Possible vaccines/treatment(s) for Coronavirus

[souljacker]

Interesting article here about Cuba's vaccine efforts and how they differ from those created by private companies:

Cuba’s COVID-19 Vaccines Serve the People, Not Profits

Cuba’s socialist approach to developing vaccines against COVID-19 differs strikingly from that of capitalist nations of the world. Cuba’s production of four vaccines is grounded in science and dedicated to saving the lives of all Cubans, and to international solidarity.

www.counterpunch.org

 

[2hats]

A single dose mRNA regimen for the previously infected might effectively vaccinate them

And now a third study reporting similar, indeed more promising, results.

Single dose injection with one of the mRNA vaccines (BNT162b2, mRNA-1273) reported to induce a strong immune response in persons recovering from natural SARS-CoV-2 infection. In particular a robust neutralising antibody response to B.1.351 was observed with up to 1000-fold increase in neutralising antibody titres against both B.1.351, early wild type variants and also even original SARS-CoV-1 (note: pseudoviruses used in vitro).


DOI: 10.1101/2021.02.05.21251182

 

[2hats]

Another early study of the potential for the Israel vaccination programme to reduce viral load through examining lab testing cycle thresholds over time. Viral loads observed to be reduced by perhaps up to four-fold 12-28 days post first dose. This might hint at some degree of reduction in transmission.

As with the previously mentioned study there are similar caveats, also including pre-immunisation transmission events and the undocumented sample collection location (in the respiratory tract) of the the PCR sampling process.

DOI: 10.1101/2021.02.06.21251283.

 

[2hats]

CanSino AD5-nCOV (single shot adenovirus viral vector) vaccine phase III reporting claims 65.7% efficacy in preventing symptomatic cases, and 90.98% efficacy in preventing severe disease (this is, maybe not unsurprisingly, very comparable to J&Js Janssen Ad26.COV2.S). No clear data on variants involved (no preprint yet).

Bloomberg - Are you a robot?

 

[2hats]

Another set of data points for variant neutralisation (albeit with pseudoviruses). Here BNT162b2 neutralising key mutations in B.1.1.7 and B.1.351 and P.1 (though note that not every mutation in each variant, that would be present in vivo, is being tested). Vaccine sera effective 0.81x (eg B.1.351, P.1) to 1.46x (eg B.1.1.7) relative to original wild type.

DOI: 10.1038/s41591-021-01270-4.

 

[2hats]

Vaxart has announced mixed but potentially promising data from the phase I trials of their VXA-CoV2-1 oral COVID-19 tablet vaccine (Ad5 adenovirus vector based). The vaccine induces immune responses to both spike and nucleocapsid proteins. A small study where some recipients received one dose and others two doses 29 days apart.

It was well tolerated, no severe, only mild GI events. Strong CD8+ T-cell responses to the spike protein were seen along with good IgA responses in both nasal mucosa and serum around 2 months. Unfortunately no IgG response seen.

This may hold promise for targeting new variants and reducing transmission. The company hopes to embark on Phase II studies, including early efficacy estimates, in the coming months.

Vaxart Announces Positive Preliminary Data from Phase 1 Clinical Trial Evaluating Its Oral COVID-19 Tablet Vaccine Candidate

Study reached primary and secondary endpoints of safety and immunogenicity, respectivelyVXA-CoV2-1 induced potent CD8+ T-cell responsesVXA-CoV2-1...

www.globenewswire.com

Notes: They have previously taken this approach to developing an influenza H1N1 vaccine VXA-A1.1 DOI: 10.1016/s1473-3099(19)30584-5. There are concerns about the use of Ad5 as a vaccine vector DOI: 10.1016/S0140-6736(20)32156-5.

 

[two sheds]

Next stupid question

Will they be able to combine covid vaccine with flu vaccine if in one vaccination if we're going to need annual shots?

I presume would for example mean they need similar storage conditions before vaccination

 

[Monkeygrinder's Organ]

Asthma drug may reduce risk of severe Covid if taken early – study

Inhaled budesonide could become first treatment in early stages of infection if study confirmed

www.theguardian.com

Sounds promising on the treatment side.

 

[William of Walworth]

Balanced article (IMO) by Sarah Boseley (Guardian Health editor) about the ups and downs of the Oxford/AstraZeneca's vaccine's reputation.

