A laboratory technician prepares COVID-19 patient samples for semi-automatic testing at Northwell Health Labs, Wednesday, March 11, 2020, in Lake Success, N.Y.
| Photo Credit: AP

Five years since Covid-19 started upending the world, the virus is still infecting and killing people across the globe — though at far lower levels than at the height of the pandemic.

Here is the current state of the play.

Still with us

Around 777 million Covid cases and more than seven million deaths have been officially recorded since the first infections emerged in December 2019, according to the World Health Organization (WHO).

However, the true toll is believed to be far higher.

The pandemic also crippled health systems, crashed economies and sent the populations of many countries into lockdown.

In the second half of 2022, infection and death rates tumbled due to growing immunity from vaccinations or prior infection. The virus also mutated to become less severe.

In May 2023, the WHO declared the emergency phase of the pandemic was over.

Since then, the virus seems to have gradually become endemic, according to experts, with occasional resurgences similar to the flu — although less seasonal.

It has also largely receded from the public eye.

“The world wants to forget this pathogen that is still with us, and I think people want to put Covid in the past as if it’s over — and in many respects pretend it didn’t happen — because it has been so traumatic,” WHO pandemic preparedness director Maria Van Kerkhove said last month.

From October to November last year, there were more than 3,000 deaths from Covid across 27 countries, according to the WHO.

More than 95 percent of official Covid deaths were recorded between 2020 and 2022.

Variants

Since the Omicron variant emerged in November 2021, a succession of its subvariants have been replacing each other as the dominant strain around the world.

At the moment, the Omicron variant KP.3.1.1 is the most common.

The rising XEC is the only “variant under monitoring” by the WHO, though the United Nations agency rates its global health risk as low.

None of the successive Omicron subvariants have been noticeably more severe than others, although some experts warn it is not out of the question that future strains could be more transmissible or deadly.

Vaccines and treatments

Vaccines were developed against Covid in record time and they proved a powerful weapon against the virus, with more than 13.6 billion doses administered worldwide so far.

However rich countries bought up a large portion of the early doses, creating unequal distribution across the world.

Booster shots updated for the JN.1 Omicron subvariant are still recommended in some nations, particularly for at-risk groups such as the elderly.

However, the WHO has said most people — including the elderly — have not kept up with their booster shots.

Even among healthcare workers, the booster uptake rate was below one percent in 2024, according to the WHO.

Long Covid

Millions of people have been affected by long Covid, a still little-understood condition that lasts months after the initial infection.

Common symptoms include tiredness, brain fog and shortness of breath.

About six percent of people infected by coronavirus develop long Covid, the WHO said last month, adding that the condition “continues to pose a substantial burden on health systems”.

Much about long Covid remains unknown. There are no tests or treatments. Multiple Covid infections seem to increase the chance of getting the condition.

Future pandemics?

Scientists have warned that another pandemic will strike sooner or later, urging the world to learn the lessons of Covid and prepare for next time.

Attention has recently focussed on bird flu (H5N1), particularly after the United States reported on Monday the first human death from the virus.

The patient in Louisiana had underlying medical conditions and contracted H5N1 after being exposed to infected birds, US health authorities said, emphasising there was no evidence of person-to-person transmission.

Since late 2021, the WHO’s member states have been negotiating a world-first treaty on pandemic prevention, preparedness and response.

However, an agreement has remained elusive ahead of a May deadline, with a key faultline lying between Western nations and poorer countries wary of being sidelined when the next pandemic occurs.

The Covid pandemic also saw a massive increase in scepticism and misinformation about vaccines.

Experts have warned about the prospect of having vaccine sceptic and conspiracy theorist Robert F. Kennedy Jr. — US President-elect Donald Trump’s pick for health secretary — in charge of the US response to a possible pandemic threat over the next four years.

The new research focused on a particular protein used by bacteriophages (representational).

Viruses called bacteriophages, or phages, target bacteria but can’t infect humans or other higher organisms. Phages inject their DNA into the bacterial cell, multiply to large numbers using the resources of the host, and then burst out to infect more bacteria in the vicinity.

