by Tawney Hammet, M.S. Individualized Genomics & Health Candidate
Johns Hopkins University
Humanity is currently facing a new mortal enemy, SARS-CoV-2, or more commonly known as the virus that causes COVID-19. As of April 9th, there are over 1,506,900 confirmed cases worldwide with 90,000 total deaths. The U.S. is nearing half of a million cases with over 14,000 deaths. The economic, physical, and mental toll of the virus and strategies to contain it have been debilitating.
COVID-19 is a zoonotic disease and the third highly pathogenic coronavirus introduced to the human population after SARS-CoV and MERS-CoV. A SARS-CoV-2 viral particle is approximately 80-160 nM in size, about a thousand times smaller than a pollen particle on average1. Its RNA genome is about 30 kb with one-third of the sequence encoding structural proteins that produce virions (mature forms of virus particles outside of host cells, capable of infecting others) and two-thirds encoding non-structural proteins essential for producing new genetic material1.
Multiple studies have identified angiotensin-converting enzyme 2 (ACE2) as the key cell receptor for SARS-CoV-2 entry, making it a critical factor in determining disease pathogenesis and investigation target for future treatment options. ACE2 is expressed in all tissues, with the greatest activity in the kidney and ileum, followed by adipose tissue, heart, brain stem, lungs, stomach, liver, and nasal and oral mucosa2. Comparison studies between SARS-CoV and SARS-CoV-2 show the ACE2 binding domain is nearly identical between the two viruses, but subtle interaction differences indicate that convergent evolution may have occurred that improved SARS-CoV-2’s ACE2 receptor binding affinity3.
Genetic differences in the ACE2 gene caused by single nucleotide polymorphisms may explain why younger people with no underlying conditions are succumbing to the virus. A study of mild to moderate essential hypertension patients found that single nucleotide polymorphisms (SNPs) in ACE2 conferred an increased risk for left ventricular hypertrophy, a form of organ damage4. Other SNPs specific to the mannose-binding lectin structure in antigen presenting cells (APCs), immune cells that alert T-cells of invaders, have been cited as an elevated risk in SARS-CoV infection. The same individual genetic risks may also apply to COVID-19 infection, highlighting that it only takes one nucleotide in 3 billion base pairs to make anyone on the planet vulnerable to infection. More widespread whole genome sequencing will not only test for COVID-19, but also help in uncovering viral complexities and assist in therapeutic development.
Understanding genetic susceptibility will be critical in treating existing cases, but determining all vectors in viral transmission will be the most effective means in preventing them. There is concrete evidence of human-to-human transmission, hence the strict efforts in social distancing and #StayHome initiatives, but COVID-19 has shown to travel by other means. COVID-19’s gastrointestinal involvement suggests the possibility of fecal-oral transmission. In one study conducted in China, samples collected from toilet bowls, sinks, and door handles of patients’ bathrooms all returned with positive COVID-19 results while post-cleaning results yielded negative5, underscoring the importance of proper disinfection methods in public restrooms. It’s also been widely cited that the virus may be airborne for up to 3 hours and viable on surfaces such as plastic, steel, cardboard, and copper for days. The possibility of transmission via sewage, waste, contaminated water, and air conditioning should also not be underestimated.
A lack of imagination in what could be the worst-case scenario can be costly in lives and time spent recovering from the viral aftermath. If we assume the worst – that the virus is not only spread by human to human transmission, but also through a fecal-oral route, fomites and is airborne- we need appropriate mitigation strategies. To protect oneself and others, mask use is now strongly encouraged especially in high-contagion areas, and people must continue to use best hygiene practices for the foreseeable future. We need sanitation at all possible exposure points as a safeguard to eliminate viral particles lingering on surfaces. We need to consider moving severe patients from crowded hospitals that may become infectious incubators to bigger, insulated areas such as arenas with maximized ventilation. We shouldn’t anticipate sports events soon, so we need to take advantage of the space and give people room to expel the virus instead of coughing directly onto all of our healthcare workers. We need to think more critically about how the virus may be mutating and adapting, or in other words, how it’s figuring us out faster than we can get a hold of it.
We also need to understand the long term impacts not only on COVID-19 survivors, but also on those risking their lives to treat patients and deliver essential services. A study conducted on SARS-CoV survivors found that long term exercise capacity and health status was significantly lower than normal controls. Some patients returned to work in 3-24 months, while nearly 30% never resumed duty6. Another study noted PTSD and depressive disorder not only amongst SARS survivors, but also in healthcare workers7. The psychological assessment and intervention in patients, rescuers, medical staff, volunteers, essential workers, and the public will be of great importance in rapid social recovery8.
We still have a long way to go in the fight against COVID-19. Global cooperation in containment, transparency, and on-going education to sustain and reinforce population acceptance of the pandemic is vital. We must celebrate our successes but also reflect on our losses. Lives depend on it.
For more information, please visit coronavirus.gov or coronavirus.jhu.edu
Questions, corrections, and feedback are welcomed and appreciated.
1.) Sahin AR, Erdogan A, Mutlu Agaoglu P, Dineri Y, Cakirci AY, Senel ME, et al. 2019 Novel Coronavirus (COVID-19) Outbreak: A Review of the Current Literature. EJMO 2020;4(1):1-7.
2.) South, A., et al. COVID-19, ACE2, and the Cardiovascular Consequences. AM J Physiology Heart Circ.
3.) Lan, J,. et al. (March 19, 2020). Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor.
4.) Fan, Z., et al. (March 24, 2019). Hypertension and hypertensive left ventricular hypertrophy are associated with ACE2 genetic polymorphism. Life Sciences.
5.) Tian, Y., et al. Review article. Gastrointestinal features in COVID-19 and the possibility of faecal transmission. Wiley.
6.) Hui, D.S., et al. (May 2005). Impact of severe acute respiratory syndrome (SARS) on pulmonary function, functional capacity and quality of life in a cohort of survivors.
7.) Mak, I., et al. Long-term psychiatric morbidities among SARS survivors. General hospital psychiatry.
8.) Li, Z., et al. Vicarious traumatization in the general public, members, and non-members of medical teams aiding in COVID-19 control. Brain Behavior and Immunity.