12.1

INTRODUCTION

In late December 2019, a new species of coronavirus was discovered in Wuhan,

China, causing a severe acute respiratory syndrome and was aptly dubbed SARS-

CoV-2. The virus quickly spread around the globe and the clinical disease it causes,

coronavirus disease 2019 (or COVID-19), was declared a global emergency of very

high risk on February 28th, 2020. Soon after, on March 12th, 2020, these COVID-19

outbreaks were declared a pandemic [1].

The clinical presentation of COVID-19 varies substantially among individuals

ranging from asymptomatic infection to multi-organ failure, which accounts for the

difficulty in controlling its transmission. It largely causes upper and lower respiratory

pathology; however, the virus has tropism for virtually every tissue-type (respiratory

tract, gastrointestinal tract, central nervous system, cardiovascular system, etc.), ac-

counting for its diverse symptomology. Clinical features include fatigue, fever,

myalgias, cough, anosmia, ageusia, headache, nausea, vomiting, diarrhea, and so

on, which makes it nearly impossible to predict the clinical course in any given in-

dividual. Further, older adults and those with underlying co-morbidities are more

likely to experience severe infection, and subsequent complications like acute re-

spiratory distress syndrome (ARDS), cytokine release syndrome (CRS), systemic

inflammatory response syndrome (SIRS), septic shock, acute kidney injury (AKI),

multi-organ failure, and cardiovascular complications like acute coronary syndrome

and stroke [2,3]. However, even in healthy individuals with mild infections, long-term

consequences can be deleterious due to loss of tissue stem cells resulting in inhibited

cellular repair and inflammatory fibrosis [2].

The global pandemic caused by this newly discovered betacoronavirus is not the

first in recorded history. In fact, betacoronaviruses were the causative agents of two

previous outbreaks in the last 20 years: namely, the SARS-CoV outbreak of 2003

and Middle Eastern respiratory syndrome (MERS-CoV) in 2012. SARS-CoV

caused a similar respiratory syndrome and resulted in 8098 cases and 774 deaths,

whereas the death rate for MERS-CoV was even higher at 35% (although this

statistic omits asymptomatic transmission) [4]. As of the writing of this chapter,

there have been approximately 235 million cases of COVID-19 and 4.8 million

deaths, which is a death rate of ~2% [5].

It is interesting to note that the incidence of pandemics and epidemics has been

steadily increasing over the last 200 years. This is most likely due to the increases in

population density and most recently, globalization. From the Middle Ages to the 19th

century there were really only two epidemics of note: the bubonic plague which began

in 1347 and smallpox from the early 1500’s. From the 19th century onwards, the

world saw the following outbreaks: influenza “Great Pandemic” (1833), cholera

(1881), Spanish influenza (1918), Asian influenza (1957), hepatitis C (1960s), Hong

Kong influenza (1968), Russian influenza (1977), HIV (1981), SARS-CoV-1 (2003),

H1N1 (2009), MERS-CoV (2012), Ebola virus (2013), chikungunya virus (2013),

Zika virus (2015), and now COVID-19 [6]. While most authorities predicted that a

new global outbreak was imminent, influenza was thought to be the most likely cause

of humanity’s next great pandemic and probabilistic modeling forecasted a 1% annual

chance of an influenza pandemic that would result in 6 million deaths [6].

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Bioprocessing of Viral Vaccines