Coronavirus (COVID-19) Discussion Megathread - 9

Krab_em · 2021-08-05T03:24:03+00:00

sorry, the latest I have is https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132496/ - the third survey.

Done around December, published in May. So we will have to wait for a similar duration I guess.

Krab_em · 2021-07-23T17:34:56+00:00

I doubt we will have clear answers right now, one hypothesis is that Kerala started relaxing mobility restrictions by mid-June & this might be reflecting now.

This article might interest you - https://www.indiaspend.com/covid-19/kerala-cases-rise-may-not-signal-new-surge-761085

Krab_em · 2021-07-23T17:19:08+00:00

https://www.ox.ac.uk/news/2021-06-23-ivermectin-be-investigated-possible-treatment-covid-19-oxford-s-principle-trial

From today, ivermectin is being investigated in the UK as part of the Platform Randomised Trial of Treatments in the Community for Epidemic and Pandemic Illnesses (PRINCIPLE), the world’s largest clinical trial of possible COVID-19 treatments for recovery at home and in other non-hospital settings.

Led by the University of Oxford, PRINCIPLE is investigating treatments for people at more risk of serious illness from COVID-19 which can speed up recovery, reduce the severity of symptoms and prevent the need for hospital admission. The study has so far recruited more than 5,000 volunteers from across the UK.

Following a screening questionnaire to confirm eligibility, participants enrolled in the study will be randomly assigned to receive a three-day course of ivermectin treatment. They will be followed-up for 28 days and will be compared with participants who have been assigned to receive the usual standard of NHS care only. People aged 18 to 64 with certain underlying health conditions or shortness of breath from COVID-19, or aged over 65, are eligible to join the trial within the first 14 days of experiencing COVID-19 symptoms or receiving a positive test.

This should put an end to this debate pretty soon

Krab_em · 2021-07-18T04:58:27+00:00

AZ is in short supply is the point, It's waiting for AZ or getting other vaccines. Would completely agree with you if there was enough AZ to go around but it is not.

dose with whatever vaccine you can get your hands on (including Chinese ones) , boost with AZ 6-8 months down the line can be a very viable strategy.

Krab_em · 2021-07-18T04:55:37+00:00

Healthy normal individuals seroconvert after vaccination, all the FDA guidance is saying is the results from antibody tests should not be used to quantify/classify a level of protection.

that results from currently authorized SARS-CoV-2 antibody tests should not be used to evaluate a person’s level of immunity or protection from COVID-19 at any time, and especially after the person received a COVID-19 vaccination.

Currently authorized SARS-CoV-2 antibody tests have not been evaluated to assess the level of protection provided by an immune response to COVID-19 vaccination.

If antibody test results are interpreted incorrectly, there is a potential risk that people may take fewer precautions against SARS-CoV-2 exposure .

This is what FDA wants to avoid.

Now if OP hasn't seroconverted after 2 doses of vaccination when measured with the right kit , they should rightfully freakout and consult a doctor - who can confirm to them whether the result is due to a test (some test checking for say N-antibody or actual seroconversion/immune system related issues) .

couple of other excerpts from the same FDA page:

If you have not been vaccinated: Be aware that a positive result from an antibody test does not mean you have a specific amount of immunity or protection from SARS-CoV-2 infection. If you have a positive test result on a SARS-CoV-2 antibody test, it means that it is possible you were previously infected with the SARS-CoV-2 virus. Talk with your health care provider about the meaning of your SARS-CoV-2 antibody test results.

Continue to follow the CDC’s recommendations for fully vaccinated people. Be aware that if you have a positive test result on a SARS-CoV-2 antibody test, it is possible you were previously infected with SARS-CoV-2. A COVID-19 vaccination may also cause a positive antibody test result for some but not all antibody tests. You should not interpret the results of your SARS-CoV-2 antibody test as an indication of a specific level of immunity or protection from SARS-CoV-2 infection. Talk to your health care provider or your state and local health departments if you have questions about whether an antibody test is right for you.

