CharonY

As briefly discussed in dog another thread, this phase I is an abridged trial which is supposed to test safety. Data collection will take at least two month. After that they need another cohort to establish efficacy (and suitable concentrations) which takes even longer. As Kartazion said the projected overall time line is the often mentioned 12-18 months. In addition other trials are underway (many in China) for other vaccinations as well as treatment.

That is why they allowed the phase I to proceed, there was a balance between need and risk. However, phase II is still needed. In this phase folks look into whether it actually has an effect. A harmless but useless vaccine can exposure folks to additional risk, as they think they are safe, while they are not. It is likely that Phase III can be cut short, essentially because there is nothing to compare it to. But again, the ~12-18 months time line is roughly what is needed to get the minimum information (and you also need to ramp up production) It does not really matter under which regulatory guideline you fall into. You always have to make sure that a) whatever you inject is not worse than the disease b) that it actually does something and c) figuring how and how much you need to apply to get and maintain the desired response. Just observing the responses even if you could inject everyone instantenously would take some time, otherwise you have no clue how you should deploy a potential vaccine. With regard to China I think I mentioned earlier that there are Chinese trials underway using a variety of approaches (inkl. using specific candidate antigens, most within Shenzhen). But as mentioned, I would be extremely surprised if someone somehow could bring anything to market by November (therapies would potentially be something, if only for severe cases). I should also add that having an immunogenic response does not mean that immunity has been acquired. On top there are international efforts in testing existing antiviral therapies some of which are intervention studies (i.e. they recruit sick folks as part of the cohort).

The capsid refers to the protein structure that encapsulates the nucleic acid (whether RNA or DNA). Some have additional lipids from their hosts. That latter part is what is considered the envelope.

It won't happen before November, and in this case in collaboration with the NIH, the pre-clinicals will run in parallel to phase I. Roughly speaking, the next steps tend to be more expensive (money and time wise) before a full roll-out can happen. Always assuming that these vaccines actually work. Also note that they are testing three different concentrations to ascertain safety and there is not guarantee that an of them will elicit an immune response (though they will also look at that as a secondary goal at day 57).

That is often a bit meaningless- after all it depends on how many folks are being tested and how widespread it already is and the latter is often an unknown. Symptoms alone are not sufficiently diagnostic. General recommendation is generally to self-isolate. Whether one should or even can get tested depends on how prepared the country is. In some enough test kits are around to test folks even with more than second degree contact. In others it is so limited that barely those in direct contact can be tested.

Just so you know, the phase I trial (which tests for safety) has a completion date in June. However, the follow up is supposed to take about a year.

That is a bit tricky. For coated viruses folks often see seasonality and it is suspected that at lower absolute humidity the viral particles stay infectious for longer (there are various hypotheses as to why, incl. osmotic pressure, staying longer in the air as aerosols etc., but no definitive answer AFAIK). While seasonality have been observed in various coronaviruses, there have been (as you noted) sustained transmission in humid regions. So folks by now assume an at best modest slowdown, but not a sharp decline.

Coronaviruses are RNA viruses. On the RNA strand they encode everything they need to replicate and form the capsids. I have mistyped earlier (ironically i did not proofread) and one of the genes it encodes a proof reading exoribonuclease. It excises mismatched nucleases. Other proteins required for basic processes such as ribosomes are hijacked from the host rather than being encoded in the viral genome.

I think it is too early to calculate mutation rates. However, coronavirus have something that is called a proof-reading polymerase. These reduce errors in while they replicate and thereby cut down errors (and hence, mutations). Right now we are pretty much past the point of containment. Even without draconian measures it can be possible to contain it, some countries managed to achieve that. However, what one need to do is quick testing and near perfect contact tracing. While Singapore, Taiwan and also South Korea did well on that end, many countries (incl USA and Europe) botched that, even with the time bought by China.

Iirc the Spanish flu put the immune system on overdrive, resulting in massive inflammation, which caused damages. Personally, I think with Covid-19 the issue is less about immune responses alone, but comorbidities. Preexisting conditions are highly correlated with worse outcomes and my guess is that those in conjunction with Covid-19 mediated lung damages are what is causing the fatalities. I.e.younger folks with those issues might also be vulnerable.

