By Alexandra Grba
Between 1918-1919, what is now known as the Spanish flu devastated the planet in the deadliest pandemic in modern human history. Arising in three distinct waves, it affected a third of the global population and took the lives of at least 50 million people (Bristow, 2012). As we descend into the second wave of the Covid-19 pandemic, the question arises: does the past offer a relevant perspective on our present?
Whilst the origin of the Spanish flu remains unclear, the mass movement of soldiers and poor sanitation during the First World War meant that the novel influenza virus spread rapidly around the globe. Although the first wave did not appear lethal, the second and third waves wreaked havoc on the global population; the virus had mutated and had become deadly. The majority of deaths were a result of secondary bacterial pneumonia, however viral pneumonia, often with either massive acute pulmonary haemorrhage or pulmonary oedema, killed directly. In the late 1990s, Taubenberger’s group at the US Armed Forces Institute of Pathology identified the pathogenic agent as influenza A virus subtype H1N1. Analysis of the viral RNA sequence showed that the virus may have been of avian origin, however, whether it was transmitted from birds remains unclear.
The uniquely violent virulence of the Spanish flu, resulting from mutation, is explained by a few key factors. The viral surface glycoprotein hemagglutinin (HA) allows for receptor binding and membrane fusion, leading to efficient replication and therefore high virulence. Additionally, the 1918 viral RNA polymerase complex genes means that the virus could replicate effectively in both the upper and the lower respiratory tract. In contrast, typical human influenza viruses do not replicate efficiently in the lungs, and, as a result, do not usually cause lethal viral pneumonia (Watanabe & Kawaoka, 2011).
One hundred years later in December 2019, cases of novel illness-causing respiratory problems, pneumonia, and death, were first reported in Wuhan, China. It was not long before the number of cases rose exponentially and the disease spread across the world, earning pandemic status. The 2019 disease is biologically different from the 1918 influenza virus, however, with the causative agent identified as a novel coronavirus. Sequence analysis of the viral genome has revealed that it is phylogenetically similar to the severe acute respiratory syndrome coronavirus (SARS-CoV) of 2002, and as a result has been named “SARS- CoV-2” by the International Committee on Taxonomy of Viruses (ICTV). Coronaviruses have very large single-stranded RNA genomes of around 26,000 to 32,000 bases (Liverpool, 2012). An envelope encapsulates the spherical particle and club-shaped spikes cover the surface. These spikes bind to receptors on human cells called angiotensin-converting enzyme 2 (ACE2), before undergoing a structural change to allow the virus to fuse with the human cell membrane and inject viral genetic information into the host cell to be replicated, producing more viruses (National Institutes of Health (NIH), 2020). Genome analysis has revealed the Rhinolophus affinis bat as the natural host of Covid-19, with evidence to suggest that transmission to humans requires an intermediary host, although further information is yet unknown (Guo et al., 2020).
Both the influenza virus and novel coronavirus harbour genetic material in the form of RNA. RNA virus replication generally has a high error rate — resulting from a lack of proofreading activity of the RNA polymerase enzyme. The low replicative fidelity allows for a rapid rate of mutation, a key factor in the occurrence of infectious ‘waves’ in 1918 and the acquisition of such lethal virulence. Conversely, coronaviruses do proofread their copied RNA during replication, hence their decreased mutation rates. From the original Wuhan SARS-CoV-2 sequence to recently banked sequences in the U.S, there have been fewer than ten mutations observed in 30,000 potential genome locations, despite the virus having travelled through numerous generations of human hosts and various geographical locations. Influenza, on the other hand, makes 6.5 times more errors per replication cycle (Webel & Freeman, 2020). The higher replicative fidelity of SARS-CoV-2 means that peaks in infection (or ‘waves’) are unlikely to be the result of higher virulence resulting from mutation as was the case in the 1918 pandemic . As a result, it is impossible to predict when and how the Covid-19 pandemic will peak, or when it will end, with reference to the Spanish flu pandemic.
Comparatively, with the lack of vaccine and antibiotic technology, prevention methods in 1918 ring familiar: social distancing, mask wearing and the use of disinfectants was encouraged, with significant reduction in death rates in areas that acted quickly to implement these measures (Centers for Disease Control and Prevention, 2019). Relaxing measures too soon proved fatal, whilst cities that kept the interventions in place avoided the stark peak in deaths seen in the second wave (Strochlic & Champine, 2020). As SARS-CoV-2 continues to circulate, we can see that implementing social distancing measures keeps infection rates steady. However, both the biological differences between the Spanish flu and Covid-19, as well as the different scientific and socio-economic landscapes, mean that we must study the pandemics within the context of their time. While the Spanish flu pandemic may give us valuable insight into precautions we can take to help curb the spread of a vaccine-less virus, comparisons must be drawn with caution.
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