Eric Meyerowitz, MD Profile picture
Sep 17, 2020 14 tweets 4 min read Read on X
1/ Our comprehensive review of transmission of SARS-COV-2 is out in @AnnalsofIM with @AaronRichterman @RMKGandhi @PaulSaxMD

acpjournals.org/doi/10.7326/M2…
2/ We review environmental viability of virus in experimental and real world settings.

RNA reported in many real world studies, but at very low copy counts

Viable virus assessed for only rarely and in those instances only isolated occasionally, also at very low levels
3/ We review viral and host factors that impact transmission

Children under ten appear half as susceptible but relative probability of transmission from children compared with adults not well understood

Virus with D614G mutation is associated with higher in vivo viral loads
4/ Respiratory transmission dominant

Droplet vs aerosol model = oversimplification

That proximity is key determinant of transmission suggests relative importance of classical droplet mode, but in indoor environments w/ poor ventilation, can transmit at a distance thru aerosols
5/ Despite concerns about fomite transmission, there is no conclusive evidence to support this mode of transmission and if it happens at all is likely only responsible for a minority of spread

That said good hand hygiene is protective against acquisition of virus
6/ Some domestic pets can be infected but no documented transmission from domestic pets to humans. However, minks can be infected and there is documented transmission from minks to humans
7/ It was unclear for a while, but there is now conclusive evidence for rare vertical transmission
8/ There is no conclusive evidence for fecal-oral spread. There is currently one cluster report potentially caused by fecal-aerosol spread, though this is likely extremely unusual

There is no current evidence for sexual or bloodborne transmission of the virus
9/ The "period of infectiousness" is best known for immunocompetent adults who develop symptoms

Infectiousness peaks just before or right around symptom onset and declines quickly after, despite ongoing RNA shedding
10/ In patients with mild or moderate disease, infectious virus cannot be cultured after around 8 days of symptom onset.

In those with severe or critical disease infectious virus can be cultured a bit longer, with the latest isolation of infectious virus 20 days after symptoms
11/ Despite isolation of infectious virus, there are no documented late transmissions, after about a week of symptoms
12/ Heterogeneous transmission is the explanation for superspreading events, which are an important feature propagating the pandemic

The figure models heterogenous transmission. An index case transmits to 2 secondary cases; 1 has no other transmissions while other transmits to 4
13/ Outside of superspreading events the household is a key site for transmission. After superspreading events further transmission frequently occurs in households
14/ Conclusions

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More from @EricMeyerowitz

Feb 12, 2021
1/ Thoughts on the exciting world of tocilizumab for treatment of COVID-19.

RECOVERY tocilizumab preprint posted earlier today is another landmark paper and an enormous contribution to our expanding COVID-19 treatment playbook

medrxiv.org/content/10.110…
2/ A quick review of 7 prior tocilizumab RCTs

First COVACTA which found no benefit with tocilizumab

medrxiv.org/content/10.110…
3/ Second CORIMUNO-TOCI also found no benefit, but there was some drama with this study when DSMB members quit after a press release they disagreed with in the late spring 2020

world-today-news.com/lively-controv…
Read 24 tweets
Jan 27, 2021
1/ Key question right now is how much SARS-CoV-2 vaccines will decrease transmission.

Data from Regeneron mAb cocktail prevention press release may help us think about this

investor.regeneron.com/news-releases/…
2/ They report their mAb cocktail had 100% efficacy in preventing symptomatic COVID-19 (8/223 placebo vs. 0/186 REGEN-COV)

They also report lower ASYMPTOMATIC infection (15/223 placebo vs. 10/186 REGEN-COV)
3/ Among the infections, way less peak viral load and viral shedding seen
- Avg peak VL >100x placebo vs REGEN-CoV
- Infections in REGEN-CoV lasted <1 week, while 40% in placebo lasted 3-4 weeks

(would be nice to see VL comparison just for asymptomatic cohorts)
Read 6 tweets
Dec 8, 2020
1/ We've learned so much since the beginning of the pandemic, but we still have not well defined the persistently asymptomatic fraction

Why is it important to describe this group and what are the limitations to doing so thus far? A thread 😷😷

sciencedirect.com/science/articl…
2/ An early transmission report of suggested transmission is possible prior to symptom onset.

Need to distinguish between: persistently asymptomatic infection (no symptoms attributable to the virus for the duration of infection) and presymptomatic state

nejm.org/doi/full/10.10…
3/ Inconsistent symptom assessment & reporting has limited defining this group

Our understanding of the possible clinical presentations has evolved since the beginning

Example: anomia/dysgeusia were described in March & increasingly reported after being featured by the media https://www.nature.com/articles/s41591-020-0916-2
Read 15 tweets
Nov 20, 2020
1/ New in CID, our review of immunomodulation as treatment for COVID-19 with @Arthur_Kim_ID, Michael Mansour, and a great team (mostly not on twitter)

academic.oup.com/cid/advance-ar…
2/ We start with a narrative review of immune changes in severe COVID-19.

Earlier it was considered a possible "cytokine storm," but now strong evidence that it is a more complex immune dysregulation

Mild dz = early, effective innate and coordinated adaptive immune response Image
3/ Severe disease is marked by attenuated early interferon response and related elevation of certain inflammatory markers

Also see a late uncoordinated adaptive immune response Image
Read 6 tweets
Aug 21, 2020
1/ In new preprint w/ @AaronRichterman @mugecevik @BogochIsaac @nicolamlow we argue limitations to understanding true asymptomatic fraction:

1) Inconsistent sx reporting

2) Inadequate f/u time to exclude "pre-symptomatic" ppl

3) Issues w/ serosurveys

papers.ssrn.com/sol3/papers.cf…
2/ Wide range of asymptomatic proportion reported in the literature from 4% to >80%. Systematic reviews provide best estimates and suggest values closer to 20% medrxiv.org/content/10.110…
3/ Our understanding of the symptom spectrum of SARS-CoV-2 infection has evolved over the last 9 months, with anosmia and GI symptoms often not included in early reports. By not including these mild or atypical symptoms, the estimated asymptomatic fraction may be overestimated
Read 7 tweets
Jun 23, 2020
Thoughts on RECOVERY preprint: dexamethasone as treatment for COVID-19 @AaronRichterman medrxiv.org/content/10.110…
Read 25 tweets

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