A series of knocks : Oxford/AstraZeneca's bumpy road to Covid vaccine confidence
From doubts about efficacy in older people to questions about variants, scientists have faced a battle to convince the public and regulators

The latest blow to the vaccine’s public image has been the small trial in just over 2,000 people under age 40 in South Africa. It found “minimal protection” – later said to be 10% – against mild to moderate disease caused by the variant. South Africa announced it was pausing its rollout of the vaccine and will give it to 100,000 people step by step, watching to see if anyone ends up in hospital.

and :

No one was severely ill, hospitalised or died, but the worry is that these were younger people, so less likely to get seriously ill. Oxford/AstraZeneca point to all the trial data showing that nobody has been seriously ill after getting their vaccine (or any of the others) and experts believe the protection is still there against the variant. Once more, however, confidence in the Oxford/AstraZeneca vaccine is likely to take a knock, whether or not it is justified

 

[2hats]

Another preprint looking at B and T cell responses to BNT162b2 and comparing with naturally acquired immunity. Here, antibody response after a single dose was significantly degraded against recent variants, B.1.1.7 to a lesser degree and B.1.351 markedly, compared to earlier wild type, but T cell response was still significant. Naturally acquired immune antibody response against new variants was similarly poor. Antibody neutralisation improved after the boost dose. Also, after two doses a significant increase in the binding antibodies to both SARS-CoV-1 and MERS was also measured.

Yet again hints that with infection by recent variants mild-moderate infections might be seen more commonly in the fully vaccinated with implications for transmission. Underlines the importance of the boost dose. Also highlights role of T cells, responding to a wider range of epitopes than the antibodies (which are more RBD focussed), so they are better able to respond to new variants.
DOI: 10.21203/rs.3.rs-226857/v1.

 

[platinumsage]

A case of the virus seen mutating in a patient with a compromised immune system:

"During the patient’s stay, 23 viral samples were available for analysis, the majority from his nose and throat. Between days 66 and 82, following the first two administrations of plasma, the team saw a dramatic shift in the virus population, with the mutated virus becoming dominant. Although this variant initially appeared to die away, it re-emerged again when the third course of remdesivir and convalescent plasma therapy were administered.

Professor Ravi Gupta from the Cambridge Institute of Therapeutic Immunology and Infectious Disease, who led the research, said: “What we were seeing was essentially a competition between different variants of the virus, and we think it was driven by the convalescent plasma therapy. “The [mutated] virus that eventually won out...initially gained the upper hand during convalescent plasma therapy before being overtaken by other strains, but re-emerged when the therapy was resumed. One of the mutations is in the new UK variant, though there is no suggestion that our patient was where they first arose.”

He added: “Given that both vaccines and therapeutics are aimed at the spike protein, which we saw mutate in our patient, our study raises the worrying possibility that the virus could mutate to outwit our vaccines. This effect is unlikely to occur in patients with functioning immune systems, where viral diversity is likely to be lower due to better immune control. But it highlights the care we need to take when treating immunocompromised patients, where prolonged viral replication can occur, giving greater opportunity for the virus to mutate.”"

Coronavirus more likely to mutate into Kent strain in chronic infections

The Cambridge University scientists were the first to observe a Kent strain-like mutation happen in real time

www.cambridge-news.co.uk

 

[Sunray]

Asthma drug may reduce risk of severe Covid if taken early – study

Inhaled budesonide could become first treatment in early stages of infection if study confirmed

www.theguardian.com

Sounds promising on the treatment side.

This is very interesting, with my sample size of one, I didn't have any breathing problems when I got COVID. Crazy cough but breathing clear as normal. I was and still do take the above-mentioned preventer.

Inhaled steroids, unlike dexamethasone which impacts your immune system, are totally safe, well understood and cheap. If they slash hospital admission would be one of the 1st real wins of this pandemic.

 

[two sheds]

I'm a tad confused because I'd thought the brown inhaler contained beclometasone rather than budesonide.

 

[Sunray]

I'm a tad confused because I'd thought the brown inhaler contained beclometasone rather than budesonide.

It does but they are similar drugs

From the beclometasone wiki " Beclometasone is mainly a glucocorticoid.[1] "
From the budesonide wiki " Budesonide is mainly acting as a glucocorticoid.[1] "

and of course, they have to test each one individually. Both are safe and cheap.
Giving people oral steroids when really sick comes across as a bit of a gamble, on the one hand, preventing ARDS and on the other increasing the time they are sick.

I can hope it prevents people from getting that sick.

 

[Badgers]

First I have heard of this

https://www.nytimes.com/2021/01/01/...itain.html#click=[URL]https://t.co/VSw1YhBvax

[/URL]

Amid a sputtering vaccine rollout and fears of a new and potentially more transmissible variant of the coronavirus, Britain has quietly updated its vaccination playbook to allow for a mix-and-match vaccine regimen. If a second dose of the vaccine a patient originally received isn’t available, or if the manufacturer of the first shot isn’t known, another vaccine may be substituted, health officials said.

