lbeltrame

> but the model says they’ll hit a nasty second wave in mid October.

I am wary of modeling "that far" in time, because while vaccines may take a little more to get ready, there are plenty of trials starting or going on for pharmacological treatments, which may give readouts as early as September.

While perhaps they won't be able to avoid infections, they might change clinical management significantly, in particular monoclonal antibodies.

I know for sure that a lot of the deaths are from nursing care homes (but I don't know in how large percentage), something seen also elsewhere in the world.

It is slightly different than a regular Phase 1 study because there's a control arm. I suspect they want to use the data as a complement to the Phase 2/3 results in the unfortunate case the volounteers end up positive for the virus.

Most of the results are unfortunately either by association (like the linked study), or on the spread of droplets without checking for infectivity. This means that the evidence is still circumstantial. There are indications of efficacy, but not how large this efficacy is.

I don't think masks are useless, but I'd love some hard data on how effective they are.

Immune systems are fairly differentiated across species, even for common mechanisms. Source: I worked from 2009 to 2011 in a project aiming at reconstructing part of these mechanisms in certain immune cells, and the differences between human and mice, where some models were made, were significant.

I can't speak for the article here, but at least some local media in my country wants to generate clicks and views, so the more horrifying the headline (but also the article contents), the better.

See the recent matter on antibody decline: few if any got it right (although it can mean a waning immune response it is not enough to tell if it is happening).

Other coronaviruses can infect the nervous system. In fact, there were papers out in 2018 describing neural infections by "human coronavirus".

Cytokine storms and their associated effects (like clotting ,etc.) are also present with other viral infections, like with the original Spanish Flu H1N1 strain (during the infamous "second wave").

"Regular" pneumonia can severely weaken you for months or a year, even if you have antibiotics.

This virus is absolutely not a magic virus. It is novel, but it is still a coronavirus.

Some of the quotes here kind of cause cognitive dissonance with those who actually saw the crisis unfold from the ground, like myself.

1. The Italian government and many experts downplayed the issue at first: on January 31st, Giuseppe Conte declared "we're fully prepared", but it wasn't so: he was far more worried about his unstable coalition.

2. The ban on China flights was so only for direct flights: passengers coming from China through other Schengen areas were not screened at all.

3. Testing policy was inconsistent: at first, test everyone, then only those with symptoms, and it took months to increase testing capacity (also privately-owned labs were forbidden from performing tests)

4. Forbidding autopsies and thus delaying findings that were found to be useful later on (when first thrombosis was found in dead patients' lungs and use of heparin suggested, some experts called the finding "colossal idiocy")

5. Procurement of PPE and ventilators was done in the most inefficient, over-bureaucratic way possible. Disclaimer: it would've been objectively difficult given the shortages, but one could've done better. The appointed person to handle the job went through all the complex bureaucratic steps to do the calls to procure tests and masks, failing to get them in time. Then, when some companies converted themselves to producing masks, the price was arbitrarily fixed at lower-than-cost (and subsequently raised for obvious reasons). The first shipments of masks to some of the hardest-hit regions weren't even close to being PPE (they looked like dust towels). The way the government also paid, 30 days after invoice, made it slower than others who were willing to pay cash immediately. In short, a lot of initiatives were delayed for, to be frank, fear of being then accused of "corruption".

6. The coordination of the emergency response teams was, for a good while, largely inefficient. Some donated masks took a while to go to the hospitals due to bureaucratic reasons.

7. Lockdown was unnecessarily harsh, shutting down stuff that could've been kept running (some factories), and totally blanket, locking both regions with lots of positive cases and regions without significant signs of community spread

8. Inconsistent mask policy (granted, there aren't clear cut data even now)

9. At first reopening, a "secret" (and not signed by anyone) report full of epidemiological errors was leaked, warning of "150,000 Italians needing ICU care" by June if activity would resume (it was then torn apart by other experts)

10. There wasn't even a clear plan of reopening. No one even mentioned it, until a politician from the majority raised the issue and then the debate started.

11. Little to no financial aid to the sectors impacted by the lockdown, and extreme delays in providing it. OTOH, massive promises were and are still being made with plenty of numbers.

Like with Moderna, if I recall (on mobile, so I can't refresh my memory by rereading it) the highest doses had some Grade 3 level fevers. So probably medium dose would be used.

> (AstraZeneca using meningitis vaccine as control instead of true placebo).

AFAICR, this was done on purpose to prevent people from figuring out they got a vaccine shot, because an inert placebo wouldn't cause any side effects.

> In other words, long story short, probably not this year.

Moderna aims at an emergency use authorization for health personnel in October or during the autumn in general if the interim data from Phase II / III is good enough.

It's also unlikely to be very effective due to it using the adenovirus Ad5 as a vector, which is a human adenovirus that many people have antibodies against. This means a marked loss of efficacy if you have them.

The most significant safety issues with this vaccine specifically regard the 250ug dose, which was not used in Phase 2 and won't be used in Phase 3.

As long as it's not a Grade 3 fever, I don't see a problem: many vaccines can cause (transient) fevers. (Part of that is due to the adjuvants used to prime the immune system by causing a localized inflammation).

