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.


COVID-19 patients with hypertension have more severe disease: a multicenter retrospective observational study

COVID-19 patients with hypertension have more severe disease: a multicenter retrospective observational study

Late last year, a number of unexplained pneumonia cases surfaced in Wuhan, China. Later scientists revealed that it is caused by a familiar group of pathogens, coronavirus. The WHO later named this virus, COVID-19. The virus is highly contagious, infecting millions in the last couple of months.

From previous studies, it is considered that angiotensin-converting enzyme (ACE2) is the receptor for the COVID-19 virus to enter the host cell. ACE2 is a widely expressed receptor in several organ systems of the human body, including cardiovascular and respiratory systems. The enzyme helps in catalyzing angiotensin II to angiotensin 1-7, which is the peptide counteracting proinflammation caused by Angiotensin II. 

Studies have proven that hypertension is a common condition that co-occurs in patients with COVID-19. A previously conducted study, involving 1099 COVID-19 patients reported that 23.4% of the population also suffered from hypertension. Due to the coexisting status of hypertension and COVID-19 and the involvement of ACE2 in hypertension, the authors of this study speculate that hypertension may directly be involved with the pathogenesis of COVID-19. 

To confirm if hypertension affects the progress and prognosis of COVID-19, the published study was conducted. The study involved 310 patients from the Central Hospital of Wuhan and Wuhan Jinyintan Hospital. All the participants according to the WHO were tested positive for COVID-19. The study was later divided according to high blood pressure (hypertensive and non-hypertensive group). To avoid unwanted complications, the hypertension group was further segregated to exclude patients with other complications other than hypertension. 

All the participants were monitored closely and the entire course of the disease was recorded. The median age of the participants in the study was 62 years and the prevalence rate of hypertension was 36.5%. The authors speculate that the high prevalence rate of hypertension in the study group could be due to the high median age. The study also revealed that COVID-19 patients with high blood pressure showed higher mortality. 

Evidence suggests that an imbalance of cytokines could be a possible correlation between COVID-19 and hypertension. An increase in cytokines like IL-6, IL-7, and tumor necrosis factor is associated with the development of hypertension. It should also be noted that the increased levels of cytokines, may potentially activate excessive inflammatory reactions, resulting in cell and lung damage. 

Overall the comparative study conducted using COVID-19 patients with and without hypertension showed that patients who were hypertensive were more likely to be severely affected with COVID-19 compared to the non-hypertensive group. It must be brought to light that there might be a small number of people with hypertension not recorded because the diagnosis of hypertension in this study was extracted from medical history data. 

Finally, the authors conclude that much larger groups need to be studied since the current result could be due to the higher aged participants. In the future, additional complications also need to be analyzed like ARDS, renal injury focusing on its risks associated with hypertension and COVID-19. 


Genetic variation in immune system may impact the severity of COVID-19

Genetic variation in immune system may impact the severity of COVID-19

Can your genes be the reason for increased susceptibility to COVID-19 infection? For years, scientists know that genes play a very important role in underlying biological mechanisms. And therefore, over these years many pieces of research have been carried to understand the link between genetic variability and diseases.  Recently, new research published in the Journal of Virology (Well-known publication of American Society for Microbiology) highlights that variation in the genes involved in the human immune system can impact the susceptibility and severity of COVID-19 infection.

Human Leukocytes Antigen Genes

You must have seen people of a certain group be more susceptible to disease than others, why? Well, the answer to this lies in your genes. Individual gene variation is known to be one of the major reasons behind the differences in the immune responses. Our immune system works with the help of multiple biomolecules. One such important component of the immune system that plays a very crucial role in determining the strength of the response is the human leukocyte antigen. The genes coding for this antigen is involved in detecting the pathogen upon invasion. The gene variation among different individuals can influence how well the immune system detects the pathogen in an individual. If a person has a weak response than a pathogen such as the Sar-CoV2 virus could easily invade making a person vulnerable to the infection.

Understanding the variation

As we all know that the number of COVID-19 cases is rising across the globe, researchers and scientist are working towards finding better solutions to curb the menace. In the present study, the author of the paper indicated the importance of understanding the variation of human leukocytes antigen (HLA), which forms a very important component of the immune system. Knowing the gene variants of HLA and their respective responses towards the condition can help identify people posing a higher risk towards the COVID-19 infection.

Antigen-Antibody complex

The researchers showed that the HLA, haplotype, and also the full genotype variation may impact the ability of an individual’s immune system to respond against Sars-CoV infection. Moreover, certain alleles can be responsible for more severe infections than others.

“This is the first study to report global distributions of HLA types and haplotypes with potential epidemiological ramifications in the setting of the current pandemic,” write the authors, from Oregon Health & Science University, Portland, and the Portland VA Research Foundation.

One of the important benefits of HLA based study is that HLA typing is quite fast and less expensive. If there is a pairing of HLA typing with that of COVID-19 tests than there can be a significant improvement in the identification of high-risk individuals. Moreover, once the vaccine against COVID-19 is available, high-risk HLA type individuals can be prioritized for the vaccination. This will help in creating herd immunity and help prevent the future spread of the disease.

COVID-19: What you need to be careful of?

COVID-19: What you need to be careful of?

More than 780000 cases of COVID-19 have been reported across the globe. The new coronavirus outbreak has the attention of the entire world as there are no effective medicines or vaccines yet. The virus originated in the Wuhan city of China and spread to numerous countries in almost no time. This does raise multiple questions like what exactly the virus is. Why its transmission rate is so high? And how an individual can avoid catching it? Well, amid this outbreak we will help you know about the virus in detail. Read ahead to gain a brief insight into the challenges the whole world is suffering from and how we all can overcome it.

