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A lucky few seem ‘resistant’ to Covid-19. Scientists want to know why

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Her husband collapsed just before reaching the top of the stairs in their small one-bedroom house in São Paulo, Brazil. Frantic, Thais Andrade grabbed the portable pulse oximeter she had purchased after hearing that a low oxygen reading could be the first sign of the novel coronavirus. Erik’s reading was hovering eight points lower than it had that morning. He also looked feverish.

“When he hit 90% [on the oximeter], I said we can’t wait anymore,” Andrade recalled. “I called an ambulance.”

At the hospital that day in June 2020, a CT scan showed multiple lesions in her husband’s lungs — an indication of severe Covid-19 infection – which was later confirmed via a blood test. Erik, 44, had likely contracted the virus up to a week earlier, from a friend who had visited their home.

He spent the next several weeks on oxygen in the ICU, a stay that was complicated by blood clots before he was discharged. But it wasn’t his sudden decline and subsequent recovery that is notable: It’s that Andrade had been sharing the same close quarters with her husband while he was infected and able to transmit the virus. She never wore a mask in the home with him. They shared the same bed. They were physically intimate. Yet when tested for an active or past infection — twice — her bloodwork came up negative.

And that wasn’t the only time she was potentially exposed. As part of her research work as a veterinary neurologist, she went to a meeting at the University of São Paulo where an infected attendee set off a chain reaction of positivity – but Andrade dodged it. Her tests were again negative.

Both experiences suggest that Andrade may have won a sort of biological lottery — that she’s one of a lucky few “resistant” to the virus that has killed more than 4 million people. But how? That’s the mystery researchers around the world have set out to unravel.

The question of viral resistance has perplexed Mayana Zatz, a University of São Paulo genetics professor, for years, beginning with exploring the clinical variability of genetic diseases in patients who carried the same pathogenic mutation. She began with neuromuscular disorders like Duchenne muscular dystrophy, and then expanded to exploring why the Zika virus caused severe brain damage in some newborns while others were healthy.

In 2018, she published a study of nine sets of twins — seven fraternal and two identical — born to Zika-infected mothers; in each pair, one twin was born with microcephaly and developmental delay while the other was spared. Zatz suspected the answer to Zika resistance lay in their genes. To test this hypothesis, she collected blood from three of the pairs and reprogrammed their cells in the lab to generate induced pluripotent stem (iPS) cells and immature brain cells called neuroprogenitor cells (NPCs) that had genomes identical to those of the resistant and non-resistant infants. Then, her team infected the NPCs with Zika and found that the virus destroyed the NPCs of only those who were not resistant — supporting the idea that resistance is genetic.

It was a serendipitous moment in early February 2020, on her daily walk, that caused Zatz to turn her interest to exploring resistance to the Covid-19 virus.

Written by Amitha


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