Medically Speaking Team

Alpaca nanobodies potently neutralize SARS-CoV-2 variants

Researchers at Sweden’s Karolinska Institutet have devised a unique method for discovering effective tiny antibodies, or nanobodies, against developing SARS-CoV-2 subtypes. The method resulted in the discovery of numerous nanobodies that efficiently inhibited infection with various SARS-CoV-2 variants in cell cultures and animals. The findings, which were published in the journals Nature Communications and Science Advances, could pave the path for new COVID-19 treatments.

“We were able to identify a panel of nanobodies that very effectively neutralised several variants of SARS-CoV-2 with the help of advanced laboratory techniques,” says Gerald McInerney, professor at Karolinska Institutet’s Department of Microbiology, Tumor and Cell Biology (MTC) and joint senior author of both studies.

Despite the availability of vaccinations and antivirals, there is still a strong demand for effective treatments against severe COVID-19 infection. Nanobodies, which are fragments of antibodies found in camelids that may be converted for human use, are attractive therapeutic options because they have various benefits over normal antibodies. They have favourable biochemical features, for example, and are simple to create on a large scale at a low cost.

Gerald McInerney and Ben Murrell’s labs at MTC uncover many effective nanobodies produced from an alpaca immunised with SARS-CoV-2 antigens in the newly published study.

The first study, published in Nature Communications, shows a single nanobody, Fu2 (named after the alpaca Funny), that drastically reduced SARS-CoV-2 viral load in cell cultures and animals. Using electron cryo-microscopy, the researchers discovered that Fu2 naturally attaches to two distinct places on the viral spike, preventing the virus from entering the host cell. This portion of the research was carried out in partnership with Hrishikesh Das and Martin Hällberg of Karolinska Institutet’s Department of Cell and Molecular Biology.

The researchers next dug deeper into the alpaca’s nanobody repertoire by combining a variety of advanced laboratory techniques and computational tools, yielding a detailed library of nanobodies.

The findings, published in Science Advances, revealed additional nanobodies that efficiently cross-neutralized both the founder and beta variants of SARS-CoV-2 in cell cultures and mice, as well as the more distantly related SARS-CoV-1.

“These nanobodies represent intriguing treatment prospects against many SARS-CoV-2 types,” explains first author Leo Hanke, a postdoctoral researcher in the McInerney lab who developed the nanobody technology.

The researchers are now using the same procedures to determine which nanobodies in this collection are most suited to neutralise Omicron, the now dominant SARS-CoV-2 subtype.

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New kind of ultraviolet light renders indoor air as safe as outdoor air

A novel type of ultraviolet light that is safe for people reduced the number of indoor airborne bacteria by more than 98 percent in less than five minutes, according to a joint study conducted by scientists at Columbia University Vagelos College of Physicians and Surgeons and in the United Kingdom. Even as more germs were sprayed into the room, the level remained relatively low as long as the lights were turned on.

According to the findings, far-UVC light from ceiling-mounted lamps could be a highly effective passive solution for minimising person-to-person transmission of airborne-mediated diseases like COVID and influenza inside, as well as lowering the danger of the next pandemic.

“Far-UVC rapidly reduces the amount of active microbes in the indoor air to almost zero, making indoor air essentially as safe as outdoor air,” says David Brenner, PhD, co-author of the study and director of the Center for Radiological Research at Columbia University Vagelos College of Physicians and Surgeons. “Using this technology in places where people congregate indoors could help to avert the next dangerous epidemic.”

The findings was published on March 23 in the Nature journal Scientific Reports.

“Far-UVC light is simple to install, inexpensive, does not require people to modify their behaviour, and most importantly, it is a safe means to prevent the transmission of any virus, including the COVID virus and its variants, influenza, and any potential future pandemic viruses,” Brenner explains.

What exactly is far-UVC light?

Disinfecting indoor air with far-UVC light is a novel way for safely and efficiently destroying airborne viruses in occupied settings, including COVID and influenza viruses.

For decades, scientists have known that a form of ultraviolet light known as UVC light rapidly destroys microorganisms such as bacteria and viruses. However, because it is potentially harmful to the skin and eyes, traditional germicidal UVC light cannot be utilised directly to eliminate airborne viruses in populated interior settings.

Around a decade ago, Columbia University researchers claimed that a distinct sort of UVC light, known as far-UVC light, would be just as effective at eliminating bacteria and viruses while avoiding the safety problems associated with traditional germicidal UVC.

Far-UVC light is harmless for humans since it has a lower wavelength than ordinary germicidal UVC and so cannot penetrate living human skin or eye cells. It is, however, as effective at killing bacteria and viruses that are considerably smaller than human cells.

Many studies conducted across the world over the last decade have proven that far-UVC is both effective at destroying airborne germs and viruses and safe to use around people. However, until today, these investigations have only been carried out in small experimental chambers, rather than full-sized rooms simulating real-world situations.

