While the world turns its attention to Qatar for the World Cup, the tiny Middle Eastern nation jutting into the Persian Gulf is more recognized in the medical research community for providing some of the earliest insights into vaccine efficacy, waning immunity, and reinfection during the COVID-19 pandemic.
With a national healthcare system and a focus on collecting the right data, researchers there were able to answer some of the most critical questions about COVID as they came up, publishing frequently in top-tier journals including the New England Journal of Medicine, JAMA, Nature Medicine, and others.
At the head of the research team are Laith Abu-Raddad, PhD, and Hiam Chemaitelly, PhD, both of Weill Cornell Medicine-Qatar, who have been working in infectious disease epidemiology for more than 15 years, and had long-standing relationships with the country’s public health sector that made their work possible.
When the pandemic hit in early 2020, Abu-Raddad and Chemaitelly worked closely with Qatar’s Ministry of Public Health to ensure that the country’s medical databases were collecting the right information — first, so they could help address the nation’s immediate healthcare capacity needs, and then, later, to do research. That included tracking every single COVID test performed in the country, collecting detailed assessments about infection severity based on WHO criteria, and capturing all vaccination data.
Abu-Raddad said two critical things had existed in the country prior to the COVID pandemic that enabled their work: a focus on advanced digital health platforms that led to national use of Cerner for all medical records, and the build-out of Education City, a conglomerate of American universities that opened branch campuses in Qatar.
Being a small nation of about 3 million people helped, too: “Lots of things can get done by a phone call,” Abu-Raddad said.
At the same time, having complete data on millions of people enabled substantial analyses.
Ruanne Barnabas, MD, chief of infectious diseases at Massachusetts General Hospital in Boston, has followed Abu-Raddad’s work since they were colleagues early in their careers. She said Abu-Raddad was the right person with the right team in the right place at the right time, given the available high-quality data and his expertise in data science and infectious disease dynamics.
“The work was driven by really rigorous scientific methods that were honed over many years,” Barnabas told MedPage Today. “You don’t just suddenly get an incredible database and know exactly what to do with it, how to manage funding, and bias, and test hypotheses.”
Another asset was the strong team that Abu-Raddad built: “He’s invested many years mentoring and building a culture of scientific curiosity and evidence-based work,” she said.
“They were so well placed to do this, given their expertise in infectious disease,” she added. “They’ve really influenced the way we handled the COVID pandemic, and how we are moving forward.”
Learning About COVID Immunity
The team’s earliest research explored infection severity, and which people were at greatest risk for hospitalization and death. Then, their focus shifted to natural immunity and risk of reinfection. They conducted the very first study of reinfection after natural infection, which was published in Clinical Infectious Diseases in December 2020.
But generally, these early papers didn’t get much attention, Abu-Raddad said. “We tried to publish in high-impact journals, but we did not have success,” he told MedPage Today during a Zoom interview. “We were a very new team in the picture, so we published but we didn’t reach the New England Journal or Lancet or Nature Medicine.”
But in time, the team’s work started getting noticed, and Abu-Raddad said the “turning point” was their first letter to the editor published in the New England Journal of Medicine in May 2021 about the efficacy of the Pfizer vaccine against the Alpha and Beta variants.
After that, the team’s work took off. Their October 2021 New England Journal of Medicine original article was one of the first to show that protection against infection from the Pfizer vaccine waned, but protection against hospitalization and death persisted for 6 months. They had originally published the study in medRxiv.
The following month, the team published an original investigation in JAMA showing that an infection prior to vaccination was tied to a lower risk of breakthrough infection, as well as a paper in Nature Medicine comparing the efficacy of the two mRNA vaccines in the face of the Delta variant.
In the year since, the team has published dozens of papers informing clinicians about immunity, mining data from millions of patient records. They found, for instance, that boosters still protected against hospitalization and death during the Omicron wave.
“At the time, this was very important for combatting hesitancy against vaccination with a third dose,” Chemaitelly told MedPage Today via Zoom.
They also found that various types of immunity — whether from vaccination, previous infection, or a combination of the two — held up similarly against Omicron.
Abu-Raddad said their work as a whole has shown that natural immunity has been underestimated. One matched retrospective study they published in Lancet Microbe, for instance, showed that natural immunity was associated with a lower incidence of infection than two doses of an mRNA vaccine.
