Coronavirus can infect, replicate in salivary gland cells

Brazilian researchers have found that tissues which specialise in saliva production and secretion can serve as reservoirs for SARS-CoV-2, the virus causing COVID-19, magnifying its infectious potential.
Researchers at the University of Sao Paulo (USP) analysed samples from three types of salivary gland obtained during a minimally invasive autopsy procedure performed on 24 patients who died from complications of COVID-19 and discovered that SARS-CoV-2 infects and replicates in the salivary glands.

The discovery, reported in an article published in the Journal of Pathology, helps explain why the virus is so abundant in saliva and has enabled scientists to develop saliva-based diagnostic tests for COVID-19.

 

 “This is the first report of a respiratory virus’s capacity to infect and replicate in salivary glands. Until now it was thought that only viruses that cause highly prevalent diseases such as herpes used salivary glands as reservoirs. The discovery may help explain why SARS-CoV-2 is so infectious,” Bruno Fernandes Matuck, doctoral candidate at USP’s Dental School.

For the study, the team extracted tissue samples from the parotid, submandibular and minor salivary glands from 24 patients who died from Covid-19 and molecular analysis detected the presence of the virus in more than two-thirds.

Further examination by an electron microscope detected not just the presence of the virus but also its replication in cells and the type of organelle it uses to replicate.

 

“We observed several viruses clustering in salivary gland cells, which showed that they were replicating there. They weren’t in these cells passively,” Matuck said.

Morepen Labs starts producing Sputnik V

Pharma major Morepen Laboratories has started the production of the test batch of the Russian vaccine Sputnik V in Himachal Pradesh, the company has said.

The first batch of the vaccine will be shipped to Russia’s Gamaleya Centre for quality control. Sputnik V, which was granted emergency use authorisation in India in April, was the third to be launched in the country for its nationwide COVID-19 vaccination programme, after the Covaxin and Covishield.
 

Russian Direct Investment Fund (RDIF) and Morepen had signed a cooperation agreement in June 2021 for transferring the technology. “Agreement with Morepen Laboratories provides for a larger amount of Sputnik V to be available both for India and our partners globally to speed up the vaccination,” said Kirill Dmitriev, CEO of the RDIF, in a statement on Tuesday.

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Does COVID-19 infect peripheral blood cells?

The emergence of the novel coronavirus outbreak in December 2019 was followed by its spread on a global scale unparalleled in the last 100 years. At present, it has claimed over 322,000 lives the world over, with over 4.88 million cases having tested positive.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequence was first uploaded in early 2020, but as of now, over 17,000 genomes have been sequenced from viral strains isolated all over the world. This allows for rapid RNA screening in human tissues as well as environmental samples.

Detection of Virus in Human Blood or Blood Cells

The current study by researchers in Cairo, Egypt, and published on the preprint server medRxiv* was designed to test for the presence of the virus in human blood or any blood cells, which could allow the virus to hide from the immune system or to be trafficked to other organs. It is especially relevant given some (doubtful) reports that the virus could infect lymphocytes.

Other scientists have claimed that the virus perhaps attacks hemoglobin, or that it is to be found in the blood of infected patients, or the peripheral blood mononuclear cells (PMBCs), as is the case with other infectious viruses like hepatitis B, hepatitis C or HIV.

The current study, therefore, used computational analysis on three genome sequences from PBMCs from active COVID-19 patients, three from healthy donor PBMCs, and two from bronchoalveolar lavage fluid (BAL) from patients. They found that traces and large amounts of SARS-CoV-2 RNA were found in the PMBCs and BAL, respectively.

Viral RNA in Blood Cells

The results showed that the BAL and PBMC samples were widely separated, as expected, while the PBMCs from healthy and patient samples were slightly separated for the most part. Viral RNA was present in all the BALF sequences at 2.15% of the total reads (median). The PBMC of one patient also showed two reads that matched the SAR-CoV-2 protein and surface glycoprotein.

