SARS-CoV-2 monoclonal antibody treatment followed by vaccination shifts human memory B cell epitope recognition suggesting antibody feedback (preprint)

Therapeutic anti-SARS-CoV-2 monoclonal antibodies (mAbs) have been extensively studied in humans, but the impact on immune memory of mAb treatment during an ongoing immune response has remained unclear. Here, we evaluated the effect of infusion of the anti-SARS-CoV-2 spike receptor binding domain (RBD) mAb bamlanivimab on memory B cells (MBCs) in SARS-CoV-2-infected individuals. Bamlanivimab treatment skewed the repertoire of memory B cells targeting Spike towards non-RBD epitopes. Furthermore, the relative affinity of RBD memory B cells was weaker in mAb-treated individuals compared to placebo-treated individuals over time. Subsequently, after mRNA COVID-19 vaccination, memory B cell differences persisted and mapped to a specific defect in recognition of the class II RBD site, the same RBD epitope recognized by bamlanivimab. These findings indicate a substantial role of antibody feedback in regulating human memory B cell responses, both to infection and vaccination. These data indicate that mAb administration can promote alterations in the epitopes recognized by the B cell repertoire, and the single administration of mAb can continue to determine the fate of B cells in response to additional antigen exposures months later. SIGNIFICANCE STATEMENTEvaluating the therapeutic use of monoclonal antibodies during SARS-CoV-2 infection requires a comprehensive understanding of their impact on B cell responses at the cellular level and how these responses are shaped after vaccination. We report for the first time the effect of bamlanivimab on SARS-CoV-2 specific human memory B cells of COVID-19 infected humans receiving, or not, mRNA immunization.

The COVID-19 Pandemic and In-Person Visit Rate Disruptions Among Patients With Hematologic Neoplasms in the US in 2020 to 2021.

Importance: The COVID-19 pandemic has led to a reduction in routine in-person medical care; however, it is unknown whether there have been any changes in visit rates among patients with hematologic neoplasms. Objective: To examine associations between the COVID-19 pandemic and in-person visits and telemedicine use among patients undergoing active treatment for hematologic neoplasms. Design, Setting, and Participants: Data for this retrospective observational cohort study were obtained from a nationwide electronic health record-derived, deidentified database. Data for patients with hematologic neoplasms who had received at least 1 systemic line of therapy between March 1, 2016, and February 28, 2021, were included. Treatments were categorized into 3 types: oral therapy, outpatient infusions, and inpatient infusions. The data cutoff date was April 30, 2021, when study analyses were conducted. Main Outcomes and Measures: Monthly visit rates were calculated as the number of documented visits (telemedicine or in-person) per active patient per 30-day period. We used time-series forecasting methods on prepandemic data (March 2016 to February 2020) to estimate expected rates between March 1, 2020, and February 28, 2021 (if the pandemic had not occurred). Results: This study included data for 24 261 patients, with a median age of 68 years (IQR, 60-75 years). A total of 6737 patients received oral therapy, 15 314 received outpatient infusions, and 8316 received inpatient infusions. More than half of patients were men (14 370 [58%]) and non-Hispanic White (16 309 [66%]). Early pandemic months (March to May 2020) demonstrated a significant 21% reduction (95% prediction interval [PI], 12%-27%) in in-person visit rates averaged across oral therapy and outpatient infusions. Reductions in in-person visit rates were also significant for all treatment types for multiple myeloma (oral therapy: 29% reduction; 95% PI, 21%-36%; P = .001; outpatient infusions: 11% reduction; 95% PI, 4%-17%; P = .002; inpatient infusions: 55% reduction; 95% PI, 27%-67%; P = .005), for oral therapy for chronic lymphocytic leukemia (28% reduction; 95% PI, 12%-39%; P = .003), and for outpatient infusions for mantle cell lymphoma (38% reduction; 95% PI, 6%-54%; P = .003) and chronic lymphocytic leukemia (20% reduction; 95% PI, 6%-31%; P = .002). Telemedicine visit rates were highest for patients receiving oral therapy, with greater use in the early pandemic months and a subsequent decrease in later months. Conclusions and Relevance: In this cohort study of patients with hematologic neoplasms, documented in-person visit rates for those receiving oral therapy and outpatient infusions significantly decreased during the early pandemic months but returned to close to projected rates in the later half of 2020. There were no statistically significant reductions in the overall in-person visit rate for patients receiving inpatient infusions. There was higher telemedicine use in the early pandemic months, followed by a decline, but use was persistent in the later half of 2020. Further studies are needed to ascertain associations between the COVID-19 pandemic and subsequent cancer outcomes and the evolution of telemedicine use for care delivery.

