How San Francisco led the way on COVID-19 research

‘Many people in the Bay Area may not realize how much we are quarterbacking this’

Through a combination of strict lockdown, masking and proof-of-vaccination policies, San Francisco managed to keep COVID-19 hospitalizations and deaths lower than in most parts of the country.

But that wasn’t the only thing that made San Francisco stand out during the pandemic. The City is home to a leading medical institution and some of the world’s top infectious disease experts at the bleeding edge of both local and global understandings of the disease.

“San Francisco is really the epicenter of SARS-COV-2 research,” said Nevan Krogan, director of the Quantitative Biosciences Institute at the University of California, San Francisco. “Many people in the Bay Area may not realize how much we are quarterbacking this.”

As San Francisco and the rest of the world now face the omicron variant, local medical leaders say we not only understand much more than we did a year ago, but we have more tools to combat rising cases and the evolving variants.

In a year where everything felt stagnant, here are the local discoveries that kept us moving forward.

Understanding the virus

Much of what we understand so far about COVID-19 revolves around transmission and how to protect individuals from spreading the virus. But Krogan’s team at the Quantitative Biosciences Institute is charting new frontiers for therapeutics and how the coronavirus impacts our immune response and mutates once an infection happens.

The alpha covid variant — regarded as the first “variant of concern”— developed mutations that allowed it to suppress the immune system’s early response to infection, according to a study published this month in Nature from researchers at QBI and University College London. Understanding these mutations and how the virus evolves is key to not only tracking future variants but also in developing new drugs to treat COVID.

“Very excitingly, what we found here is that this new variant, in comparison to the older lineage of the virus, suppressed the immune response,” said Nevan. “After the virus gets into our cells, other mutations could aid in its survival and replication. But nobody is talking about the immune response.”

The researchers also observed similar mutations in the delta and omicron variants. As breakthrough cases continue to surge with the omicron variant, Krogan believes the need for better therapeutics is ever-pressing and hopes the new findings can help explain why COVID-19 symptoms have extended for months for some individuals.

First U.S. omicron case

Only a couple of weeks after the omicron variant was first reported in South Africa, a small team of scientists led by Charles Chiu at UCSF successfully identified the first known case of the variant in the United States.

The team received a sample from an infected traveler, who had returned to San Francisco from South Africa, around 6 p.m. Nov. 30. By sunrise, the team had produced the genomic sequence confirming it was omicron using a tiny device called a nanopore sequencer.

“We were able to confirm the detection of omicron in five hours and had nearly the entire genome in eight hours,” Chiu said Dec. 2. “At 4 a.m. last night we were able to conclusively demonstrate that this was an infection of the omicron variant.”

Omicron is now the dominant version of the coronavirus in the country and Bay Area, and its quick detection has allowed researchers to more rapidly begin to understand how it aligns or differs from delta and other variants.

Pregnant women

As one of the largest inoculation campaigns in history took off this year across the country, questions circulated about the vaccine’s effect on expecting mothers and their babies. On the heels of a wave of misinformation around how the vaccine affects fertility, UCSF researchers provided some of the earliest evidence showing the messenger RNA vaccine is indeed safe for expecting mothers and that it was not transferred through human milk.

The small study analyzed breast milk from seven women who had each received either a Pfizer or Moderna mRNA vaccine.

“The results strengthen current recommendations that the mRNA vaccines are safe in lactation, and that lactating individuals who receive the COVID vaccine should not stop breastfeeding,” said Stephanie L. Gaw, assistant professor of Maternal-Fetal Medicine at UCSF and author of the study which appeared in JAMA Pediatrics.

COVID-neutralizing antibodies

Another blockbuster this year came in April when the QBI Coronavirus Research Group and researchers from the Agency of Science, Technology and Research in Singapore published a study that showed varying efficacy among different neutralizing antibodies used in COVID-19 therapies.

The joint study, published in Cell, found different antibodies may inhibit or enhance the formation of syncytia, which occurs in the airway tissues of COVID-infected patients and has been linked to severe tissue damage.

“For vaccine design, first we have to find the right spots for where to develop antibodies to. The technology for putting mRNA into an individual… is phenomenal. Now, how do you engineer the right (antibody) substitutions?” said Charles S. Craik on a virtual panel in September about the findings. “It makes it extremely exciting to continue to try to probe how do we get at these dynamics… but in the end, you have to find something to work by making the right antibodies.”

The findings are increasingly important now as some early research is showing the tools and therapies that worked well against the delta variant may not be as effective against omicron.

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