The truth is that much of what we were told in the early days of the COVID-19 pandemic was not entirely accurate. Many of the messages in the United States and other countries implied that the disease was “mild” for anyone who was not elderly or did not have a pre-existing respiratory condition. We were told the main symptoms were fever, coughing and difficulty breathing. It would be like a bad cold.
None of that is false. Data still shows that elderly individuals and those with pre-existing conditions are the most likely to experience severe disease. However, over the past few months we have seen how the SARS-CoV-2 virus can present serious complications in almost every organ system, and how its effects aren’t limited to the most vulnerable populations. We have also seen a growing number of cases where individuals are still experiencing life-altering symptoms for months after their supposed recovery.
To gain a full understanding of SARS-CoV-2 and COVID-19, we have to explore every system in the body and track down the causes of all the unexpected clinical presentations of the disease.
Multiple battles are being fought in the war against the SARS-CoV-2 coronavirus that causes COVID-19. Currently, there are nearly 3,000 clinical trials listed in the World Health Organization (WHO) database, either underway or in the recruiting stage, for vaccines and antiviral drugs. Two recent announcements of data from phase 3 vaccine trials, by Pfizer/BioNTech and Moderna, have offered some hope for global efforts to fight the pandemic. At the time of writing, Pfizer and BioNTech had submitted an application for emergency use authorization (EUA) to the Food and Drug Administration (FDA), and Moderna had planned to do so shortly.
Both vaccines are mRNA-based, as opposed to most conventional vaccines against established diseases that are protein-based. Typically, the key ingredient in viral vaccines is either part of an inactivated virus, or one or more expressed proteins (antigens) that are a part of the virus. These protein antigens are responsible for eliciting an immune response that will fight future infection by the actual virus. Another approach is to use a replication-deficient viral vector (such as adenovirus) to deliver the gene encoding the antigen into human cells. This method was used for the coronavirus vaccine developed by Oxford University in collaboration with AstraZeneca; phase 3 interim data were announced on the heels of the Pfizer/BioNTech and Moderna announcements. All three vaccines target the SARS-CoV-2 spike protein, because it is the key that unlocks a path of entry into the host cell.
Since the COVID-19 pandemic swept the world in early 2020, many scientists in the viral research community have shifted their focus to study the SARS-CoV-2 coronavirus. Dr. Colleen Jonsson is one of them. She’s the Director of the Regional Biocontainment Laboratory, and Director of the Institute for the Study of Host-Pathogen Systems at the University of Tennessee Health Science Center (UTHSC) in Memphis.
Dr. Jonsson has been studying highly pathogenic human viruses for more than three decades. She has led several cross-institutional projects using high-throughput screens to discover small molecule antiviral compounds that could be used as therapeutics. And now, she’s using that experience to find an antiviral therapeutic against SARS-CoV-2.
The spike protein of the SARS-CoV-2 virus is a very commonly researched target in COVID-19 vaccine and therapeutic studies because it is an integral part of host cell entry through interactions between the S1 subunit of the spike protein with the ACE2 protein on the target cell surface. Viral proteins important in host cell entry are typically highly glycosylated. Looking at the sequence of the SARS-CoV-2 virus, researchers predict that the spike protein is highly glycosylated. In a recent study, researchers conducted a glycosylation analysis of SARS-CoV-2 proteins using mass spec analysis to determine the N-glycosylation profile of the subunits that make up the spike protein.
Glycans assist in protein folding and help the virus avoid immune recognition by the host. Glycosylation can also have an impact on the antigenicity of the virus, as well as potential effects on vaccine safety and efficacy. Mass spectrometry is widely used for viral characterization studies of influenza viruses. Specifically, mass spec has been used to study influenza protein glycosylation, antigen quantification, and determination of vaccine potency.
14-year-old Anika Chebrolu spent the early months of the COVID-19 pandemic identifying a potential anti-SARS-CoV-2 drug candidate. Originally, she was screening potential anti-influenza treatments, but as she watched COVID-19 case numbers rising around the world, she pivoted to focus instead on the SARS-CoV-2 virus. Several months later, Anika not only discovered a strong candidate for further testing, but she earned the title of 2020 Top Young Scientist in a competition sponsored by 3M.
