Multimodal surveillance of SARS-CoV-2 at a university enables development of a robust outbreak response framework (preprint)

Universities are particularly vulnerable to infectious disease outbreaks and are also ideal environments to study transmission dynamics and evaluate mitigation and surveillance measures when outbreaks occur. Here, we introduce a SARS-CoV-2 surveillance and response framework based on high-resolution, multimodal data collected during the 2020-2021 academic year at Colorado Mesa University. We analyzed epidemiological and sociobehavioral data (demographics, contact tracing, and wifi-based co-location data) alongside pathogen surveillance data (wastewater, random, and reflexive diagnostic testing; and viral genomic sequencing of wastewater and clinical specimens) to characterize outbreak dynamics and inform policy decisions. We quantified group attributes that increased disease risk, and highlighted parallels between traditional and wifi-based contact tracing. We additionally used clinical and environmental viral sequencing to identify cryptic transmission, cluster overdispersion, and novel lineages or mutations. Ultimately, we used distinct data types to identify information that may help shape institutional policy and to develop a model of pathogen surveillance suitable for the future of outbreak preparedness.

A coordinated national response maintained a safe and effective UK liver transplant program during the first year of the COVID-19 pandemic

P091 Figure 1Number of livers from UK deceased doners offered, retrieved and transplanted, 4 February 2020 to 5 April 2021[Figure omitted. See PDF]DiscussionA sophisticated national response has maintained a safe and effective UK LT program throughout the first year of COVID. We adapted our resources, implementing phased donor restrictions and a new category for recipient prioritisation. Patients benefitted from collaborative working, enabling those in most need to be transferred and transplanted in protected centres. Consequently, we mitigated against a significant fall in LT activity. Our collaborative response serves as an as exemplar for other specialist healthcare services.

Messages That Increase COVID-19 Vaccine Willingness: Evidence From Online Experiments in Six Latin American Countries (preprint)

As safe and effective vaccines become widely available, attaining herd immunity and limiting the spread of COVID-19 will depend on individuals choosing to vaccinate and doing so quickly enough to outpace mutations. Using online surveys conducted in January 2021 across six Latin American countries - where mass vaccination programs have only recently begun and are expected to continue into 2022 - we experimentally assess messages designed to counteract informational deficiencies and collective action problems that may drive hesitancy. We first find that basic vaccine information persuades around 8% of hesitant individuals to become willing to vaccinate, reduces the time individuals intend to wait before vaccinating once a vaccine is available to them by 0.4 months, and increases willingness to encourage others to vaccinate. Rather than facilitating free riding, learning, or social conformity, providing information about others’ behavior increases vaccine willingness and willingness to encourage others to vaccinate among respondents induced to expect that herd immunity will be achieved in their country. Finally, priming the social approval benefits of vaccinating also increase each dimension of vaccine acceptance, and is more effective than messages highlighting economic or altruistic benefits of vaccination. These results suggest that providing information and shaping social expectations and incentives could both be important in encouraging vaccine uptake.

The Case for Altruism in Institutional Diagnostic Testing (preprint)

Amid COVID-19, many institutions deployed vast resources to test their members regularly for safe reopening. This self-focused approach, however, not only overlooks surrounding communities but also remains blind to community transmission that could breach the institution. To test the relative merits of a more altruistic strategy, we built an epidemiological model that assesses the differential impact on case counts when institutions instead allocate a proportion of their tests to members' close contacts in the larger community. We found that testing outside the institution benefits the institution in all plausible circumstances, with the optimal proportion of tests to use externally landing at 45% under baseline model parameters. Our results were robust to local prevalence, secondary attack rate, testing capacity, and contact reporting level, yielding a range of optimal community testing proportions from 18% to 58%. The model performed best under the assumption that community contacts are known to the institution; however, it still demonstrated a significant benefit even without complete knowledge of the contact network.