I got a shot for the yellow fever a few years ago and I felt quite bad for a couple of days. When I was asked for a booster shot for measles, I was warned of the possibility of developing fever for a couple of days as well.

The goal is not to immunize, but to prevent hospitalizations (at least their goal according to the article). If this infection is downgraded to a cold level that doesn't damage the lungs, would that be a problem?

That said, I'm not sure other vaccines will be dropped. If any of the other candidates can give sterilizing immunity, that would be preferred.

The "race" is just to avoid shutting down the whole world again, and many governments are afraid of an uptick of cases in the winter.

It has not exited yet. This is an interim evaluation at day 56. The whole trial will last a year.

Link to the actual study: https://www.nejm.org/doi/full/10.1056/NEJMoa2022483

Some preclinical work is ongoing for per-os administration of vaccines against SARS-CoV-2, which would make things much better.

"Antibody responses".

Not discussed:

- Immunological memory (or lack thereof): we don't have antibodies in our bloodstream for all the vaccinations we did - they're triggered by infections

- T cell responses (which seem to play a part in some mild cases, although the Swedish study discussing this was criticized)

In fact, from the discussion in the paper, it is mentioned:

> However, the role T-cell responses generated through either infection or vaccination play in controlling disease cannot be discounted in these studies [vaccination studies quoted before] and defining further the correlates and longevity of vaccine protection is needed.

The only thing one can do is to wait, at this point, and see whether there are reinfections (and by reinfections it does not mean a PCR-positive test: it would require testing for infectious virus in cell cultures).

Actually, the study makes more interesting points than this one, including using classes of antibodies as markers of acute infection. Too bad the press seems interested in something else (without realizing that the appeals at the "miracle vaccine" will not work if immunity is not long-lasting).

That's also something the sentence at the end of the trial may cover: "not having carried out the fact" versus "the fact has not occurred".

At this point, there is neither indication (nor a guilt sentence, either).

Short immunity, assuming this is a general case and that this is a real reinfection, wouldn't also affect vaccination, which is mentioned as a solution? This article is contradictory.

EDIT: I'm much in favor of vaccination, FTR. But when I read pieces like this, I wonder if people fully understand the consequences of the scenarios they describe.

Yet another epidemiological model. These can be useful, but it's hard to apply them when the actual biology is unknown. And currently, the actual weight of asymptomatic infections is unknown (what is also the definition of "asymptomatic"?)

At this point in the pandemic, I think we can ask for some hard data, instead.

A few good points (like the PCR detecting only RNA which does not equate to live virus) in a sea of "interesting" spin about the current data.

I really don't understand why it's "us vs them" in either camp ("doom and gloom" and "skeptics"). This makes things worse, since both camps tend to quote only evidence which support their respective claim (two examples: the Guardian saying that asymptomatic people spread more virus than the symptomatic ones, despite the study they quote saying that it can't be said, because they did not check for live virus; and some web page called "Swiss policy research" which quotes only the parts of the studies which conform to the "skeptical" narrative).

I will wait for the final decision, personally, as I think presumption of innocence still holds, even if I might disagree at a personal or political level with the accused.

This is different from the recorded cases, after all it's a "perception" index.

> In recent experience, I remember the World Expo Milan fair in 2015

I don't think the trials have been finished yet.

The Twitter thread seems to contradict this claim.

> Seconda domanda: da cosa dipendono allora le lungaggini, se non dall’affidamento? La risposta è esattamente quella che state pensando: dalla burocrazia.

"Second question: what is the cause of slowness, if not when a work is actually given [to whoever got the contract]? The answer is exactly what you're thinking about: bureaucracy."

The next few tweets bring data which supports this.

> This, unfortunately, is the story for every public infrastructure in Italy.

I argue it's not the case. Over-bureaucracy (ironically, to fight "corruption", like the useless "anti-corruption authority") is one of the major reasons things get done at glacial paces (and the same reason sometimes people use "other ways" to speed up things). The replacement of Ponte Morandi in Genova is a prime example of this fact: to rebuild it lots of "rules" had to be suspended.

This is, I assume, an answer to the open letter sent to the WHO last week. I took a look at the letter: it doesn't bring many data to the table unfortunately.

In fact, it advocates the precautionary principle. I can understand (but not agree with) that in a context of public safety, but those people do science, and the precautionary principle is not scientific.

Previous posts:

- https://news.ycombinator.com/item?id=23780357

- https://news.ycombinator.com/item?id=23777155

The way this result is presented is misleading. Antibodies are just one form of immunity.

> It's likely CoV-2, like other coronaviruses, don't generate long lasting antibodies (6~12 months)

Please see https://news.ycombinator.com/item?id=23777175 for a comment on this study.

Antibodies aren't the end of all.

Also, SARS-CoV prompted a humoral (antibody) responses even years after the first exposure. The truth is that we don't know, and I hate when the press and the experts go with absolutes. What's wrong in saying that you don't know?

Not discussed:

- Cell mediated immunity (T cells)

- Immunological memory

- Mucosal (hence undetectable in the bloodstream) antibodies like IgA

Antibodies aren't the end of all. I really dislike that instead of "we don't know", people, including experts, put out absolutes that aren't such in their public communication.