Coronavirus questions we haven’t answered, six months later

The confusion surrounding transmission has led to a misunderstanding by the public that their own behavior can’t have drastic effects, according to Mary-Louise McLaws, an epidemiologist at the University of New South Wales and member of the WHO’s COVID-19 advisory panel. 

“One person’s breach in infection control (e.g. going to work with symptoms) can have long-term consequences for the course of the pandemic and on others’ health,” she says. McLaws adds that social inequity — like an employee having to attend work, even when sick — helps amplify the spread of COVID-19 and that authorities should be thinking about how to address social problems in conjunction with providing health advice.

How does the immune system respond?

The immune system forms the first line of defense against COVID-19. To combat infection, it produces antibodies, Y-shaped proteins that stop the coronavirus from hijacking human cells. Recent evidence suggests this response may be short-lived and differs greatly from person to person.

“This has huge implications for the spread of the virus and also how effective a vaccine may be,” says Hassan Vally, an infectious diseases epidemiologist at Australia’s La Trobe University.

A recent preprint study, yet to undergo peer review, shows around 60% of patients were able to generate a “potent” antibody response to natural infection — but within three months, only 17% of patients maintained that potency. In another preprint study, of COVID-19 patients in New York, the level of antibodies in a cohort of 370 patients varied greatly. Some had very low levels, while others showed a much stronger response. 

And that poses problems for potential vaccines. If a vaccine can only stimulate antibodies in the same way natural infection does, we may not be able to achieve long-lasting immunity.

“It’s key to get an understanding of what level of immunity is required for protection from reinfection, which is difficult to assess right now,” says Jennifer Juno, an immunologist at the Doherty Institute in Australia. 

Juno and her colleagues published a study in the journal Nature Medicine on June 13 detailing the importance of particular cells of the immune system in responding to a COVID-19 infection. Her team looked at patients who had recovered from a bout of COVID-19 and discovered that a subset of immune cells, known as T-follicular helper cells, were associated with the best immune responses. 

As Juno — and others — are showing, antibodies form one branch of the immune system’s armed forces, but they may not be enough to stop COVID-19 from invading. To understand how the body eliminates SARS-CoV-2 and protects against future infection, researchers are turning their attention to responses in other branches of the system, from immune cells to proteins and cytokines. 

Where did the coronavirus come from?

One of the more puzzling mysteries is where the coronavirus originated. Researchers sequenced the genetic code of SARS-CoV-2 only weeks after the virus was first discovered and have attempted to work backward to a starting point ever since. The most likely scenario is SARS-CoV-2 jumped from bat to human sometime in late 2019, possibly through an intermediate species.

“The search for the origin is incredibly important to prevent reemergence of SARS-CoV-2-like viruses,” said Alina Chan, a scientist at the Broad Institute of MIT and Harvard, in May.

Studies have shown it’s closely related to a group of coronaviruses isolated from Chinese horseshoe bats sharing significant genetic similarities with a virus known as RaTG13. But that virus was found in 2013, and a direct ancestor of SARS-CoV-2 has not been discovered. In its absence, conspiracy theories and speculation have run rampant. 

The first cases of COVID-19 were clustered around a wet market in Wuhan, where a menagerie of wildlife and animal meat was sold. Chinese scientists recently ruled it out as a starting point. However, it clearly facilitated the spread of the disease in late December 2019 through Wuhan. 

The market is critical for the conspiracy theories that have been shared across social media, because it is in close proximity to the Wuhan Institute of Virology. The laboratory was known to hold coronaviruses related to SARS-CoV-2. That has led to speculation the coronavirus may have accidentally been carried out of the lab unknowingly. The lab director, Yuan Zhiming, in April told CGTN, a Chinese state-run media outlet, that the virus “definitely” did not come from the lab but most scientists agree it cannot be ruled out as a source.

Complicating matters is how politically charged the origin story has become. In May, US Secretary of State Mike Pompeo, suggested there was “enormous” evidence the virus originated from a lab. Chinese officials quickly demanded he back up those claims, and Pompeo later walked them back. Similarly, a war of words between Australia and China flared after the Australian government pushed for an independent inquiry in the origins of COVID-19. 

On May 18, the World Health Organization pledged it would launch an independent evaluation of the global response to the pandemic. In early July, it sent two scientists to Beijing to begin preliminary investigations into the virus’ origin, though it has been criticized for coming “six months too late”

Some scientists have argued that the search for a starting point is ultimately of little value and won’t halt the pandemic. But without understanding where the virus came from, or which species it may lurk in, there’s a chance we may see a recurrence. 

What’s next?

The scientific questions are numerous, but it’s clear the pandemic is a source of confusion and worry. The public holds numerous concerns: when restaurants and bars will open, when international travel might resume, when a vaccine might arrive. The list goes on. But each question, at its core, is asking the same thing: When can things go back to normal? 

“I think we need to come to that realization that this is going to be around for a very long period of time,” says Bruce Thompson, respiratory expert at Swinburne University. Potentially, he says, we will be living through the pandemic until 2022, even with a successful vaccine.

It’s a sobering thought, Thompson says, but recalibrating our new normal is necessary to prepare for the future and be more preemptive in combating the spread of disease. “This is how it’s going to be, and it’s OK,” he says. “We’re just going to have to adapt.”

There is reason to be hopeful. Over two dozen vaccines are in human clinical trials, and dozens more are in the preclinical testing phase. There has been an unprecedented effort to develop a safe and effective vaccine, and some of the clinical trials are beginning to bear fruit. By the end of the year, it’s unlikely we’ll have something ready to roll out on a global scale, but we likely will have homed in on the most promising candidates.

“In six months, we should have some good data from human vaccine trials to evaluate their immunogenicity and see which approaches drive strong immune responses,” says Juno. 

With our increasing knowledge of the disease, its severity and how it affects different populations, scientists will be in a position to tease out which treatments will be most effective — and for whom. In recent months, two candidates, remdesivir and dexamethasone, have attracted a lot of media attention, but there are opportunities to repurpose other medications which could improve patient outcomes, too.

As we move into the final six months of the year, it will also be important to address pandemic fatigue within the community, says McLaws. The exhaustion is compounded by rolling lockdowns that isolate many and weigh heavily on mental health. Accepting this as the new normal, public health authorities will need to pivot, providing support not just for the current impacts of the pandemic, but to those that will be felt for years to come. 

And though we might think a pandemic is a freak, once-in-a-century event, there are ways to mitigate and prevent future outbreaks. Alina Chan believes the public misunderstands the “level of agency” they have in preventing future pandemics. Increasing the surveillance of pathogens in agriculture, in workplaces like mines and in villages bordering wildlife habitats could help us stamp out a pandemic before it has the chance to get started. 

To do so requires timely and transparent communication of potential threats. Funding more research programs and sampling pathogens is one way to do that, but without international cooperation we will continue to run the risk of new, highly infectious and deadly diseases spreading across the globe.

“We were unprepared for this pandemic,” says Chan. “We have to think of new ways to be vigilant and prepared for future outbreaks.”