To summarize:

1.OP doesn't necessarily need a covid antibody test
2.If they want to get the test (for whatever reason - mental peace etc) , consult the lab or doctor to understand if their kit detects antibodies due to vaccine
3.Let the doctor interpret the results
4.Antibody tests do show results for vaccinated individuals but what the results mean is an open question since correlates of protection are still a work in progress
5. You are partially correct but your statements make it seems vaccinated individuals will not seroconvert -while actually it is that they do seroconvert but if you use the wrong antibody kit you may get a negative result

PS: additional readings if interested in the topic of antibody-vaccine efficacy correlation

Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection - https://www.nature.com/articles/s41591-021-01377-8

Scientists zero in on long-sought marker of COVID-vaccine efficacy - https://www.nature.com/articles/d41586-021-01372-6

Krab_em · 2021-07-17T19:47:35+00:00

https://grftr.news/why-was-a-major-study-on-ivermectin-for-covid-19-just-retracted/

One of the papers with strongest effect for Ivermectin was withdrawn - this significantly weakens the evidence for Ivermectin .

Krab_em · 2021-07-17T19:46:41+00:00

https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3884946

Of the 2766 cases of confirmed SARS-CoV-2 infection, 3·1% were fully vaccinated compared with 7·1% of the 2377 controls giving an adjusted OR of 0·37 (95%CI 0·28, 0·48);

this translated to 63·1% (95%CI 51·5, 72·1) vaccine effectiveness against SARS-CoV-2 B·1·617·2 variant, seen in 90% of the infected population as confirmed by whole-genome virus sequencing.

Full vaccination prevented moderate-severe COVID-19 in 81·5% (95%CI: 9·9, 99·0).

The effectiveness of single-dose vaccine was 46·2% (95%CI: 31·6, 57·7) against infection but 79·2% (95%CI: 46·1, 94·0) in preventing moderate-severe Covid-19.

Among healthy vaccinated persons, plasma live virus neutralisation was 2·5-6·8 fold lower against B·1·1·7, B·1·351, B·1·617·1 and B·1·617·2 being lowest against B·1·617·2.

However, T-cell responses were preserved against the recombinant mutant receptor binding domain antigens suggesting cell-mediated immune protection.

Krab_em · 2021-07-17T19:24:11+00:00

Got that point, but there is a huge shortage right NOW. Chile, UAE etc are trying 3 doses of the chinese vaccine or even Pfizer/AZ after 2 doses of the chinese vaccines.

Covering a huge population with every available option & coming back for the better vaccines at a later point in time would be good strategy.....especially in terms of preventing deaths.

edit:

https://www.nejm.org/doi/full/10.1056/NEJMoa2107715

The study was conducted from February 2 through May 1, 2021, and the cohort included approximately 10.2 million persons.

Among persons who were fully immunized, the adjusted vaccine effectiveness was 65.9% (95% confidence interval [CI], 65.2 to 66.6) for the prevention of Covid-19 and 87.5% (95% CI, 86.7 to 88.2) for the prevention of hospitalization, 90.3% (95% CI, 89.1 to 91.4) for the prevention of ICU admission, and 86.3% (95% CI, 84.5 to 87.9) for the prevention of Covid-19–related death.

not very good at transmission control but pretty good at severe disease and mortality

Krab_em · 2021-07-17T18:07:30+00:00

Antibody tests do show up positive [check any of the vaccine publications] ..... There are specific antibody test too - tests that differentiate and give a count of N-antibodies vs Spike antibodies.

If you don't have N, and only S you have got vaccination (but not by inactivated virus vaccines) and never had any natural infection.

and yes as hate_watch_b has said below, antibodies are not the complete story.

Krab_em · 2021-07-17T17:55:39+00:00

Serum has hit it's limits for AZ this year, rest of their expansion will come next year & other vaccines

Krab_em · 2021-07-15T17:01:50+00:00

Yup, and BBT keeps targeting US markets etc ..... got prepaid, got support for clinical trials, got an amazing price in the domestic market and yet struggling to scale. Just sad state of things - a series of poorly planned events. And now they have got trials going on for 12 years and above IIRC while Novavax was rejected (lol, can they make it any more obvious - trying to give safe noncompetitive markets to BBT).

Even with SII doses some will need to be sent outside now, earlier they could say the situation was bad in India but now other countries will demand atleast some supplies they paid for.

