Study: COVID-19 Virus Is Evolving to Get Better at Becoming Airborne

Results of a new study led by the University of Maryland School of Public Health show that people infected with the virus that causes COVID-19 exhale infectious virus in their breath – and those infected with the Alpha variant (the dominant strain circulating at the time this study was conducted) put 43 to 100 times more virus into the air than people infected with the original strains of the virus. The researchers also found that loose-fitting cloth and surgical masks reduced the amount of virus that gets into the air around infected people by about half. The study was published in Clinical Infectious Diseases.

“Our latest study provides further evidence of the importance of airborne transmission,” said Dr. Don Milton, professor of environmental health at the University of Maryland School of Public Health (UMD SPH). “We know that the Delta variant circulating now is even more contagious than the Alpha variant. Our research indicates that the variants just keep getting better at travelling through the air, so we must provide better ventilation and wear tight-fitting masks, in addition to vaccination, to help stop spread of the virus.”

The amount of virus in the air coming from Alpha variant infections was much more—18-times more—than could be explained by the increased amounts of virus in nasal swabs and saliva. One of the lead authors, doctoral student Jianyu Lai explained that, “We already knew that virus in saliva and nasal swabs was increased in Alpha variant infections. Virus from the nose and mouth might be transmitted by sprays of large droplets up close to an infected person. But, our study shows that the virus in exhaled aerosols is increasing even more.” These major increases in airborne virus from Alpha infections occurred before the Delta variant arrived and indicate that the virus is evolving to be better at travelling through the air.

To test whether face masks work in blocking the virus from being transmitted among people, this study measured how much SARS-CoV-2 is breathed into the air and tested how much less virus people sick with COVID-19 exhaled into the air after putting on a cloth or surgical mask. Face coverings significantly reduced virus-laden particles in the air around the person with COVID-19, cutting the amount by about 50%. Unfortunately, the loose-fitting cloth and surgical masks didn’t stop infectious virus from getting into the air.

Dr. Jennifer German, a co-author said, “The take-home messages from this paper are that the coronavirus can be in your exhaled breath, is getting better at being in your exhaled breath, and using a mask reduces the chance of you breathing it on others.” This means that a layered approach to control measures (including improved ventilation, increased filtration, UV air sanitation, and tight-fitting masks, in addition to vaccination) is critical to protect people in public-facing jobs and indoor spaces.

Source: University of Maryland School of Medicine

Graphene Can be Used to Detect COVID-19 Quickly, Accurately

Researchers at the University of Illinois Chicago have successfully used graphene — one of the strongest, thinnest known materials — to detect the SARS-CoV-2 virus in laboratory experiments. The researchers say the discovery could be a breakthrough in coronavirus detection, with potential applications in the fight against COVID-19 and its variants.

In experiments, researchers combined sheets of graphene, which are more than 1,000 times thinner than a postage stamp, with an antibody designed to target the infamous spike protein on the coronavirus. They then measured the atomic-level vibrations of these graphene sheets when exposed to COVID-positive and COVID-negative samples in artificial saliva. These sheets were also tested in the presence of other coronaviruses, like Middle East respiratory syndrome, or MERS-CoV.

The UIC researchers found that the vibrations of the antibody-coupled graphene sheet changed when treated with a COVID-positive sample, but not when treated with a COVID-negative sample or with other coronaviruses. Vibrational changes, measured with a device called a Raman spectrometer, were evident in under five minutes.

Their findings are published in the journal ACS Nano.

“We have been developing graphene sensors for many years. In the past, we have built detectors for cancer cells and ALS. It is hard to imagine a more pressing application than to help stem the spread of the current pandemic,” said Vikas Berry, professor and head of chemical engineering at the UIC College of Engineering and senior author of the paper. “There is a clear need in society for better ways to quickly and accurately detect COVID and its variants, and this research has the potential to make a real difference. The modified sensor is highly sensitive and selective for COVID, and it is fast and inexpensive.”

“This project has been an amazingly novel response to the need and demand for detection of viruses, quickly and accurately,” said study co-author Garrett Lindemann, a researcher with Carbon Advanced Materials and Products, or CAMP. “The development of this technology as a clinical testing device has many advantages over the currently deployed and used tests.”

Berry says that graphene — which has been called a “wonder material” — has unique properties that make it highly versatile, making this type of sensor possible.

Graphene is a single-atom-thick material made up of carbon. Carbon atoms are bound by chemical bonds whose elasticity and movement can produce resonant vibrations, also known as phonons, which can be very accurately measured. When a molecule like a SARS-CoV-2 molecule interacts with graphene, it changes these resonant vibrations in a very specific and quantifiable way.

