Thread by @Bob_Wachter

1/ Covid (@UCSF) Chronicles, Day 93

Grand Rounds today, available here: Today we cover two hot topics: 1) New data on therapies (including news on dexamethasone) & 2) Covid patients w/ persistent symptoms.

2/ First, a local update. As you may recall, last wk we saw doubling of @UCSF Covid pts, odd since SF overall admits/cases stable. I thought it might be a blip, and it probably was. Today we’re down to 11 pts @UCSFHospitals hospital (from 17 last wk), only 1 on ventilator (Fig).

3/ SF also stable. Grateful given many places that were spared in Mar-Apr that are now getting hit (AZ, AL, TX). SF city cases stable at ~20/d (Fig on L), hospitalizations ~35 (Fig R). Just 1 death in 2 weeks. Rest of NorCal also good. Few hot spots in SoCal, though LA improved.

4/ On to grand rounds. First, @SDoernberg gives best review of the dexamethasone trial I’ve heard. Point one @ 04:15: dex is an old drug, tons of experience w/ it, & mixed history in respiratory failure, flu, ARDS. But certainly enough promise to merit rigorous Covid trial (Fig).

5/ @ 05:45 : And some preliminary observational studies suggested possible benefit, including one in Covid pts bit.ly/2zIPb19 and another in early ARDS bit.ly/2Naiaht. Hard to be sure when it’s observational, & many other steroid studies have had mixed results.

6/ @ 07:30, SD describes Recovery Trial recoverytrial.net
– hugely complex design. Patients randomized to 1 of 4 arms: HCQ, steroids (dex), azithromycin, or Lopinavir/Ritonavir. Then 2nd randomization to convalescent plasma or not, then 3rd (!) to Tocilizumab or not. Wow.

7/ Taken together, patients could be in one of 20 different intervention arms. In other words, we’ll be hearing results from this study for many months! We already heard one arm last week @NEJM: no benefit to hydroxychloroquine for prophylaxis bit.ly/2UZ2WAm

8/ @ 11:05, steroid results came out via press release on Tues. Key findings below, with significant improvements in patients on mechanical ventilation and those receiving oxygen; no benefit in pts not on oxygen. Overall impact of steroids across all pts: 17% mortality benefit.

9/ @ 13:20: Sarah compares the steroid data with results of Remdesivir trial bit.ly/2AOAPNn Similar % benefit, tho mortality difference didn’t reach stat. significance for RDV. Importantly, placebo vent group in dexameth trial had 41% mortality; vs. 14% in RDV trial.

10/ @ 14:10, Sarah summarizes the questions she has about steroids based on the study results. Concerns: not knowing about adverse events, patients crossing over into other groups. Her conclusion: intriguing but not yet ready to become standard of care yet (@ 19:20).

11/ @ 20:50: I tend to disagree with her, siding more w/ @VPrasadMDMPH’s argument: bit.ly/2UVCd7y (& slightly hyperbolic Fig below). Sarah wants to wait for more data, partly because our mortality rate @UCSFHospitals for vented patients is far less than 41% (~15-20%).

12/ Why am I with Vinay (now @UCSF)? Steroids: low risk (w/ short-term use), low cost, respected research group @UniofOxford, robust methods published, results strong. Putting that all together, I judge the risk of waiting to be higher than risks of giving dexameth in right pts…

13/ … Though I, like many, am annoyed that the data came out via press release. Harkens back to our discussion at last week’s Grand Rounds, where we debated the delicate balancing act between speed and safety in the setting of a pandemic bit.ly/3hiXTEx

14/ @ 23:50, I asked Sarah re: Dexamth vs Remdesivir, or both. A) “No reason not to give both…no reason to think that steroids may hamper effectiveness of RSV.” We already give steroids plus antimicrobials in other illnesses, so prob. OK. But “steroids make ID people nervous.”

15/ @ 25:45: I (RMW) won’t be shocked if folks start taking steroids at home (since they're oral & cheap). Sarah: “I think that is a bad idea.” (I agree, BTW.) Trial results: no benefit in people who didn’t require oxygen, and no theoretical benefit to starting steroids v. early.

16/ @ 30:30, we switched to our panel discussing patients with persistent Covid symptoms, which first came to popular (and my) attention through @edyong209's terrific piece @TheAtlantic bit.ly/2BuuJBF

17/ Starting @ 34:00, Coleen Kivlahan, a family practice MD & head of primary care @UCSFHospitals, describes her protracted Covid course. Two unusual features. 1) persistent PCR positivity for ~3 months, and 2) “phantosmia”: chronic perception of smelling a forest fire….

18/ …It's a very disturbing symptom that isn’t rare. Her case was described @sfchronicle bit.ly/30Sw0xf & she has received many calls from others w/ similar phantom smell. After about 10 + PCRs, Coleen is finally testing negative, feeling better, and now has antibodies.

19/ @ 38:00, Cliff Morrison, an RN, describes his prolonged & troubling symptoms: fever, body pain, shortness of breath, weakness, poor memory, confusion. His case also described @sfchronicle: bit.ly/2YIASCk And weird food cravings: “I lived on watermelon for a month.”

20/ Starting @ 45:00, @ucsf’s Michael Peluso, Jeff Martin, & Tim Henrich describe @UCSF's “Long-term Impact of Infection with Novel Coronavirus” study (LIINC: liincstudy.org), designed to understand clinical, immune, and virologic manifestations of persistent Covid.

21/ @ 1:02:00, Henrich talks about other post-infectious syndromes. Lasting immunologic, autoimmune, and neuro problems aren't rare. He also describes Coleen’s positive PCRs: quite sure she had non-replicating dead virus; no longer pathogenic or infectious. No test for this yet.

22/ @ 1:11:30: Cliff on stigma & anxiety w/ this illness. “I became so depressed that people around me were getting concerned.” Also wild mood swings, “almost bipolar but I missed the euphoria.” People thought he was faking it – good to be part of the study & see he’s not alone.

23/ @ 1:13:40: Coleen on her personal experience. “The most fun thing: being a citizen-scientist.” Her questions for study: 1) Why me?; 2) Why many partners are neg despite long-time Covid housemates; 3) How to interpret + viral tests, esp. how to be sure you’re not infectious…

24/ … 4) What's the future impact on pts like her: “I wonder about my heart, lung and brain.” Finally, she worries about the stigma – people haven't wanted to see or touch her. And stigma is "likely worse for those who also have the stigma of race or poverty" on top of Covid.

25/ That's it. Next wk, I’ll interview John Barry, author of The Great Influenza. We'll discuss historical lessons from the 1918 pandemic.

Again, hope you have a chance to watch this terrific Grand Rounds:

Back tomorrow with weekly update. Stay safe.