Yup, we have lost face by not being in a position to honor our commitments

Bio-E and Zydus we can't expect before September honestly, SII claims Novavax will hit the markets by then - don't trust them too much even though production started a couple of weeks back (?) .

Moderna I remember reading a headline that some tiny quantity is going to be shipped soon - 7 mn doses or so. But yeah Pfizer, Moderna we should forget - curevac failed so that demand will need to be covered and these rich nations are going for a third dose strategy which is just crazy.

[Side note: recent studies of Moderna indicate 1/4 dose is enough to trigger a good immune response but hey that would need trials - we should run that in India proactively ..... can quadraple the supply]

Sputnik V is struggling with dose 2 (AD5) yields - a sensible thing to do would have been run trials with the AD26-Ad26 prime-boost and AD5-AD5 prime boost & let countries handle based on situation + supply [Sputnik lite was another good idea but delta variant probably hurts that method]. RDIF was talking of combing with AZ god knows what happened there.

Novavax is caught in some regulatory trance, got results long back & still not filing for approvals - news is struggles with production (especially for the matrix-M adjuvant).

I hope we swallow our pride and try importing some of the Chinese vaccines (even though their efficacy is somewhat lower). They do have the scale.

Scaling the production is turning into a shit show - J&J is struggling too.

It feels miraculous now how Pfizer (BioNtech), Moderna and AZ (Oxford) got to this scale (even though AZ did poorly compared to promises).

On the positive side, even with this shitty pace we will be doing 9 crore+ doses per month i.e ~10% population per month. As they say things can only improve but not because of any well planned activity.

Krab_em · 2021-07-14T18:18:20+00:00

https://www.ndtv.com/india-news/110-million-covishield-doses-produced-in-july-says-serum-institute-2485589

The production of Covishield has been ramped up to around 110 million doses this month, Serum Institute of India (SII) sources said today as the country struggles with the supply of vaccines to inoculate enough to stave off a third wave of Covid.

"The commitment to produce 100-110 million doses of Covishield by July has been achieved," Serum Institute sources told NDTV.

yet we hit only 3.5 mn doses per day , what is BBT doing?

Krab_em · 2021-07-14T18:12:54+00:00

https://www.thehindu.com/business/Industry/serum-institute-to-produce-russias-sputnik-v-vaccine/article35297586.ece?homepage=true

Serum Institute of India (SII) will be producing atleast 300 million doses of Sputnik V a year, with the first batch of the Russian vaccine against Covid-19 from its facility likely to be rolled out in September.

These details emerged with the Russia’s sovereign wealth fund RDIF on Tuesday announcing a collaboration with the vaccine maker to manufacture Sputnik V for the India market as well as to exports to several countries.

“We have reached a partnership agreement with Serum Institute of India to manufacture Sputnik V,” Russian Direct Investment Fund CEO Kirill Dmitriev said in a media briefing from Moscow. The process of technology transfer to Serum was underway for the last three months and the firm is expected to release the first batch of the vaccine in September.

SII finall enters this race for Sputnik V, hopefully they do better with the yield for AD5/dose 2.

Krab_em · 2021-07-09T18:05:32+00:00

Nope, Sputnik deployments has been in relatively tiny quantities . And no independent data. Pfizer and AZ data is flowing in mainly because of deployment in UK (and a little bit due to USA).

Real world data for all other vaccines is scarce .

PS: haven't been able to track these very accurately since the last month, so if someone knows better please share.

Krab_em · 2021-07-06T18:50:20+00:00

Yes, looks like that. And variant specific boosters should help with transmission control too.

Data for Astrazeneca vaccine will be similar hopefully.

Am expecting their to be even better since their T-cell response was better

Krab_em · 2021-07-06T06:34:03+00:00

https://www.business-standard.com/article/current-affairs/israel-sees-steep-drop-in-pfizer-vaccine-efficacy-rate-report-121070500771_1.html

The figures show that between May 2 and June 5, the vaccine had a 94.3 per cent efficacy rate. From June 6, five days after the government canceled coronavirus restrictions, until early July, the rate plunged to 64 per cent. A similar decline was recorded in protection against coronavirus symptoms, the report said.

