Research Dynamics within a New Multi-Institutional Cross-Disciplinary Translational Team (MCTT): A Formative Study

OBJECTIVES/GOALS: This report evaluates participants'experiences from three universities who assembled a complex grant proposal related to research on post-acute sequala of COVID-19 (PASC), also called long COVID. Activities reviewed ranged from the assembly of the team to responses to reviews by the National Center for Advancing Translational Sciences (NCATS). METHODS/STUDY POPULATION: Data were collected by means of semi-structured interviews, conducted and recorded on Zoom, with a sample of 15 scientists and staff both during proposal assembly and following proposal review. The sample comprised 40% of the total team equally selected from the 3 universities, The interview protocol was reviewed by the IRB at UTMB and the interviews were recorded on Zoom, and analyzed by means of the constant comparative strategy in the grounded theory method of qualitative research. Given the relatively small number of interviews in this project, we paid special attention to preserving the confidentiality of respondents. Only the verbal tracks of the interviews were professionally transcribed. Respondents were asked to suggest changes for future inter-organizational proposals. RESULTS/ANTICIPATED RESULTS: FIRST INTERVIEWS *LEADERSHIP: The scope of leadership opportunities was expanded as sub-teams in specific areas such as community engagement were formed. *TEAM: Each university's community engagement team specializes in a different ethnic clientele, precluding a singular statement for the proposal. SECOND INTERVIEWS *LEADERSHIP: Staff members noted that the team concept too easily evolved into a bureaucratic format, resulting in less negotiation and more direction. *ASSEMBLY TASKS: The Writing Team turned out to be one of the most critical staff teams. *COMMUNICATION: The behavioral scientists in community engagement do not necessarily share paradigms (e.g., public health, psychology, and social work). They had difficulty generating productive communication and a unified statement for the proposal. DISCUSSION/SIGNIFICANCE: The scientists, as a group, suggested that future proposals should focus on one general topic, such as the microbiome, as opposed to attempting to integrate widely divergent interests. The scientists as a group should decide a priori whether to treat innovative ideas such as machine learning science as a science or a service.

Duration of viral infectiousness and correlation with symptoms and diagnostic testing in non-hospitalized adults during acute SARS-CoV-2 infection: A longitudinal cohort study

Background Guidelines for SARS-CoV-2 have relied on limited data on duration of viral infectiousness and correlation with COVID-19 symptoms and diagnostic testing. Methods We enrolled ambulatory adults with acute SARS-CoV-2 infection and performed serial measurements of COVID-19 symptoms, nasal swab viral RNA, nucleocapsid (N) and spike (S) antigens, and replication-competent SARS-CoV-2 by viral growth in culture. We determined average time from symptom onset to a first negative test result and estimated risk of infectiousness, as defined by positive viral growth in culture. Results Among 95 adults, median [interquartile range] time from symptom onset to first negative test result was 9 [5] days, 13 [6] days, 11 [4] days, and >19 days for S antigen, N antigen, culture growth, and viral RNA by RT-PCR, respectively. Beyond two weeks, virus growth and N antigen titers were rarely positive, while viral RNA remained detectable among half (26/51) of participants tested 21-30 days after symptom onset. Between 6-10 days from symptom onset, N antigen was strongly associated with culture positivity (relative risk=7.61, 95% CI: 3.01-19.22), whereas neither viral RNA nor symptoms were associated with culture positivity. During the 14 days following symptom onset, the presence of N antigen remained strongly associated (adjusted relative risk=7.66, 95% CI: 3.96-14.82) with culture positivity, regardless of COVID-19 symptoms. Conclusions Most adults have replication-competent SARS-CoV-2 for 10-14 after symptom onset. N antigen testing is a strong predictor of viral infectiousness and may be a more suitable biomarker, rather than absence of symptoms or viral RNA, to discontinue isolation within two weeks from symptom onset. Funding Bill and Melinda Gates Foundation

Duration of viral infectiousness and correlation with symptoms and diagnostic testing in non-hospitalized adults during acute SARS-CoV-2 infection: A longitudinal cohort study.

