Covid-19: Japan scientists discover a new defense mechanism for SARS-CoV-2

Scientists from Hokkaido University in Japan have discovered a novel defensive response to SARS-CoV-2 or Covid-19 that involves the viral pattern recognition receptor RIG-I. Upregulating expression of this protein could strengthen the immune response in COPD patients.

In the 18 months since the first report of COVID-19 and the spread of the pandemic, there has been a large amount of research into understanding it and developing menas to treat it. COVID-19 does not affect all infected individuals equally. Many individuals are asymptomatic; of those who are symptomatic, the large majority have mild symptoms, and only a small number have severe cases. The reasons for this are not fully understood and are an important area of ongoing research.

The team of scientists from Hokkaido University, led by Professor Akinori Takaoka of the Institute for Genetic Medicine, has shown that RIG-I, a biological molecule that detects RNA viruses, restrains SARS-CoV-2 replication in human lung cells. Their findings, which could help predict COVID-19 patient outcomes, were published in the journal Nature Immunology.

Covid pandemic

To date, over 162 million people have been affected by COVID-19. About 40% – 45% of these individuals are asymptomatic; as for the rest, around 35% – 40% experienced a mild form of the disease, while the remaining 19% were affected by symptoms that were severe enough to warrant hospitalisation or were fatal, which are usually associated with comorbidities and risk factors such as chronic obstructive pulmonary disease (COPD). This range of symptoms indicates that there are vast differences between individual responses to the virus.

 

SARS-CoV-2 replication is suppressed by RIG-I. When pulmonary cells that do not express RIG-I (left) are exposed to SARS-CoV-2, viral spike proteins (green) are detected as soon as 5 days (72 hours) after exposure. In normal cells (right), SARS-CoV-2 replication is suppressed / Taisho Yamada, et al. Nature Immunology. May 11, 2021

Microbial pathogens in our body are detected by proteins called pattern recognition receptors (PRRs), which also trigger immune responses to these pathogens. Viral infections are detected by a subset of PRRs; the scientists focused their attention on the protein RIG-I, which belongs to this subset. RIG-I is known to be critical for the detection and response to RNA viruses such as the influenza virus.

In experiments carried out in cell culture lines, the scientists found that there was little innate immune response to SARS-CoV-2 in pulmonary cells, suggesting the signaling pathway leading to immune response was aborted. Nevertheless, viral replication was suppressed. The scientists investigated the role of RIG-I and found that its deficiency caused increased viral replication. Further experiments confirmed that the suppression of viral replication was dependent on RIG-I.

A single previous study has shown that RIG-I expression is downregulated in pulmonary cells of COPD patients. Using primary pulmonary cells from two COPD patients, the scientists showed that this downregulation of RIG-I resulted in the detection of viral replication after 5 days .

 

Taisho Yamada (left), first author, and Akinori Takaoka (right), communicating author of the paper / Photo: Taisho Yamada, Akinori Takaoka

 

 

 

 

 

They also demonstrated that treatment of these COPD cells with all-trans retinoic acid (ATRA), which upregulates the expression of RIG-I, significantly reduced viral titres in the cells. Furthermore, using RIG-I mutants, they were able to elucidate the mechanisms by which RIG-I suppressed SARS-CoV-2 replication: The helicase domain, a structural element in RIG-I, interacts with the viral RNA, blocking a virus-derived enzyme responsible for replication.

This study has demonstrated a unique viral recognition mode of RIG-I, termed the RIG-I-mediated signaling-abortive anti-SARS-CoV-2 defense mechanism. It has also indicated that RIG-I expression levels are one of the potential parameters for the prediction of COVID-19 patient outcomes. Further work must be done to uncover factors or conditions that modulate RIG-I expression levels, and may lead to new strategies to control SARS-CoV-2 infection.

Krishnapatnam Medicine for Covid-19: AP expert panel finds no ill-effects; ICMR team rushed to study

 

As the town of Krishnapatnam hit headlines for a local medicine capable to cure Covid-19 instantly within minutes reviving critically ill patients. While AYUSH ministry’s Ayurvedic doctors are conducting study on the medicine in the town, the person who has been giving the medcine by name Anandaiah, has emerged as the savior for now.

With Vice President Venkaiah Naidu ordering the ICMR to conduct a study and submit a report, a team of experts has been rushed to study the medicine, its constituents and side effects. While the report may not be ready even in a week’s time, the precarious situation of Covid-19 has forced many relatives of critical patients to rush for any succour that can save them.

