COVID-associated pernio: Mechanistic insights to an abortive, seronegative SARS-CoV-2 infection

Introduction: SARS-CoV-2 replicates primarily in the airways but generates a systemic immune response mediated by Type I interferons (IFN-I). Pernio is a rare skin manifestation of disorders characterized by excessive IFN-I signalling. Although pernio increased in incidence during the pandemic, the relationship to SARS-CoV-2 remains controversial. Because of the pivotal nature of interferons in COVID-19 outcomes, pernio offers a window to investigate the biology underlying host resiliency to SARS-CoV-2 infection. Method(s): To further assess COVID-associated pernio, we characterized clinical samples from affected patients across 4 waves of the pandemic and investigated mechanistic feasibility in a rodent model. Patients were followed longitudinally with banking of blood and tissue. Golden hamsters were mock-treated or intra-nasally infected with SARS-CoV-2 and harvested at 3-and 30-days post-infection. Result(s): In affected tissue, immunophenotyping utilizing multiplex immunohistochemistry profiled a robust IFN-1 signature characterized by plasmacytoid dendritic cell activation. Viral RNA was detectable in a subset of cases using in situ hybridization for the SARS-CoV-2 S gene transcript. Profiling of the systemic immune response did not reveal a durable type 1 interferon signature. Consistent with previous literature, antibody and T-cell specific responses to SARS-CoV-2 were not detected. Nasopharyngeal SARS-CoV-2 inoculation in hamsters resulted in rapid dissemination of viral RNA and the generation of an IFN-I response that were both detectable in the paws of infected animals. Conclusion(s): Our data support a durable local IFN signature, with direct evidence of viral SARS-CoV-2 RNA in acral skin and suggest that COVID-associated pernio results from an abortive, seronegative SARS-CoV-2 infection.

Portable HEPA filtration successfully augments natural-ventilation-mediated airborne particle clearance in a legacy design hospital ward.

As the severe acute respiratory syndrome coronavirus-2 pandemic has proceeded, ventilation has been recognized increasingly as an important tool in infection control. Many hospitals in Ireland and the UK do not have mechanical ventilation and depend on natural ventilation. The effectiveness of natural ventilation varies with atmospheric conditions and building design. In a challenge test of a legacy design ward, this study showed that portable air filtration significantly increased the clearance of pollutant aerosols of respirable size compared with natural ventilation, and reduced spatial variation in particle persistence. A combination of natural ventilation and portable air filtration is significantly more effective for particle clearance than either intervention alone.

IMPACT OF SERUM IGG LEVELS AGAINST SARS-COV-2 ON CLINICAL OUTCOMES FOR HOSPITALIZED COVID PATIENTS

BACKGROUND: The SAR-CoV-2 pandemic continues to negatively impact the healthcare system globally with over 800,000 deaths in the United States and millions more worldwide. The cases are rising despite availability of vaccines. For most immunocompetent patients these vaccines will generate a humoral response and also a memory T-cell response. Few if any studies have reported data that measure anti-spike IgG titers and also correlate those titers with clinical outcomes in the instance of breakthrough infection. METHODS: We conducted a pilot prospective observational clinical study enrolling 30 immunocompetent patients who were admitted with a positive SARS-CoV-2 PCR. Leftover blood from admission was used to obtain antispike and anti-nucleocapsid antibody levels. Baseline characteristics were collected and patients were divided into two categories based on anti-spike antibody level and vaccination status. Clinical outcomes including mortality, major adverse cardiac events (MACE), overall length of stay (LOS), ICU LOS, maximum oxygen support needs, and mechanical ventilation needs were analyzed on day 28 in both categories. RESULTS: On analyzing the patients enrolled, the median age was 59 years, 56.67% were female and 73.3% were Caucasian. 6 patients (20%) were asymptomatic, and 63.3% patients had hypertension. Among all patients, the median duration of symptoms was 7 days, and the median LOS was 7 days as well.Anti-spike antibody was detected in 22 patients (73.33%), and the median value was 956. Anti-nucleocapsid antibody was positive only in 9 patients (30%). Three patients (10%) were admitted to ICU, and all 3 were mechanically ventilated. Four patients (13.33%) had a MACE event in those 28 days, and 5 patients (16.67%) died. Comparing vaccinated vs unvaccinated: 3/5 deceased patients were unvaccinated, and 2/3 mechanically ventilated were unvaccinated as well but these were not statistically significant. 0.6% patients were asymptomatic in unvaccinated group versus 33% in the vaccinated group. Among the 7 patients with high oxygen needs (fio2 100%), 5 had undetectable anti-spike antibodies, and one had low value (89.6). 2 out of 3 mechanically ventilated and 3 out of 5 deceased patients had undetectable anti-spike antibodies. CONCLUSIONS: Our pilot study did not show significance in outcomes between vaccinated and unvaccinated patients, but this relation has been verified in multiple larger studies. We also noted patients with undetectable/ low anti- spike antibody levels had increased fio2 needs, ICU admission, and mortality.However, it was not feasible to compare both these findings between groups due to less number of patients. This demands a larger study to better describe these relations.

