COVID-19: Medical and Scientific Information

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NationalTitles18

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Welcome to the COVID-19: Medical and Scientific Information thread.

The goal of this thread is to share and discuss medical and scientific information related to COVID-19 infection, the SARS-COV-2 virus, symptoms, course of disease, treatments, vaccines, and other directly related topics in a straightforward and apolitical manner.

Although many of these have been discussed in other threads, the information there is more difficult to uncover and recover due to the fast pace of unrelated content and the obvious political nature of many of the posts (in the NS thread).

If you wish to avoid the politics but would like to share and find information on this subject, then this is the TideFans thread for you.

We need to throw out a couple of caveats and disclaimers before we get started here:

1. Nothing on TideFans should be construed as medical advice, even if it comes from a medical professional. Everything posted on TideFans is for informational and entertainment purposes only, even if stated otherwise. Nothing here is to be construed as diagnosing or treating a disease or recommending a treatment or diagnosis. If you are concerned about your health (or another's) you should seek medical treatment in the way you best see fit.

2. We are attempting to offer a place where factual information can be shared, found, and discussed. Although TideFans attempts to allow many viewpoints and ideas to be discussed freely, false information can take many forms and may pose a danger. TideFans is not responsible for the information posted, whether true or false, but posts containing false, misleading, and/or dangerous information are subject to removal based on moderator/administrator discretion. If you make a post and it disappears please check with us prior to posting the same again. If you feel a post was wrongly removed for any reason please check with us.

3. We are hoping to have reasoned discussion of mainly scientific and medical studies and articles and other information pertinent to this discussion.

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Your questions and input are welcomed.

I'll kick things off with a few links regarding symptoms of COVID-19 and the course of illness.

Here's one from the CDC.

Here's another from Mayo Clinic.

And another from Worldometer that is a little more complete and includes information about the course of illness.

The symptoms vary from the classic and often reported symptoms of fever, cough, and shortness of breath. Some have primarily or mostly GI symptoms like nausea and diarrhea. Others may experience fatigue, achiness, or confusion or other flu-like symptoms.

The course of the disease is quite variable. Some seem to have mild or even no symptoms while others progress to not only respiratory distress and failure but also multiorgan dysfunction syndrome (MODS), organ failure, and death. No one currently understands why some have only mild symptoms and others have more severe disease.

There are currently NO APPROVED and PROVEN medical treatments for COVID-19. (Source)

Information for Clinicians on Therapeutic Options for Patients with COVID-19

Updated April 7, 2020
There are no drugs or other therapeutics approved by the US Food and Drug Administration to prevent or treat COVID-19. Current clinical management includes infection prevention and control measures and supportive care, including supplemental oxygen and mechanical ventilatory support when indicated. Interim guidelines for the medical management of COVID-19 will be provided soon by the Department of Health and Human Services COVID-19 Treatment Guidelines Panel.
Remdesivir
Remdesivir is an investigational intravenous drug with broad antiviral activity that inhibits viral replication through premature termination of RNA transcription and has in-vitro activity against SARS-CoV-2 and in-vitro and in-vivo activity against related betacoronaviruses. Information about clinical trials of remdesivir is available at ClinicalTrials.govexternal icon. Remdesivir is also available through an expanded access programexternal icon from the manufacturer, Gilead Sciences.
Hydroxychloroquine and Chloroquine
Hydroxychloroquine and chloroquine are oral prescription drugs that have been used for treatment of malaria and certain inflammatory conditions. Hydroxychloroquine and chloroquine are under investigation in clinical trials for pre-exposure or post-exposure prophylaxis of SARS-CoV-2 infection, and treatment of patients with mild, moderate, and severe COVID-19. More information on clinical trials can be found at ClinicalTrials.govexternal icon. FDA issued an Emergency Use Authorization (EUA) to authorize use of chloroquine and hydroxychloroquineexternal icon from the Strategic National Stockpile for treatment of hospitalized adults and adolescents (weight ≥50 kg) with COVID-19 for whom a clinical trial is not available or participation is not feasible.
Other Drugs
Several other drugs (e.g., investigational antivirals, immunotherapeutic, host-directed therapies) are under investigation in clinical trials or are being considered for clinical trials of pre-exposure prophylaxis, post-exposure prophylaxis, or treatment of COVID-19 in the United States and worldwide. Information on registered clinical trials for COVID-19 in the United States is available at ClinicalTrials.govexternal icon. FDA has issued guidance for administering or studying use of convalescent plasma for treatmentexternal icon of patients with COVID-19.
Treatment is supportive. IOW, if you can't effectively breathe on your own then your breathing will be supported with oxygen, ventilator, and/or other methods.

