COVID-19
A Song for the Holidays
Posted on by Dr. Francis Collins
Study of Healthcare Workers Shows COVID-19 Immunity Lasts Many Months
Posted on by Dr. Francis Collins

Throughout the COVID-19 pandemic, healthcare workers around the world have shown willingness to put their own lives on the line for their patients and communities. Unfortunately, many have also contracted SARS-CoV-2, the coronavirus that causes of COVID-19, while caring for patients. That makes these frontline heroes helpful in another way in the fight against SARS-CoV-2: determining whether people who have recovered from COVID-19 can be reinfected by the virus.
New findings from a study of thousands of healthcare workers in England show that those who got COVID-19 and produced antibodies against the virus are highly unlikely to become infected again, at least over the several months that the study was conducted. In the rare instances in which someone with acquired immunity for SARS-CoV-2 subsequently tested positive for the virus within a six month period, they never showed any signs of being ill.
Some earlier studies have shown that people who survive a COVID-19 infection continue to produce protective antibodies against key parts of the virus for several months. But how long those antibodies last and whether they are enough to protect against reinfection have remained open questions.
In search of answers, researchers led by David Eyre, University of Oxford, England, looked to more than 12,000 healthcare workers at Oxford University Hospitals from April to November 2020. At the start of the study, 11,052 of them tested negative for antibodies against SARS-CoV-2, suggesting they hadn’t had COVID-19. But the other 1,246 tested positive for antibodies, evidence that they’d already been infected.
After this initial testing, all participants received antibody tests once every two months and diagnostic tests for an active COVID-19 infection at least every other week. What the researchers discovered was rather interesting. Eighty-nine of the 11,052 healthcare workers who tested negative at the outset later got a symptomatic COVID-19 infection. Another 76 individuals who originally tested negative for antibodies tested positive for COVID-19, despite having no symptoms.
Here’s the good news: Just three of these more than 1400 antibody-positive individuals subsequently tested positive for SARS-CoV-2. What’s more, not one of them had any symptoms of COVID-19.
The findings, which were posted as a pre-print on medRxiv, suggest that acquired immunity from an initial COVID-19 infection offers protection against reinfection for six months or maybe longer. Questions remain about whether the acquired immunity is due to the observed antibodies alone or their interplay with other immune cells. It will be important to continue to follow these healthcare workers even longer, to learn just how long their immune protection might last.
Meanwhile, more than 15 million people in the United States have now tested positive for COVID-19, leading to more than 285,000 deaths. Last week, the U.S. reported for the first time more than 200,000 new infections, with hospitalizations and deaths also on the rise.
While the new findings on reinfection come as good news to be sure, it’s important to remember that the vast majority of the 328 million Americans still remain susceptible to this life-threatening virus. So, throughout this holiday season and beyond—as we eagerly await the approval and widespread distribution of vaccines—we must all continue to do absolutely everything we can to protect ourselves, our loved ones, and our communities from COVID-19.
Reference:
[1] Antibodies to SARS-CoV-2 are associated with protection against reinfection. Lumley, S.F. et al. MedRxiv. 19 November 2020.
Links:
Coronavirus (COVID) (NIH)
Combat COVID (U.S. Department of Health and Human Services, Washington, D.C.)
David Eyre (University of Oxford, England)
Caught on Camera: Neutralizing Antibodies Interacting with SARS-CoV-2
Posted on by Dr. Francis Collins

As this long year enters its final month, there is good reason to look ahead to 2021 with optimism that the COVID-19 pandemic will finally be contained. The Food and Drug Administration is now reviewing the clinical trial data of the Pfizer and Moderna vaccines to ensure their safety and efficacy. If all goes well, emergency use authorization could come very soon, allowing immunizations to begin.
