SARS-CoV-2 innate effector associations and viral load in early nasopharyngeal infection.

COVID-19 causes severe disease with poor outcomes. We tested the hypothesis that early SARS-CoV-2 viral infection disrupts innate immune responses. These changes may be important for understanding subsequent clinical outcomes. We obtained residual nasopharyngeal swab samples from individuals who requested COVID-19 testing for symptoms at drive-through COVID-19 clinical testing sites operated by the University of Utah. We applied multiplex immunoassays, real-time polymerase chain reaction assays and quantitative proteomics to 20 virus-positive and 20 virus-negative samples. ACE-2 transcripts increased with infection (OR =17.4, 95% CI [CI] =4.78-63.8) and increasing viral N1 protein transcript load (OR =1.16, CI =1.10-1.23). Transcripts for two interferons (IFN) were elevated, IFN-λ1 (OR =71, CI =7.07-713) and IFN-λ2 (OR =40.2, CI =3.86-419), and closely associated with viral N1 transcripts (OR =1.35, CI =1.23-1.49 and OR =1.33 CI =1.20-1.47, respectively). Only transcripts for IP-10 were increased among systemic inflammatory cytokines that we examined (OR =131, CI =1.01-2620). We found widespread discrepancies between transcription and translation. IFN proteins were unchanged or decreased in infected samples (IFN-γ OR =0.90 CI =0.33-0.79, IFN-λ2,3 OR =0.60 CI =0.48-0.74) suggesting viral-induced shut-off of host antiviral protein responses. However, proteins for IP-10 (OR =3.74 CI =2.07-6.77) and several interferon-stimulated genes (ISG) increased with viral load (BST-1 OR =25.1, CI =3.33-188; IFIT1 OR =19.5, CI =4.25-89.2; IFIT3 OR =245, CI =15-4020; MX-1 OR =3.33, CI =1.44-7.70). Older age was associated with substantial modifications of some effects. Ambulatory symptomatic patients had an innate immune response with SARS-CoV-2 infection characterized by elevated IFN, proinflammatory cytokine and ISG transcripts, but there is evidence of a viral-induced host shut-off of antiviral responses. Our findings may characterize the disrupted immune landscape common in patients with early disease.

SARS-CoV-2 Innate Effector Associations and Viral Load in Early Nasopharyngeal Infection.

To examine innate immune responses in early SARS-CoV-2 infection that may change clinical outcomes, we compared nasopharyngeal swab data from 20 virus-positive and 20 virus-negative individuals. Multiple innate immune-related and ACE-2 transcripts increased with infection and were strongly associated with increasing viral load. We found widespread discrepancies between transcription and translation. Interferon proteins were unchanged or decreased in infected samples suggesting virally-induced shut-off of host anti-viral protein responses. However, IP-10 and several interferon-stimulated gene proteins increased with viral load. Older age was associated with modifications of some effects. Our findings may characterize the disrupted immune landscape of early disease.

Evaluation of an electronic esophageal detector device in patients with morbid obesity and pulmonary failure.

OBJECTIVE: Undetected esophageal intubation can result in permanent injury or death. Clinical confirmation of tube location may be misleading. Adjunctive methods should be used to supplement clinical judgment. Unfortunately, end-tidal carbon dioxide may misidentify properly placed tracheal tubes in low perfusion situations, while esophageal detector devices (EDDs) may misidentify properly placed tracheal tubes in situations where little airway dead space exists (morbid obesity, pulmonary failure). This study evaluated a modified EDD (the electronic esophageal detector device, or EEDD) designed to eliminate the problem of misidentified tracheal intubations. METHODS: Intubated morbidly obese or pulmonary failure patients were eligible for study entry. All endotracheal tubes (ETTs) were confirmed to be tracheal by waveform capnography and clinical judgment prior to study entry. Following consent, all patients were attached to the EEDD and a "measurement" was made to determine the "location" of their ETTs. Probability of misidentifying a tracheal intubation in these high-risk populations was calculated using a log-normal distribution method. RESULTS: Twenty-seven morbidly obese patients and 37 pulmonary failure patients were entered. The EEDD correctly identified all tracheal intubations in these patients, giving a false-negative rate of zero. The probability of misidentifying a tracheal intubation in the combined group was 0.06%. CONCLUSION: This study demonstrates that the EEDD reliably identifies tracheal intubations in situations where standard EDDs may fail. However, future studies must determine the reliability of this device for identification of esophageal intubations and the reliability of this device in the less controlled emergency department and prehospital settings.