This should get the conversation started. Feel free to bring in articles that have been posted in other threads as well as new articles and links to studies and other reliable information sources.
 

NationalTitles18

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Cardiologists recommend that everyone who takes an ACE inhibitor (most generics end in -pril) or ARB (most end in -sartan) continue taking their medication. If you have questions or concerns you should contact your prescriber.

 

B1GTide

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Cardiologists recommend that everyone who takes an ACE inhibitor (most generics end in -pril) or ARB (most end in -sartan) continue taking their medication. If you have questions or concerns you should contact your prescriber.
Thanks - my wife's doctor that she would have a far greater chance of dying if she stopped taking hers than from COVID.
 
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TIDE-HSV

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Cardiologists recommend that everyone who takes an ACE inhibitor (most generics end in -pril) or ARB (most end in -sartan) continue taking their medication. If you have questions or concerns you should contact your prescriber.

One thing which bothers me about the current advice is that it seems to assume that the choice between ARBs and ACE inhibitors or absolutely nothing. This is a false choice. Patients are switched among the various hypertensives on a regular basis. I have been. Calcium channel blockers are a respected alternative, with only one minor side effect the other two don't have. I discussed the Lancet article with my cardiologist and he agreed that the ARBs we were on could, I say "could" pose a risk with Covid-19. If a calcium channel blocker will control BP as well, why take the risk of not switching? I like my choice...
 
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B1GTide

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That's a false choice...
Not for my wife - she has very specific health conditions. We almost stopped taking them but she saw her doctor and her cardiologist and both told her that she absolutely could not stop taking hers. It took her years to find the right medications for her, and get the dosage right.

When it comes to our bodies, we are all an experiment of one.
 

NationalTitles18

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Yeah, CCBs are a viable alternative for many people. The particulars of that choice involve consideration of the condition(s) being treated, other health issues, medication interactions, and at times patient preference, among others.

It's vitally important to have good communication between provider and patient, including a discussion for anyone who is considering stopping or changing medication prior to taking action.
 
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Bazza

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Does anyone have a link to the latest model showing the trajectory of what is expected through at least the next few weeks, here in the US?

I realize the models are in constant fluctuation and dependent on many variables but I find them of interest when looking at the big picture.

Even though they are not etched in stone.

Thank you!
 

Bamaro

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Does anyone have a link to the latest model showing the trajectory of what is expected through at least the next few weeks, here in the US?

I realize the models are in constant fluctuation and dependent on many variables but I find them of interest when looking at the big picture.

Even though they are not etched in stone.

Thank you!
 

TIDE-HSV

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Not for my wife - she has very specific health conditions. We almost stopped taking them but she saw her doctor and her cardiologist and both told her that she absolutely could not stop taking hers. It took her years to find the right medications for her, and get the dosage right.

When it comes to our bodies, we are all an experiment of one.
If so, then she needs to be in communication with her provider and discuss alternatives, as she has. The fact is that most people respond well to ARBs, ACE inhibitors and CCBs. TBF, the choices normally come down to selecting among the side effects of each medication. The CCB doesn't interfere with ACE2 metabolism, which the virus utilizes to co-opt our cells' membrane protection. Anyone on an ARB or ACE2 inhibitor owes themselves a conversation with his/her provider...

Medicinenet
 

PA Tide Fan

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What's interesting about that projected graph is that it shows the virus almost gone by early June if social distancing is maintained until then. It also does not show any rise in new cases after the guidelines are relaxed.
 

