Non-Political Coronavirus Thread

[plama]

The whole point being you can't wait until September while written back in May and let a few hundred thousand people die because of a 9/100,000 chance that it might cause heart problems that results in a death, and that you have to have an outpatient treatment to prevent the hospitals from getting overloaded because contact tracing or stopping the spread was implausible. It's fairly hard to argue against that.

 

[plama]

This is from May 27th, so it’s now quite outdated with several randomized trials since then. It’s also not a study, just a review of the literature. If there is a specific study you find compelling I would be happy to look at it.

Were any of the randomized trials in an outpatient setting?

 

[ConnorEl]

In particular, hydroxychloroquine has received considerable attention as an agent with possible antiviral activity, but trials have not suggested a clear clinical benefit for patients with COVID-19, including those managed in the outpatient setting [65,66]. As an example, in an open-label trial including 293 patients with mild COVID-19 who did not warrant hospitalization, hydroxychloroquine administered within five days of symptom onset did not reduce viral levels at day 3 or 7 compared with no treatment [65]. In addition, there was no statistically significant reduction in hospitalization rates or time to symptom resolution. The rate of adverse effects, primarily gastrointestinal symptoms, were greater with hydroxychloroquine.

Reference 65...

Clin Infect Dis
. 2020 Jul 16;ciaa1009. doi: 10.1093/cid/ciaa1009. Online ahead of print.
Hydroxychloroquine for Early Treatment of Adults with Mild Covid-19: A Randomized-Controlled Trial

Oriol Mitjà 1 2 3 , Marc Corbacho-Monné 1 , Maria Ubals 2 , Cristian Tebe 4 , Judith Peñafiel 4 , Aurelio Tobias 5 , Ester Ballana 6 , Andrea Alemany 1 , Núria Riera-Martí 1 , Carla A Pérez 1 , Clara Suñer 1 , Pep Laporte 1 , Pol Admella 1 , Jordi Mitjà 1 , Mireia Clua 1 , Laia Bertran 1 , Maria Sarquella 1 , Sergi Gavilán 1 , Jordi Ara 2 , Josep M Argimon 7 , Jordi Casabona 8 9 , Gabriel Cuatrecasas 10 , Paz Cañadas 11 , Aleix Elizalde-Torrent 6 , Robert Fabregat 12 , Magí Farré 2 , Anna Forcada 13 , Gemma Flores-Mateo 14 , Esteve Muntada 8 , Núria Nadal 15 , Silvia Narejos 16 , Aroa N Gil-Ortega 1 , Nuria Prat 17 , Jordi Puig 1 , Carles Quiñones 2 , Juliana Reyes-Ureña 8 9 , Ferran Ramírez-Viaplana 1 , Lidia Ruiz 6 , Eva Riveira-Muñoz 6 , Alba Sierra 1 , César Velasco 18 , Rosa Maria Vivanco-Hidalgo 18 , Alexis Sentís 8 , Camila G-Beiras 1 , Bonaventura Clotet 1 2 19 , Martí Vall-Mayans 1 2 , BCN PEP-CoV-2 RESEARCH GROUP
Affiliations expand
PMID: 32674126 DOI: 10.1093/cid/ciaa1009
Full-text links Cite
Abstract

Background: No therapeutics have yet been proven effective for the treatment of mild-illness caused by SARS-CoV-2. We aimed to determine whether early treatment with hydroxychloroquine (HCQ) would be more efficacious than no-treatment for outpatients with mild Covid-19.

Methods: We conducted a multicenter, open label, randomized controlled trial in Catalonia (Spain) between March 17, and May 26, 2020. Eligible Covid-19 cases were non-hospitalized adult patients with recently confirmed SARS-CoV-2 infection and less than five days of symptoms. Patients were assigned to receive HCQ (800 mg on day 1, followed by 400 mg once daily for 6 days) or no antiviral treatment (not-placebo controlled). Study outcomes were the reduction of viral RNA load in nasopharyngeal swabs up to 7 days after treatment start, patient disease progression using the WHO scale up to 28 days, and time to complete resolution of symptoms. Adverse events were assessed up to 28 days.