Predictors of SARS-CoV-2 RNA From Nasopharyngeal Swabs and Concordance With Other Compartments in Nonhospitalized Adults With Mild to Moderate COVID-19.

Background: Identifying characteristics associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA shedding may be useful to understand viral compartmentalization, disease pathogenesis, and risks for viral transmission. Methods: Participants were enrolled August 2020 to February 2021 in ACTIV-2/A5401, a placebo-controlled platform trial evaluating investigational therapies for mild-to-moderate coronavirus disease 2019 (COVID-19), and underwent quantitative SARS-CoV-2 RNA testing on nasopharyngeal and anterior nasal swabs, oral wash/saliva, and plasma at entry (day 0, pretreatment) and days 3, 7, 14, and 28. Concordance of RNA levels (copies/mL) across compartments and predictors of nasopharyngeal RNA levels were assessed at entry (n = 537). Predictors of changes over time were evaluated among placebo recipients (n = 265) with censored linear regression models. Results: Nasopharyngeal and anterior nasal RNA levels at study entry were highly correlated (r = 0.84); higher levels of both were associated with greater detection of RNA in plasma and oral wash/saliva. Older age, White non-Hispanic race/ethnicity, lower body mass index (BMI), SARS-CoV-2 immunoglobulin G seronegativity, and shorter prior symptom duration were associated with higher nasopharyngeal RNA at entry. In adjusted models, body mass index and race/ethnicity associations were attenuated, but the association with age remained (for every 10 years older, mean nasopharyngeal RNA was 0.27 log10 copies/mL higher; P < .001). Examining longitudinal viral RNA levels among placebo recipients, women had faster declines in nasopharyngeal RNA than men (mean change, -2.0 vs -1.3 log10 copies/mL, entry to day 3; P < .001). Conclusions: SARS-CoV-2 RNA shedding was concordant across compartments. Age was strongly associated with viral shedding, and men had slower viral clearance than women, which could explain sex differences in acute COVID-19 outcomes.

Bamlanivimab therapy for acute COVID-19 does not blunt SARS-CoV-2-specific memory T cell responses.

Despite the widespread use of SARS-CoV-2-specific monoclonal antibody (mAb) therapy for the treatment of acute COVID-19, the impact of this therapy on the development of SARS-CoV-2-specific T cell responses has been unknown, resulting in uncertainty as to whether anti-SARS-CoV-2 mAb administration may result in failure to generate immune memory. Alternatively, it has been suggested that SARS-CoV-2-specific mAb may enhance adaptive immunity to SARS-CoV-2 via a "vaccinal effect." Bamlanivimab (Eli Lilly) is a recombinant human IgG1 that was granted FDA emergency use authorization for the treatment of mild to moderate COVID-19 in those at high risk for progression to severe disease. Here, we compared SARS-CoV-2 specific CD4+ and CD8+ T cell responses of 95 individuals from the ACTIV-2/A5401 clinical trial 28 days after treatment with 700 mg bamlanivimab versus placebo. SARS-CoV-2-specific T cell responses were evaluated using activation induced marker (AIM) assays in conjunction with intracellular cytokine staining. We demonstrate that most individuals with acute COVID-19 develop SARS-CoV-2-specific T cell responses. Overall, our findings suggest that the quantity and quality of SARS-CoV-2-specific T cell memory was robust in individuals who received bamlanivimab for acute COVID-19. Receipt of bamlanivimab during acute COVID-19 neither diminished nor enhanced SARS-CoV-2-specific cellular immunity.