NationalTitles18

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What's interesting about that projected graph is that it shows the virus almost gone by early June if social distancing is maintained until then. It also does not show any rise in new cases after the guidelines are relaxed.

Quote:

SOCIAL DISTANCING
When can social distancing measures be relaxed?

Our model assumes social distancing stays in place until the pandemic, in its current phase, reaches the point when deaths are less than 0.3 per million people. Based on our latest projections, we expect social distancing measures to be in place through the end of May.


The timeline could change based on what data show about the trajectory of the pandemic. In the meantime, we are working to forecast what would happen if social distancing measures are lifted before the pandemic is under control, and we will share these projections as soon as our work is complete.

Our forecasts of zero deaths in July and August assume that appropriate measures are put in place to guard against the reintroduction of COVID-19 from another state or country. These measures may include mass screening, contact tracing, testing of all individuals entering the country, and quarantine of people who test positive. Details on what these strategies need to be will be analyzed in future editions of the forecasts.
 

Ole Man Dan

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Is it just me Or...
Does anyone else question the numbers we are given concerning Covid-19?

There seems to be numbers on Deaths, but then again they also have Confirmed Deaths by Corona virus. In Alabama these numbers are off by 20 or more.
There seems to be little if any numbers on the Dead about race.
I have read an unconfirmed reports that a larger percentage of deaths are Black Males or Asian ancestry. Any validity to that story?
Then...
The media delights in ghoulish reports of daily or hourly deaths. Scares the hell out of lots of people. (Maybe it should)...
BUT... Cases where people recover are seldom mentioned.
Another mentioned fact concerns the Death Rate. Rumor is that of infected people,
2-3 percent of the people die.

IMO: One of the big problems is that suddenly everybody is an expert, and lots of those giving interviews may not know much more than those of us on this forum.
As for me, I wear a mask when I have to go out, but mostly we stay home.
I question info given out as fact, when the same info from a different source disagrees.

SORRY FOR THE RANT GUYS.
I HAVE A HARD TIME BELIEVING SOME OF THE 'FACTS' I'M READING AND HEARING.
 
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NationalTitles18

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Is it just me Or...
Does anyone else question the numbers we are given concerning Covid-19?

There seems to be numbers on Deaths, but then again they also have Confirmed Deaths by Corona virus. In Alabama these numbers are off by 20 or more.
There seems to be little if any numbers on the Dead about race.
I have read an unconfirmed reports that a larger percentage of deaths are Black Males or Asian ancestry. Any validity to that story?
Then...
The media delights in ghoulish reports of daily or hourly deaths. Scares the hell out of lots of people. (Maybe it should)...
BUT... Cases where people recover are seldom mentioned.
Another mentioned fact concerns the Death Rate. Rumor is that of infected people,
2-3 percent of the people die.

IMO: One of the big problems is that suddenly everybody is an expert, and lots of those giving interviews may not know much more than those of us on this forum.
As for me, I wear a mask when I have to go out, but mostly we stay home.
I question info given out as fact, when the same info from a different source disagrees.

SORRY FOR THE RANT GUYS.
I HAVE A HARD TIME BELIEVING SOME OF THE 'FACTS' I'M READING AND HEARING.
We've had two main threads - one here on NSNP and one in NS - and anyone can go back and read concerns about the numbers reported going back to January and spanning multiple countries.

Alabama counts its COVID-19 deaths the Alabama way. Alabama has a small group review the reported deaths and they "confirm" they were COVID-19 related deaths before Alabama reports them. Statistical methods vary by state. Some have been better with gathering and releasing that information than others. Those reporting those numbers do show a disparity in reported deaths. Healthcare disparities are a well-known phenomenon. The federal government is studying the current problem. The issue is discussed here in more detail - see quotes below.

Quotes:

In Michigan, Blacks make up 15% of the state population but represent 35% of people diagnosed with COVID-19...

In Louisiana, Blacks represent about one-third of the state population but 70% of COVID-19 deaths...