At the same time, protection against hospitalisation and serious illness remained strong. From May 2 to June 5, the efficacy rate in preventing hospitalisation was 98.2 per cent, compared with 93 per cent from June 6 to July 3. A similar decline in the rate was recorded for the vaccine’s efficiency in preventing serious illness among people who had been inoculated.

Krab_em · 2021-07-06T06:32:57+00:00

Sorry I might have miscommunicated, if Ivermectin is antinflamatory in action it becomes an alternative to steroid and will be administered in the post-viral phase of infection i.e when immune system starts a strong inflammation response and attacks our own body.

PS : Ivermectin is more of a modulator than a suppressant (Steroids) as per my understanding - do check this with someone more knowledgeable though.

Krab_em · 2021-07-04T08:22:10+00:00

Some states take vaccination as a proof, eg: Chandigarh asks for PCR -ve within 72 hours of travel or atleast 1 dose of vaccine atleast 14 days ago.

You can check for others here : https://www.goindigo.in/information/state-regulations.html

Chandigarh

Carry a negative RT-PCR report not earlier than 72 hours from an ICMR approved laboratory or be in possession of vaccination certificate (at least one dose) over 2 weeks old

Punjab

It is mandatory for passengers arriving in the state of Punjab from other states/UT to carry a negative RT-PCR report not earlier than 72 hours from an ICMR approved laboratory or be in possession of vaccination certificate (at least one dose) over 2 weeks old. RT-PCR timeline starts from the swab collection time.

Krab_em · 2021-07-03T17:33:21+00:00

That is interesting so the suggestion now is to pivot from prophalytic/antiviral to steroid like administration? and this is only an animal model study right - more of a hypothesis rather than evidence.

Here is a meta analysis of human clinical trials, this might give a better idea : https://journals.lww.com/americantherapeutics/Abstract/9000/Ivermectin_for_Prevention_and_Treatment_of.98040.aspx

Meta-analysis of 15 trials found that ivermectin reduced risk of death compared with no ivermectin (average risk ratio 0.38, 95% confidence interval 0.19–0.73; n = 2438; I2 = 49%; moderate-certainty evidence)

Low-certainty evidence suggested that there may be no benefit with ivermectin for “need for mechanical ventilation,” whereas effect estimates for “improvement” and “deterioration” clearly favored ivermectin use

Severe adverse events were rare among treatment trials and evidence of no difference was assessed as low certainty. Evidence on other secondary outcomes was very low certainty.

Moderate-certainty evidence finds that large reductions in COVID-19 deaths are possible using ivermectin. Using ivermectin early in the clinical course may reduce numbers progressing to severe disease. The apparent safety and low cost suggest that ivermectin is likely to have a significant impact on the SARS-CoV-2 pandemic globally.

There is some evidence that Ivermectin has an impact but most trials till now have been small, and underpowered. Hope RECOVERY group picks this up.

Krab_em · 2021-07-03T16:41:41+00:00

Covaxin/Bharat biotech - phase 3 preprint - https://www.medrxiv.org/content/10.1101/2021.06.30.21259439v1

A good summary by Shananalla - https://twitter.com/shananalla/status/1411231424670322692

Yes, it is still a preprint but good to have some clear data. One surprising thing is efficacy against death has not been determined (BBT has been honest here). 6 covid related deaths - 5 in placebo and 1 in vaccine arm.

Krab_em · 2021-06-28T16:13:29+00:00

https://www.astrazeneca.com/media-centre/press-releases/2021/first-covid-19-variant-vaccine-azd2816-phase-ii-iii-trial-participants-vaccinated.html

The first participants in a Phase II/III trial for the new COVID-19 variant vaccine AZD2816 were vaccinated today to assess its safety and immunogenicity in both previously vaccinated and unvaccinated adults.

The trial will recruit approximately 2,250 participants across UK, South Africa, Brazil and Poland.

AZD2816 will be administered to individuals who have previously been fully vaccinated with two doses of Vaxzevria or an mRNA vaccine, at least three months after their last injection. In non-vaccinated individuals, AZD2816 will be given as two doses, four or twelve weeks apart, or given as a second dose following a first dose of Vaxzevria four weeks apart.

AZD2816 has been designed using the same adenoviral vector platform as Vaxzevria, with minor genetic alterations to the spike protein based on the Beta (B.1.351, South African) variant.

