FRONTIERS OF THE PANDEMIC

More than a year on, after millions of deaths, here’s what we know — and don’t — about the coronavirus and Covid-19, writes Tanya Farber

It has caused havoc in India but now the variant called B.1.617 has spread to dozens of countries and scientists are working around the clock to understand what it could be up to next.

So far they’ve found it has three subtypes, each with a “slightly different genetic make-up”, according to science journal Nature.

Experts are investigating these subtypes and evaluating how they might affect the trajectory of the pandemic in countries where they have gained a foothold.

“Reassuringly, no mutation in any of the B.1.617 variant subtypes is associated with increased disease severity,” according to researchers. However, “some lab studies indicate that vaccines could be less effective against the B.1.617.1 subtype”.

Another breakthrough relates to the extremely rare cases of blood clots that have killed a few vaccine recipients.

“Preliminary research suggests these rare blood clots may be related to the DNA delivery mechanism” of the Oxford/AstraZeneca and Johnson & Johnson vaccines, said Rolf Marschalek and colleagues at Goethe University in Frankfurt.

The DNA is meant to be delivered into the surrounding fluid of cells where the virus would usually produce proteins, but instead it is getting into the nucleus, they said.

There, parts of the DNA “split apart”, creating “incomplete versions” that can’t bind to the cell’s outer membrane and instead “are released into the blood, where, in very rare cases, they may trigger blood clots”, said Marschalek , adding that “modifying the gene sequence” may solve the problem.

Another major event recently in the science of the virus itself is to do with black fungus disease.

Known as mucormycosis, it is normally seen in patients with diabetes or a compromised immune system, but some states in India have declared a “black fungus epidemic” as cases of this “fatal, rare infection shoot up in patients recovering from Covid-19”, The Guardian reported.

Scientists are trying to figure out why this is but suspect it’s in cases where steroids have been overused in treating the virus, leading to an acute compromise of the immune system.

So far more than 200 people who survived Covid in India have later died from black fungus disease, and “it has also been reported in Covid patients who were on ventilators in intensive care units, due to their airways being exposed to humidity and moisture”.

The first bit of good news this week was that new information on immunity after Covid infection bodes well for how long immunity from vaccines can last.

The science journal Nature reported that “people who have been infected with SARS-CoV-2 will probably make antibodies against the virus for most of their lives”.

This means immunity triggered by infection could be “extraordinarily long-lasting” and suggests that “vaccines will have the same durable effect”, though only time will tell.

It also emerged this week that the Pfizer vaccine, which had much heftier cold storage needs than the Johnson & Johnson jab, is not as needy as we thought.

Based on new research, the South African Health Products Regulatory Authority approved changes to storage conditions for Pfizer doses being rolled out across the country.

The shelf life of the doses in a normal refrigerator has been shown to be 31 days, rather than five, which means rollout logistics will be far easier to manage.

Also, it has been known for a while that the relatively weak immune reaction after the first of two Pfizer doses can more than double after the second.

But a new study by Public Health England — yet to be peer-reviewed — says “a second dose does more than shield you from a SARS-CoV-2 infection — it provides powerful protection against coronavirus strains like the one first detected in India (B.1.617.2)”.

As vaccine science evolves, the numbers reveal its real-life impact. For example, according to The Times, the average age of those testing positive in the UK for Covid is now 29, the youngest yet recorded, and two-thirds of Covid hospital patients are now under 65.

At the end of April, the median age of those testing positive was 35; at the beginning of the year it was 41.

The shift to younger age groups is likely to reflect the success of the vaccination campaign, which began in December with over-80s. Over-30s in England became eligible on Wednesday.

Nasal sprays are also grabbing attention as a preventative intervention. Scientists say they directly target the respiratory system, which is where the virus reproduces, and are cheaper and easier to administer than injections.

But while research is looking promising, findings are not yet concrete. While biotech companies claim their products could kill up to 99% of the viral load, regulatory authorities are not yet ready to approve them.

Over the past year, milestones have included the use of dexamethasone, a corticosteroid, and putting patients in the prone position, which means lying them on their stomachs so the lungs can take in more air.

The British Medical Journal said this week that dexamethasone had saved as many as a million lives worldwide

Staples such as high doses of vitamin D for those with mild disease at home, and high-flow nasal oxygen for hospital patients struggling with more severe forms, are now well established.