In Illinois, Blacks represent about 16% of the state but 30% of people diagnosed with COVID-19. In Chicago, Blacks represent 70% of people who have died from coronavirus. North Carolina, South Carolina, and New York show the same pattern with slightly smaller gaps. Among the four states shown below, Blacks are 74% more likely to contract coronavirus than their percentage of the state. These disparities are likely to continue as the virus spreads to new areas.
____________________________________________________________________________________

Healthcare disparities are not so much a controversy in the field - just a simple recognized fact. The statistics, where available, provide evidence of the same in relation to COVID-19. These disparities seem more prevalent in Black and Hispanic populations.

If you wish to rant about media reporting then the NS thread is the place to do that. If you have questions about how states are reporting the numbers or the validity of the numbers that can be done here if done properly. John Hopkins and Worldometer report confirmed cases, deaths, and recovered cases from an aggregate of the data being reported. Alabama reports it's methods here and has a map that reports stats by county.

What you call the "Death Rate" is more accurately described as the Case Fatality Rate. This number currently has to be taken with a large grain of salt because there is no way to know the total number of infected since the testing being done cannot undercover even the majority of cases. Worldwide the rate varies greatly by country, ranging from less than 1% to well over 10%. The overall rate does seem to settle into that 2% range of reported cases. That means the real rate of fatalities is likely lower. The experts seem to think the real number is 0.5% to 1%, which is 5-10 times more deadly than seasonal flu.

The whole point of this thread is to cut through the BS and present and discuss the facts in an apolitical manner and with as much personal and media bias removed as is reasonably possible. It seems your complaint lies not so much with the fact as such, but with media reporting of them. Anyone who expects the media to report as dispassionately on any subject as an educational or governmental institution is very likely to be disappointed.

As for who qualifies as an "expert", it is important to consider the source. The self appointed experts on social media often give a "different take" which helps them garner attention. Those who the media outlets choose are often chosen for different reasons. This thread may help someone evaluate the "experts" since we are attempting to use the least biased sources possible to answer the medical and scientific questions. The more informed you are the more likely you are to have the knowledge needed to critically evaluate those experts.

Regarding disagreement of sources - again, biases in traditional media and social media are there. Some are better than others with the facts. That's why getting closer to the original sources who report with as much bias removed as possible is important. (another way to say that is "with the least bias introduced as possible") You do have to understand that different methods in reporting or collecting data can lead to relatively minor discrepancies that usually and mostly disappear with time as the data are clarified.

There are some fairly well informed people on these forums. None of us claim to be infectious disease experts, but a number among us do have sufficient education and knowledge to have an intelligent conversation on the subject.

If you are having trouble trusting what you "read and hear" then good! You are being critical of the source. Excellent. Now you just have to be sure that you want to know the truth and not the truth you'd rather hear - or put another way, to know the truth one has to try to discard biases and not introduce one's own biases in the process of uncovering the truth. Or put another way entirely: the truth/facts can inform our opinions but the truth/facts should NOT be shaped by our opinions/biases. It helps to first be aware of our own biases and to critically evaluate whether our biases or the biases of others is clouding the truth.

We are walking a fine line here, but biases are a constant problem up for discussion in scientific literature. If this discussion gets more political it would be better to have it in the other thread. If the goal is to discount scientific sources whole cloth for vague and poorly described and poorly evidenced biases then this isn't the place. If the goal is to get to a better understanding of COVID-19 by cutting through the nonsense then we hope this is the place.

Thanks for the joining us here!
 
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NationalTitles18

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There is a lot of good information, including critical evaluation of studies on medications to potentially treat COVID-19, from this Infectious Disease Society of America guideline.

Quote:

Executive Summary
COVID-19 is a pandemic with a rapidly increasing incidence of infections and deaths. Many pharmacologic therapies are being used or considered for treatment. Given the rapidity of emerging literature, IDSA felt the need to develop living, frequently updated evidence-based guidelines to support patients, clinicians and other health-care professionals in their decisions about treatment and management of patients with COVID-19 infection.

