Biases in Evaluating the Safety and Effectiveness of Drugs for the Treatment of COVID-19: Designing Real-World Evidence Studies.

The coronavirus disease 2019 pandemic, which was caused by the severe acute respiratory syndrome coronavirus 2, has led to an unprecedented effort to generate real-world evidence on the safety and effectiveness of various treatments. A growing number of observational studies in which the effects of certain drugs were evaluated have been conducted, including several in which researchers assessed whether hydroxychloroquine improved outcomes in infected individuals and whether renin-angiotensin-aldosterone system inhibitors have detrimental effects. In the present article, we review and illustrate how immortal time bias and selection bias were present in several of these studies. Understanding these biases and how they can be avoided may prove important for future observational studies assessing the effectiveness and safety of potentially promising drugs during the coronavirus 19 pandemic.

SARS-CoV-2: vaccines in the pandemic era.

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused millions of infections and deaths worldwide since its emergence in December 2019. As there is little or no natural immunity in the human population or specific anti-COVID-19 drugs, researchers from the government, academia and industry are developing vaccines at an unprecedented speed to halt the pandemic. In this review, the results of animal experiments and clinical trials on several vaccine technical platforms are summarized, and several challenges are also discussed to further promote the development, evaluation and application of vaccines during the challenging situation of the global pandemic.

The 2020 Pandemic: Current SARS-CoV-2 Vaccine Development.

Coronaviruses are enveloped viruses with a positive-sense single-stranded RNA genome infecting animals and humans. Coronaviruses have been described more than 70 years ago and contain many species. Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) are lethal species caused by human coronaviruses (HCoVs). Currently, a novel strain of HCoVs, named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (Covid-19). SARS-CoV-2 was first identified in December 2019 in Wuhan, the capital city of the Hubei province of China, and has since spread worldwide causing an outbreak in more than 200 countries. The SARS-CoV-2 outbreak was declared a pandemic on March 11th, 2020 and a public health emergency of international concern (PHEIC) in late January 2020 by the World Health Organization (WHO). SARS-CoV-2 infects the respiratory tract causing flu-like symptoms and, in some, may cause severe illness like pneumonia and multi-organ failure leading to death. Today, Covid-19 cases almost reaching 9 million, with more than 450 thousand deaths. There is an urgent demand for developing a vaccine since no effective therapies or vaccines have been approved to this day to prevent or minimize the spread of the infection. In this review, we summarized the furthest vaccines in the clinical pipeline.

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.