Significant Unresolved Questions and Opportunities for Bioengineering in Understanding and Treating COVID-19 Disease Progression

Abstract

COVID-19 is a disease that manifests itself in a multitude of ways across a wide range of tissues. Many factors are involved, and though impressive strides have been made in studying this novel disease in a very short time, there is still a great deal that is unknown about how the virus functions. Clinical data has been crucial for providing information on COVID-19 progression and determining risk factors. However, the mechanisms leading to the multi-tissue pathology are yet to be fully established. Although insights from SARS-CoV-1 and MERS-CoV have been valuable, it is clear that SARS-CoV-2 is different and merits its own extensive studies. In this review, we highlight unresolved questions surrounding this virus including the temporal immune dynamics, infection of non-pulmonary tissue, early life exposure, and the role of circadian rhythms. Risk factors such as sex and exposure to pollutants are also explored followed by a discussion of ways in which bioengineering approaches can be employed to help understand COVID-19. The use of sophisticated in vitro models can be employed to interrogate intercellular interactions and also to tease apart effects of the virus itself from the resulting immune response. Additionally, spatiotemporal information can be gleaned from these models to learn more about the dynamics of the virus and COVID-19 progression. Application of advanced tissue and organ system models into COVID-19 research can result in more nuanced insight into the mechanisms underlying this condition and elucidate strategies to combat its effects.

First‐in‐Human Study of Bamlanivimab in a Randomized Trial of Hospitalized Patients With COVID‐19

“…Blood samples obtained for pharmacokinetics (PK) analysis were assessed on Days 1 (pre-infusion and just before end of infusion), 4, 15, 29 and follow-up visits up to Day 60. Symptom-related physical examinations and assessments of clinical symptoms were performed on Days 1,2,3,4,7,11,15,22,29, and day of discharge from the hospital, with additional follow-up examinations every 7 days thereafter until Day 60 if the patient was not discharged from the hospital by Day 29. Participants' clinical status and concurrent procedures of special interest were recorded, including limitation on activities due to COVID-19 and any requirements for the following procedures of special interest: ongoing hospital medical care, supplemental oxygen, non-invasive ventilation or a high flow oxygen device, mechanical ventilation, extracorporeal membrane oxygenation, additional organ support, or consciousness status using alert, consciousness, verbal, pain, unresponsive scale.…”

Co-distribution of Light At Night (LAN) and COVID-19 incidence in the United States

“…More circadian disruptions might lead to more adverse impacts on human immunity, such as causing people to become more vulnerable to infectious diseases and other hormone-related diseases. This provides more opportunities to analyze how circadian disruptions such as LAN correlate with hormone-related health outcomes and temporal immune dynamics [34].…”

Biomaterials-Based Opportunities to Engineer the Pulmonary Host Immune Response in COVID-19

“… 298 − 303 Additionally, there exist underlying opportunities in utilizing organ-on-a-chip model systems to study the effects on other organs systems in recovered COVID-19 patients. 304 − 307 Utilizing these model systems with primary cells derived from recovered patients would facilitate a hypothesis-based approach to understand post-COVID-19 symptoms and recovery in a physiologically relevant manner and could allow for prescreening of therapeutics in a microenvironment resembling that of COVID-19 long haulers.…”