The COVID-19 pandemic, driven by a novel coronavirus (SARS-CoV-2), has spread rapidly around the world. Some people (and even global leaders in the USA and Brazil) mistakenly believe that COVID-19 infection is just seasonal influenza as they produce similar symptoms. You might have even tried to convince some of your relatives that COVID-19 infection is different to that of seasonal flu. You also know that COVID-19 is more contagious and deadlier than seasonal influenza.

In this blog post, I will be taking a different tack on the issue. I will be comparing the viruses themselves to show you how COVID-19 is similar and different to seasonal influenza. This blog post will describe what these viruses are, where they come from and how they infect and cause disease. I hope that this blog post will give you a new way to persuade other people that COVID-19 is different from seasonal influenza.

Classification and animal hosts of viruses

Coronaviruses and influenza viruses are both enveloped RNA viruses. They possess both an outer membrane taken from the cell’s plasma membrane and ribonucleic acid (RNA) containing the virus’ genetic information. However, these viruses are classified differently. Coronaviruses belong in the Coronaviridae family which is split into four types: alpha-, beta-, gamma- and delta-. The most well-known coronaviruses that cause SARS, MERS and COVID-19 infections in humans are beta-coronaviruses. On the other hand, influenza viruses belong in the Orthomyxoviridae family and are split into four types: A, B, C and D. Of these, humans can be infected by influenza A and B.

These viruses also occupy different animal hosts. The most well-known animal host for coronaviruses is bats. However, bat coronaviruses may further mutate and develop in other animal hosts (called intermediate hosts) before they infect humans. The bat coronaviruses for SARS and MERS, for example, further developed in palm civet and dromedary camels respectively, where they acquired the ability to infect and transmit between humans. Conversely, influenza viruses can be commonly found in humans, birds and pigs. There are seasonal influenza strains that can infect humans, but influenza strains from pigs (like the 2009 influenza pandemic) and birds (like H5N1 and H7N9 flu) can also, albeit rarely, cross over and cause severe infections in humans.

Biological characteristics of viruses

The physical sizes of both viruses are similar to each other at 80-120 nm in diameter. However, this is where their similarities end. First, both viruses organise their RNA genomes differently. Coronaviruses possess one of the largest genomes among all viruses at 27-32 kilobases. This is all contained in one piece of RNA, where two-thirds of the genome is occupied by one gene that codes for the replicase enzyme. In contrast, influenza viruses have a genome size of 13.6 kilobases, separated in eight segments of RNA which code for one to two proteins each.

The proteins of each virus are also different. The surface of a coronavirus contains S (spike), E (envelope), M (membrane) and sometimes HE (haemagluttinin-esterase) proteins (which is absent in SARS and MERS viruses). The only other protein coronaviruses have is N (nucleocapsid) which covers the RNA inside the virus, forming a nucleocapsid. In contrast, influenza viruses have more proteins. On the surface of a typical influenza virus are viral proteins HA (haemagglutinin), NA (neuraminidase) and M2 (matrix protein 2). M1 (matrix protein 1) forms a protein layer underneath the membrane. Inside the influenza virus, PB1 and PB2 (polymerase basic proteins 1 and 2), PA (polymerase acidic protein) and NP (nucleoprotein) associate with RNA to form ribonucleoprotein complexes. Inside the influenza virus, there are also accessory proteins such as NS1 and NS2 (non-structural proteins 1 and 2) which assist in the replication of influenza viruses.

Infection cycle of viruses

Both coronaviruses and influenza viruses infect epithelial cells in the lungs and airways. However, there are variations in how these viruses infect cells. For coronaviruses, they enter cells with their S protein, where the S1 (bulb) subunit binds to the receptor while the S2 (stalk) subunit fuses the viral and host membranes to release the nucleocapsid inside the cell. The nucleocapsid is then uncovered in the cytoplasm, exposing the RNA. That RNA is used to produce viral proteins that associate with the infected cell’s proteins to form the replication-transcription complex (RTC). The RTC produces more coronavirus RNA and proteins inside the infected cell’s cytoplasm. New nucleocapsids are formed by joining N protein to viral RNA. These nucleocapsids join in the assembly of new coronaviruses inside the cell. Newly-constructed coronaviruses are then packaged into vesicles which travel to the cell surface where they are released to infect other cells.

In contrast, influenza viruses enter cells by having haemagglutinin bind to sialic acid (a carbohydrate) on the cell surface. Inside the cell, the viral and host membranes fuse inside the endosome, releasing the nucleocapsid. Viral RNA and proteins are produced in different parts of the cell. While viral RNA is produced in the nucleus, influenza proteins are produced in the cytoplasm. New ribonucleoprotein complexes are assembled from newly synthesised viral proteins and RNA inside the cell. These complexes travel to the cell surface which is studded with viral surface proteins. Here, new influenza viruses bud off from the infected cell, wrapping around ribonucleoprotein complexes. Influenza viruses are freed by neuraminidase cutting off the bonds between haemagglutinin and sialic acid, allowing the virus to infect other cells.

Development of disease of viruses

Although coronavirus and influenza virus infections produce slightly different symptoms, they can cause similar infections. Normally, coronaviruses and influenza viruses are self-contained infections, producing no or mild symptoms such as fever, coughing and fatigue in most people. However, if coronaviruses or influenza viruses infect and replicate productively in the lungs, they can damage the lungs. This can lead to breathing difficulties which can contribute to organ failure and death.

Initially, both coronaviruses and influenza viruses infect and kill respiratory epithelial cells. This degrades the epithelial barrier between the blood and the lungs, allowing plasma and proteins from the blood to leak into the alveoli. Along with dead cells, they can block gas exchange, causing breathing difficulties. This is worsened by a dysfunctional immune system. Both viruses can suppress antiviral and immune responses that would normally restrict its spread in the lungs, allowing them to grow unhindered. Furthermore, they can stimulate a hyper-inflammatory response that damages the lungs even after the viruses are gone. This can lead to disorganised repair and remodelling of the lungs which aggravates the breathing difficulties, increasing the chances of death.

Conclusion

Coronaviruses and influenza viruses can produce similar diseases and symptoms in that they both infect and replicate in the lungs. When looked closely; however, they are two different viruses, each with various animal hosts, contrasting appearances and diverse ways of infecting cells. Importantly, while we have treatments and vaccines to protect humanity against seasonal influenza, so far we do not have any approved treatments and vaccines for COVID-19 infection. In addition, the whole population is not immune against this novel virus as this is the first time that it has emerged.

Hence, it is essential that we practise social distancing measures (e.g., keep your distance, avoid physical greetings…) and good hygiene (e.g., wash your hands often, cover your cough and sneezes with your elbow or tissue…) to ensure that we buy time to have vaccines and treatments developed, approved and available for everyone to conclusively end the pandemic. In addition, I hope that you understand the difference between influenza viruses and coronaviruses more so that you can convince other people why COVID-19 is different to that of seasonal influenza.