According to a new study, far-UVC is extremely effective in a real-world situation.

Researchers from the Universities of St. Andrews, Dundee, Leeds, and Columbia University examined the efficacy of far-UVC light in a big room-sized chamber with the same ventilation rate as a normal home or workplace (about three air changes per hour).

Throughout the experiment, an aerosol mist of S. aureus germs was continually discharged into the room by a sprayer. (The researchers chose this microbe because it is significantly less susceptible to far-UVC radiation than coronaviruses, presenting them with an appropriately conservative model.) When the microorganism concentration in the room had stabilised, the researchers switched on commercially available overhead far-UVC lights.

The far-UVC lamps inactivated more than 98 percent of the airborne microorganisms in just five minutes at an intensity based on the existing regulation limit on far-UVC light exposure set by the American Conference of Governmental Industrial Hygienists. Even though microorganisms were still sprayed into the room, the low amount of viable germs was maintained throughout time.

The effectiveness of various methods for lowering indoor virus levels is often quantified in terms of equivalent air changes per hour. Far-UVC lamps produced the equivalent of 184 equivalent air exchanges per hour in this investigation. This outperforms any other method of disinfecting inhabited indoor environments, where the most that can be achieved effectively is five to twenty equivalent air changes each hour.

“Our trials produced spectacular results, far exceeding what is possible with ventilation alone,” says Kenneth Wood, PhD, lecturer in the School of Physics and Astronomy at the University of St. Andrews and senior author of the study. “In terms of preventing airborne disease transmission, far-UVC lights could make indoor places as safe as being outside on the golf course on a breezy day at St. Andrews.”

Far-UVC light is resistant to variations

“Previous research has demonstrated that far-UVC light can kill the COVID virus, other human coronaviruses, influenza, and drug-resistant microorganisms,” explains Brenner. “What makes far-UVC technology particularly appealing as a practical method of preventing indoor disease transmission is that it will be equally effective at inactivating all future COVID variants, as well as new infectious viruses that have yet to emerge, while retaining efficacy against ‘old fashioned’ viruses like influenza and measles.”

Finally, because ultraviolet light kills germs in the same way that vaccinations and medicine treatments do, viruses and bacteria cannot build resistance to it.

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Coronavirus mixed with flu increases risk :

Adults in the hospital who have Covid-19 and the flu at the same time have a substantially higher risk of severe sickness and death than individuals who have Covid-19 alone or in combination with other viruses, according to study.

Experts discovered that patients who had SARS-CoV-2, which causes Covid-19, and influenza viruses co-infected were nearly four times more likely to require ventilator assistance and 2.4 times more likely to die than if they only had Covid-19.

The findings, according to the researchers, underline the necessity for more flu testing of Covid-19 patients in hospitals, as well as the need of comprehensive vaccination against both Covid-19 and the flu.

The findings were made in a study of more than 305,000 hospitalised patients with Covid-19 by a team from the Universities of Edinburgh, Liverpool, Leiden University, and Imperial College London.

The study, which was conducted as part of the International Severe Acute Respiratory and Emerging Infection Consortium’s (ISARIC) Coronavirus Clinical Characterisation Consortium, is the largest yet conducted on persons infected with Covid-19 and other endemic respiratory viruses.

The ISARIC research was established in 2013 in anticipation of a pandemic like this.

The researchers examined data from patients hospitalised with Covid-19 in the United Kingdom between 6 February 2020 and 8 December 2021.

For 6965 Covid-19 patients, test results for respiratory virus co-infections were collected. There were 227 of them who also had the influenza virus and had much worse results.

Dr. Maaike Swets, a PhD student at the Universities of Edinburgh and Leiden, stated: “In the last two years, we have frequently seen patients with Covid-19 become critically unwell, necessitating ICU treatment and the need of an artificial ventilator to assist with breathing.

It was already recognised that an influenza infection may result in a similar condition, but little was known about the consequences of a double infection with SARS-CoV-2 and other respiratory viruses.”

Professor Kenneth Baillie, of the University of Edinburgh’s Department of Experimental Medicine, stated: “We discovered that combining Covid-19 and flu viruses is especially harmful. This is significant since many countries are reducing their usage of social distance and containment tactics. We anticipate that Covid-19 will circulate alongside flu, increasing the possibility of co-infections. As a result, we should revise our testing strategy for Covid-19 patients in hospitals and test for flu much more broadly.”

Professor Calum Semple, of the University of Liverpool’s Department of Outbreak Medicine and Child Health, stated: “As people resume normal mingling, we are seeing an increase in the usual seasonal respiratory viruses. As a result, we should expect flu to circulate alongside Covid-19 this winter. We were astonished to learn that when persons were infected with both the flu and the Covid-19 viruses, their chance of mortality more than doubled. It is now critical that people get completely vaccinated and boosted against both viruses as soon as possible, rather than waiting until it is too late.”