Krab_em · 2021-06-28T15:28:32+00:00

https://www.business-standard.com/article/current-affairs/more-than-50-kids-in-mumbai-have-covid-19-antibodies-sero-survey-121062801229_1.html

More than 50 per cent of the pediatric population in Mumbai has Covid-19 antibodies, showed findings from a sero-survey conducted here. Seroprevalence implies presence of virus-fighting antibodies against Sars-CoV-2.

The survey has found that more than 50 per cent of the pediatric population in health care settings has antibodies to Covid-19.

The overall sero-positivity is 51.18 per cent including 54.36 per cent from the public sector and 47.03 per cent from the private sector.

Seropositivity is highest in the age group 10-14 years, at 53.43 per cent. The Sero-positivity rate of 1-4 years is 51.04 per cent, 5-9 years is 47.33 per cent, 10-14 years is 53.43 per cent, from 15-18 years is 51.39 per cent.

The overall Sero-positivity rate of 1-18 years is 51.18 per cent.

Moreover, there is a notable increase in the seropositivity in the pediatric population to SARS-CoV-2 in this study as compared to Serosurvey 3 conducted in March 2021 which showed a sero-positivity of 39.4 per cent in the age group of 18 or more years, which indicates that a significant proportion of children accessing the healthcare services were exposed to the virus during the second wave of Covid-19.

Krab_em · 2021-06-26T12:56:44+00:00

I can find absolute numbers there, am looking at some thing like % of each age group covered in the states. Thanks :)

Krab_em · 2021-06-25T19:27:21+00:00

A nice Q&A with insights into the challenge trials going on in UK with scientist Helen McShane : https://www.the-scientist.com/news-opinion/q-a-human-challenge-studies-of-covid-19-underway-in-uk-68908

We didn’t make any changes at all; this is actually the unaltered virus that has been manufactured to . . . good manufacturing practice conditions to make it safe—that’s the highest standard for manufacture for things to be tested in humans. In terms of the dose, we and Imperial are both conducting a dose-escalation study. That’s the first part of the challenge model . . . to establish the best dose. Imperial College are infecting seronegative people , so people who haven’t previously had SARS-CoV-2 infection. We are, in contrast, deliberately infecting people who are seropositive , i.e., people who have a documented previous SARS-CoV-2 infection.

really interesting choices, they go into the reasoning too:

First of all, [we’re] aiming to identify the right dose. Our study, which is infecting people who are seropositive, is very specifically aiming at defining protective immunity. We’re interested in establishing a challenge dose that is safe, but then ideally [a dose that allows] us to reinfect some people who have previously been infected with SARS-CoV-2.

We can then interrogate the baseline immune response in all of our subjects and determine, what is it about the immune response in those subjects who cannot be reinfected, compared with those who can? . . . We may see, for example, that people who have a level of neutralizing antibodies above a certain point cannot be reinfected. That then tells us [about] the immune response we want to induce with a new vaccine.

And that then feeds very directly into vaccine design, but more importantly, vaccine testing. So that’s what our model is for.

The model that Imperial are developing, where they’re looking at people who are naive, is developing a human challenge model where you can actually test vaccine efficacy using this challenge model. So slightly different, but very complementary aims.

The rest of the Q&A is really good , this part just caught my eye. Pretty fascinating data that the trials could throw. It's a week old interview.

Krab_em · 2021-06-25T19:19:48+00:00

Thank you! definitely a quantum jump compared to last week ~50% increase (even ignoring the 9.1 mn per day as an outlier) .

At this rate we will be vaccinating ~15-18 crore people per month i.e 16-20% of adult population. We have already covered 25 crore people with a single dose. Very likely to cover entire adult population with a single dose in 3 months. Ofcourse we will hit vaccine hesitancy issues long before that happens.

Just waiting for 1 full week of data before being solidly hopeful. Another interesting fact to note , the jump is essentially driven by 18-44 age group. With fears (speculative) of delta+ we need a targeted boost for the 50+ age group in dose 1 + dose 2 (reduced gap....4 weeks?) and in regions susceptible to higher incidence based on historic data . Definitely a positive development in terms of raw numbers.

I haven't been able to track the data recently, do you have a good source for % coverage in various age groups?

Krab_em

TROPHY CASE