Summarized below are the recommendations with comments related to the clinical practice guideline for the treatment and management of COVID-19. A detailed description of background, methods, evidence summary and rationale that support each recommendation, and research needs can be found online in the full text. In brief, per GRADE methodology, recommendations are labeled as “strong” or “conditional”. The word “recommend” indicates strong recommendations and “suggest” indicates conditional recommendations. In situations where promising interventions were judged to have insufficient evidence of benefit to support their use and with potential appreciable harms or costs, the expert panel recommended their use in the context of a clinical trial. These recommendations acknowledge the current “knowledge gap” and aim at avoiding premature favorable recommendations for potentially ineffective or harmful interventions.

  • Recommendation 1. Among patients who have been admitted to the hospital with COVID-19, the IDSA guideline panel recommends hydroxychloroquine/chloroquine in the context of a clinical trial. (Knowledge gap)
  • Recommendation 2. Among patients who have been admitted to the hospital with COVID-19, the IDSA guideline panel recommends hydroxychloroquine/chloroquine plus azithromycin only in the context of a clinical trial. (Knowledge gap)
  • Recommendation 3. Among patients who have been admitted to the hospital with COVID-19, the IDSA guideline panel recommends the combination of lopinavir/ritonavir only in the context of a clinical trial. (Knowledge gap)
  • Recommendation 4. Among patients who have been admitted to the hospital with COVID-19 pneumonia, the IDSA guideline panel suggests against the use of corticosteroids. (Conditional recommendation, very low certainty of evidence)
  • Recommendation 5. Among patients who have been admitted to the hospital with ARDS due to COVID-19, the IDSA guideline panel recommends the use of corticosteroids in the context of a clinical trial. (Knowledge gap)
  • Recommendation 6. Among patients who have been admitted to the hospital with COVID-19, the IDSA guideline panel recommends tocilizumab only in the context of a clinical trial. (Knowledge gap)
  • Recommendation 7. Among patients who have been admitted to the hospital with COVID-19, the IDSA guideline panel recommends COVID-19 convalescent plasma in the context of a clinical trial. (Knowledge gap)
The panel expressed the overarching goal that patients be recruited into ongoing trials, which would provide much needed evidence on the efficacy and safety of various therapies for COVID-19. The panel determined that when an explicit trade-off between the highly uncertain benefits and the known putative harms of these therapeutic agents were considered, a net positive benefit was not reached and could possibly be negative (risk of excess harm). The panel acknowledges that enrolling patients in RCTs might not be feasible for many frontline providers due to limited access and infrastructure. Should lack of access to clinical trials exist, we encourage setting up local or collaborative registries to systematically evaluate the efficacy and safety of drugs to contribute to the knowledge base. Each clinician can play a role in advancing our understanding of this disease through a local registry or other data collection efforts.
_________________________________________________________________________________
 

NationalTitles18

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Continued:

I haven't read through all the data but here's an example of their evaluations:

Quote:

Summary of the evidence
Two RCTs of patients with confirmed COVID with mild pneumonia (e.g., positive CT scan without oxygen requirement) or non-severe infection admitted to the hospital treated with hydroxychloroquine (HCQ) reported on mortality at 14 days, clinical progression (radiological progression on CT scan), clinical improvement, failure of virologic clearance (PCR), and adverse events (both) [11, 12] (Table 1).

In addition, we identified four publications describing three trials of combination treatment with HCQ plus azithromycin (AZ) among hospitalized patients with COVID-19 reporting on the outcomes of mortality, failure of virologic clearance (assessed with PCR test), and adverse events (i.e., significant QT prolongation leading to treatment discontinuation) [13-16] (Table 2).

Benefits
The currently available best evidence failed to demonstrate or to exclude a beneficial effect of HCQ on clinical progression of COVID-19 (as inferred by radiological findings; RR: 0.61; 95% CI: 0.26, 1.43; see Figure s2), or on viral clearance by PCR tests (RR: 2.00; 95% CI: 0.02, 20.00; see Figure s2), although a somewhat higher proportion in the HCQ group experienced clinical improvement (RR: 1.47; 95% CI 1.02, 2.11). However, the certainty in the evidence was rated as very low mainly due to small sample sizes (sparse data), co-interventions, and risk of bias due to methodological limitations. In addition, the selected outcomes should be considered indirect, as important patient outcomes (e.g., mortality, rate of progression to ARDS and need for mechanical ventilation) were unavailable.