“Understanding the consequences of double infections of SARS-CoV-2 and other respiratory viruses is critical as they have implications for patients, hospitals, and ICU capacity during seasons when SARS-CoV-2 and influenza circulate together,” said Dr Geert Groeneveld of Leiden University Medical Center’s infectious diseases department.

Professor of Experimental Medicine at Imperial College London, Professor Peter Openshaw, stated: “Although being infected with more than one virus is uncommon, it is crucial to be aware that co-infections sometimes occur. The vaccines used to defend against Covid-19 and flu are not the same, and patients require both. Because these two diseases are handled differently, it is crucial to test for other viruses even if you have a diagnosis of a respiratory infection in someone who is hospitalised. The ISARIC consortium’s latest discovery contributes greatly to enhancing the way we manage patients.”

The study’s findings were reported in The Lancet. As part of the UK Government’s Covid-19 quick research response, the research was financed by UKRI and the Department of Health and Social Care via the National Institute for Health Research (NIHR).

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Aspirin may reduce death in hospitalized COVID-19 patients

Researchers at George Washington University presented the results of the world’s biggest cohort study, which found that hospitalised patients with moderate COVID-19 who were given aspirin early in their therapy had a decreased risk of dying than patients who were not given aspirin.

Jonathan Chow, the lead researcher, stated, “This is our third trial and the culmination of 15 months of research into aspirin use in COVID-19 hospitalised patients. Aspirin use continues to be related with better outcomes and decreased rates of death in hospitalised patients. Furthermore, it is inexpensive and widely available, which is significant in places of the world where more expensive treatments may be unavailable.”

The largest data set included in the study included 112,269 patients hospitalised with mild COVID-19. Patients registered from January 1, 2020, to September 10, 2021, at 64 health systems in the United States participating in the National Institute of Health’s National COVID Cohort Collaborative were included in the study (N3C).

When aspirin was given on the first day of admission to patients with intermediate illness severity, researchers discovered a 1.6 percent reduction in mortality and that patients were less likely to form blood clots. They also discovered that elderly individuals and those with one or more comorbidities benefit the most from early aspirin therapy.

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Could length of one’s fingers provide a clue to how ill one might get after contracting COVID-19?

A longer ring finger is widely recognised as a marker of higher levels of testosterone prenatally, whereas a longer index finger is a marker of higher levels of oestrogen. Men tend to have longer ring fingers, while women tend to have longer index fingers.

Swansea University is involved in a new study that is looking into the relationship between sex hormone levels in the womb and during puberty and Covid hospitalizations.

The majority of people who contract the virus only have minor symptoms. However, when it comes to patients who require hospital care, the rates vary according to age (with the elderly being the most affected) and gender (with males experiencing a higher severity than females).

This has prompted scientists to dig deeper into the relationship between testosterone and Covid-19 severity. One hypothesis links high testosterone levels in severe cases to a poor prognosis, while another links low testosterone levels in elderly men to a poor prognosis.

Professor John Manning of the Applied Sports Technology, Exercise and Medicine (A-STEM) research team has been working with colleagues from the Medical University of Lodz in Poland and Sweden’s Karolinska University Hospital to look more closely at digit ratios (ratios of the second, third, fourth, and fifth digits) as predictors of Covid-19 symptom severity.

The researchers discovered that patients with “feminised” short little fingers relative to their other digits have a higher risk of hospitalisation, and that patients with large right hand–left hand differences in ratios 2D:4D and 3D:5D have a significantly higher risk of hospitalisation.

These preliminary findings were recently published in the journal Scientific Reports.

According to Professor Manning: “Our findings suggest that the severity of Covid-19 is associated with low testosterone and possibly high oestrogen in both men and women.

“‘Feminized’ differences in digit ratios in hospitalised patients support the theory that individuals who have had low testosterone and/or high oestrogen levels are predisposed to severe Covid-19 expression. This could explain why elderly males are the most vulnerable group.

“This is significant because identifying more precisely who is likely to be prone to severe Covid-19 would aid in targeting vaccination. Differences in digit ratios between the right and left sides (particularly 2D:4D and 3D:5D) may be useful in this regard.”

Several anti-androgen (testosterone) drug trials are currently underway as a treatment for Covid-19. In contrast, testosterone is being studied as an anti-viral against Covid-19.

“Our research is contributing to our understanding of Covid-19 and may bring us closer to improving the repertoire of antiviral drugs, allowing us to shorten hospital stays and reduce mortality rates,” he added.

Professor Manning stated that the team’s work would now be resumed: “The sample size is small, but ongoing work has increased it. We hope to have more information soon.”

His previous research in the field demonstrated how the length of children’s fingers correlates with the income level of their mothers and indicates susceptibility to diseases that begin in the womb.

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