Understanding the Coronavirus

Coronaviruses are a group of viruses whose exterior layers reflect a crown-like structure. Corona is a Latin word which means crown. There are various types of viruses in this group but most of them cause very slight illness and cold-like symptoms. The pathogenicity of novel Coronavirus has led researchers and scientists across the world to study more about it as there is very little information in the scientific community. Wuhan city of China is considered to be the epicenter of the disease initially from where it spread to numerous countries in no time. The origin of the virus is still not known but some studies suggest that it has been transmitted to humans from the animals.

Symptoms of COVID-19

The symptoms of the COVID-19 are often confusing as they are somewhat similar to the symptoms of common flu. However, the characteristics difference between them is the presence of high fever, sore throat, dry cough, difficulty in breathing and pneumonia in severe conditions. The incubation time for the development of symptoms is considered to be 14 days due to which people suspected of COVID-19 are suggested to quarantine themselves for this period.

Since very little information is available about the virus, researchers and doctors across the globe are contributing crucial information from the recent cases. It is observed that the virus mainly infects people with low immunity. This is the reason that countries with coronavirus outbreak have high infection and death rate among the elderly population. However, it doesn’t stipulate that young people and children are not prone to it. Having weak immunity irrespective of age can make you prone to infections. Therefore, doctors are prescribing for regular exercise and healthy food as a primary effort to protect yourself from the infection.

The major concern over here with the condition is that at the beginning people might not be able to assess the situation (as the grave) due to the mild symptoms associated. In some cases, people confuse the symptoms with that of normal flu and avoid going to the doctor until it becomes severe. During this period, the patient must have come in contact with say ‘n’ number of people which will further infect other ‘n+y’ number of people. This chain continues as the severe symptoms take 14 days to be physically visible. A point comes where there is a sudden outburst of diseases leading to chaos and panic which is often observed in present cases of countries like China, Italy, Iran, the USA, etc.

Precautions to avoid infections

The transmission of coronavirus from an infected person into the atmosphere takes place through the tiny droplets of a sneeze. These droplets though don’t stay suspended in the air for long, it descends and settles onto the surfaces. It is therefore very crucial for every individual to maintain at least 1m of distance from the infected person. Also, one must avoid touching such infected surfaces and later touching their eyes, nose or face. It is therefore very important to wash your hands thoroughly at regular intervals.
To prevent the transmission of the coronavirus, the doctors also suggest avoiding any kind of physical contact with other people such as avoiding handshakes. In case if you are infected with the disease or even with the normal flu, you must sneeze in your elbows rather than in your palms. You can also use handkerchief or tissue to cover your mouth during the sneeze as these practices reduce the chances of the spread of infectious droplets in the atmosphere.

Way ahead

COVID-19 is a disease that may look normal to you due to its mild symptoms at the initial stage. However, the experience in other countries shows that its completely the opposite and one must take effective care as soon as there are visible symptoms. One of the best ways to prevent the spread is to self isolate yourself and undertake prescribed medications. Researchers and scientists across the globe are working hard to come up with potential vaccines and medicine for the disease. But till then we need to consider the basic precautionary steps to avoid escalation of the situation. So, stay safe and spread awareness among your family to help the world fight this disease together. Let’s not forget we all are together in it and we will come out of it together.

The first line of treatment for COVID-19

The first line of treatment for COVID-19

As the number of cases of COVID-19 is increasing worldwide, researches has been carried out rigorously across the globe to curb this inflection to some extent and providing the first line of treatment with existing drugs. A coalition of European researchers has published in the International Journal of Infection that existing approved drugs can help in combating new viruses and help the patients to survive through viral infections.

According to WHO, the coronavirus has symptoms like fever, runny nose, sore throat and cough in the beginning.  In severe cases, for some people, it can lead to pneumonia or breathing problems. It can be even fatal if initial precautions are ignored. More vulnerable are people with medical conditions like diabetes and heart diseases.

Can drug repurposing help?

Drug repurposing  (Drug repositioning, re-profiling, etc.) is the use of an approved drug for the treatment of another disease by generating additional value. Drug repurposing can be a good option until some treatment or vaccine for COVID -19 is discovered.  Many such potential drugs are under testing to see their effect on overcoming the menace of coronavirus. Some of the approved drugs include Teicoplanin, Oritavancin, Dalbavancin, and Monensin, which has shown efficient response in curbing the infectious coronavirus symptoms in the laboratory.

Is drug repurposing a good option?

As the task of drug repurposing is to take out additional value from already approved drugs, the drug development details, chemical synthesis process, manufacturing process and information regarding different phases of clinical testing are already known. Moreover, they have translational opportunities such as the high probability of success to market compared with developing new drugs or vaccines and significantly reduced cost and timeline to clinical availability.

Development of BSSAs (Broad Spectrum Antiviral Agents) 

Broad-Spectrum Antiviral Agents are the drugs that target viruses from two or more different viral families. Nearly 120 drugs are found to be safe for human use and a database is created which is freely accessible. Thirty-one of these are a possible candidate for prophylaxis and treatment of the COVID-19 infection. Five possible drug candidate is under clinical investigation to treat the virus that causes COVID-19.

Way ahead

BSAAs will have a global impact in the future by decreasing morbidity and mortality from viral and other diseases, maximizing life expectancy, improving quality of life and decreasing costs of patient care.  As no concrete treatment is there in place to cure COVID-19, the mentioned discoveries and researches portray hope as a potential step towards overcoming achieving victory against COVID-19.