Studies evaluating the addition of azithromycin to HCQ provided indirect comparisons of failure of virologic clearance to historical controls. The observed risk of mortality among patients receiving HCQ+AZ during hospital stay was 3.4% (6/175 patients). However, an estimated mortality rate in an untreated cohort was not provided in the manuscript. When compared to a lack of viral clearance in historical controls (100% virologic failure), 12 symptomatic patients were compared at day 5 or 6 from a separate hospital in France. Patients receiving treatment with HCQ+AZ experienced numerically fewer cases of virologic failure (43% pooled virologic failure; 29/71 patients) (Figure s3). There is very low certainty in this comparison of treatment effect mainly due to very high-risk selection bias, making any claims of effectiveness highly uncertain. In addition, relying on intermediary outcomes, such as viral clearance to determine patient-important outcomes (including a reduction in development of pneumonia, hospital or ICU admission, or need for intubation) add another layer of imprecision.

Harms
Two studies described significant QT prolongation in 10 of 95 treated patients, either resulting in an QT increase to over 500 ms or discontinuation of the HCQ/AZ treatment, illustrating the high risk for clinically relevant arrhythmias for this treatment [15, 16]. In addition, several case reports of QT prolongation related to hydroxychloroquine have also been published [17-20].

In another prospective cohort study in 224 COVID uninfected patients with SLE who received either chloroquine or hydroxychloroquine for routine care, gastrointestinal side effects occurred in 7% of patients [21].

Several case reports have been published citing the risk of a prolonged QT prolongation, torsades de pointes, and ventricular tachycardia in patients receiving azithromycin alone. In a large cohort study, patients taking a five-day course of azithromycin had an increased risk of sudden cardiac death with a hazard ratio of 2.71 (1.58-4.64) vs. 0.85 (0.45-1.60), compared to patients receiving no antibiotic or amoxicillin, respectively [22]. Given the cumulative effect on cardiac conduction seen with hydroxychloroquine and azithromycin, if this combination was to be used in the context of a clinical trial, baseline and follow-up ECG monitoring would be indicated, as well as careful surveillance for other concomitant medications known to prolong the QT interval.

Renal clearance accounts for 15-25% of total clearance of hydroxychloroquine, however dose adjustments are not recommended according to package labeling. Chloroquine and hydroxychloroquine are metabolized by cytochrome P450 isoenzymes 2C8, 2D6, and 3A4 [23], therefore inhibitors and inducers of these enzymes may result in altered pharmacokinetics of these agents.

Providers are encouraged to visit resources such as the newly created website, https://www.covid19-druginteractions.org/ to aid in the evaluation and management of drug interactions with current and emerging investigational agents for COVID-19.

Azithromycin is low risk for cytochrome P450 interactions [24]; however additional pharmacologic adverse events including gastrointestinal effects and QT prolongation need to be carefully considered particularly in the outpatient setting where frequent ECG monitoring is not feasible.

Other considerations
The panel agreed that the overall certainty of evidence was very low due to concerns with risk of bias, inconsistency, indirectness, imprecision, and publication bias.

Conclusions and research needs for this recommendation
The guideline panel recommends that the use of HCQ or the HCQ+AZ combination only be used in the context of a clinical trial. This recommendation does not address the use of azithromycin for secondary bacterial pneumonia in patients with COVID-19 infection. Additional randomized controlled trials and prospective outcome registries are needed to inform research for treatment with HCQ alone or in combination with azithromycin for patients with COVID-19 (Table s2. Best practices/suggestions for research of treatments for patients with COVID-19).

____________________________________________________________________

No hype. No politics. These are the types of things we are looking for here.
 

NationalTitles18

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