Transmission and Disease

Welcome to the COVID-19 information page offered by the basic science departments at the University of Michigan. The COVID-19 pandemic has caused a huge disruption in our daily lives and presents a monumental, ongoing public health crisis affecting our community. We recognize that it is difficult to find credible information about COVID-19. Thus, we intend this site as a source of reliable information that is curated by members of our basic science departments with expertise in virology, immunology, epidemiology, genetics, pharmacology, cell biology, biochemistry, informatics, science communication, medicine, and public health. It features new content and links to additional resources that we hope you will find useful.

A virus is a sub-microscopic particle consisting of nucleic acid encased in some type of protective shell (the viral capsid) to form the viral genome Viruses with this structure are often called “naked” (panel a). Some viruses also pick up a lipid bilayer of plasma membrane when they replicate in mammalian cells. These viruses are called “enveloped” viruses (panel b). The genomes of viruses can be RNA or DNA and can be single or double-stranded and, in some cases, the virus can have several genome segments. Proteins on the surface of the viral capsid, or that extend through the viral envelope (e.g., spike proteins), are generally the proteins used for attachment to host cells.

SARS-CoV-2 is a coronavirus of the beta-coronavirus subfamily. It is an enveloped virus with an RNA genome. The spike glycoproteins (which are formed by a trimer of identical molecules) are embedded in the viral envelope and appear “crown-like” when viewed under a microscope and this is where the name comes from. The spike glycoprotein is the molecule the virus uses to bind to mammalian cells.

What is the receptor for SARS-CoV-2 in humans?

The virus is believed to be transmitted in large droplets (5-10 µM) in size that are large enough that they fall to the ground quickly. Thus, the virus is thought to be transmitted by coughing or sneezing when people are within 1 meter (~3 feet) of each other. This is the reason for the recommended 6 feet of distance between people under current social distancing guidelines. Transmission can also occur if you touch a contaminated object (known as a fomite) that has been contaminated by a virus-containing respiratory droplet. This is the reason for the recommended hand hygiene (washing hands often or using alcohol based sanitizer with >60% alcohol content). Airborne transmission (as occurs with the much more contagious measles virus) is the spread by small droplets (<5 µM) that stay suspended in air for long periods of time such that someone walking through a room where an infected person has been is more likely to breathe in a contaminated small droplet.  Under certain conditions that generate aerosols (e.g. ventilation in hospitalized patients), it is possible that SARS-CoV-2 could be transmitted by aerosolized small droplets. This is the reason for health care workers in high risk settings to use specialized N-95 masks that limit inhalation of small droplets. There is some evidence that SARS-CoV-2 can replicate in the GI tract and viral RNA can be found in feces, but live virus has only been cultured in a single specimen thus far. Under certain conditions that generate aerosols (e.g. ventilation in hospitalized patients), it is possible that SARS-CoV-2 could be transmitted by aerosolized small droplets. This is the reason for health care workers in high risk settings to use specialized N-95 masks which limit inhalation of small droplets.

It is clear that handwashing is a major deterrent to spreading disease.  Dr. Joel Howell recently gave a Grand Rounds lecture on the history of Ignaz Semmelweis and the discovery that this saved lives!  See link below.

KQED, a Bay Area PBS station has created a very short and informative video about how SARS-CoV-2 attacks the lungs.  See the 5 minute Deep Look episode here:

In this Nature Reviews Microbiology article,Thiel and colleagues discuss the key aspects of coronavirus biology and their implications regarding infection, treatment and prevention: https://www.nature.com/articles/s41579-020-00468-6

Dr. Oveta Fuller, Associate Professor of Microbiology and Immunology and ordained minister was interviewed on the webinar: Michigan Black Caucus of Local Elected Officials COVID-19 Discussion on April 14, 2020. Content includes a lay summary of virus origin, transmission, biology of coronavirus respiratory disease and why available preventions work. It also covers discussion of how this pandemic has hit the African American community especially hard and explores some of the reasons such as underlying co-morbidities, medical care access and overrepresentation in essential jobs that put this community at greater infection risk.

The clinical microbiology lab has to operate under CLIA certified rules and regulations…which dictate what type of machine can be used, what controls are used, training for the personnel and how often they are inspected, etc. The limit in testing for virus currently is the ability of the supply chain to meet demand of the viral transport media and the testing swabs for weeks to come…causing them to limit usage now. Pharmacy is now helping to make the viral transport media. The testing swabs are quite unique. Apparently they are truly an engineering marvel. They are plastic and flexible and THIN to allow to reach from the nasal cavity all the way back to the nasopharynx to get a good sample (see image below). They are flocked in such a way that they capture sample and then release it when it hits liquid so that they can extract the sample for PCR. Regular Q-tips with wooden shafts can break off while collecting sample in people’s noses. They also have cotton fibers that shed and inhibit the PCR reactions. Using an oropharyngeal swab is less sensitive, although easier to get. Regarding the serology tests, there are a lot of potential issues there as well, including sensitivity and specificity…especially when most of the population should be negative. Even if the test has a small error rate, when lots of people are getting tested, that could mean a lot of false positives or negatives.

A very accessible NPR article about the potential problems with antibody testing can be read or heard here.

Also, a UM article regarding considerations for antibody testing before returning to work at UM can be found here.

A lay summary regarding the possibility of saliva testing is found here.

While respiratory failure associated with COVID-19 has received most of the attention, this disease also disrupts the function of the nervous system at many levels. Initially, during the early phases of infection the immune response causes an increase in the level of cytokines that can mediate the headaches associated with the disease (Lancet 2020; 395: 497 and The Journal of Headache and Pain 2020; 21:38).  Rare reports of acute necrotizing encephalopathy and encephalitis associated with COVID-19 may also be mediated by the so-called “cytokine storm.” and Brain Beh Immun Patients with COVID-19 may also experience an increase in blood clots, which increases the risk for stroke caused by blood clots in the brain (The New England Journal of Medicine. 10.1056/NEJMc2009787). The longer-term effects of COVID-19 are uncertain, but the SARS-CoV-2 coronavirus is a member of the betacoronavirus genus which also includes the SARS-CoV-1 and MERS-CoV viruses.  A significant concern for the neuroscience community is that like SARS-CoV-1, the SARS-CoV-2 may spread either transsynaptically or by crossing the blood-brain barrier to infect neurons and glia of the central nervous system to produce long-lasting effects following infection of COVID-19 patients. Read more here. This will certainly be an area of active research for the future.

COVID-19 illness triggers a perfect storm of events that will leave survivors and their loved ones at high risk for symptoms of depression, anxiety, and post-traumatic stress disorder (JAMA Intern Med. Doi:10.1001/jamainternmed.2020.1562). These include the experience of social isolation during illness and quarantine, traumatic memories from the time in the hospital such as feeling unable to breathe or pain from medical procedures, and the long-lasting impact of inflammation and the hormonal stress response in the brain itself. At the Michigan Neuroscience Institute many of our faculty are working hard in and out of the laboratory to understand the impact of this disease on the brain and behavior.

A short opinion piece about how loss of smell and taste hint about effects of COVID-19 in the nervous system can be found here.