Emergence of SARS-CoV-2 escape mutations during Bamlanivimab therapy in a phase II randomized clinical trial.

SARS-CoV-2 mutations that cause resistance to monoclonal antibody (mAb) therapy have been reported. However, it remains unclear whether in vivo emergence of SARS-CoV-2 resistance mutations alters viral replication dynamics or therapeutic efficacy in the immune-competent population. As part of the ACTIV-2/A5401 randomized clinical trial (NCT04518410), non-hospitalized participants with symptomatic SARS-CoV-2 infection were given bamlanivimab (700 mg or 7,000 mg) or placebo treatment. Here¸ we report that treatment-emergent resistance mutations [detected through targeted Spike (S) gene next-generation sequencing] were significantly more likely to be detected after bamlanivimab 700 mg treatment compared with the placebo group (7% of 111 vs 0% of 112 participants, P = 0.003). No treatment-emergent resistance mutations among the 48 participants who received 7,000 mg bamlanivimab were recorded. Participants in which emerging mAb resistant virus mutations were identified showed significantly higher pretreatment nasopharyngeal and anterior nasal viral loads. Daily respiratory tract viral sampling through study day 14 showed the dynamic nature of in vivo SARS-CoV-2 infection and indicated a rapid and sustained viral rebound after the emergence of resistance mutations. Participants with emerging bamlanivimab resistance often accumulated additional polymorphisms found in current variants of concern/interest that are associated with immune escape. These results highlight the potential for rapid emergence of resistance during mAb monotherapy treatment that results in prolonged high-level respiratory tract viral loads. Assessment of viral resistance should be prioritized during the development and clinical implementation of antiviral treatments for COVID-19.

The Use of Nitric Oxide as a Rescue Modality for Severe Adult Acute Respiratory Distress Syndrome Patients, Including COVID-19, in Critical Care Rotor Transport: A Retrospective Community Outcome Study.

OBJECTIVE: Severe acute respiratory distress syndrome (ARDS) mortality increases in smaller outlying facilities, and patients (especially those diagnosed with coronavirus disease 2019 [COVID-19]) are often "stuck" at these facilities. These patients are on maximal ventilator settings and are often in the prone position. Our purpose was to show that with the use of inhaled nitric oxide (iNO), a "community-based" rotor wing critical care transport (CCT) team can safely, consistently, and effectively transport these extremely precarious patients to the tertiary care that is needed. METHODS: This was a retrospective database review of 50 patients (39 patients with COVID-19) transported between 2017 and 2021 in whom iNO was brought to the bedside and initiated by the rotor wing critical care transport team. The review included patient demographics, vital signs, and ventilator settings from the sending hospital, in-flight, and the receiving hospital. We reviewed the transition from transport to venovenous extracorporeal membrane oxygenation (if applicable), hospital disposition, and length of stay from the receiving hospital side. Concerning the actual transport, we reviewed the mode of transport, the sending facility size, and the distances covered. RESULTS: Upon arrival at the sending facilities, we found severely ill patients with almost half (46%) in the prone position or recently transitioned from a prone position within the last 2 hours. Eighty-six percent were pharmaceutically paralyzed, and 44% were in shock. There was a younger and heavier predominance with an average age of 44 years and an average weight of 103 kg. Thirty-nine patients were diagnosed with COVID-19. The other 11 had a mix of non-COVID-19 ARDS, pulmonary embolism, and pulmonary edema. The patients presented from 27 different community hospitals. Forty-four percent were from small referring hospitals that had less than 200 beds. Twenty-eight patients were transported by a Bell 407 helicopter, 18 with an Airbus H135 helicopter, and 4 by ground ambulance. Forty-one percent of patients were transported within 25 miles, and 4 patients were transferred from > 100 miles away. All 50 patients were safely transported without significant deterioration or significant pulmonary pressure increases. Thirty-seven patients were placed on venovenous extracorporeal membrane oxygenation (34 of those patients cannulated within 2 hours of arrival). The overall mortality rate was 27%, and the COVID-19 mortality rate was 24%. CONCLUSION: iNO retrieval for severe ARDS can be safely and effectively completed within the COVID-19 population and the nonacademic community setting using helicopters prevalent in the global air medical industry (Bell 407 and Airbus H135).