Work also continues on developing better therapeutics against SARS-CoV-2, the novel coronavirus that causes COVID-19. Though we’ve learned a great deal about this coronavirus in a short time, structural biologists continue to produce more detailed images that reveal more precisely where and how to target SARS-CoV-2. This research often involves neutralizing antibodies that circulate in the blood of most people who’ve recovered from COVID-19. The study of such antibodies and how they interact with SARS-CoV-2 offers critical biological clues into how to treat and prevent COVID-19.
A recent study in the journal Nature brings more progress, providing the most in-depth analysis yet of how human neutralizing antibodies physically grip SARS-CoV-2 to block it from binding to our cells [1]. To conduct this analysis, a team of NIH-supported structural biologists, led by postdoc Christopher Barnes and Pamela Björkman, California Institute of Technology, Pasadena, used the power of cryo-electron microscopy (cryo-EM) to capture complex molecular interactions at near-atomic scale.
People infected with SARS-CoV-2 (or any foreign substance, for that matter) generate thousands of different versions of attack antibodies. Some of these antibodies are very good at sticking to the coronavirus, while others attach only loosely. Barnes used cryo-EM to capture highly intricate pictures of eight different human neutralizing antibodies bound tightly to SARS-CoV-2. Each of these antibodies, which had been isolated from patients a few weeks after they developed symptoms of COVID-19, had been shown in lab tests to be highly effective at blocking infection.
The researchers mapped all physical interactions between several human neutralizing antibodies and SARS-CoV-2’s spike protein that stud its surface. The virus uses these spiky extensions to infect a human cell by grabbing on to the angiotensin-converting enzyme 2 (ACE2) receptor. The molecular encounter between the coronavirus and ACE2 takes place via one or more of a trio of three protein domains, called receptor-binding domains (RBDs), that jut out from its spikes. RBDs flap up and down in the fluid surrounding cells, “reaching up” to touch and enter, or “laying down” to hide from an infected person’s antibodies and immune cells. Only an “up” RBD can attach to ACE2 and get into a cell.
Taken together with other structural information known about SARS-CoV-2, Barnes’ cryo-EM snapshots revealed four different types of shapes, or classes, of antibody-spike combinations. These high-resolution molecular views show that human neutralizing antibodies interact in many different ways with SARS-CoV-2: blocking access to either one or more RBDs in their “up” or “down” positions.
These results tell us a number of things, including underscoring why strategies that combine multiple types of antibodies in an “antibody cocktail” might likely offer broader protection against infection than using just a single type of antibody. Indeed, that approach is currently being tested in patients with COVID-19.
The findings also provide a molecular guide for custom-designing synthetic antibodies in the lab to foil SARS-CoV-2. As one example, Barnes and his team observed that one antibody completely locked all three RBDs into closed (“down”) positions. As you might imagine, scientists might want to copy that antibody type when designing an antibody-based drug or vaccine.
It is tragic that hundreds of thousands of people have died from this terrible new disease. Yet the immune system helps most to recover. Learning as much as we possibly can from those individuals who’ve been infected and returned to health should help us understand how to heal others who develop COVID-19, as well as inform precision design of additional vaccines that are molecularly targeted to this new foe.
While we look forward to the arrival of COVID-19 vaccines and their broad distribution in 2021, each of us needs to remember to practice the three W’s: Wear a mask. Watch your distance (stay 6 feet apart). Wash your hands often. In parallel with everyone adopting these critical public health measures, the scientific community is working harder than ever to meet this moment, doing everything possible to develop safe and effective ways of treating and preventing COVID-19.
Reference:
[1] SARS-CoV-2 neutralizing antibody structures inform therapeutic strategies. Barnes CO, Jette CA, Abernathy ME, et al. Nature. 2020 Oct 12. [Epub ahead of print].
Links:
Coronavirus (COVID-19) (NIH)
Combat COVID (U.S. Department of Health and Human Services, Washington, D.C.)
Freezing a Moment in Time: Snapshots of Cryo-EM Research (National Institute of General Medical Sciences/NIH)
Björkman Lab (California Institute of Technology, Pasadena)
NIH Support: National Institute of General Medical Sciences; National Institute of Allergy and Infectious Diseases
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