This is the basic idea for attenuated vaccines. However, ascertaining how is not trivial. That is unclear. If the dosage is too low it may not result in disease, but may also not trigger immune responses. Again, same idea for attenuated vaccines, but without studying what levels of inactivation and required dosages, it is rather risky (or useless). You can think in terms of inactivation. If you destroy their structure they become ineffective. As discussed before, cold is a not a specific disease and given the wide range of viruses causing such mild symptoms there was little incentive to develop a vaccine for each of these viruses. However, there have been work on SARS and from what I remember it was difficult but they were close. But funding effectively dried up as outbreaks were small and there was no sufficient economic incentives, I imagine. Any level of immunization as well as immune population reduces the transmission rate. Even if no perfect herd immunity is achieved it would make other measures (such as contact tracing) more effective.

So the paper discussing the use of cholorquine (and Remdesivir) is authored by Wang et al. (Cell Research volume 30, pages269–271 2020). The mechanism is not actually known but based on other viral data it is suspected to work by increasing the endosomal pH and interfering with glycosylation. The authors also speculate that modulating the immune system may also play a factor. Edit: apparently some studies with SARS suggest a role of zinc in inhibition, but from the looks of it most are in vitro data and I am not sure whether there are more studies out there.

Yes, they are called opportunistic pathogens. However, it is not specific to viral infections but can be any situation that negatively affects host defense mechanisms or otherwise create situations that are allows certain pathogens to strive. A famous example of a genetic disease is cystic fibrosis, which creates a lung environment allowing Pseudomona aeruginosa to cause harmful opportunistic infections.

I think the whole infection process is sufficiently complicated so that there is not clear answer. At the onset of infection your body ups its response. At this time some pathogens may have a harder time to get in, while others may use the inflammatory cascade to their advantage. Malaria, for example was actually used as a treatment of neurosyphilis in order to induce fevers. Then, as String mentioned, there are interactions between pathogens. With respect to respiratory infections, folks have detected frequently co-infections with multiple respiratory viruses, but their effect on disease outcome are unclear. Conversely viral and bacterial co-infection seem to be more commonly related to the development of pneumonia and other severe illnesses. This is why COVID-19 infections are often treated with antibiotics. And of course in severe stages of illnesses the immune system can be weakened to such a level that opportunistic infections can happen with a higher likelihood. So in other words, precise answers are unlikely to be forthcoming, especially not with a disease whose pathophysiology is not fully explored yet. Edit: Quite unrelated to that, but I think it is a bit worrisome that the US seems to be fumbling the response a bit. There was time to prepare and normally the CDC is quite on top of things.

Please don't do that. It hurts my eyes. For the rest, what Phil said. One can add that there are antibody therapies in development, but they generally require highly specific antibodies, whereas those antibodies produced by infected folks are very broad range (and not all will be effective).

It is less a property of the pathogen but rather that of the immune response. Specifically, our ability to mount specific responses is called the adaptive immune response and it works against most pathogens.

Could you provide details in which contexts that happens? I am somewhat aware that in regular influenza seasons clinicians often do not test for viral co-infection, which can be problematic as they actually do occur. However, it is not (or should not be) used as an exclusionary criterion. If they do it right now, I could only imagine that it is due to lack of a reliable test for the detection of SARS-CoV-2 but not sure why else it would happen. As a side note, several European countries have ramped up testing. So far over 7000 in UK, ~900 France. However, US is definitely lagging behind. Edit: there is a joint report by the WHO, which I finally got to read (together with some interviews and other articles). There is little fundamentally new, mostly a validation of what has been reported earlier, but with better validation: - Transmission are likely droplet based (little evidence of other means as potential drivers, but still under investigation) and most are family-driven (ca. 80%) - So far there is no evidence that folks are immune against it - Most infections of health care workers happened in the early stages, once defenses were deployed. In addition, many happened outside of the workplace (i.e. contracted at home from family members). - Children are barely affected (2.4% of all cases) -Conversely over 60 year-olds are at high risk with significant fatality risk, especially if comorbidities exist. - Many symptoms as in cold are found, most commonly dry cough and fever; running nose is not a symptom, however There is also a closer look at the responses and as a whole there is for example no evidence for internet-fueled speculation of mass-fudged numbers. Another, perhaps rather obvious observation was that the crude death rate was much higher at the beginning of the outbreak. This is mostly because mostly very sick folks were tested and tests had to be ramped up to get a better view on the actual ratio between infections and fatalities. We will see similar things pan out in countries with low test rates. This also contributes to the rather low fatality rates in South Korea (over 66k tested; 4,335 positive cases, 28 deaths). Some accessory information appear to suggest that despite being heavily overworked in many areas, most folks received good care (there is not information, however, regarding folks that may not have received the needed care due to illnesses not related to coronavirus). Looking at crude fatality rates, early cases had a higher crude fatality rate which declined over time. This has been discussed both in terms of increased detection (which reduces fatality ratios) as well as better handling of care. Various reports indicate massive efforts to track contacts in China combined with high-efficiency testing and same-day reporting. These efforts are apparently less pronounced in other countries so far, which could (in theory) allow broader spread before containment.