Results: A total of 293 patients were eligible for intention-to-treat analysis: 157 in the control arm and 136 in the intervention arm. The mean age was 41.6 years (SD 12.6), mean viral load at baseline was 7.90 (SD 1.82) Log10 copies/mL, and median time from symptom onset to randomization was 3 days. No significant differences were found in the mean reduction of viral load at day 3 (-1.41 vs. -1.41 Log10 copies/mL in the control and intervention arm, respectively; difference 0.01 [95% CI -0.28;0.29]) or at day 7 (-3.37 vs. -3.44; d -0.07 [-0.44;0.29]). This treatment regimen did not reduce risk of hospitalization (7.1%, control vs. 5.9%, intervention; RR 0.75 [0.32;1.77]) nor shortened the time to complete resolution of symptoms (12 days, control vs. 10 days, intervention; p = 0.38). No relevant treatment-related AEs were reported.

Conclusions: In patients with mild Covid-19, no benefit was observed with HCQ beyond the usual care.

Keywords: Covid-19; Hydroxychloroquine; Randomized Controlled Trial; SARS-CoV-2; Therapy.

© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Reference 66...

Ann Intern Med
. 2020 Jul 16;M20-4207. doi: 10.7326/M20-4207. Online ahead of print.
Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19: A Randomized Trial

Caleb P Skipper 1 , Katelyn A Pastick 1 , Nicole W Engen 1 , Ananta S Bangdiwala 1 , Mahsa Abassi 1 , Sarah M Lofgren 1 , Darlisha A Williams 1 , Elizabeth C Okafor 1 , Matthew F Pullen 1 , Melanie R Nicol 1 , Alanna A Nascene 1 , Kathy H Hullsiek 1 , Matthew P Cheng 2 , Darlette Luke 3 , Sylvain A Lother 4 , Lauren J MacKenzie 4 , Glen Drobot 4 , Lauren E Kelly 5 , Ilan S Schwartz 6 , Ryan Zarychanski 4 , Emily G McDonald 2 , Todd C Lee 2 , Radha Rajasingham 1 , David R Boulware 1
Affiliations expand
PMID: 32673060 PMCID: PMC7384270 DOI: 10.7326/M20-4207
Free PMC article
Full-text links Cite
Abstract

Background: No effective oral therapy exists for early coronavirus disease 2019 (COVID-19).

Objective: To investigate whether hydroxychloroquine could reduce COVID-19 severity in adult outpatients.

Design: Randomized, double-blind, placebo-controlled trial conducted from 22 March through 20 May 2020. (ClinicalTrials.gov: NCT04308668).

Setting: Internet-based trial across the United States and Canada (40 states and 3 provinces).

Participants: Symptomatic, nonhospitalized adults with laboratory-confirmed COVID-19 or probable COVID-19 and high-risk exposure within 4 days of symptom onset.

Intervention: Oral hydroxychloroquine (800 mg once, followed by 600 mg in 6 to 8 hours, then 600 mg daily for 4 more days) or masked placebo. Measures: Symptoms and severity at baseline and then at days 3, 5, 10, and 14 using a 10-point visual analogue scale. The primary end point was change in overall symptom severity over 14 days.