Determination of reliable whole-lung CT features for robust standard radiomics and delta-radiomics analysis in a crab-eating macaque model of COVID-19: stability and sensitivity analysis

As of 14 December 2021, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), caused nearly 269 million confirmed cases and almost 5.3 million deaths worldwide. Chest computed tomography (CT) has high diagnostic sensitivity for the detection of pulmonary disease in COVID-19 patients. Toward timely and accurate clinical evaluation and prognostication, radiomic analyses of CT images have been explored to investigate the correlation of imaging and non-imaging clinical manifestations and outcomes. Delta (∆) radiomics optimally performed from pre-infection to the post-critical phase, requires baseline data typically not obtained in clinical settings;additionally, their robustness is affected by differences in acquisition protocols. In this work, we investigated the reliability, sensitivity, and stability of whole-lung radiomic features of CT images of nonhuman primates either mock-exposed or exposed to SARS-CoV-2 to study imaging biomarkers of SARS-CoV-2 infection. Images were acquired at a pre-exposure baseline and post-exposure days, and lung fields were segmented. The reliability of radiomic features was assessed, and the dynamic range of each feature was compared to the maximum normal intra-subject variation and ranked. © 2022 SPIE

Effectiveness of a plasma treatment device on microbial air quality in a hospital ward, monitored by culture.

This study analysed the effectiveness of plasma treatment on airborne bacteria and surface counts during a 14-day intervention within a four-bedded bay in an adult respiratory ward at Cork University Hospital, Ireland. One-hundred-litre air samples were collected twice daily every weekday for 4 weeks, with settle plates and surface swabs. The plasma treatment did not have an effect on airborne bacteria and fungi that was detectable by culture. However, the possibility that culture-based sampling may be insufficiently sensitive to detect an effect, or that the duration of the study was insufficient for plasma treatment to affect a complex environment, cannot be excluded.

Containment of procedure-associated aerosols by an extractor tent: effect on nebulized drug particle dispersal.

BACKGROUND: Several medical procedures involving the respiratory tract are considered as 'aerosol-generating procedures'. Aerosols from these procedures may be inhaled by bystanders, and there are consequent concerns regarding the transmission of infection or, specific to nebulized therapy, secondary drug exposure. AIM: To assess the efficacy of a proprietary high-efficiency-particulate-air-filtering extractor tent on reducing the aerosol dispersal of nebulized bronchodilator drugs. METHODS: The study was conducted in an unoccupied outpatient room at St. James's Hospital, Dublin, Ireland. A novel real-time, fluorescent particle counter, the Wideband Integrated Bioaerosol Sensor (WIBS), monitored room air continuously for 3 h. Baseline airborne particle count and count during nebulization of bronchodilator drug solutions were recorded. FINDINGS: Nebulization within the tent prevented any increase over background level. Nebulization directly into room air resulted in mean fluorescent particle counts of 4.75 x 105/m3 and 4.21 x 105/m3 for Ventolin and Ipramol, respectively, representing more than 400-fold increases over mean background level. More than 99.3% of drug particles were <2 µm in diameter and therefore small enough to enter the lower respiratory tract. CONCLUSION: The extractor tent was completely effective for the prevention of airborne spread of drug particles of respirable size from nebulized therapy. This suggests that extractor tents of this type would be efficacious for the prevention of airborne infection from aerosol-generating procedures during the COVID-19 pandemic.

Older age and comorbidity are independent mortality predictors in a large cohort of 1305 COVID-19 patients in Michigan, United States.

INTRODUCTION: Higher comorbidity and older age have been reported as correlates of poor outcomes in COVID-19 patients worldwide; however, US data are scarce. We evaluated mortality predictors of COVID-19 in a large cohort of hospitalized patients in the United States. DESIGN: Retrospective, multicenter cohort of inpatients diagnosed with COVID-19 by RT-PCR from 1 March to 17 April 2020 was performed, and outcome data evaluated from 1 March to 17 April 2020. Measures included demographics, comorbidities, clinical presentation, laboratory values and imaging on admission. Primary outcome was mortality. Secondary outcomes included length of stay, time to death and development of acute kidney injury in the first 48-h. RESULTS: The 1305 patients were hospitalized during the evaluation period. Mean age was 61.0 ± 16.3, 53.8% were male and 66.1% African American. Mean BMI was 33.2 ± 8.8 kg m-2 . Median Charlson Comorbidity Index (CCI) was 2 (1-4), and 72.6% of patients had at least one comorbidity, with hypertension (56.2%) and diabetes mellitus (30.1%) being the most prevalent. ACE-I/ARB use and NSAIDs use were widely prevalent (43.3% and 35.7%, respectively). Mortality occurred in 200 (15.3%) of patients with median time of 10 (6-14) days. Age > 60 (aOR: 1.93, 95% CI: 1.26-2.94) and CCI > 3 (aOR: 2.71, 95% CI: 1.85-3.97) were independently associated with mortality by multivariate analyses. NSAIDs and ACE-I/ARB use had no significant effects on renal failure in the first 48 h. CONCLUSION: Advanced age and an increasing number of comorbidities are independent predictors of in-hospital mortality for COVID-19 patients. NSAIDs and ACE-I/ARB use prior to admission is not associated with renal failure or increased mortality.