BACKGROUND: Guidelines for SARS-CoV-2 have relied on limited data on duration of viral infectiousness and correlation with COVID-19 symptoms and diagnostic testing. METHODS: We enrolled ambulatory adults with acute SARS-CoV-2 infection and performed serial measurements of COVID-19 symptoms, nasal swab viral RNA, nucleocapsid (N) and spike (S) antigens, and replication-competent SARS-CoV-2 by viral growth in culture. We determined average time from symptom onset to a first negative test result and estimated risk of infectiousness, as defined by positive viral growth in culture. RESULTS: Among 95 adults, median [interquartile range] time from symptom onset to first negative test result was 9 [5] days, 13 [6] days, 11 [4] days, and >19 days for S antigen, N antigen, culture growth, and viral RNA by RT-PCR, respectively. Beyond two weeks, virus growth and N antigen titers were rarely positive, while viral RNA remained detectable among half (26/51) of participants tested 21-30 days after symptom onset. Between 6-10 days from symptom onset, N antigen was strongly associated with culture positivity (relative risk=7.61, 95% CI: 3.01-19.22), whereas neither viral RNA nor symptoms were associated with culture positivity. During the 14 days following symptom onset, the presence of N antigen remained strongly associated (adjusted relative risk=7.66, 95% CI: 3.96-14.82) with culture positivity, regardless of COVID-19 symptoms. CONCLUSIONS: Most adults have replication-competent SARS-CoV-2 for 10-14 after symptom onset. N antigen testing is a strong predictor of viral infectiousness and may be a more suitable biomarker, rather than absence of symptoms or viral RNA, to discontinue isolation within two weeks from symptom onset.

Scientific priorities and relational dynamics during the COVID-19 pandemic: A qualitative study.

To rapidly respond to the COVID-19 public health crisis, researchers have been called upon to prioritize pandemic research, while simultaneously modifying their existing research to maintain the safety of all stakeholders. This study aims to explore the experiences of health science researchers in their scientific practices, research priorities, and professional relational dynamics due to COVID-19. Specifically, we interviewed 31 researchers from diverse fields at the University of Texas Medical Branch. Participants worked on COVID-19, non-COVID-19 related research, or both. We integrated inductive and deductive coding using a thematic coding method. The following four themes were explored: 1) impact of research, 2) research priorities, 3) professional relationships and 4) contextual influences on science. Participants were drawn to COVID-19 work for a diversity of reasons including social need, scientific interest, professional duty, and increased access to funding opportunities. While collaborations have increased for COVID-19 researchers, interpersonal relationships have been challenging for participants. Additionally, political, familial, and personal stresses due to the pandemic have taken a toll on researchers in very different and often inequitable ways. To ensure team cohesion, there is a need to develop research practices, policies and systems that value empathy, flexibility, and interdependence.

Reimagining the peer-review system for translational health science journals.

Retractions of coronavirus disease 2019 (COVID-19) papers in high impact journals, such as The Lancet and the New England Journal of Medicine, have been panned as major scientific fraud in public media. The initial reaction to this news was to seek out scapegoats and blame individual authors, peer-reviewers, editors, and journals for wrong doing. This paper suggests that scapegoating a few individuals for faulty science is a myopic approach to the more profound problem with peer-review. Peer-review in its current limited form cannot be expected to adequately address the scope and complexity of large interdisciplinary science research collaboration, which is central in translational research. In addition, empirical studies on the effectiveness of traditional peer-review reveal its very real potential for bias and groupthink; as such, expectations regarding the capacity and effectiveness of the current peer review process are unrealistic. This paper proposes a new vision of peer-review in translational science that, on the one hand, would allow for early release of a manuscript to ensure expediency, whereas also creating a forum or a collective of various experts to actively comment, scrutinize, and even build on the research under review. The aim would be to not only generate open discussion and oversight respecting the quality and limitations of the research, but also to assess the extent and the means for that knowledge to translate into social benefit.

SARS-CoV-2 Infects Human Pluripotent Stem Cell-Derived Cardiomyocytes, Impairing Electrical and Mechanical Function.

COVID-19 patients often develop severe cardiovascular complications, but it remains unclear if these are caused directly by viral infection or are secondary to a systemic response. Here, we examine the cardiac tropism of SARS-CoV-2 in human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) and smooth muscle cells (hPSC-SMCs). We find that that SARS-CoV-2 selectively infects hPSC-CMs through the viral receptor ACE2, whereas in hPSC-SMCs there is minimal viral entry or replication. After entry into cardiomyocytes, SARS-CoV-2 is assembled in lysosome-like vesicles and egresses via bulk exocytosis. The viral transcripts become a large fraction of cellular mRNA while host gene expression shifts from oxidative to glycolytic metabolism and upregulates chromatin modification and RNA splicing pathways. Most importantly, viral infection of hPSC-CMs progressively impairs both their electrophysiological and contractile function, and causes widespread cell death. These data support the hypothesis that COVID-19-related cardiac symptoms can result from a direct cardiotoxic effect of SARS-CoV-2.