Hopeful research findings 7 months into the COVID-19 pandemic.

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In this installment, we look at the latest research around SARS-CoV-2 infection prevention, emerging evidence that could help inform new COVID-19 therapies, and what specialists are doing to advance knowledge about the mysterious “long COVID” and support people it affects.

Alpaca nanobodies to the rescue?

At the start of September, researchers from Karolinska Institutet in Sweden published a study paper in the journal Nature Communications. In it, they suggest that a nanobody, or an antibody fragment, that alpacas naturally produce could help prevent infection with SARS-CoV-2.

Antibodies are a type of protein that recognize antigens. Antigens are structural sequences that are present on infectious agents.

Nanobodies, which amount to around one-tenth of the size of antibodies, can nevertheless be as effective in recognizing markers of foreign agents inside the body.

The researchers zeroed in on Ty1, which is a nanobody that alpacas produce. They say that Ty1 is able to bind strongly to a specific part of the SARS-CoV-2 spike protein, which is what allows the virus to penetrate and infect healthy cells.

These promising initial observations have led the scientists to argue that, subject to future investigation and experiments, the nanobody may eventually help prevent SARS-CoV-2 infection in people at high risk.

“We hope our findings can contribute to the amelioration of the COVID-19 pandemic by encouraging further examination of this nanobody as a therapeutic candidate against this viral infection,” says senior study author Prof. Gerald McInerney.

Gaining ground on SARS-CoV-2 behavior

Researchers from various United States institutions — including the University of Washington in Seattle and Vanderbilt University Medical Center in Nashville, TN — are claiming to have drawn “complete escape maps” predicting the various mutations through which SARS-CoV-2 may be able to avoid the detection of antibodies.

Their findings do not yet appear in a peer reviewed journal, but the study paper is available online on the preprint platform bioRxiv.

In the paper, the authors explain how they created a model that allows them to map out all the possible mutations of SARS-CoV-2’s spike receptor-binding domain (RBD), which helps the virus infect healthy cells.

RBD mutations, which can occur over time, could provide SARS-CoV-2 with an escape mechanism that would allow it to avoid detection by the immune system.

However, being able to predict these mutations could also allow scientists to come up with ways of blocking this mechanism, the study authors argue.

“The extent to which mutations that substantially affect the antigenicity of SARS-CoV-2 will fix during viral evolution remains an open question,” they write in the study paper.

“The escape mutation maps we have generated, as well our methodology for rapidly creating such maps for additional antibodies and sera, should help answer this question,” they add.

Existing drug may halt hyperinflammation

A team from the University of Málaga in Spain and the University of California, Los Angeles has also recently suggested that an existing drug may help prevent excessive inflammation in COVID-19.

In a study paper that appears in the journal in Cytokine & Growth Factor Reviews, the scientists propose that 4-phenylbutyric acid (4-PBA) — which is a drug for the treatment of urea cycle disorders — may help prevent hyperinflammation. This is a response that can have fatal effects in severe cases of COVID-19.

According to the researchers, 4-PBA may be able to do this by preventing stress on the endoplasmic reticulum. This is a part of the cell where some proteins are modified and moved to other parts of the cell.

This idea is based on observations about the mechanisms that SARS-CoV triggers. SARS-CoV is the coronavirus that caused the SARS outbreak in 2002–2003.

According to the investigators, the stress on the endoplasmic reticulum due to SARS-CoV also occurs in infections with SARS-CoV-2. Therefore, a drug that would prevent this stress in one case could also do the same in the other.

“When cells are stressed by infection, they call the cytokines, and the more stressed they are, the more persistent they become, provoking this uncontrolled inflammation. Hence, one possible treatment for COVID-19 is to reduce cellular stress.”

Senior study author Prof. Iván Durán

Vaccine candidate promising in older adults

A report that appears in the New England Journal of Medicine suggests that the experimental vaccine, which many people refer to as the Moderna vaccine, has shown promise in a further phase 1 trial. Scientists are already testing this vaccine candidate in adults aged 18 years and over in a phase 3 trial.

This vaccine was developed by researchers from the National Institute of Allergy and Infectious Diseases (NIAID) and the biotechnology company Moderna in Cambridge, MA.

The experimental vaccine, called mRNA-1273, is an mRNA vaccine. Some scientists consider this to be safer because it uses genetic material rather than a virus.

The phase 1 clinical trial took place at various centers, including the Kaiser Permanente Washington Health Research Institute in Seattle, Emory University in Atlanta, and the NIAID’s Vaccine Research Center in Bethesda, MD.

According to the report, the trial showed that mRNA-1273 is well tolerated by older adults and is able to trigger an immune response.

For this trial stage, the researchers recruited 40 healthy participants. Of these, 20 were aged 56–70 years, and 20 were aged 71 years and older.

At first, the researchers administered low doses (25 micrograms) of the experimental vaccine to 10 participants aged 56–70 years and 10 participants aged 71 years and older. They then reinoculated the participants with the same dosage after 1 month.

The vaccine was well-tolerated overall. Among the participants who experienced some adverse effects, such as fever or fatigue, these only lasted for a short period of time.

The researchers emphasize that the older participants experienced an immune response following vaccination. This was similar to the immune response that the younger volunteers experienced.

Learning more about ‘long COVID’

Researchers are reckoning not just with preventing infections with SARS-CoV-2 and treating COVID-19; they are also concerned with supporting those who are having a hard time recovering from the disease.

An increasing number of people around the world are reporting that they are struggling to cope with long COVID. This is a phenomenon in which people who have had confirmed or suspected COVID-19 still have not completely recovered weeks or even months after the disease is supposed to have subsided.

This has prompted researchers and healthcare professionals to team up to find an explanation for this phenomenon and to put together care guidelines for people with long COVID.

At the start of September, six specialists based in the United Kingdom came together in a BMJ webinar to discuss best practices for diagnosing long COVID and supporting those who experience it.

Some of the most important points from the webinar were that:

  • A diagnosis of long COVID should not depend on whether or not a person has tested positive for COVID-19.
  • Doctors and their patients must understand and accept that people with long COVID may take a long time to recover.
  • Healthcare professionals should support people with long COVID to recover through rest.
  • Family doctors should listen to their patients carefully and refer those with long COVID for specialist care based on the symptoms that affect them the most.

Speaking of people with long COVID, Prof. Paul Garner — from the Liverpool School of Tropical Medicine in the U.K. — who has long COVID himself, said that: “You have to drop by 90% from what you were doing before. You are a different person, and you have to be very careful about overdoing it, because as soon as you overdo it, you throw yourself back into bed and [feeling] unwell.”

Prof. Trish Greenhalgh, from the University of Oxford in the U.K., advised that:

“[General practitioners] can actually manage most of these patients in general practice, using the clinical skills that [they] already have, and those clinical skills are things like: listening to the patient, documenting when the illness started, documenting what the symptoms are and how they’ve changed and how they fluctuate […], [and] being alert to symptoms that might suggest that the patient needs referring [to various specialists].”

Source: Medical News Today/ Maria Cohut.

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