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Written by Calla Reed

**For more information on how to get your flu shot at Vanderbilt, click here.**

A seemingly innocent sneeze in this cool autumn weather could mean anything from COVID-19, the flu, the common cold, or – if you’re really lucky- simple allergies. But what if you’re not so lucky and happen to be exposed to all three at similar times, all of which have similar and shared symptoms? Scientists are now saying we are at risk for a ‘twindemic’, a combined pandemic of the flu/influenza and COVID-19. Having combined epidemics of both influenza and COVID-19 will not only be difficult for afflicted individuals, but also for the general population as a whole, due to the decreased resources in healthcare and the increased fear of becoming sick. 

So, what are the differences between influenza, COVID-19, and the seasonal Common Cold? What are the similarities?

The Flu

While influenza has been known to infect human populations for at least 500 years, very little is understood about these historic strains. It is theorized that Type A influenza existed naturally in aquatic birds as a disease reservoir and would periodically mutate to infect humans and cause isolated epidemics throughout history. 

The 1918 Influenza pandemic, also known as the Spanish Flu, has often been compared to the current pandemic due to parallels in infection rate (both are extremely contagious), outbreak season (both outbreaks started in the winter), and the role of increased global movement (the movement of troops in 1918 and widespread international travel today) in spreading the disease. Mask mandates, shortages in healthcare professionals and equipment, and the shuttering of public places also occurred during the height of the 1918 pandemic (sound familiar?). Overall, at least 50 million (675,000 in the United States) died from that outbreak. 

In April 2009, the mutant influenza A H1N1 strain was detected in California. Also known as swine flu, the disease reached global proportions by June, and by December there was a successful vaccine available to the public. Overall, anywhere from 150,000 to 575,000 people died during this outbreak. 

Both previous flu pandemics (1918 and 2009) involved H1N1 strains of influenza A, first  characterized in 1931, twelve years after the decline of the Spanish Flu.  It is believed that the H1N1 strain zoonotically “jumped” from pigs to humans and a specific H1N1 strain became endemic to humans. The 2009 Swine Flu pandemic was caused by a reassortment of two preexisting H1N1 influenza viruses, which is why younger people who didn’t possess the necessary antibodies to protect against this newly mutated strain were particularly vulnerable to infection. 

On the other hand, the seasonal flu is caused by both Type A and Type B influenza strains. Type A strains, specifically H1N1 and H3N2, tend to mutate more rapidly in their genetics and antigens (the viral proteins host cells use to alert the immune system to “invaders”). Type B strains are less varied and mutate at a slower rate than Type A strains. 

Type A influenza virions under transmission electron microscope
Pictured Above: Type A influenza virions using a transmission electron microscopic (TEM) image. Credit CDC/F.A. Murphy

The Common Cold

The Common Cold, also known as the Rhinovirus, was discovered in 1956. It is the most common viral agent in humans and the main cause of cold-like symptoms. There are three species of rhinoviruses (A, B, and C) that include 160 recognized types of human rhinoviruses, which are mainly seasonal in prevalence during the spring and winter. While rhinoviruses don’t tend to trigger severe symptoms in most individuals, those with chronic conditions such as asthma may experience serious illness and complications if infected with a more vigorous strain.        

With both the flu and common cold being respiratory infections, it can be difficult to distinguish between the two. In general, flu symptoms tend to be more intense than cold symptoms and tend to result in more severe complications such as pneumonia and bacterial infections. Below is a helpful chart put together by the CDC to illustrate some of the main differences in symptoms between the two illnesses:

Infographic describing differences between cold and flu
Infographic from CDC about the symptom differences between the cold and flu.


What happens if we add in a global pandemic to a winter season already known for two respiratory diseases? Well, the biology and mechanisms of COVID-19 are still being elucidated. We know that COVID-19 has one of the largest genomes of any infectious virus, allowing for strains to swap sections of the large genome and have increased variability in comparison to other viruses. It is the ability of RNA viruses to easily swap genome sections with other viruses (also known as recombination) that allows for mutant strains to develop and zoonotically “jump” from animals to infect humans. Additionally, COVID-19 is one of the few RNA viruses to have a proof-reading mechanism for its genome. This pathway significantly increases the genomic integrity of the virus by “checking” for errors as it mutates. 

While the common cold and flu initially infects the upper respiratory tract (nose and throat), COVID-19 is able to successfully infect both the upper and the lower respiratory tract (lungs). This results in a wider range of symptoms, with an infection of only the upper respiratory tract resulting in less severe symptoms such as coughing and loss of taste/smell. Infection of the lower respiratory tract, however, could result in decreased lung capacity for that individual. Scientists are still trying to determine if certain individuals have natural antibodies that prevent the virus from moving into the lower respiratory tract and proliferating there.  

Image of COVID-19 virus (ball-like structures) on the ends of cilia in the respiratory tract
Pictured above: Image of COVID-19 virus (ball-like structures) on the ends of cilia in the respiratory tract (Image: © The New England Journal of Medicine ©2020.)

So How Can We Tell the Difference?

Despite all three being respiratory illnesses, there are some key differences between COVID-19 and the common cold and the flu. COVID-19 tends to be the most severe of all, takes the longest to show symptoms (up to 14 days), and can be contagious for the longest period of time (at least 10 days since testing positive, but this figure is still being researched). All three have symptoms associated with the upper respiratory tract such as sore throat, runny/stuffy nose, and cough. Both the flu and COVID-19 have more severe symptoms in common, such as fever, muscle pain, fatigue, and shortness of breath. All three can be spread by close contact with an infected person, but COVID-19 tends to be more contagious in certain populations and has more superpreading potential due to low levels of protective antibodies within populations. Both the flu and COVID-19 can cause complications in high-risk groups, such as pneumonia and even death. However, individuals are less likely to fully recover from COVID-19 and more likely to develop severe complications such as multiple-organ failure and blood clots throughout the body.

What Can We Do to Protect Ourselves?

In order to protect ourselves from the severe symptoms and complications associated with both COVID-19 and the flu, along with the symptoms associated with the Common Cold, we need to increase the country’s herd immunity through voluntary vaccination for the flu. Already, 20% of COVID-19 patients in a recent American Medical Association (AMA) study were infected with another respiratory virus, demonstrating that there is a significant probability that individuals can become infected with two or all three illnesses. By getting a flu shot, a cocktail of low-dose Type A/Type B influenza viruses, we can boost our immunity to the seasonal flu, making it easier to determine if our sickness is COVID-19 related. With flu shots, we can take one severe illness out of the equation in the uncertainty of this pandemic and flatten the impending sickness curve.