Accountability and assessment in U.S. education: let’s not allow another crisis go to waste!

State education systems in the U.S. experienced major disruptions due to the COVID-19 pandemic. Results from assessments administered during, and at the conclusion of, the 2020-21 school year indicate substantial ‘unfinished learning’, with the losses generally greater among disadvantaged and marginalized students. States’ assessment systems are strongly tilted toward meeting Federal accountability requirements, especially state-wide comparability of end-of year test results, which severely limits innovation. The two-year pause in accountability due to the pandemic presents an opportunity to radically rethink school accountability, allowing states greater flexibility in developing creative interventions and more balanced assessment systems to better support student learning. A new trade-off between comparability and local flexibility is long overdue, especially given the poor record of the current system in promoting learning and closing achievement gaps. We offer some examples of how the trade-off can be accomplished and the potential benefits that would ensue. [ FROM AUTHOR] Copyright of Assessment in Education: Principles, Policy & Practice is the property of Routledge and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Planning the “New Normality” to Address the Pandemic in Higher Education: Blended Scenarios at the Catholic University of the Sacred Heart

Since the early spring 2020, universities had to accept the impact of the first wave of Covid-19 disease and manage the emergency: students and teachers experienced a massive shift from traditional face-to-face education to online education. This new situation has been more properly defined “emergency remote teaching”. Catholic University of Sacred Heart has guaranteed the regular course of study to all the students. The contribution intends to present the #eCatt plan for the academic year 2020/21: it provides for a blended solution which moves on four scenarios, two in synchronous and two in asynchronous modes of learning (Dual mode, Online interactive lecture, Talking head, Voice-over presentation). To accompany the faculty to lesson design, self-training modules have been developed. In addition, weekly webinars have been planned and proposed, focusing on the scenarios, available technological solutions and educational tools. Data collection aims to provide a quantitative overview of the access to the online courses, participation in training sessions, adoption of synchronous and asynchronous solutions, focusing on teaching practices in synchronous sessions. © 2022, Springer Nature Switzerland AG.

SARS-CoV-2 Spike Protein Destabilizes Microvascular Homeostasis.

SARS-CoV-2 infection can cause compromised respiratory function and thrombotic events. SARS-CoV-2 binds to and mediates downregulation of angiotensin converting enzyme 2 (ACE2) on cells that it infects. Theoretically, diminished enzymatic activity of ACE2 may result in increased concentrations of pro-inflammatory molecules, angiotensin II, and Bradykinin, contributing to SARS-CoV-2 pathology. Using immunofluorescence microscopy of lung tissues from uninfected, and SARS-CoV-2 infected individuals, we find evidence that ACE2 is highly expressed in human pulmonary alveolar epithelial cells and significantly reduced along the alveolar lining of SARS-CoV-2 infected lungs. Ex vivo analyses of primary human cells, indicated that ACE2 is readily detected in pulmonary alveolar epithelial and aortic endothelial cells. Exposure of these cells to spike protein of SARS-CoV-2 was sufficient to reduce ACE2 expression. Moreover, exposure of endothelial cells to spike protein-induced dysfunction, caspase activation, and apoptosis. Exposure of endothelial cells to bradykinin caused calcium signaling and endothelial dysfunction (increased expression of von Willibrand Factor and decreased expression of Krüppel-like Factor 2) but did not adversely affect viability in primary human aortic endothelial cells. Computer-assisted analyses of molecules with potential to bind bradykinin receptor B2 (BKRB2), suggested a potential role for aspirin as a BK antagonist. When tested in our in vitro model, we found evidence that aspirin can blunt cell signaling and endothelial dysfunction caused by bradykinin in these cells. Interference with interactions of spike protein or bradykinin with endothelial cells may serve as an important strategy to stabilize microvascular homeostasis in COVID-19 disease. IMPORTANCE SARS-CoV-2 causes complex effects on microvascular homeostasis that potentially contribute to organ dysfunction and coagulopathies. SARS-CoV-2 binds to, and causes downregulation of angiotensin converting enzyme 2 (ACE2) on cells that it infects. It is thought that reduced ACE2 enzymatic activity can contribute to inflammation and pathology in the lung. Our studies add to this understanding by providing evidence that spike protein alone can mediate adverse effects on vascular cells. Understanding these mechanisms of pathogenesis may provide rationale for interventions that could limit microvascular events associated with SARS-CoV-2 infection.