“Graphene is just one atom thick, so a molecule on its surface is relatively enormous and can produce a specific change in its electronic energy,” Berry said. “In this experiment, we modified graphene with an antibody and, in essence, calibrated it to react only with the SARS-CoV-2 spike protein. Using this method, graphene could similarly be used to detect COVID-19 variants.”

The researchers say the potential applications for a graphene atomic-level sensor — from detecting COVID to ALS to cancer — continue to expand.

A provisional patent has been submitted based on this work.

Source: University of Illinois Chicago

In the Blood: Which Antibodies Best Neutralize the Coronavirus In COVID-19 Patients?

Blood tests to detect antibodies against SARS-CoV-2, the virus that causes COVID-19, are an important tool for diagnosing the disease, developing potential treatments, and checking vaccine efficacy. Although such tests are available, we have very little understanding on how different antibodies interact with virus antigens. Scientists from Fujita Health University set out to assess various antigen-specific antibodies and determined which of them had the strongest neutralizing activity against SARS-CoV-2.

The COVID-19 pandemic has now claimed over 2 million deaths worldwide, and this number is only increasing. In response, health agencies have rolled out tests to diagnose and understand the disease. Besides the now widely known PCR test, there is interest in serological (blood) tests that detect “antibodies” against SARS-CoV-2, the virus that causes COVID-19. These blood tests have considerable applications, from identifying blood donors with high levels of anti-SARS-CoV-2 antibodies, whose blood can be used for convalescent plasma therapy, to measuring vaccine effectiveness.

So, what are antibodies? These are proteins produced by the body’s immune system to combat foreign proteins, such as the SARS-CoV-2 virus. Antibodies function by binding to a specific part of the virus that the immune system recognizes, called “antigens.” SARS-CoV-2 is composed of four major proteins, with two being highly immunogenic (capable of producing an immune response). These immunogenic proteins are called spike (S) and nucleocapsid (N) proteins. Presence of antibodies specific to the S protein means there is a higher amount of virus-neutralizing activity while antibodies specific to N protein indicate the presence of previous SARS-CoV-2 infection.

Despite this general awareness, we actually have only a vague understanding of how different antibodies (or antibody “isotypes”) interact with the various antigens produced by SARS-CoV-2. Hence, a team of scientists led by Senior Assistant Professor Hidetsugu Fujigaki and Professor Yohei Doi from Fujita Health University, in collaboration with National Institute of Infectious Diseases, Japan, FUJIFILM Wako Pure Chemical Corporation, and FUJIFILM Corporation undertook the first detailed investigation of these interactions. “Our goal was to quantify the neutralizing activity of these different antibodies against SARS-CoV-2,” Dr. Fujigaki explains, “We looked at antibodies specific to different parts of the S protein and the N protein to determine which of them was the best predictor of stopping the virus.”

They did this through an analysis of blood samples from 41 COVID-19 patients at the Fujita Health University Hospital. The team developed assays using three common antibodies (IgG, IgM, and IgA), each of them split into isotypes that bind specifically to five antigens (three parts of the S protein, including the receptor binding domain [RBD], the full S protein, and the full N protein).

The results of their experiments showed that all antibody isotypes that bind to the S protein (full and parts) were highly specific, but antibody isotypes binding to the N protein were less so. With minor variations, all antibodies are detectable in patients at approximately 2 weeks after symptoms appear, and detection sensitivity was higher than 90% (except in the case of IgM binding to N protein). Importantly, the researchers showed that IgG specific to the RBD of S protein had the highest correlation with virus neutralizing activity and disease severity. In other words, measuring RBD-specific IgG levels could tell us a lot about the immune response of COVID-19 patients, and could be the foundation for improving COVID-19 blood tests.

“We are also very excited by our findings because of their implications for convalescent serum/plasma therapy, a type of treatment where you transfuse blood from people who recovered from COVID and have high levels of antibodies against SARS-CoV-2,” Dr. Fujigaki adds, “Being able to show that the IgG antibody against RBD is highly correlated with neutralizing activity means we can identify appropriate blood donors for this treatment.”

The world is hopefully moving into the final stages of the pandemic, and this information could be the tools needed to carve out the final few steps to a safe post-pandemic world.

Source: Fujita Health University

SARS-COV-2 Infection Induces Antibodies Capable of Killing Infected Cells Regardless of Disease Severity

Drawing on epidemiological field studies and the FrenchCOVID hospital cohort coordinated by Inserm, teams from the Institut Pasteur, the CNRS and the Vaccine Research Institute (VRI, Inserm/University Paris-Est Créteil) studied the antibodies induced in individuals with asymptomatic or symptomatic SARS-CoV-2 infection. The scientists demonstrated that infection induces polyfunctional antibodies. Beyond neutralization, these antibodies can activate NK (natural killer) cells or the complement system, leading to the destruction of infected cells. Antibody levels are slightly lower in asymptomatic as opposed to symptomatic individuals, but polyfunctional antibodies were found in all individuals. These findings show that infection induces antibodies capable of killing infected cells regardless of the severity of the disease. The research was published in the journal Cell Reports Medicine.

