Thread by @Bob_Wachter

1/ Covid (@UCSF) Chronicles, Day 51

Thursday, so Medicine Grand rounds day. Video here: bit.ly/2SMdTnC We covered virology, immunology, prospects for vaccine/treatments; pandemic update; & report from Navajo Nation. Local update first:

2/ Stable @ucsf; 15 cases (down 1), 8 vented (up 1). Today we disbanded Covid command center, whose leaders comported themselves w/ skill, grace & heart.

SF also remains on plateau, averaging ~40 new cases/day. Hospitalizations 80, down from peak of 94. 32 deaths, up 1.

3/ Grand Rounds:

@ 02:16: Sri Shamasunder (@srijeeva; @healinitiative) is 1 of 20 @ucsf RNs/MDs helping Navajo Nation. It's 2700 sq mi, ~ size of New England; ~350K people) & has 220 hospital beds & 6 ICU beds. Covid surge exposes huge shortage of MDs, RNs, vents, hi-flow O2.

4/ @ 10:30: Sri describes local successes & resourcefulness, but national failure. The Indian Health Service @IHSgov receives 1/3 the funding that VA receives. @UCSF clinicians are helping now but can’t change fundamental conditions. “Our colleagues here are running a marathon.”

5/ Next, George Rutherford (@Rutherford_UCSF)

@ 17:00: Amalgam of different curves, with NY getting better but rest of US plateaued or getting worse. “We’re in a steady state, 25-30K cases being reported daily. Nothing to suggest this is dropping off.”

6/ @ 17:50: Growing epidemic in small towns, “I know a ton about geography & I’ve heard of 3 of these [top 10 cities] before.” Mostly from outbreaks, in food processing plants, prisons, ships, etc. Disproportionate cases among minority populations, particularly Latinx.

7/ @ 21:00: Per White House: by 6/1, 200,000 Covid cases PER DAY in U.S; surge due to relaxing distancing. George: "Really sobering.” WH also projecting 3000 deaths/day by 6/1: Korean War-like toll in a month. Northern CA will likely continue to do well; more worried about SoCal.

8/ @ 23:30: History of 1918 flu may presage big outbreak in fall, which’ll make experience to date “pale in comparison.” Premature opening “will be paid for in blood.” “People have to wear masks, socially distance... or things will get much worse." Disparities are a huge concern.

9/ @ 27:05: Some early evidence that Covid may “not be hyper-transmissible” in children, good news as we think about opening schools. George reviews evidence (“it needs to be repeated about 800 times for us to believe it”) and describes why kids might not be very contagious.

10/ Switching gears, @ 32:32, @ucsf ID leader Joel Ernst describes why vaccines are needed, & varied approaches for potential Covid vaccine. Fact that asymptomatic people can transmit is strong argument for vaccine, & high mortality is argument against aiming for herd immunity.

11/ Fascinating discussion re mucosal immunity (@ 41:40): virus invades mucosal surfaces (nose/respiratory tract). I asked @ 1:28:30 whether a nasal spray could work. Don Ganem: many practical problems w/ pharmacokinetics. Melanie Ott: “the blood is not the [key] place to look.”

12/ @ 36:00, discussion re: “needing the right antibodies.” Neutralizing antibodies are protective; there are actually some antibodies that can be harmful. For many coronaviruses, immunity is not long lasting, tends to wane in 1-2 years.

13/ @ 46:10: Melanie Ott, head of virology @GladstoneInst, gave elegant description of how viruses work. “Viruses are quintessential pirates… they hijack host factors to set up little viral factories in the cell… [and these genomes] infect the neighboring cells.” @TheOttLab

14/ @ 53:55: Cool discussion re: target cells for the virus. GI tract: lots of virus but little GI clinical disease, & no fecal transmission. @ 1:31:00 Don Ganem describes amazing study that analyzed fecal waste stream (in sewers) to detect Covid hot spots bit.ly/2SP9f8C

15/ @ 59:12, Nevan Krogan @QB3 discusses amazing team effort @ucsf & around world to attack virus. @ 1:33:08, he sees elimination of silos as key advance in science (more important than any new machine or technology). Described in great @sfchronicle piece: bit.ly/3daqWae

16/ @ 1:04:00: As part of this team effort, Krogan offered to distribute plasmids to others, “with no lawyers involved,” and in weeks shipped plasmids to 318 labs in 38 countries. “These plasmids spread around the world faster than the virus did.”

17/ Study bit.ly/3duXDQ3 identified 10 existing drugs that seem likely to have efficacy in Covid. At 1:37:15, Don Ganem, @ucsf prof & former head of ID Research @Novartis, was skeptical that repurposed drugs would be blockbusters. Thinks we’ll have to find something new.

18/ Q&A @ 1:13:30: Ganem described how biopharma firms think re drugs/vaccines. More than 90 companies working on vaccine. But we’ll need to not only find vaccine but figure out distribution/supply chain. Past coronavirus studies don't give confidence that vaccine will be easy.

19/ On treatment side, Ganem is a bit more hopeful. Remdesivir proves Covid drugs can work, but limited value since requires IV, which means patients who get it will be fairly late in their course. Need oral drugs that can be given early, during active viral replication phase.

20/ Finally @ 1:35:00 I asked all four experts to take out their crystal balls and predict when a blockbuster (treatment or vaccine) would be available, and which (drug or vaccine) would come first. Results in next tweet: 3 moderately optimistic and one quite a bummer.

21/ Ernst: Drugs will come before vaccines. Blockbuster drug: 7/14/21.

Krogan: Drugs 1st, need drug combo; available late 2020.

Ott: Drugs first, also need combo, early '21.

Ganem: Drugs really hard. Partially effective vaccine (good enough to be a gamechanger): 2023 (3 yrs).

22/ Sobering way to end, but there you have it.

Once again, Grand Rounds here: bit.ly/2SMdTnC Worth 90ish minutes if you have the time.

Stay safe, I'll be back tomorrow.