Triage-HF plus: 12-month study of remote monitoring pathway for triage of heart failure risk initiated during the Covid-19 pandemic

Background: The Covid-19 pandemic necessitated rapid adoption of remote monitoring across cardiovascular patient cohorts. Most patients with cardiac implantable electronic devices (CIEDs) are now able to be remotely monitored using either scheduled, patient- or threshold-triggered transmissions. The validated Triage Heart Failure Risk Score (Triage-HFRS) is a medical algorithm within company-specific CIEDs that can risk-stratify patients as low-, medium- or high-risk of worsening heart failure (WHF) in the next 30 days based on integrated monitoring of physiological parameters. Building on a previous proof-of-concept of the Triage-HF Plus pathway, we integrated remote data with simple 5-question telephone triage within a clinical pathway to identify WHF during the first year of the Covid-19 pandemic. Purpose: Prospective evaluation of clinical remote monitoring pathway integrating Triage-HFRS with protocolised telephone triage (Triage-HF Plus pathway). Methods: Prospective, real-world evaluation of clinical pathway serving a large urban region over a 12-month period, using data from April 2020 to April 2021 (initiated during the first wave of Covid-19 pandemic in the UK). From a population of 435 patients with CIEDs, 87 high Triage-HFRS alerts were received and patients contacted for telephone triage assessment. Screening questions were designed to identify episodes of WHF and non-HF events. Intervention was at discretion of the clinical practitioner and in line with guideline-directed practice. A consecutive sample of 115 medium risk scores received the same triage. Results: Successful contact was made with 72 (82.8%) high-risk patients. Classification for high scoring patients confirmed on triage included isolated heart failure (18.3%), heart failure concurrent to medical problem (5.7%), alternative medical problem (10.3%), and recent hospital admission (8.0%);triage reassured absence of acute cause of high score in 40.2%. The sensitivity and specificity for detection of WHF was 87.9% (0.77-0.99) and 59.4% (0.50-0.69) respectively. Positive and negative predictive values were 40.3% and 94.0%, respectively. Overall accuracy was 66.2%. Conclusions: The Triage-HF Plus pathway served as a useful remote monitoring tool for identifying patients with WHF whose care had been otherwise disrupted by the Covid-19 pandemic, allowing timely intervention and cementing the longer-term role for such models of care delivery. Crucially, in this multimorbid, high-cost population, relevant non-HF issues were also identified. The high negative predictive value further highlights the potential of proactive surveillance over conventional, periodic follow up.

Data automated bag breathing unit for COVID-19 ventilator shortages.

