutrophils isolated from healthy donors while control plasma did not. Conclusion: NET formation is increased in plasma from patients with ARDS compared to healthy donor plasma, consistent with the inflammatory alveolar injury seen in ARDS. Additionally, plasma from ARDS patients induces NET formation in vitro in PMNs isolated from healthy adult donors. We speculate that exaggerated NET formation may serve as a novel biomarker for inflammatory lung injury in ARDS resulting from multiple etiologies and that strategies targeting NET formation may improve outcomes in ARDS.

Vaping in the time of COVID

Electronic-cigarette or vaping product use-associated lung injury (EVALI) is a disease of acute respiratory failure related to the use of e-cigarette or vape products. Coronavirus disease 2019 (COVID-19) is a viral infection which primarily affects the lungs and, in some cases, causes acute respiratory failure which can present very similarly clinically to EVALI. Here we present a 25-year-old man with no past medical history who presented to the hospital with a positive SARS-Cov2 test and clinical symptoms of COVID-19. He improved with oxygen and went home. 3 days later his respiratory and GI symptoms returned. He had an outside SARS-Cov2 PCR test which was negative;however, two days later a second PCR was done at our facility which was positive after 40 amplification cycles. Of note, the initial test was positive after 28 amplification cycles. Upon further discussion the patient reported marijuana smoking three times daily and vaping THC throughout the day. He was treated for EVALI and improved rapidly. This case highlights some complex clinical decisions presented to physicians in the current climate as well as difficulty in interpreting SARS-Cov2 PCR in relation to clinical presentation.