Nearly half of those infected with SARS-CoV-2 do not develop symptoms. Yet, the immune response induced by asymptomatic forms of COVID-19 remains poorly characterized. The extent of the antiviral functions of SARS-CoV-2 antibodies is also poorly characterized. Antibodies are capable of both neutralizing the virus and activating “non-neutralizing” functions. The latter include antibody-dependent cellular cytotoxicity (ADCC) and complement activation, which are major components of the immune response and play a key role in the efficacy of some vaccines. ADCC is a two-stage process in which infected cells are first recognized by antibodies, then destroyed by NK cells. The complement system consists of a series of plasma proteins that also enable the elimination of cells targeted by antibodies. The ability of antibodies to activate these non-neutralizing functions has been little described for SARS-CoV-2 infection so far.

The teams from the Institut Pasteur, the CNRS and the VRI (Inserm/University Paris-Est Créteil) initially developed new assays to measure the various antibody functions. They produced assays to study cell death induced by NK cells or by complement in the presence of antibodies. By analyzing cultures in real time using video microscopy, the scientists showed that NK cells kill infected cells in the presence of antibodies, demonstrating new antiviral activity employed by SARS-CoV-2 antibodies.

The scientists then examined the serum of patients with symptomatic or asymptomatic forms of COVID-19 with their new assays. They also used methods previously developed at the Institut Pasteur, such as the S-Flow assay, to detect SARS-CoV-2 anti-spike antibodies, and the S-Fuse assay, to measure the neutralization capacity of these antibodies

“This study demonstrated that individuals infected with SARS-CoV-2 have antibodies that are capable of attacking the virus in different ways, by preventing it from entering cells (neutralization) or by activating NK cells to kill infected cells (via ADCC). We therefore use the term polyfunctional antibodies,” explains Timothée Bruel, co-last author of the study and a scientist in the Institut Pasteur’s Virus & Immunity Unit[1] and at the VRI.

By comparing different groups of patients, the scientists then showed that asymptomatic individuals also have polyfunctional antibodies and that their response is slightly weaker than those of patients with moderate forms of COVID-19.

“The study reveals new mechanisms of action of SARS-CoV-2 antibodies and suggests that the protection induced by an asymptomatic infection is very close to that observed after a symptomatic infection,” concludes Olivier Schwartz, co-last author of the study, head of the Virus & Immunity Unit and at the VRI.

Source: Institut Pasteur

One Year of SARS-CoV-2 Evolution

Today, researchers published an in-depth look at the SARS-CoV-2 mutations that have taken place during the past year in the Journal of General Virology. The review discusses the findings of over 180 research articles and follows the changes that have taken place in the SARS-CoV-2 genome, and the variants that have occurred as a result.

A number of SARS-CoV-2 variants have emerged from immunocompromised hosts, research has identified. It is thought that variants of concern – including B.1.1.7, a variant first identified in Kent – were a result of long-term infection in people with a weakened immune system.

Persistent infections in immunocompromised people could cause the virus to mutate more frequently because the person’s immune system cannot clear the virus as quickly as the immune system of a healthy person.

Authors Professor Wendy Barclay, Dr Thomas Peacock, Professor Julian Hiscox and Rebekah Penrice-Randal explain the importance of monitoring genetic changes in SARS-CoV-2 for future control of the virus: “As more and more variants appear, we are getting a better picture of their shared similarities and differences and can better predict what other new variants will look like. Putting all this information together will also help us design booster vaccines that protect against as many variants as possible or design targeted diagnostics” they said.

Their review discusses where mutations have occurred, what part of the virus they affect and how the resulting variants could impact vaccination efforts. According to the authors, mutations in SARS-CoV-2 are expected, as the virus is adapting to humans. “Sequencing of human seasonal coronaviruses has not been done on a scale like SARS-CoV-2, particularly when they would have initially spread into humans. SARS-CoV-2 is at the start of its journey in humans whereas other human coronaviruses have been around, in some cases, for many decades” they said.

Variants with the same or similar mutations have emerged independently in different countries: “SARS-CoV-2 is probably still finding its way in humans in terms of optimal infection and transmission. The scale of the outbreak and the massive sequencing efforts will identify concurrent mutations; basically, the virus is undergoing the same types of selection pressures wherever you are in the world, and the outbreak was all seeded by the same original virus,” explained the authors.