But there is still a vast amount to learn and discover. Globally, the hunt is on for the “perfect pill” — an antiviral that can be taken orally to stop the disease at an early stage after infection.

This week, the American Chemical Society said: “Creating a new antiviral drug is a tricky business. Viruses mutate and replicate quickly, and their structures differ greatly even within the same class.”

Also, “the current pandemic has created a sense of urgency in creating new antivirals” but it takes time, and an unavoidable part of the process “is proving that the drug works, first in cells and animals, then humans”.

The first generation of antivirals in the fight against Covid-19 were existing drugs that were re-purposed to reduce symptoms and hasten recovery, but none has been a miracle cure.

The best-known example is remdesivir, which was originally developed to treat hepatitis C. It was also used to combat Ebola disease.

It was authorised for emergency use in some countries but a trial led by the World Health Organisation showed it did not reduce the risk of dying from Covid-19 or the length of a patient’s hospital stay.

Other “off-label” antivirals also did not stand up to scrutiny. Global public health nonprofit organisation Wellcome said: “So far none of the existing antivirals under research have proved to work. It’s really important to know this, so researchers and clinicians can look at other potential treatments … It would be great to have an antiviral specific to Covid-19, but that could take years to discover.”

The next generation of antivirals is likely to rely on a technology known as small-interfering RNA (ribonucleic acid), or siRNA, which uses gene-silencing RNA to “attack the virus’s genome directly” so it cannot replicate, say scientists at Griffith University in Australia.

Working with researchers from City of Hope, a US medical research institute, they are at the forefront of this antiviral research and say siRNA has the ability to reduce viral loads by up to 99.9%.

They are also looking at ways to deliver the treatment directly to the lungs, the critical site of Covid-19 infection.

In the US, it is monoclonal antibody treatment that is making waves in the world of antiviral research. Monoclonal antibodies are proteins made in a laboratory that “mimic the immune system’s ability to fight off harmful viruses”.

This week, the US Food & Drug Administration issued an emergency-use authorisation of one such treatment, sotrovimab, so it can be investigated in patients aged 12 and over.

The drug targets the spike protein of SARS-CoV-2 and is designed to block the virus’s ability to break into human cells. Like siRNA, it shows promise, but there is a long way to go.

Polymerase chain reaction (PCR) testing remains the most sensitive and reliable method of testing for

Covid-19, but scientists have come up with various innovations in the field, especially for rapid testing at places such as ports of entry.

The latest study in the UK suggests dogs could become key to this effort. Six dogs were trained to sniff out people infected with Covid-19, using their natural ability to smell up to 100,000 times better than humans.

They picked up 88% of active cases but incorrectly sniffed out 16% of participants. Now scientists believe canine detectors could become crucial at mass events, airports and other ports of entry.

“Further research is needed to see if the dogs can replicate these results in a real-world setting, but these findings are hugely encouraging,” said Professor James Logan of the London School of Hygiene and Tropical Medicine, which led the trial.

In Singapore, the national university has developed a Covid-19 breathalyser that takes just a minute to detect infection.

After achieving a 93% accuracy rate in tests on 180 local people, the researchers are now testing their device on 2,500 people in Dubai.

A field of research and innovation that took off at the start of the pandemic is antibody testing, which checks if the body has mounted a response to Covid-19. However, experts say it is not a reliable way to tell if someone has immunity.

Last week, Tim Stenzel of the Food & Drug Administration in the US said: “We are reminding the public of the limitations of Covid-19 antibody — or serology — testing.”

The test is not used to check for active infection, but even its role in checking if you’ve already been sick is limited.

Stenzel said the tests can play an important role “in identifying individuals who may have been exposed to SARS CoV-2” — the virus that causes Covid-19 — but “should not be used at any time to determine immunity or protection”.

Wits vaccinology expert Professor Shabir Madhi said: “Antibody testing is very useful for community surveillance, but for a single family it means nothing. You’d be better off spending the money on takeaways from Nando’s.”

Then there is antigen testing, a “rapid diagnostic technique” that looks for bits of protein on the surface of the virus. This differs from the PCR test, the “gold standard”, which finds viral genetic material. It is less sensitive than PCR tests but far quicker and cheaper and is playing a role in urgent containment.

In Nepal, for example, where Covid-19 cases are rising exponentially, the health ministry said this week it is dispatching 1.7-million antigen test kits “to figure out hot spots and clusters”.