Results: Of 491 patients randomly assigned to a group, 423 contributed primary end point data. Of these, 341 (81%) had laboratory-confirmed infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or epidemiologically linked exposure to a person with laboratory-confirmed infection; 56% (236 of 423) were enrolled within 1 day of symptoms starting. Change in symptom severity over 14 days did not differ between the hydroxychloroquine and placebo groups (difference in symptom severity: relative, 12%; absolute, -0.27 points [95% CI, -0.61 to 0.07 points]; P = 0.117). At 14 days, 24% (49 of 201) of participants receiving hydroxychloroquine had ongoing symptoms compared with 30% (59 of 194) receiving placebo (P = 0.21). Medication adverse effects occurred in 43% (92 of 212) of participants receiving hydroxychloroquine versus 22% (46 of 211) receiving placebo (P < 0.001). With placebo, 10 hospitalizations occurred (2 non-COVID-19-related), including 1 hospitalized death. With hydroxychloroquine, 4 hospitalizations occurred plus 1 nonhospitalized death (P = 0.29).

Limitations: Only 58% of participants received SARS-CoV-2 testing because of severe U.S. testing shortages.

Conclusion: Hydroxychloroquine did not substantially reduce symptom severity in outpatients with early, mild COVID-19.

Primary funding source: Private donors.

 

[Rafi]

Were any of the randomized trials in an outpatient setting?

This illustrates the problem here. For some reason, some people are just insistent that HCQ only works in certain settings. So when another trial fails to show benefit they’ll say, “well, the tincture of zinc wasn’t right in that study.” Why must HCQ be used as an outpatient?

But to answer you question, yes, there are trials looking at outpatient treatments. In fact, there is an NEJM trial looking at HCQ prophylactically (it didn’t work).

 

[plama]

Got it, although the Yale argument is based solely on HCQ + azithromycin

Evidenceabout use of hydroxychloroquine alone, or of hydroxychloroquine+azithromycin in inpatients, is irrelevant concerning efficacy of the pair in early high-risk outpatient disease.

 

[plama]

This illustrates the problem here. For some reason, some people are just insistent that HCQ only works in certain settings. So when another trial fails to show benefit they’ll say, “well, the tincture of zinc wasn’t right in that study.” Why must HCQ be used as an outpatient?

But to answer you question, yes, there are trials looking at outpatient treatments. In fact, there is an NEJM trial looking at HCQ prophylactically (it didn’t work).

I believe the answer here is you have to find an outpatient treatment because with early viral respiratory disease once someone's already admitted the disease has progressed too far. I believe once the trials he referenced come out , he could change his tune, but the first such trial isn't released until September, and at the time of writing in May the difference is a few hundred thousand more deaths if he's right versus a few hundred more deaths if he's wrong.

Logically we also need to find a way to keep people out of the hospital to begin with, as our hospitals don't have the capacity to treat those that need to be admitted. So we have to go with the best data on early outpatient treatment, even if the data isn't rock solid. Logically, it's hard to argue against.

 

[plama]

Reference 65...





Reference 66...

Also excuse my ignorance but in the first one hydroxy looks to be about ~17% effective: 5.9% vs 7.1%.

This treatment regimen did not reduce risk of hospitalization (7.1%, control vs. 5.9%, intervention; RR 0.75 [0.32;1.77]) nor shortened the time to complete resolution of symptoms (12 days, control vs. 10 days, intervention; p = 0.38). No relevant treatment-related AEs were reported.

And these numbers are slightly better as well 24% vs 30% and 4 hospitalizations vs 10.

At 14 days, 24% (49 of 201) of participants receiving hydroxychloroquine had ongoing symptoms compared with 30% (59 of 194) receiving placebo (P = 0.21). Medication adverse effects occurred in 43% (92 of 212) of participants receiving hydroxychloroquine versus 22% (46 of 211) receiving placebo (P < 0.001). With placebo, 10 hospitalizations occurred (2 non-COVID-19-related), including 1 hospitalized death. With hydroxychloroquine, 4 hospitalizations occurred plus 1 nonhospitalized death (P = 0.29).

Might not be a statistical game changer, but at least it's heading in the right directions.

 

[PhDeac]

Is there a clearer sign of the lack of (non-political) leadership than the fact that regular schmoes all over the country and trying to become experts on one specific drug?