Earlier studies showed that with the use of RT-PCR, CoV-RNA was found in plasma samples from COVID-19 patients, but they did not confirm the presence of infectious viral particles in the blood. For this reason, they called their finding ‘RNAemia’ rather than viremia.

The current report is, however, the first to show the presence of viral RNA in PBMC. In fact, a prior study that examined RNA isolated from PBMC made it clear that no viral sequences were found.
The researchers used high-throughput sequencing, which has been demonstrated to be effective in identifying and measuring the number of viral particles in the blood. For this reason, they used this method to do a comprehensive search for viral RNA sequences within the only public dataset now available. They found that viral RNA was present within all BAL samples, at a concentration of 2.15% of the total RNA. Two RNA reads corresponded to the SARS-CoV-2 genome. However, as expected, the PBMC from the controls did not contain any RNA.

Implications

Though the amount of viral RNA is small, it is undoubtedly that of the SARS-CoV-2. One of the reads encodes a polyprotein, which takes part in viral transcription and replication, and which is the largest of the coronavirus proteins. Another encoded the spike protein, which is responsible for the viral entry into human cells that carry the ACE2 molecule receptor.

The possibility is always alive that the viral RNA reads are the result of cross-contamination or one barcode bleeding into another. However, this is a rare chance because none of the control samples showed similar correspondence. Again, they could be the result of virus sampling by antigen-presenting cells, especially dendritic cells, or virus presentation to T cells, which form part of the PBMC population.

There is a third possibility, which can be analyzed only with a much larger number of samples. This is that the virus may have been engulfed either on purpose or by accident by one of the PBMCs. This occurrence could be one mechanism for chronic SARS-CoV-2 infection, but the theory must be tested rigorously.

One hypothesis that is not supported by the current experiment is T cell targeting by the virus in vivo, which arose from an earlier cell culture experiment using pseudotyped viruses.

The current experiment will help to take the present understanding of the progress and replication of the SARS-CoV-2 infection in humans.

 

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Researchers find antibody that blocks infection by covid in cell

Researchers have identified a fully human monoclonal antibody that prevents the SARS-CoV-2 (COVID-19) virus from infecting cultured cells.

The discovery, detailed in the journal Nature Communications, is an initial step towards developing a fully human antibody to treat or prevent the respiratory disease COVID-19 caused by the novel coronavirus SARS-CoV-2.

The COVID-19 pandemic has spread rapidly across the globe infecting more than 3.3 million people worldwide and killing more than 235,000 people so far.

This research from Utrecht University, Erasmus Medical Center and Harbour BioMed (HBM) builds on the work they have done in the past on antibodies targeting the SARS-CoV that emerged in 2002/2003.

“Using this collection of SARS-CoV antibodies, we identified an antibody that also neutralizes infection of SARS-CoV-2 in cultured cells,” said study co-lead author Berend-Jan Bosch, Associate Professor at Utrecht University in the Netherlands.

“Such a neutralising antibody has the potential to alter the course of infection in the infected host, support virus clearance or protect an uninfected individual that is exposed to the virus,” Bosch added.

The researchers noted that the antibody binds to a domain that is conserved in both SARS-CoV and SARS-CoV-2, explaining its ability to neutralize both viruses.

This cross-neutralising feature of the antibody is very interesting and suggests it may have potential in mitigation of diseases caused by future-emerging related coronaviruses, Bosch said.

This discovery provides a strong foundation for additional research to characterise this antibody and begins development as a potential COVID-19 treatment.

“The antibody used in this work is ‘fully human,’ allowing development to proceed more rapidly and reducing the potential for immune-related side effects,” said study co-author Frank Grosveld.

Conventional therapeutic antibodies are first developed in other species and then must undergo additional work to ‘humanize’ them, according to the researchers.

The antibody was generated using Harbour BioMed’s H2L2 transgenic mouse technology.

“This is groundbreaking research. Much more work is needed to assess whether this antibody can protect or reduce the severity of disease in humans,” said Dr Jingsong Wang, Founder, Chairman and Chief Executive Officer, Harbour BioMed.

