Pathophysiology and treatment strategies for COVID-19.

The outbreak of Coronavirus disease of 2019 (COVID-19) caused by the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), has posed a serious health threat. The increasing number of COVID-19 cases around the world is overwhelming hospitals and pushing the global death toll to over 746,000, which has pushed the sprint to find new treatment options. In this article, we reviewed the SARS-CoV-2 pathophysiology, transmission, and potential treatment strategies.

Approaches and Challenges in SARS-CoV-2 Vaccine Development.

The explosive spread of SARS-CoV-2 suggests that a vaccine will be required to end this global pandemic. Progress in SARS-CoV-2 vaccine development to date has been faster than for any other pathogen in history. Multiple SARS-CoV-2 vaccine candidates have been evaluated in preclinical models and are currently in clinical trials. In this Perspective, we discuss three topics that are critical for SARS-CoV-2 vaccine development: antigen selection and engineering, preclinical challenge studies in non-human primate models, and immune correlates of protection.

COVID-19: Progress in diagnostics, therapy and vaccination.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has recently become a pandemic. As the sudden emergence and rapid spread of SARS-CoV-2 is endangering global health and the economy, the development of strategies to contain the virus's spread are urgently needed. At present, various diagnostic kits to test for SARS-CoV-2 are available for use to initiate appropriate treatment faster and to limit further spread of the virus. Several drugs have demonstrated in vitro activity against SARS-CoV-2 or potential clinical benefits. In addition, institutions and companies worldwide are working tirelessly to develop treatments and vaccines against COVID-19. However, no drug or vaccine has yet been specifically approved for COVID-19. Given the urgency of the outbreak, we focus here on recent advances in the diagnostics, treatment, and vaccine development for SARS-CoV-2 infection, helping to guide strategies to address the current COVID-19 pandemic.

SARS-CoV-2 pandemic and research gaps: Understanding SARS-CoV-2 interaction with the ACE2 receptor and implications for therapy.

The COVID-19 pandemic is an emerging threat to global public health. While our current understanding of COVID-19 pathogenesis is limited, a better understanding will help us develop efficacious treatment and prevention strategies for COVID-19. One potential therapeutic target is angiotensin converting enzyme 2 (ACE2). ACE2 primarily catalyzes the conversion of angiotensin I (Ang I) to a nonapeptide angiotensin or the conversion of angiotensin II (Ang II) to angiotensin 1-7 (Ang 1-7) and has direct effects on cardiac function and multiple organs via counter-regulation of the renin-angiotensin system (RAS). Significant to COVID-19, ACE2 is postulated to serve as a major entry receptor for SARS-CoV-2 in human cells, as it does for SARS-CoV. Many infected individuals develop COVID-19 with fever, cough, and shortness of breath that can progress to pneumonia. Disease progression promotes the activation of immune cells, platelets, and coagulation pathways that can lead to multiple organ failure and death. ACE2 is expressed by epithelial cells of the lungs at high level, a major target of the disease, as seen in post-mortem lung tissue of patients who died with COVID-19, which reveals diffuse alveolar damage with cellular fibromyxoid exudates bilaterally. Comparatively, ACE2 is expressed at low level by vascular endothelial cells of the heart and kidney but may also be targeted by the virus in severe COVID-19 cases. Interestingly, SARS-CoV-2 infection downregulates ACE2 expression, which may also play a critical pathogenic role in COVID-19. Importantly, targeting ACE2/Ang 1-7 axis and blocking ACE2 interaction with the S protein of SARS-CoV-2 to curtail SARS-CoV-2 infection are becoming very attractive therapeutics potential for treatment and prevention of COVID-19. Here, we will discuss the following subtopics: 1) ACE2 as a receptor of SARS-CoV-2; 2) clinical and pathological features of COVID-19; 3) role of ACE2 in the infection and pathogenesis of SARS; 4) potential pathogenic role of ACE2 in COVID-19; 5) animal models for pathological studies and therapeutics; and 6) therapeutics development for COVID-19.

Bioengineering tools to speed up the discovery and preclinical testing of vaccines for SARS-CoV-2 and therapeutic agents for COVID-19.

This review provides an update for the international research community on the cell modeling tools that could accelerate the understanding of SARS-CoV-2 infection mechanisms and could thus speed up the development of vaccines and therapeutic agents against COVID-19. Many bioengineering groups are actively developing frontier tools that are capable of providing realistic three-dimensional (3D) models for biological research, including cell culture scaffolds, microfluidic chambers for the culture of tissue equivalents and organoids, and implantable windows for intravital imaging. Here, we review the most innovative study models based on these bioengineering tools in the context of virology and vaccinology. To make it easier for scientists working on SARS-CoV-2 to identify and apply specific tools, we discuss how they could accelerate the discovery and preclinical development of antiviral drugs and vaccines, compared to conventional models.

COVID-19 human challenge studies: ethical issues.

COVID-19 poses an extraordinary threat to global public health and an effective vaccine could provide a key means of overcoming this crisis. Human challenge studies involve the intentional infection of research participants and can accelerate or improve vaccine development by rapidly providing estimates of vaccine safety and efficacy. Human challenge studies of low virulence coronaviruses have been done in the past and human challenge studies with severe acute respiratory syndrome coronavirus 2 have been proposed. These studies of coronaviruses could provide considerable benefits to public health; for instance, by improving and accelerating vaccine development. However, human challenge studies of severe acute respiratory syndrome coronavirus 2 in particular might be controversial, in part, for ethical reasons. The ethical issues raised by such studies thus warrant early consideration involving, for example, broad consultation with the community. This Personal View provides preliminary analyses of relevant ethical considerations regarding human challenge studies of severe acute respiratory syndrome coronavirus 2, including the potential benefits to public health and to participants, the risks and uncertainty for participants, and the third-party risks (ie, to research staff and the wider community). We argue that these human challenge studies can reasonably be considered ethically acceptable insofar as such studies are accepted internationally and by the communities in which they are done, can realistically be expected to accelerate or improve vaccine development, have considerable potential to directly benefit participants, are designed to limit and minimise risks to participants, and are done with strict infection control measures to limit and reduce third-party risks.