Mutations of particular interest include those in the spike protein. This protein allows the virus to enter host cells and is the main target of the immune system, including immunity generated by all current SARS-CoV-2 vaccines.

Mutations in the gene that codes for spike could change the shape of the protein, allowing it to no longer be recognised by the immune system. Because this protein is so important for SARS-CoV-2 entry, favourable mutations are more likely to succeed and create new, dominant variants of the virus.

Changes that give the virus an advantage can quickly become dominant. For example, one mutation, named D614G, was found in 80% of SARS-CoV-2 viruses sequenced just four months after it was first detected. Now, viruses without the D614G mutation are only commonly seen in parts of Africa.

Another mutation, N501Y, is found in the SARS-CoV-2 variant B.1.1.7. This mutation is believed to be the result of infection of an immunocompromised individual and may contribute to the virus being more contagious. Infections with this variant have a higher fatality rate. In the UK, B.1.1.7 became the dominant variant within three months and is now responsible for over 90% of infections there.

Significant spike protein mutations discussed in the review include:

D614G:

In February 2020, a mutation was detected in the spike protein of SARS-CoV-2 and named D614G. This mutation was found to makes SARS-CoV-2 more infectious, however does not make the virus more harmful. This increase in infectivity led to a significant fitness advantage and within four months, 80% of SARS-CoV-2 viruses sequenced around the world were found to have the mutation. Now, only parts of Africa have circulating viruses without the D614G mutation.

Despite initial concerns, D614G does not have an effect on vaccine efficiency and in some cases, viruses with the D614G mutation are more readily cleared by antibodies against SARS-CoV-2.

Y435F:

In mid-2020, reports of mink becoming infected by humans became frequent. In mink, the spike protein of the virus commonly developed two mutations called Y435F and N501T. These mutations allow for stronger binding of the virus to human receptor cells. Viruses with these mutations were found in a cluster of human infections in Denmark, believed to have originated from mink. Concerningly, this variant was able to infect people who had previously been infected with SARS-CoV-2 and were thought to have some immunity to the virus. As a result, 17 million mink were culled.

The mutation Y435F has also been reported to have developed in an immunocompromised person, possibly as a result of chronic infection with the virus allowing it to adapt.

N501Y:

In December 2020, a highly transmissible variant of the virus was isolated in Kent, UK. This variant, named B.1.1.7, contained a mutation in the spike protein called N501Y. Not only does this mutation make the virus more contagious, but it was also found to have a higher fatality rate. In the UK, B.1.1.7 is now the dominant variant, and is responsible for over 90% of infections.

The mutation N501Y has been found to have little effect on immunity from both vaccines and previous infections.

E484K:

The spike protein mutation E484K has emerged in recent months, once in South Africa and at least twice in Brazil. Variants with the mutation of E484K are able to evade the immune system of both vaccinated and previously infected individuals.

It is thought that this mutation was driven by high levels of population immunity, which drove mutations in the spike protein to evade the immune system. In Brazil, there have been several reports of healthcare workers and other people with antibodies against SARS-CoV-2 being reinfected with variants with the E484K mutant, raising concerns about vaccine protection against this variant.

The review also examines mutations which make changes to other parts of the virus, such as ORF8, an accessory protein that is thought to supress the host immune system. Viruses with a deletion in the gene that encodes for ORF8 has been found to cause less severe clinical disease.

The authors of the review have called for increased global efforts to monitor SARS-CoV-2 mutations. Currently the United Kingdom and Denmark perform disproportionately high sequencing of the SARS-CoV-2 genome. Regular monitoring of the virus allows early identification of emerging variants and allows researchers to identify the associated mutations.

“Although the genomic surveillance in Europe and the USA is fairly strong it is becoming clear there are large areas of the world that we simply have no idea what variants are circulating. These are starting to appear in Europe as imports or community outbreaks. Better surveillance across a broader range of countries would allow us to better risk assess what the next stage of the pandemic might look like,” said the authors. “If we want to monitor the ongoing emergence, spread, and import of potential vaccine escape mutants we have to continue this effort or risk further pandemic waves and vaccine failure. Furthermore, understanding the genomic epidemiology of the virus as early as possible will allow us to rapidly develop updated vaccine boosters.”

Professor Alain Kohl, Deputy Editor-in-Chief of the Journal of General Virology said “The emergence of SARS-CoV-2 variants is one of the great challenges in the ongoing pandemic. This review article summarises our current knowledge and understanding of the evolution of the virus, as well as the consequences – for example in terms of vaccination. It is of great interest to anyone wishing to learn more about the history of this virus and what the future may hold.”

Source: Microbiology Society