Is it sad that I cannot tell whether that is a joke or not...?

And also connected to the thread, lung damages and other comorbidities seem to be strongly connected with poor COVID-19 infection outcomes.

Yeah I have seen various articles regarding safety of shipment from China. Evidently that has folks concerned. Meanwhile, I tell students not to lick door knobs.

Nope, it is a typical droplet infection with similar risks. Utensils are only a higher risk if they have been relatively freshly sneezed upon. It is unclear how high the risk for indirect exposure is, but is not considered the main route. Shipped products have even lower risk. Based on what is known based on SARS-CoV there is no real indication that dried droplets shipped over days post any risk. In order to further minimize risks I probably would not recommend putting random things into your mouth, though.

Well that is then not something you can compare with the influenza data then. There hospitalization is only indicated in severe cases, which roughly corresponds to the ~20% of the case of covid-2019. It is not that they need to be taken care of, it is more that they are monitored to limit spread, which is not the case with influenza. As such it is not an apple to apple comparison. Or was your point not regarding the severity of the disease but regarding the personnel and medical effort put in place in order to contain them? In that case yes, folks are putting more effort into containing the disease than for flu.

As a side note, from an co-evolutionary standpoint, diseases that have stuck around for a longer time in a population tend to become less virulent over time, due to an ongoing interplay between host and pathogen.

Ok that is clearly wrong. You may be confused by some studies who studied the characteristics of those hospitalized in the first place. Current data suggest that ca. 20% of patients have severe symptoms and are likely in need to be hospitalized. There are potentially more if they have added risk (e.g. other pulmonary issues). While the number are higher than for influenza it is way below 100%. Edit: perhaps I should add that the Chinese government implemented a strict quarantine system, where all infected people (I believe) are isolated either in hospitals and/or quarantine systems. In other words, even mild cases would be isolated, whereas the numbers for influenza are only looking at severe cases that need to be hospitalized. From there, we also see that the rate is similar when it comes to death rates- COVID-2019 is associated with a ~10-20 fold increase of severe cases and death. As shown by the data, the current outcome is still way below the annual effects of influenza, even if only looking at US numbers. It does not mean that it cannot reach or even surpass those numbers eventually, but we are certainly not there yet. As an interesting side note, the CDC numbers also clearly show how undervaccinated folks are when it comes to influenza. Up to half of the population are estimated to contract it with an estimated vaccination coverage of 40-odd percent. It should also be noted that there is often an inverse correlation between severity of a disease and its spread. The coronavirus is far more effective in spreading compared to MERS, for example, because its symptoms as a whole are mild for most folks. I.e. similar to flu there is a significant time period where folks can spread the disease without being aware of it.

A) we do not know the actual fatality rate yet. The ~2% are based on current estimates, but it is higher than influenza (0.2-0.3%) but lower than either earlier SARS or MERS; B) Influenza is worse as it affects more people each season (at least so far), the result are overall more deaths; C) Deaths alone are not necessarily a great indicator, one should also consider other health burdens' D) Quarantines are enacted to curb spread. If a similar number of folks are allowed to be infected as seasonal influenza, the results are potentially devastating. Think about that way, seasonal influenza deaths are estimated to be around 250-645k worldwide each year. If the same amount of folks are infected (and ignoring demographic differences in outcome) we may end with upward to 20 times the number of fatalities. No need for conspiracy theories to see the need for intervention. Edit: sorry forgot to address the point about hysteria: I guess social media and the internet.