Essentially, they are a naturally occurring, self-replicating and specific antibiotic. Discovered more than 100 years ago, their use against bacteria was largely sidelined in favour of antibiotics.

Our new research looked at one particular protein used by phages to bypass the natural defences of bacteria. We found this protein has an essential control function by binding to DNA and RNA.

This increased understanding is an important step towards using phages against bacterial pathogens in human health or agriculture.

Bacterial defence systems

There are hurdles to using phages to target bacteria. Much like our bodies have immune mechanisms to fight off viruses, bacteria have also evolved defences against phage infections.

One such defence is “clustered regularly interspaced short palindromic repeats”, or CRISPR, now better known for its applications in medicine and biotechnology. CRISPR systems in general act as “molecular scissors” by cutting DNA into pieces, be it in a lab-based setting or, in nature, inside a bacterium to destroy a phage.

Imagine wanting to use a phage against an antibiotic-resistant bacterial infection. The only thing standing in the way of that phage killing the bacteria and eradicating the infection might be the bacterium’s CRISPR defence which renders the phages useless as an antimicrobial.

That’s where knowing as much as possible about phage counter-defences becomes important. We are investigating so-called anti-CRISPRs: proteins or other molecules that phages use to inhibit CRISPR.

A bacterium that has CRISPR might be able to stop a phage from infecting. But if the phage has the right anti-CRISPR, it can neutralise this defence and kill the bacterium regardless.

The importance of anti-CRISPRs

Our recent research focused on how an anti-CRISPR response is controlled.

When faced with a powerful CRISPR defence, phages want to automatically produce large amounts of anti-CRISPR to increase the chance of inhibiting CRISPR immunity. But excessive production of anti-CRISPR prevents the replication of the phage and is ultimately toxic. This is why control is important.  

To achieve this control, phages have another protein in their toolbox: an anti-CRISPR-associated (or Aca) protein that frequently occurs alongside the anti-CRISPRs themselves.

Aca proteins act as regulators of the phage’s counter-defence. They make sure the initial burst of anti-CRISPR production that inactivates CRISPR is then rapidly dampened to low levels. That way, the phage can allocate energy to where it is most needed: its replication and, eventually, release from the cell.

We found this regulation occurs at multiple levels. For any protein to be produced, the gene sequence in the DNA first needs to be transcribed into a messenger–RNA. This is then decoded, or translated, into a protein.

Many regulatory proteins function by inhibiting the first step (transcription into messenger-RNA), some others inhibit the second (translation into protein). Either way, the regulator often acts as a “road block” of sorts, binding to DNA or RNA.

Intriguingly and unexpectedly, the Aca protein we investigated does both – even though its structure would suggest it is merely a transcriptional regulator (a protein that regulates the conversion of DNA to RNA), very similar to ones that have been investigated for decades.

We also examined why this extra-tight control at two levels is necessary. Again, it seems to be all about the dosage of the anti-CRISPRs, especially as the phage replicates its DNA in the bacterial cell. This replication will invariably lead to the production of messenger-RNAs even in the presence of transcriptional control.

Therefore, it appears additional regulation is required to reign in anti-CRISPR production. This comes back to the toxicity of excessive production of this counter-defence protein, to the harm done when there’s “too much of a good thing”.

Fine-tuned control

What does this research mean in the grand scheme of things? We now know a lot more about how anti-CRISPR deployment occurs. It requires fine-tuned control to enable the phage to be successful in its battle against the host bacterium.

This is important out in nature, but also when it comes to using phages as alternative antimicrobials.

Knowing every detail about something as obscure-sounding as anti-CRISPR-associated proteins might make all the difference between the phage succeeding or succumbing —and between life or death, not just for the phage, but also for a person infected with antibiotic-resistant bacteria.

Nils Birkholz, Postdoctoral Fellow in Molecular Microbiology, University of Otago
This article is republished from The Conversation under a Creative Commons license. Read the original article.