“At the end of the day, [natural immunity] might be equally important to vaccine immunity,” he said.
Unfortunately, he noted, “all forms of immunity against this virus don’t last long. In the short term, they work great, but in the long term, we have to keep getting boosted.”
Focus on Immune Imprinting
Repeated vaccine dosing has raised questions, however, about immune imprinting, which has also been called original antigenic sin.
Abu-Raddad said his team is now focused on studying whether different immune histories can convey different types of protection. So far, they’ve completed two studies that show some profiles “enhance the protection against future infection, while others actually compromise the protection.”
For instance, the first study showed that those who got a booster had reduced protection against infection after the booster waned compared with those who only had two doses of vaccine.
“Those who got the booster benefitted immensely,” Abu-Raddad said. “But after 6 months, when the protection against infection waned, this is when we started seeing immune imprinting.”
The most likely explanation for that finding, he added, is that “by giving three doses of the same vaccine, we are telling the immune system to prepare for a challenge that’s similar to the original virus. The immune response thinks this is where the challenge is, but the actual challenge was of course something completely different. It was an Omicron, immune-evasive BA.4/5 variant.”
However, Abu-Raddad is quick to acknowledge that while the findings are intriguing from an academic perspective, “at the end of the day, I’m not sure how important they are, honestly, because it’s probably not going to change how we are confronting the virus.”
The best solution to prevent infection and the damage that can come from disease waves is giving boosters, he said, even though it’s a short-term solution.
“Thank goodness for the booster,” Chemaitelly said. “We had a massive Omicron wave here, and we avoided overwhelming the hospitals with the booster.”
Abu-Raddad said there’s evidence of immune imprinting with other viral infections, including influenza. But annual vaccinations usually provide enough protection against infection during peak season to negate any ill effects of imprinting. And there’s no evidence that imprinting affects protection against severe disease at this point, he added.
“I wouldn’t dismiss it completely, but it wouldn’t appear for years because protection against severe disease lasts much longer than protection against infection,” he said.
Abu-Raddad concluded that boosters that are updated to match circulating strains “will be critical, especially in those who are vulnerable.”
Funding and the Future of Randomized Controlled Trials
The researchers made it a priority to keep the funding of their data conflict-free, they said. That hasn’t been hard to do in a resource-rich country like Qatar. Its public health infrastructure was well-funded before COVID, thanks to income from the country’s huge natural gas reserves, as well as corporate taxes. (The country has no income tax for its citizens.)
That means there is no pharmaceutical company funding behind any of its data, the researchers said.
Another benefit to establishing data collection standards early in the pandemic was that they were able to include strict criteria for defining illness, which means they didn’t struggle with distinguishing deaths “with” versus “from” COVID, Abu-Raddad said.
In addition to the Ministry of Public Health and Weill Cornell Medicine-Qatar, other key players on the data team included Hamad Medical Corporation — the country’s hospital system, considered “the backbone of the healthcare system here,” Abu-Raddad noted — and Primary Health Care Corporation, a national network of primary care clinics. Qatar University and Sidra Medicine, both in Doha, worked on sequencing and genotyping of variants, he said.
Abu-Raddad and Chemaitelly both strongly advocate for the potential of big data in answering important questions in healthcare. As high costs of clinical research have gone up even further, databases have become more sophisticated and complex, Abu-Raddad said.
“We can use big data to answer questions that can’t be answered by clinical trials,” he added. “What combinations of diabetes drugs are most effective? It would be difficult to do that in a clinical trial. But [with big data], you’ll look at millions of people, not just 30,000 in a clinical trial.”
He refers to such analyses as “retrospective randomized controlled trials” and noted they’re far less costly than randomized controlled trials.
Barnabas said Abu-Raddad and team have been ahead of the curve on COVID and is convinced of their future success. While important research on COVID has come out of the U.S., she noted, its data systems could use an upgrade. And even then, there’s much more work to be done on a global scale.
“We should think about how we can do this in a bigger way and have data for more than one country,” Barnabas said. “All databases should talk to each other. We should share data, and we should do this on a global scale.”
Source: MedicalNewsToday.com