 

[Rafi]

Got it, although the Yale argument is based solely on HCQ + azithromycin

Again, this reinforces my point. Why would one need to combine an antimalarial drug with an antibacterial drug to treat a virus? So much time and effort has been spent on these drugs that show little promise.

Obviously people in the US are taking these drugs based on prescriptions rising 2000% compared to last year, but here we sit still discussing these drugs despite numerous negative clinical trials and 150,000 deaths.

 

[ConnorEl]

Is there a clearer sign of the lack of (non-political) leadership than the fact that regular schmoes all over the country and trying to become experts on one specific drug?

And eagerly adopting firmly grasped biases.

It’s fascinating.

Kind of like a bad accident on the highway.

 

[PhDeac]

We need to answer this question. Why are politicians and political figures so invested in this one drug? Is it like trying to turn covfefe into a real word? Are they so desperate for Trump to be right?

 

[ConnorEl]

...or wrong?

Either way, we’re all poorly served by a potus who is rightly identified as a chronic pathological liar, megalomaniac, and narcissist.


Non-politically.

 

[birdman]

Again, this reinforces my point. Why would one need to combine an antimalarial drug with an antibacterial drug to treat a virus? So much time and effort has been spent on these drugs that show little promise.

Obviously people in the US are taking these drugs based on prescriptions rising 2000% compared to last year, but here we sit still discussing these drugs despite numerous negative clinical trials and 150,000 deaths.

Feels a little bit like the tremendous effort the medical research community has invested in demonstrating that vaccines don't cause autism.

 

[Louis Gossett Jr]

You are largely talking about a group of people that listen to and absorb all kinds of crazy information from a whole host of characters whose only actually goal is to sell things like supplements.

 

[JuiceCrewAllStar]

non-politically and all, but roughly what year would you estimate was the inflection point for a critical mass completely disregarding all public health advice?

like, if this happens in the 80s, I imagine all the Reganites wear masks

I guess it's sometime during the Obama years and correlates directly with the Tea Party, so I'll say like 2009

 

[Louis Gossett Jr]

Well Wakefield’s MMR and vaccines Lancent article came out in 1998 so definitely earlier than 2009. He was also given a platform by the media just like crazy alien DNA demon sperm lady. I would say a combination of common access to the internet, amplified by the invention of social media, all with a foundation of news media revenue, clicks, and entertainment over factual reporting.

 

[dartsndeacs]

Again, this reinforces my point. Why would one need to combine an antimalarial drug with an antibacterial drug to treat a virus? So much time and effort has been spent on these drugs that show little promise.

Obviously people in the US are taking these drugs based on prescriptions rising 2000% compared to last year, but here we sit still discussing these drugs despite numerous negative clinical trials and 150,000 deaths.

I mean there was a reason these two drugs were picked, right? The malarial drug suppresses an over active immune system and the antibacterial drug treats pneumonia.

The point my cousin has is that it’s criminal to not try and test anything that might work, and you seem to not even want to investigate it. Meanwhile he’s got frontline doctors who firmly believe in it, and some data which suggests it may work really well, is cheap, and relatively harmless. He’s not a crazy mouth breather. He’s loud because he thinks liberals with an agenda are helping cause unneccessary death.

None of those clinical trials have combined the two drugs and at least since May that’s been recommended. Why the aversion to even run a clinical trial on it? It’s not like we have a lack of patients.

 

[Biff Tannen]

It's all about that blood type.

 

[Kory]

non-politically and all, but roughly what year would you estimate was the inflection point for a critical mass completely disregarding all public health advice?

like, if this happens in the 80s, I imagine all the Reganites wear masks

I guess it's sometime during the Obama years and correlates directly with the Tea Party, so I'll say like 2009

less about politics and more about information, imo.

whenever you feel the transition from broadcast/gatekept/curated media to web/low-cost/networked/algorithmically-curated media take over

probably ID'ing a single year isn't helping much

 

[dartsndeacs]

It's all about that blood type.

https://hms.harvard.edu/news/covid-19-blood-type