BACKGROUND: The COVID-19 pandemic has caused a global mechanical ventilator shortage for treatment of severe acute respiratory failure. Development of novel breathing devices has been proposed as a low cost, rapid solution when full-featured ventilators are unavailable. Here we report the design, bench testing and preclinical results for an 'Automated Bag Breathing Unit' (ABBU). Output parameters were validated with mechanical test lungs followed by animal model testing. RESULTS: The ABBU design uses a programmable motor-driven wheel assembled for adult resuscitation bag-valve compression. ABBU can control tidal volume (200-800 ml), respiratory rate (10-40 bpm), inspiratory time (0.5-1.5 s), assist pressure sensing (- 1 to - 20 cm H2O), manual PEEP valve (0-20 cm H2O). All set values are displayed on an LCD screen. Bench testing with lung simulators (Michigan 1600, SmartLung 2000) yielded consistent tidal volume delivery at compliances of 20, 40 and 70 (mL/cm H2O). The delivered fraction of inspired oxygen (FiO2) decreased with increasing minute ventilation (VE), from 98 to 47% when VE was increased from 4 to 16 L/min using a fixed oxygen flow source of 5 L/min. ABBU was tested in Berkshire pigs (n = 6, weight of 50.8 ± 2.6 kg) utilizing normal lung model and saline lavage induced lung injury. Arterial blood gases were measured following changes in tidal volume (200-800 ml), respiratory rate (10-40 bpm), and PEEP (5-20 cm H2O) at baseline and after lung lavage. Physiological levels of PaCO2 (≤ 40 mm Hg [5.3 kPa]) were achieved in all animals at baseline and following lavage injury. PaO2 increased in lavage injured lungs in response to incremental PEEP (5-20 cm H2O) (p < 0.01). At fixed low oxygen flow rates (5 L/min), delivered FiO2 decreased with increased VE. CONCLUSIONS: ABBU provides oxygenation and ventilation across a range of parameter settings that may potentially provide a low-cost solution to ventilator shortages. A clinical trial is necessary to establish safety and efficacy in adult patients with diverse etiologies of respiratory failure.

Emergence of SARS-CoV-2 Resistance with Monoclonal Antibody Therapy (preprint)

Resistance mutations to monoclonal antibody (mAb) therapy has been reported, but in the non-immunosuppressed population, it is unclear if in vivo emergence of SARS-CoV-2 resistance mutations alters either viral replication dynamics or therapeutic efficacy. In ACTIV-2/A5401, non-hospitalized participants with symptomatic SARS-CoV-2 infection were randomized to bamlanivimab (700mg or 7000mg) or placebo. Treatment-emergent resistance mutations were significantly more likely detected after bamlanivimab 700mg treatment than placebo (7% of 111 vs 0% of 112 participants, P=0.003). There were no treatment-emergent resistance mutations among the 48 participants who received bamlanivimab 7000mg. Participants with emerging mAb resistant virus had significantly higher pre-treatment nasopharyngeal and anterior nasal viral load. Intensive respiratory tract viral sampling revealed the dynamic nature of SARS-CoV-2 evolution, with evidence of rapid and sustained viral rebound after emergence of resistance mutations, and worsened symptom severity. Participants with emerging bamlanivimab resistance often accumulated additional polymorphisms found in current variants of concern/interest and associated with immune escape. These results highlight the potential for rapid emergence of resistance during mAb monotherapy treatment, resulting in prolonged high level respiratory tract viral loads and clinical worsening. Careful virologic assessment should be prioritized during the development and clinical implementation of antiviral treatments for COVID-19.

Changes in Adolescents' Psychosocial Functioning and Well-Being as a Consequence of Long-Term COVID-19 Restrictions.

This work studied self-reports from adolescents on how the COVID-19 pandemic has changed their behaviors, relationships, mood, and victimization. Data collection was conducted between September 2020 and February 2021 in five countries (Sweden, the USA, Serbia, Morocco, and Vietnam). In total, 5114 high school students (aged 15 to 19 years, 61.8% females) responded to our electronic survey. A substantial proportion of students reported decreased time being outside (41.7%), meeting friends in real life (59.4%), and school performance (30.7%), while reporting increased time to do things they did not have time for before (49.3%) and using social media to stay connected (44.9%). One third of the adolescents increased exercise and felt that they have more control over their life. Only a small proportion of adolescents reported substance use, norm-breaking behaviors, or victimization. The overall COVID-19 impact on adolescent life was gender-specific: we found a stronger negative impact on female students. The results indicated that the majority of adolescents could adapt to the dramatic changes in their environment. However, healthcare institutions, municipalities, schools, and social services could benefit from the findings of this study in their work to meet the needs of those young people who signaled worsened psychosocial functioning, increased stress, and victimization.

