The first Harvard Medical Grand Rounds of the fall 2020 featured a guest who has become a household name since the COVID-19 pandemic began: Anthony Fauci, MD, the director of the National Institutes of Infectious and Immune Diseases (NIAID).

In an hourlong event co-hosted by Massachusetts General Hospital, Brigham and Women's Hospital and Beth Israel Deaconess Medical Center, Dr. Fauci shared his insights on the ongoing COVID-19 pandemic, including updates on vaccine development, treatment options, risk factors for severe disease, research challenges and more.

Here are some key takeaways (you can watch the full replay here):

Epidemiology and Infection Control

One reason the United States has fared so poorly in containing the virus is that the average baseline of daily new cases never dropped to what he considers an acceptable level before reopening efforts began, Fauci said.

When the rate of new infections in the U.S. stabilized in May and June 2020, it was at a "disturbingly high" rate of 20K per day in comparison to the European Union, which was well below 10K new cases per day.

"We saw the effects of this when we tried to reopen the economy in southern states such as Florida, Texas, Arizona and southern California and had a dramatic surge in cases," Fauci said. "These surges associated in many respects with holiday weekends such as Memorial Day and the Fourth of July."

As a result, the U.S. peaked at 70K cases per day during the summer. That has now fallen to an average of 40K to 50K new cases a day, which is “an extraordinary unacceptable baseline” when you think about entering the fall and winter season, he said. Fauci added that he will be watching carefully over the next three weeks to see if there is a similar spike in cases after Labor Day weekend.

Another factor could be that the U.S. did not shut down to the extent that other countries did during the spring surge, he said. In comparison to similarly hard-hit countries of Spain and Italy, the U.S. had much smaller reductions in terms of:

  • The number of visits to parks and outdoor spaces
  • The presence of employees in workplaces
  • The number of individuals visiting grocery stores and pharmacies

Treatment Options

After remdesivir was shown to be effective in reducing the time to discharge for patients hospitalized with severe COVID-19, clinical trials are now underway to test combinations of remdesivir combined with other drugs such as immune modulators, using treatment with remdesivir only as the control group.

However, both remdesivir and dexamethasone, the two therapies that have been confirmed effective thus far, are for patients in the later, more severe stages of disease.

Fauci said that scientists at the National NIH are optimistic that monoclonal antibodies, laboratory-made versions of proteins naturally produced by the immune system in response to invading viruses or other pathogens, could be an important therapeutic for early disease and have just launched clinical trials to explore this further.

Testing

Antigen tests—tests that identify the presence of viral proteins rather than viral RNA as an indicator of infection—are now assuming a much greater role, Fauci said.

The government has ordered 150 million of Abbot's Binax Now antigen test, which Fauci described as an inexpensive, highly sensitive, highly specific test that delivers results in 15 minutes. The tests will be distributed throughout the country to nursing homes, prisons, schools and other places in need of rapid testing, he said.

Transmission

A key challenge in limiting spread of the SARS-CoV-2 virus is that about 40%–50% percent of infected individuals are asymptomatic—and these individuals are likely responsible for 50% of all transmissions, Fauci said. This makes identification, contract tracing and isolation efforts more difficult.

Aerosol and particle physicists have also corrected a key misunderstanding about respiratory droplets, namely that droplets greater than 5 micrometers in size stay in the air much longer than previously believed.

"We used to say that droplets greater than five micrometers immediately dropped to the ground and those less than five micrometers might be aerosolized." The sustained presence of large droplets in the air may explain why the virus has been able to spread so fast in settings such as choirs and churches.

Clinical Presentation and Risk Factors

Fauci is still perplexed by the range of symptoms and disease severity in COVID-19. This is likely due to a variety of factors such as individual genetics and the state of immune system activation, he said. "It's a very interesting disease—too little immunity is no good, too much immunity is really bad."

The number of asymptomatic individuals is also puzzling, and is unlikely to be solely due to those individuals mounting a more efficient immune response, he said. There may be other factors such as individual expression of ACE2—a gene encoding the enzyme that the virus uses to hijack cells—that contribute to asymptomatic cases.

Vaccine Development

Fauci, who played a leading role in establishing the COVID-19 Prevention Trials Network to standardize and support national efforts to develop a vaccine, believes there will be one or more viable vaccines identified by the end of the year.

His "cautious optimism" is based on encouraging data from Phase I and II studies, as well as steady progress on large scale Phase III trials for safety and efficacy in humans. "But with vaccines you never say 'never' and you never say 'always,'" he added. "There’s nothing guaranteed, we’ll just have to see."

Fauci also praised the CEOs of all the companies involved in vaccine development, who pledged earlier this month not to push for vaccine approval until they had significant confirmation of safety and efficacy.

"It is really unprecedented for industry to do that, especially as there has been a lot of talk about trying to rush a vaccine through before the election."