CharonY

After SARS folks started working on therapeutics and vaccines. However, quite a few studies were ended or stopped once it became clear that SARS appeared to be fairly contained, so research funding stopped or was severely reduced. The clinicals are the expensive bit so often if money is lacking, they do not continue. The good news is that current therapeutics in pipelines are often based on previous data collected on SARS-CoV or other coronaviruses. Otherwise the start would be much slower. It depends on what is being the antigen. Often folks concentrate on essential proteins such as the spike protein as if that one changes significantly, the virus may have a harder time to infect. These essential proteins are therefore often conserved (which means that the amino acid sequenece of the proteins is going to change less than non-conserved proteins).

There are several mechanisms, including the courts, senate and house. You have seen what happened during the impeachment trial, for example, which would be the ultimate policing action against the president.

No doubt, trying things on the fly and in the middle of an emergency is not something take lightly. There will be an urgent need for mental health care. That is not the reason per se, as obviously in both RNA and DNA viruses the genetic material needs to be amplified and both can incorporate errors. There are a few mechanisms, such as polymerases, exoribonucleases and other enzymes that may proofreading functions and thereby reduce mutations. Coronaviruses have such functions and therefore have a lower mutation rate compared to other RNA viruses and put them in the upper range of DNA viruses (~10^-7 - 10^-6 for SARS-CoV, I believe similar for SARS-CoV-2). The mutations are not necessarily in the spike protein, if that is what you are asking. Mutations are going to accumulate in areas that do not inhibit the ability of the virus to propagate. In fact, some of the mutations observed are "silent" meaning that the codon changes, but as a whole still codes for the same amino acid (this includes mutations in the spike and nucleocapsid genes). These mutations are unlikely to result in significant phenotypic differences.

Yes there were two studies I have seen, one showing modest effects, but again only in cases with mild symptoms (making it harder to assess whether it is useful, especially based on small cohorts), whereas the other one got a note that it is being on hold, not sure why yet.

Data from some compassionate uses of treatments are starting to come up. I do not the time to follow them closely, but the antiviral Remdesivir seems to show beneficial effects in a small cohort of 61 patients. The important bit here is that among the cohort were folks with stronger symptoms with 57% being on ventilators, and 8% even being on ECMO (in comparison hydroxycholoroquine, showed no beneficial effect for patients with such advanced symptoms). In 68% of the patients improvement in oxygen-support were detected. However, a controlled trial will be necessary to ascertain that these improvements are indeed due to the drug. The antiviral used for HIV/AIDS treatment (LPV/r) did not seem to show any benefits or at best very weak ones. For favipiravir one recently published study seems to be on hold, so no idea what the issue is there. But from another weak benefits were reported.

Certain key numbers, such as infectious doses are still missing for proper evaluation. The fairly low reproductive number is at least one hint that widespread airborne transmission is probably not a driving infections. That being said, it is not wrong to take precautions, of course.

That is not a case of reinfection (or at least that is not the assumption). Rather it is likely that the titer slipped below detection limit and then increased above in the specimen. This is especially likely when the levels hover near the limit of detection.

For the first part, it is certainly of interest to some, as a number of folks have collected the existing data. For the second, the issue is probably urgency. The data would need to be collected in situations that are currently overburdened and there are only limited capabilities to do additional testing. Once the situation winds down (as it has in China) I am sure folks will try to collect more data in general and figure out the relevance of co-morbidities. At the same time, folks are actually collecting as much data as they can. And again, often it means more work for medical staff as they need to collect the data, code it appropriately on top of the work they need to do. As with all research it often boils down to expected impact, available personnel and funding. Though for the latter, there is a lot of money injected into everything COVID-19 related.

Most tests require isolation of RNA. It is a bit difficult and requires a lab (not to mention the subsequent RT-PCR). Antibody based assays are coming but are not optimized yet, and most (that I know of) require lab conditions to yield accurate results. To make it possible for accurate (diagnostic) self testing, they need to be highly optimized and error proof. That takes time and is not a priority, considering that other tests are running low in many areas. I should add that there are lateral flow immunoassays, but they alone are not good for diagnosis of ongoing infections as the immunoresponse is not fully characterized yet. I.e. they may be good if there was a strong response, but a negative test will have uncertainties associated with it. Fundamentally self-tests are also prone to user errors, even with simple tests, which is why even well-established tests (e.g. pregnancy tests) usually require additional confirmation. Here, the uncertainty is higher.

It is unclear as a) we do not know whether or in which patients influenza may result in different clinical manifestations b) studies are local with small sample sets which makes it difficult to build representative cohorts c) we do not know whether there is a relationship in infection process regardless of clinical outcome. That all being said, there is a paper (but I cannot quite recall the authors) which indicated that the influenza cases went down as COVID-19 went up in Wuhan. I do not recall the precise dates of the patients, so not sure whether it coincided with the shutdown. Edit: And did not come across any studies in the US yet.

As mentioned there are only few reports, mostly on cases with positive outcomes. One by Ding et al. (2020) J Med Vir has not found any more severe clinical indicators. The numbers of co-infection are based on small sample sizes and depending on how the cohorts are built (e.g. severity of symptoms) the outcome may be biased.