This post is written by guest blogger, Melanie Dart, PhD, Sr. Research Scientist at Promega.
Along with lockdowns and sheltering in place efforts, the COVID-19 pandemic brought a unique challenge to our doorstep this spring: developing a clinical serological test for COVID-19 to detect the presence of antibodies against the SARS-CoV-2 virus. The project was one of the fastest, most dynamic development efforts ever undertaken at Promega. In general, in vitro diagnostic (IVD) tests take at least one to two years to develop. Nothing about 2020, however, has been typical.
It was important to move quickly. We set an aggressive timeline, and to meet it we needed not only dedication of our internal team, but also contributions from the local community.
It is almost November, and in the Northern hemisphere the cold and flu season is about to start. Most years that means people schedule flu shots, dust off chicken soup recipes and stock up on tissues. If they start to feel sick, they stay home for a day or two, drink hot tea, eat warm soup and—for the most part— go on with their lives.
This is not, however, most years. This year the world is battling a pandemic virus, SARS-CoV-2. Symptoms of COVID-19, the disease caused by this virus, mirror those of the flu and common cold, and that overlap in symptoms is going to make life more complicated. Most years, a mild cough or minor body aches wouldn’t even warrant a call to the doctor. This year these, and other undiagnosed cold- and flu-like symptoms, won’t be easily ignored. They could mean kids have to stay home from school, and adults have to self-quarantine from work, for up to 2 weeks. In years past people might have been comfortable treating their symptoms at home, this year people will want answers: Is it the flu? Or is it COVID-19?
Antibody tests are often used to determine whether individuals have been exposed to certain bacteria or viruses. For most existing antibody tests, the process goes something like this: A vial of blood is drawn from the individual, the vial is sent to a lab, then a trained technicians performs the antibody test and sends back the results. The current process is less than ideal for a few reasons. For one, blood draws are invasive and can be painful. Also, getting results could take days due to the time required to deliver and process the sample. Lastly, costs can be high, since the need for trained professionals and specialized instruments in laboratory settings adds to the cost of each test.
What if all you needed to do for an antibody test was apply a single drop of blood onto a thin piece of film, and you would get results on the spot within five minutes? Scientists have recently developed an antibody test based on bioluminescent technology that could make this a reality. They describe their findings in a recent study published in ACS Sensors.
When the COVID-19 pandemic descended on New York in March 2020, Christopher Mason, PhD, knew he was in a unique position to contribute. The Mason Lab specializes in sequencing and computational methods in functional genomics – valuable expertise for addressing an emerging infectious disease. Within days, Chris and his team were helping to analyze patient data, as well as developing new tests and detection methods for the SARS-CoV-2 virus.
The Mason Lab developed protocols for a simple COVID-19 detection test that requires less time and equipment than common PCR methods. Their subsequent preprint detailing these methods quickly gained widespread attention, and Chris found himself fielding an endless stream of questions and requests.
During the frenzy, Chris received a call from his older brother. Cory Mason is the mayor of Racine, Wisconsin, the brothers’ hometown.
“He said he saw me tweeting about our new test,” Chris says. “Then he asked me, ‘What if we set it up here in Wisconsin?’’
There is still a lot we don’t know about COVID-19 and the virus, SARS-CoV-2, that caused the pandemic and changed the way we live. But there are two things we do know about the disease: 1) Patients with diabetes and high blood glucose levels are more likely to develop severe COVID-19 symptoms with higher mortality. 2) Patients that experience an uncontrolled inflammatory response, called the cytokine storm, also develop more severe COVID-19 symptoms. The fact that both high glucose levels and an exaggerated immune response drive severe disease suggests that the two may be linked. But how? The answer may lie in the metabolism of immune cells in the lungs of COVID-19 patients, according to a recent study published in Cell Metabolism.