Automated Bag Breathing Unit for COVID-19 Ventilator Shortages (preprint)

Background: The COVID-19 pandemic has caused a global mechanical ventilator shortage for treatment of severe acute respiratory failure. Development of novel breathing devices has been proposed as a low cost, rapid solution when full-featured ventilators are unavailable. Here we report the design, bench testing and preclinical results for an 'Automated Bag Breathing Unit' (ABBU). Output parameters were validated with mechanical test lungs followed by animal model testing.Results:  The ABBU design uses a programmable motor-driven wheel assembled for adult resuscitation bag-valve compression. ABBU can control tidal volume (200-800 ml), respiratory rate (10-40 bpm), inspiratory time (0.5-1.5 sec), assist pressure sensing (-1 to -20 cm H2O), manual PEEP valve (0- 20 cm H2O).   All set values are displayed on an LCD screen. Bench testing with lung simulators (Michigan 1600, SmartLung 2000) yielded consistent tidal volume delivery at compliances of 20, 40 and 70 (mL/cm H2O). The delivered fraction of inspired oxygen (FiO2) decreased with increasing minute ventilation (VE), from 98% to 47% when VE was increased from 4-16 L/min using a fixed oxygen flow source of 5 L/min. ABBU was tested in Berkshire pigs (n=6, weight of 112±5.8 lb) utilizing normal lung model and saline lavage induced lung injury. Arterial blood gases were measured following changes in tidal volume (200-800 ml), respiratory rate (10-40 bpm), and PEEP (5-20 cm H2O) at baseline and after lung lavage. Physiological levels of PaCO2 (≤40 mm Hg [5.3 kPa]) were achieved in all animals at baseline and following lavage injury. PaO2 increased in lavage injured lungs in response to incremental PEEP (5-20 cm H2O) (p<0.01). At fixed low oxygen flow rates (5 L/min), delivered FiO2 decreased with increased VE.Conclusions: ABBU provides oxygenation and ventilation across a range of parameter settings that may potentially provide a low-cost solution to ventilator shortages. A clinical trial is necessary to establish safety and efficacy in adult patients with diverse etiologies of respiratory failure.

A cohort study of men infected with COVID-19 for presence of SARS-CoV-2 virus in their semen.

INTRODUCTION: Whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be detected in semen and transmitted sexually is a vital question that has, thus far, been inconclusive. Prior studies, with limited numbers, have included men in various stages of infection with most in the recovery phase of the illness. The timing of test results and severity of illness has made recruiting study participants a significant challenge. Our pilot study will examine semen from men with a recent diagnosis of COVID-19 as well as those in the convalescent phase to determine if SARS-CoV-2 can be detected and its relationship, if any, with the severity of the disease. METHODS: Eighteen men with a median age of 32 (range, 24-57) who tested positive for COVID-19 by rt-PCR analysis were enrolled and provided a semen sample. The study group demonstrated symptoms of COVID-19 ranging from asymptomatic to moderate and none required hospitalization. Samples were subjected to viral RNA extraction and then processed by real-time RT-PCR using the US Centers for Disease Control and Prevention (CDC, USA) panel of 2019-Novel Coronavirus (2019-nCoV) primers and probes to detect the presence of SARS-CoV-2 RNA. RESULTS: Length of time from diagnosis to providing a specimen ranged from 1 to 28 days (median, 6 days). Fifteen participants were symptomatic and three were asymptomatic, including recovering men, at the time of semen collection. No SARS-CoV-2 was detected in any of the semen samples. CONCLUSION: Based on these preliminary results and consistent with prior findings, we suggest SARS-CoV-2 is not present in semen during the acute or convalescent phase of COVID-19.