Learning how SARS-CoV2 hijacks and damages lung cells

Learning how SARS-CoV2 hijacks and damages lung cells

The emergence of the SARS-CoV2 virus has caused turmoil across the globe, forcing the researchers to study it in more detail. However, the behavior of the virus has been quite notorious. The frequent mutations and very less prior knowledge has caused some obstacles. However, scientists were acquainted that if they understand the underlying pathways in lung cells and host protein being impacted during the viral infection then there can be chances of identifying potential solutions. Considering this, scientists have recently found out how SARS-CoV2 hijacks and damages the lung cells.

The study was a multi-group collaboration between the Center for Network Systems Biology (CNSB), Center for Regenerative Medicine (CReM), and National Emerging Infectious Disease Laboratory (NEIDL). The researchers have mapped the molecular responses emerging from lung cells infected with the SAR-CoV2 virus. The finding of the study has been published in the Journal of Molecular Cell.

To understand the disease pathology and gain new insights to discover potential therapeutic targets, the researchers bioengineered the human alveolar cells. The cells when combined with high-end mass spectroscopy technology, it helped the researchers to identify potential host proteins and pathways changing during SARS-CoV2 infection. The researchers found out that lung cells infected with SAR-CoV2 have abnormal phosphorylation.

Phosphorylation is a very crucial protein modification process contributing to protein functionality in the cells. The proper phosphorylation process is important for healthy cells. However, it was noticed that the infection alters this process leading to cascading abnormal changes. These changes increase the chances of the virus to thrive within the cells and eventually destroy it.

The study also showed that as soon as the virus encounters the lung cells, it initiates exploiting the resources required for the normal functioning and growth of the cell. The invasion of the virus further disrupts the functioning of the cell and damaging it extensively. The resources used, powers the virus eventually leading to rapid proliferation and expansion in nearby regions. As a result, the exhausted and damaged cells undergo self-destruction and the virus starts infecting the cells in the vicinity while evading the body’s immune system. This cycle repeats continuously leading to the hijacking of lung cells and widespread damage.

The researchers examined lung alveolar cells from one to 24 hours after infection with SARS-CoV-2 to understand what changes occur in lung cells immediately (at one, three, and six hours after infection by SARS-CoV-2) and what changes occur later (at 24 hours after infection). These changes were then compared to uninfected cells. All proteins from infected and uninfected alveolar cells, corresponding to the different time-points were extracted and labeled with unique barcoding tags called “tandem mass tag.” These tags, which can be accurately detected only by a mass spectrometer, permit robust quantification of protein and phosphorylation abundance in cells.

“Our results showed that in comparison to normal/uninfected lung cells, SARS-CoV-2 infected lung cells showed dramatic changes in the abundance of thousands of proteins and phosphorylation events,” said Darrell Kotton, MD, BUSM, CReM.

“Moreover, our data also showed that the SARS-CoV-2 virus induces a significant number of these changes as early as one-hour post-infection and lays the foundation for a complete hijack of the host lung cells,” adds Elke Mehlberger, PhD, NEIDL.

Scientists also tried to examine the data obtained from the study to identify any potential opportunities for COVID-19 treatment. They found that about more than 18 existing drugs that have been already clinically approved can be re-purposed for the treatment. The research team believes that the current findings are very crucial and can contribute a lot to the field, specifically in terms of devising a cost-effective, robust and life-saving treatment to overcome COVID-19.


FDA approves the first saliva test for COVID-19 testing

FDA approves the first saliva test for COVID-19 testing

With a rising death toll across the globe, researchers are looking for ways to develop highly effective detection tests for early diagnosis of COVID-19. Though there are tests based on the nasal swabs, other alternative methods like saliva-based tests can prove to be highly robust. In light of this, scientists have created an easy test that uses saliva instead of the nasal swabs as a sample.

The US Food and Drug Administration approved the first saliva test for COVID-19 testing for emergency early this month, which can be used as an alternative to existing tests.

“Considering the high transmission rates of coronavirus and rising cases, it is very crucial to have all types of testing options to carry out as much testing as possible in any form. The only way one can prevent the spread of coronavirus virus is by mass testing and self- isolation”, said by one of the researchers working on infectious disease and pandemic preparedness at the Johns Hopkins University.

Why lookout for alternatives?

Presently, COVID-19 testing involves the use of nasal swabs based tests where health professionals need to insert a swab into each nostril, reaching out at the back of the nasal cavity where the nasopharynx is located. The swab is gently scraped over the tissues to collect the sample and later sent for the analysis. Though the present method is robust, it proved to be very cumbersome to an extent. The nasal swab based testing requires highly professional health practitioners to perform the sample collection. In the present time where we are facing the shortage of healthcare professionals, the nasal swabs based tests increase the burden further. Moreover, extra precautions are needed to carry out this test, which includes wearing fresh gloves, personal protective equipment, and face shield that are in short supply.

On the other side, the collection of saliva samples is quite easy and can be performed by any individual without the requirement of expertise.  Saliva tests have been used in the market for the various genetic tests and are quite common to people. The process involves thoroughly cleaning the hands and spitting the saliva sample into the collection tube up to the mark indicated. The entire process is very easy and doesn’t require a large number of safety requirements such as PPE. However, as per the recent guidelines shared by Food and Drug Administration (FDA), saliva-based testing will still be carried out in the healthcare setting under the guidance and supervision of expert & qualified healthcare professionals.

Saliva testing – a robust alternative

“Saliva testing will help with the global shortage of swabs for sampling and increase testing of patients, and it will not require health care professionals to be put at risk to collect samples,” Andrew Brooks, the chief operating officer of RUCDR Infinite Biologics, a biorepository backed by Rutgers University that developed the spit test, explains in a statement.

The saliva-based testing uses TaqPath Sars-CoV2 Assay which is used in existing coronavirus tests for identifying the viral RNA. Scientists shared that apart from identifying the potential carriers of the COVID-19 virus, the present saliva-based testing can help in re-testing the people who have shown recovery to help them end the self-isolation.

Way ahead

To assess the robustness of the saliva-based test for COVID-19 detection, researchers collected 60 samples from COVID-29 patients using the saliva swab tests. The results for Sars-CoV2 RNA in these saliva samples showed the same results as conventional nasal swab based tests taken from the same infected patients. This highlights the robustness and effectiveness of saliva as high as a nasal based test without any false-negative results.