Thread by @Bob_Wachter

1/ Covid (@UCSF) Chronicles, Day 135

UCSF Medical Grand rounds today, available here tinyurl.com/y2tpw3h4. If there could be such a thing as a “classic” set of topics in a pandemic that’s only 6 months old, today was it: Updates in testing, treatments and vaccines.

2/ Very brief local updates today to save room for grand rounds:

@UCSFHospitals, 35 pts, 9 vents. Possibly plateaued but significantly up over last few weeks (Fig L). SF hospitalizations also up, 112 today (R). Deaths still just 58 since March.

3/ Grand rounds. First, Chaz Langelier on testing. @ 7:00, 193 Covid tests approved by @US_FDA (Fig on L), incl. at-home tests: you swab your own nose (studies show it's as good as fancier deep swab), send it off, & get a result, hopefully (but not always) in few days (Fig R).

4/ @ 9:50, test timing matters. Fig L: association between day of infection & test positivity (viral & antibody). Viral load falls over time, as does test sensitivity. While PCR remains positive for a while, viral cultures (correlates w/ live virus) become neg by ~2 wks (Fig R).

5/ @ 14:00, graph on left shows that Ct value (measure of infectiousness) is high in first days, then falls. Graph on R shows that patients are actually most infectious in the 1-2 days BEFORE they have symptoms; infectiousness falls off quickly after 2-3 days of symptoms.

6/ @ 16:00, newer thinking re: tests: perhaps better to focus on rapid tests (vs super-sensitive PCR tests). Rapids are less sensitive but may be good enough to detect infectious pts. Tradeoff of deploying more/cheaper tests may be net +: might miss a few cases, but few spreaders

7/ @ 20:30, so when do we require a very sensitive test? High risk settings, hospitalized pts: yes. But in the community, Chaz argues that widespread use of faster, less sensitive tests might do more to decrease transmission than limiting ourselves to slower, PCR-based tests.

8/ @ 18:30 Test turnaround matters too. Study demonstrated that daily use of quick but less sensitive test would lower Ro a lot. If you test less frequently, doesn't help decrease transmission as much. Once you're @ 1-2 wk turnaround times, does very little to lower transmission.

9/ @ 21:20, on pooled testing: reasonable if prevalence very low (<~5%; note that CA is ~7.5%) since you’ll won't have many +'s to follow-up. But once prevalence is >5%, not cost effective, since you’ll spend more time retesting samples than doing individual tests in first place.

10/ Next, @annieluet on therapies. @ 28:30, NIH guidelines on Remdesivir use: prioritize RDV for pts on supplemental O2, over pts on high flow O2 or intubated. Annie reviews data: yes, more benefit for less sick pts, but underpowered in hi-flow O2, ICU. May be benefit there too.

11/ @ 35:30: Annie on dexamethasone. Benefit seen in ICU pts (41%→29% mortality). Pts who are hypoxic but out of ICU: real but small benefit. Patients not on O2: no benefit, and maybe even some worsening. So don't start steroids too early (such as in floor pt off O2 or outpt).

12/ @ 40:00: Exciting preliminary data on inhaled interferon beta. In study out via press release, Synairgen's interferon resulted in 79%↓ in intubation/death. “Intriguing” but need to see actual study. Other studies ongoing, incl. sub-q interferon & inhaled interferon at home.

13/ @ 44:00: Annie hoped we were done w/ hydroxychloroquine, but its in news again. 8 (!) randomized controlled studies: none found benefit; some possible harm. @ 1:19:30, she comments on Detroit study; far weaker study design than studies below. No indication for HCQ in Covid.

14/ @ 45:30: Outpatient therapy is “the next frontier.” Multiple promising approaches listed below, none proven. Would be great to prevent deterioration & spread. @ 1:17:30: we may give an outpt med only to high-risk pts; depends on how expensive & risky the meds turn out to be.

15/ @ 48:30: Convalescent plasma. Currently studying it @UCSF. In U.S., >50K pts have received it already. “While early signals look good, we don’t have randomized controlled data.” New meta-analysis does show mortality benefit. “Stay tuned for more info, but it looks promising.”

16/ @ 53:00: Joel Ernst on vaccines. Status report below. 3 vaccines have reported from Phase 1/2 trials, all showed neutralizing antibody production w/ acceptable side effects. Several different vaccine types; each w/ plusses & minuses. Also seeing T-cell responses in early data

17/ @ 57:45: Also promising: two published mice studies show transferring neutralizing antibodies induced by vaccination from one mice to another reduced the viral load. Shows that “neutralizing antibodies are actually a mechanism of protection, not just a phenomenon.”

18/ @ 1:00:35: Joel addresses studies showing waning antibodies over time. He’s not very concerned – “this is back to Immunology 101.” We have memory B cells that respond to infection by waking up when they see their pathogen. “I would not use this data as source of pessimism.”

19/ @ 1:04:30, how to test efficacy of vaccines. It may take >1yr to learn if vaccines work via nl trials; he describes benefits/drawbacks of human challenge trials (Fig). “There’s no precedent for doing challenge trials in infection that lacks reliable treatment.” Tricky stuff!

20/ @ 1:10:30: To finish talk, Joel discusses other challenging issues, including who should get vaccines first (Fig on L), and fact that 50% of Americans say they might not take an approved vaccine (Fig R). We need a new approach to public outreach and marketing.

21/ Starting at 1:12:30, a free-wheeling Q&A, including: 1) When is the earliest we'll know a vaccine works (Joel: “pretty unrealistic” that we’ll know at end of 2020); 2) Whether proving that a vaccine works in a 25 year old proves it’ll also work in 75 yo (Joel: probably so)…

22/ … 3) Have there been any re-infections? (Chaz: no definitive evidence; “cases” may be new non-Covid case w/ persistent PCR + from 1st infection); 4) What happened to saliva for viral testing? (Chaz: hasn’t gained traction, though it works just as well as swab)…

23/ Finally, @ 1:25:45, I asked all 3 when we’ll have a game-changing strategy that gets us to normal life, and what it would be: meds, vaccine, testing. All three say a year from now; only Joel thinks it’ll be with a vaccine. Chaz: testing. Annie, surprisingly, agrees: testing.

24/ Another superb and eye-opening session. Hope you have a chance to watch it (90 minutes). Again, it’s here: tinyurl.com/y2tpw3h4

Back tomorrow with some thoughts about San Francisco’s Covid performance, surge and all. Till then, stay safe.