“We expect to advance the development of the antibody with partners. We believe our technology can contribute to addressing this most urgent public health need and we are pursuing several other research avenues,” Wang noted.

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How the Novel Coronavirus Can (Maybe) Infect You

Scientists are still trying to determine how the coronavirus that’s triggered a global health emergency spreads. Pinpointing where, when and how the pneumonia-causing virus transmits is key to formulating the most effective ways to protect people and stop the epidemic. In the absence of detailed, rigorously gathered and validated data, the current understanding about how the virus that causes Covid-19 spreads is largely based on what is known about similar coronaviruses. Doctors in China have investigated, and seemingly discarded, the possibility it could be passed in utero after the infection appeared in babies born to mothers with the disease.

Here are the main hypotheses about how it does spread:

Respiratory Droplets

It’s widely assumed that the virus spreads in respiratory droplets -- spatters of liquid that are sometimes visible to the naked eye -- forcefully expelled from an infected person’s cough or sneeze. These are usually heavy enough to fall immediately to the ground or surrounding surfaces. Infection could occur if the droplets reach the mouth, nose or possibly the eye of someone nearby, perhaps from an unwashed hand that’s touched a contaminated surface. The World Health Organization recommends avoiding close contact with anyone who has a fever and a cough or other respiratory symptoms. That means keeping at least 1 meter (3 feet) from a sick person and avoiding shaking hands, hugging and kissing people with the symptoms.

The possibility of transmission through the eyes hasn’t been thoroughly investigated, but Guangfa Wang, a member of China’s national expert panel on pneumonia, has said he thought he’d contracted the disease that way during an inspection of patients in which he wore a face mask. A group of ophthalmologists has supported his hypothesis in a letter to the Lancet. The tissue known as the conjunctiva that lines the inside of the eyelids and covers the whites of the eye has been shown to be the gateway for other infections. The eye doctors writing to the Lancet called for their colleagues examining suspected cases to wear protective eyewear.

Tiny Aerosol Particles

When people sneeze, cough or even breath, they also emit particles so small that instead of falling right to the ground, these aerosols can float for a time through the air. When a virus is carried by such particulates, its odds of infecting people are higher because of the potential for them to be inhaled. More studies are needed to determine if this is the case with the Covid-19 virus. If it is, it might mean health-care workers interacting with infected people require extra precautions, similar to those taken when treating other infectious diseases that travel in this way, such as tuberculosis, according to Benjamin Cowling, a professor of public health at the University of Hong Kong. For the hordes of regular people rushing out to buy masks, however, Cowling says it’s less clear how helpful they would be even if this is the primary mode through which the novel coronavirus spreads. The confusion has prompted shortages of protective gear from face masks to surgical gloves to hand sanitizer, and even toilet paper around the world.

Fecal-to-Oral

Another possible route of transmission is infected people improperly washing their hands after using the toilet, and then touching surfaces or preparing food that comes in contact with healthy people. Recent research suggests this fecal-oral route may be an important and under-recognized pathway for the novel coronavirus.

It may also explain how the virus has spread among hundreds of passengers and crew aboard cruise ships. If that’s the case, regular hand-washing and sanitizing bathrooms, food-preparation and serving areas could be more effective in slowing the virus than outfitting people with face masks, according to John Nicholls, a professor of pathology at Hong Kong University, who was part of the research team that isolated and characterized the virus responsible for the 2002-2003 epidemic of severe acute respiratory syndrome, or SARS. “Masks will be of benefit in this condition only because they stop you from putting contaminated fingers in your mouth,” he said.

Fomites

Water, food, and so-called fomites -- inanimate objects or materials, such as clothing or utensils -- may be a source of infection, especially if they have been contaminated by an infected person’s respiratory secretions or feces. In recognition of that risk, Chinese health officials recommend measures to strengthen sanitation and hygiene in epidemic areas. These include drinking boiled water, avoiding eating raw food, washing hands frequently, disinfecting toilets, and preventing water and food from being contaminated by patients.

This is only for your information, kindly take the advice of your doctor for medicines, exercises and so on.     

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