A person just a few minutes away from losing the battle against Covid-19 was rushed to the place and given the medicine in the form of eye drops and the person recovered within minutes. Since the long term effects remain questionable, the question before the administration is to make the process systematic, if not abandon entirely.

Not exactly Ayurveda but traditional medicine

B. Anandaiah, who has been giving the traditional medicine, which does not entirely fit into Ayurvedic medicinal traits, has been open about the contents, which are to be tested by the team of experts on Saturday. He says the medicine was a mixture of several locally available herbals that has been given by his family for centuries. The medicine, being given in the form of five medicines, is given based on the severity of Covid infection in a patient, said Anandaih in an interview to the TV9 channel on Friday.

Anandaiah, who is giving traditional medicine to save severely ill Covid-19 patients in Krishnapatnam, Nellore District, Andhra Pradesh.

Meanwhile, a team of Ayurvedic doctors from the Department of Ayush that visited the village on Wednesday has submitted a report to the government, saying the medicine preparation, treatment process and the side effects should be studied scientifically. Since nobody is complaining about any ill effects after taking the medicine, the team could not provide any negative report on the medicine for now, pending the ICMR study next.

Anandaiah has been preparing five different medicines using natural herbs, honey and spices, which he claims to have been giving for lung diseases for long. “One of the COVID-19 patients saw his oxygen level rise to 95 from 83 in an hour after getting two drops of the medicine administered in his eyes. We have spoken to the patients,” the Ayurvedic doctors said in their report in which the district medical and health officer and Nellore Revenue Divisional Officer were also part.

The only point the team made was that nobody was following the rules of Covid safety such as wearing mask or maintaining the social distance. Local YSR Congress MLA K Govardhan Reddy supporting the medicine distribution, AP Deputy Chief Minister (Health) A K K Srinivas said, “We have decided to get it studied by the ICMR and other experts to determine its efficacy.”

However, doctor-turned-bureaucrat P V Ramesh, termed the Krishnapatnam medicine as “yet another recipe for disaster” and called for the government “to stop such epidemics of superstition. Those preparing and promoting this Krishnapatnam concoction are punishable under the Pharmacy Act, 1948, and Drugs and Magic Remedies Act, 1954.”

The SPS Nellore district medical and health officer and Nellore Revenue Divisional Officer were also part of the official team. The team, however, said no COVID-19 rules were being followed in the village where the medicine was being given. On Friday, there was a virtual stampede at Krishnapatnam as over 10,000 people thronged there for the medicine, the supply of which was resumed after a break for a few days.

Doctors use old CPAP treatment to cure patients from Covid-19

 

The lives of patients hospitalised with COVID-19 are being saved by doctors who are using an existing medical treatment at an earlier stage. Dr Luigi Sedda of Lancaster University analysed the results from the team at Wrightington, Wigan and Leigh Teaching Hospitals NHS Trust (WWL). Their research has now been published in the prestigious medical journal BMJ Respiratory Open.

He said: “We show that Continuous Positive Airway Pressure (CPAP) in the first days of hospitalisation seems to save between 10% to 20% of patients. However it is important to underline that this was a pilot study with a small sample size, although comforting evidence is starting to emerge elsewhere.”

According to NHS England, 96% of people who died with Covid had at least one serious health condition and the majority are over the age of 80. The team led by Dr Abdul Ashish used the CPAP machines on patients with COVID-19 admitted to the Royal Albert Edward Infirmary in Wigan.

In the case of patients with severe acute respiratory syndrome, COVID-19 may cause the lungs to swell and collapse. Using CPAP treatment, which is often used at home to help people with sleep problems, helps to keep the lungs open and makes breathing easier.

The research conducted by the team showed how CPAP treatment can be delivered effectively in a ward setting, with low resources both across the country and worldwide where intensive care bed availability is limited. The research has so far helped almost a hundred patients at the Royal Albert Edward Infirmary.

Consultant Respiratory Physician Dr Ashish said: “When you use CPAP early in the admission it stops the patient getting worse, therefore avoiding invasive ventilation techniques. As CPAP is readily available and can be used in a ward setting, we have demonstrated that, when used early, it can be very effective way of treating severe COVID-19 pneumonia.

“We are one of the early adopters of ward based CPAP in the North West and have developed local protocols and pathways by modifying our existing CPAP machines to deliver good outcomes for our patients.”

The researchers also found that the early use of CPAP potentially reduces lung damage during the worst of the COVID-19 infection and allows the patient to recover from the inflammatory effects. However, when used later, CPCP does not prevent lung damage thus leading to additional inflammation and a reduction in survival chances.