Sustained Dysregulation of the Plasma Renin-angiotensin System in Acute COVID-19 (preprint)

SARS-CoV-2 enters cells by binding to angiotensin-converting enzyme 2 (ACE2), and COVID-19 infection may therefore induce changes in the renin-angiotensin system (RAS). To determine the effects of COVID-19 on plasma RAS components, we measured plasma ACE, ACE2, and angiotensins I, (1-7), and II in 46 adults with COVID-19 at hospital admission and on days 2, 4, 7 and 14, compared to 50 blood donors (controls). We compared survivors vs. non-survivors, males vs. females, ventilated vs. not ventilated, and angiotensin receptor blocker (ARB) and angiotensin-converting enzyme (ACE) inhibitor-exposed vs. not exposed. At admission, COVID-19 patients had higher plasma levels of ACE (p=0.012), ACE2 (p=0.001) and angiotensin-(1-7) (p<0.001) than controls. Plasma ACE and ACE2 remained elevated for 14 days in COVID-19 patients, while plasma angiotensin-(1-7) decreased after 7 days. In adjusted analyses, plasma ACE was higher in males vs. females (p=0.042), and plasma angiotensin I was significantly lower in ventilated vs. non-ventilated patients (p=0.001). In summary, plasma ACE and ACE2 are increased for at least 14 days in patients with COVID-19 infection. Angiotensin-(1-7) levels are also elevated, but decline after 7 days. The results indicate dysregulation of the RAS with COVID-19, with increased circulating ACE2 throughout the course of infection.Clinical Trial Registration: https://clinicaltrials.gov/ Unique Identifier: NCT04510623

Surfactant Therapy for COVID-19 Related ARDS: A Retrospective Case-Control Pilot Study. (preprint)

Background: . COVID-19 causes acute respiratory distress syndrome (ARDS) and depletes the lungs of surfactant, leading to prolonged mechanical ventilation and death. The feasibility and safety of surfactant delivery in COVID-19 ARDS patients have not been established. Methods: . We performed retrospective analyses of data from patients receiving off-label use of natural surfactant during the COVID-19 pandemic. Seven COVID-19 PCR positive ARDS patients received liquid Curosurf (720 mg) in 150 ml normal saline, divided into five 30 ml aliquots) and delivered via a bronchoscope into second-generation bronchi. Patients were matched with 14 comparable subjects receiving supportive care for ARDS during the same time period. Feasibility and safety were examined as well as the duration of mechanical ventilation and mortality. Results: . Patients showed no evidence of acute decompensation following surfactant installation into minor bronchi and lung retention for up to 2 hours. Cox regression showed a reduction of 28-days mortality within the surfactant group, though not significant. The surfactant did not increase the duration of ventilation, and health care providers did not convert to COVID-19 positive. Conclusions: . Surfactant delivery through bronchoscopy at a dose of 720 mg in 150 ml normal saline is feasible and safe for COVID-19 ARDS patients and health care providers during the pandemic. Surfactant administration does not cause acute decompensation, and it could be related to improved survival and reduction of mechanical ventilation duration. This study supports the future performance of randomized clinical trials evaluating the efficacy of meticulous surfactant delivery.

Pan-cancer analysis of RNA expression of ANGIOTENSIN-CONVERTING ENZYME II (ACE2) and cellular proteases reveals high variability and possible impact on COVID-19 clinical outcomes (preprint)

Patients with cancer demonstrate particularly poor outcomes from COVID-19. To provide information essential for understanding the biologic underpinnings of this association, we analyzed whole-transcriptome RNA expression data obtained from a large cohort of cancer patients to characterize expression of ACE2, TMPRSS2, and other proteases that are involved in viral attachment to and entry into target cells. We find substantial variability of expression of these factors across tumor types and identify subpopulations expressing ACE2 at very high levels. In some tumor types, especially in gastrointestinal cancers, expression of ACE2 and TMPRSS2 is highly correlated. Furthermore, we found infiltration with T-cell and natural killer (NK) cell infiltration to be particularly pronounced in ACE2-high tumors. These findings suggest that subsets of cancer patients exist with heightened susceptibility to SARS-CoV-2 infection in whom malignant tumors function as viral reservoir and possibly promote the frequently detrimental hyper-immune response in patients infected with this virus.