Took a look at the first posts and they look very good. Certainly more effort were put into them than I would realistically do. Don't think I would have anything to contribute (unless there are specific questions that went unanswered and I happen to have read something about it or have general molecular biological knowledge that applies). I don't think that there there is a database that would try to deconvolute that information. Given the current situation folks are probably more likely to be tested for COVID-19 than for influenza, meaning that after a positive I suspect that this would take precedence. There are case reports with co-infections reported in small studies (e.g. individual clinics) but I am not aware of large-scale surveys. Within hospitals the cases detected with co-infections were fairly low (but rarely quantified in detail).

There is some data out there, but typical molecular information are derived from animal models, rather than autopsies. It takes time to develop good animal or in vitro models and conduct the experiments. On top of that, creating targeted treatments based on biological information is really, really tricky, and takes even longer. Which is why medical research often skips the deeper biological parts at the beginning and focuses on outcomes instead. The ultimate reason is that biology is one of the most complex subjects out there and there is simply a ton we do not fully understand. Moreover, similar to the overall thrust of the post, more folks are interested in the applied bits. I.e. "treatment for the disease" is going to get more funds than "understanding the fundamentals of host-pathogen interactions", for example. While I may lament that from scientific and research interest point of view, I do see that the long-term research needs to take a seat on the back on this one. That being said, much of the pathophysiology is centered around the mechanisms related to adult respiratory stress syndromes (ARDS). The pattern is very similar to secondary haemophagocytic lymphohistocytosis and related hyperinflammation (or cytokine storm). One strategy is there to use cytokine-inhibition therapies, though they still remain to be tested.

Nope but considering that there are not really large scale reports of relapses, the signs are positive as a whole I'd say.

Why not both?

I do not think it is. Or rather there is no evidence that it might be the case. Rather the issue many countries is still undertesting and prioritizing tests on folks with symptoms. If you look at more fully tested populations there does not seem to be a vast discrepancy compared to China at comparable time points. On this point, the hygiene hypothesis is mostly used in the context of autoimmune diseases and allergies. I.e. low exposure to foreign substances might result in inbalances that cause the immune system to overreact (I think atrophy is not a good analogy, the responses are strong, but confused). Also when it comes to the adaptive part of the immune system, actual exposure is needed. At least in theory exposure to another related virus might raise imperfect antibodies which may attenuate the infection. But there is no data that suggests that at this point. Finally, especially when comparing to strongly urbanized countries like Taiwan and South Korea, I doubt that there are many differences in terms of hygiene. I think you will find larger differences within each country between, say rural and urban centres. Especially in areas with a lot of of livestock.

I am not sure whether it was the same one that I have seen, but if I understood it correctly these are total positive for virus but asymptomatic cases, rather than exclusively new ones (but I may be mis-remembering and can't find the report now). In their official reports China only listed symptomatic cases (originally via RNA test, later also those with confirmed symptoms via CT but without additional test). While it may have made clinical sense at that time to focus on symptomatic cases, especially since all positive cases were isolated anyway, it is now a liability. Exactly that.

No, I get that. I was just hoping naively that such essential agencies would be left to do their work, especially during emergencies. But similar to FEMA, it does not seem to be the case. Yes and some countries (Swededen, I think for example) have stopped as in addition to low or lack of efficacy, there are also more reports on side effects.

SJ, thanks for the link. I was not aware of that and it is very worrying. I generally hold the CDC in high regard, but that has dampened quite a bit.

There is also the other explanation that he is not able to deal with complex situations. When offered a potential solution, he seized it as in his world things become truth if repeated often enough.

There is actually also the issue that some practitioners have taken to prescribe it as a prophylaxis agent, without any proven benefit. The broader issue here is probably that especially in times of crisis folks would normally (and perhaps rightfully) assume that the information provided by the government is based on the current best available information and is part of the (inter)national strategy to address the issue. But the current US administration is not stepping back and let the health professionals provide the info (contrast that with the briefings in Canada for a start difference) but rather provides contradicting information. As such it is no unsurprising that folks take it to themselves to do things, unfortunately.

There are also concerns that pitching hydrocholorquine as an unproven drug can (and starts) to cause shortages for their intended use.

Folks, can I ask everyone to stay on topic and/or open a new thread elsewhere to discuss this?

Partially, a lot is also because of the imbalance between public dissemination and the strength of the data. Scientists are usually very critical to overhyping results (and specific endorsement from POTUS could amplify it). There a couple of letters you might find interesting: https://annals.org/aim/fullarticle/2764199/use-hydroxychloroquine-chloroquine-during-covid-19-pandemic-what-every-clinician https://annals.org/aim/fullarticle/2764065/rush-judgment-rapid-reporting-dissemination-results-its-consequences-regarding-use

Well, there are no strong evidence. While numerous treatment options have been and are being tested, so far the reports are at best weak. As perhaps discussed earlier hydroxychloroquine (either alone or in combination) has shown some faster recovery in cohorts with weak symptoms (based on a French and Chinese study). Most recent studies that included patients with more severe symptoms did not see any benefit over placebos. Molina et al (2020) Med et Mal Inf.. It still in pre-proof (i.e. peer reviewed but not typeset yet) so here is also the title, which is pretty clear: "No Evidence of Rapid Antiviral Clearance or Clinical Benefit with the Combination of Hydroxychloroquine and Azithromycin in Patients with Severe COVID-19 Infection". All were pilot studies, so more studies would be needed to establish effects (or lack thereof) fully. Some researchers find the strong focus on it a bit worrying as the evidence for efficacy is still rather lacking. For vitamin C as well as for plasma treatment I have not seen any trial results yet, so I am not sure how solid the data can be.