#97 – Peter Hotez, M.D., Ph.D.: COVID-19: transmissibility, vaccines, risk reduction, and treatment

KEYPOINTS

• 01

  This is a snapshot from mid-March 2020

  The conversation was recorded around March 13, 2020, when the US had run roughly 75,000 tests and had about 1,600 known cases. Hotez, a vaccine scientist at Baylor College of Medicine and Texas Children's Hospital, repeatedly says how much was still unknown. Treat the numbers as early estimates, not settled facts.

• 02

  Third major coronavirus outbreak this century

  SARS in 2003 and MERS in 2012 preceded SARS-CoV-2. Hotez notes that when he trained, coronaviruses were considered minor causes of colds in children. Having had a serious coronavirus outbreak each decade is his argument for prioritising coronavirus vaccines from now on.

• 03

  Moderate lethality plus high transmission made SARS-CoV-2 dangerous

  SARS-1 made people so sick that they ended up in hospital rather than spreading it in the community, so it burned out. SARS-CoV-2 leaves many children, adolescents and young adults mildly ill while they shed virus. Severe disease concentrates in people over 70 and in those with diabetes, hypertension or heart disease. Hotez's working reproductive number was about 2.2–3.6, compared with roughly 1.2–1.3 for seasonal flu and 12–18 for measles.

• 04

  Early fatality estimates ranged widely

  Hotez cited a case fatality rate of 0.6–3.4%, which he called four to twenty times higher than influenza, and 10–20% among older people. He pointed to the nursing home in Kirkland, Washington, where about 13 of roughly 100 residents died. Attia relayed Marc Lipsitch's scenario of half the world infected within two years at a 0.5% fatality rate. Hotez called it plausible, but noted that small changes in a model's assumptions can shift its outputs by orders of magnitude.

• 05

  Losing healthcare workers hurts more than their numbers suggest

  In Wuhan at least 1,000 healthcare workers were infected, and about 15% became seriously ill or needed intensive care, more than their ages would predict, possibly because of larger viral exposures. Attia points out that losing 10–15% of physicians, nurses and respiratory therapists reduces care by far more than 10–15%. First responders forced into quarantine compound the problem.

• 06

  Catching spread early decided how hard cities were hit

  Hotez cites work by his colleague Marc Lipsitch's group: Wuhan, where transmission went unchecked for about six weeks, was overwhelmed. Guangdong detected it within roughly a week and had about 20 people in intensive care. Given US testing delays, Hotez expected case counts to rise as much as tenfold in a week as testing moved to Quest, LabCorp and Roche.

• 07

  Convalescent plasma was the treatment available immediately

  Hotez publicly backed the idea, promoted by Johns Hopkins' Arturo Casadevall, of collecting antibodies from recovered patients to use both as treatment (large doses) and as prevention for healthcare workers (small doses). He drew on precedent from the 1918 flu, SARS and MERS. Attia flagged the bottleneck that collection requires plasmapheresis. Remdesivir, Gilead's Ebola drug then in compassionate use, still needed clinical trials.

• 08

  Vaccines carry a specific coronavirus safety risk

  In the 1960s, an inactivated RSV vaccine made vaccinated children sicker when they later caught the virus, with more hospitalizations and two deaths. After SARS in 2003, killed-virus vaccines and whole-spike vaccines caused similar 'immune enhancement' damage in animals, in the lungs or liver. Because vaccines are given to healthy people, trials normally run through three phases over years, so Hotez didn't expect a vaccine within 12 months.

• 09

  ACE2 receptors throughout the body may explain the varied symptoms

  The receptor occurs in the intestine, the heart and the lining of blood vessels as well as the lungs. Many critically ill patients had acute heart injury, and it was unclear whether that was myocarditis, heart attack or a consequence of ARDS and shock. At least 10% of some Wuhan patients first had GI symptoms, were sent to surgery and infected staff. Paul Offit speculated that cruise-ship outbreaks pointed to gastrointestinal spread, as with norovirus.