 

[LDC]

It's been mentioned before, it's not for routine use, it's for limited situations when clinical need of the patient over rides concerns about mixing vaccines. That article is scare mongering and bad reporting tbh.

 

[prunus]

It's been mentioned before, it's not for routine use, it's for limited situations when clinical need of the patient over rides concerns about mixing vaccines. That article is scare mongering and bad reporting tbh.

There are reasonable theoretical reasons why boosting with a different vaccine (from the current pool of largely similarly targeted vaccines) might in fact be more efficacious than same-vaccine boosting - obviously this will need to be tested (and is being tested at the moment I believe), but any kind of ‘OMG this is crazy risky what are they doing’ reporting is way off the mark, in my opinion.

 

[LDC]

There are reasonable theoretical reasons why boosting with a different vaccine (from the current pool of largely similarly targeted vaccines) might in fact be more efficacious than same-vaccine boosting - obviously this will need to be tested (and is being tested at the moment I believe), but any kind of ‘OMG this is crazy risky what are they doing’ reporting is way off the mark, in my opinion.

bellaozzydog is taking one for the team and undertaking a one person U75 mixing vaccine trial.

 

[cupid_stunt]

Here's an interesting suggestion from France.

France's top health authority has recommended that people who've had coronavirus only get one vaccine dose.

Those who have recovered from the virus have built an immune response similar to that brought on by a vaccine, said the High Authority of Health (HAS).

It said a single shot would "play the role of reminding" the person's body how to fight the infection.

A small study at New York's Mount Sinai medical school found people who had recovered from COVID had 10 to 20 times higher antibody levels after a first vaccine shot than people who had never had the virus.

COVID-19: Previously-infected people only need one vaccine shot, say French experts

A small study recently found that previously-infected people had 10 to 20 times higher antibody levels after a first vaccine shot.

news.sky.com

 

[2hats]

Here's an interesting suggestion from France.

Three studies mentioned upthread (#1157, #1232) and here another study which in part touches upon that...

Here for the first time (to my knowledge) a preprint for a small study (two lots of ~30 individuals, one of ~20) testing vaccine mediated and recovered patient sera against an earlier B.1 clade (D614G type), B.1.1.7 (aka "Kent"/"UK") and B.1.351 ("South African") variants using real viral isolates (as oppose to laboratory constructed pseudoviruses or just selected antibodies).

In convalescents strong immune responses were seen to D614G and B.1.1.7 at months 3 and 6. Degree of neutralising activity depended on the severity of original infection, as has been observed in other studies. A noticeable reduction (5-10x) in neutralisation titres at both time points was seen with respect to B.1.351. In a separate group sampled at month 9 all titres were significantly lower still but particularly so against B.1.351. The fraction of persons producing neutralising antibodies also dropped off and markedly so for B.1.351.


The studies were repeated with BNT162b2 mRNA vaccine mediated sera and also nasal swabs taken at weeks 2 and 3 post first dose and week 4 (1 week post second dose). D614G started to be neutralised at week 2, but it took till week 3 to see any response to B.1.1.7 (and then less than D614G). By week 4 both were similarly neutralised, and only then was a response to B.1.351 seen (ie after the booster shot) albeit at a lower level than for the other two variants.


In the nasal mucosal samples no antiviral effect was seen at weeks 2 or 3 in vaccine recipients. However, in a very small number of cases, who were determined to be seropositive at vaccination (had naturally acquired immunity due to earlier infection), very high titres were seen by week 2, capable of neutralising D614G and B.1.1.7 but inactive to B.1.351.

These results underline the importance of the second (booster dose), where posology indicates, though a strong response to the first (prime) dose was seen in seropositives (as at least three previous studies have observed). They also highlight the challenge posed by B.1.351 (and likely other E484K featuring variants) to both vaccines and reinfection, and the poor mucosal (upper respiratory tract) response suggests that a degree of transmission and asymptomatic/mild/moderate infection is quite possible but without the severe disease associated with progression of the infection to the lower respiratory tract.

(Note: small study numbers, vaccinated participants age range 46-63 years, no T-cell response analysis.)
DOI: 10.1101/2021.02.12.430472.

 

[2hats]

Data from one of Israel's main health service organisations for ~600k unvaccinated and ~600k BNT162b2 fully vaccinated (two doses) may suggest that that vaccine is about 94% effective in preventing symptomatic infection and 92% in preventing serious illness, in all age groups (16+ though over 70s could not be fully assessed). Data indicated high vaccine efficacy over a period of seven days or more after the second dose. Effectiveness against a serious illness a week after the second dose appeared to range from 91% to 99%.

Note however that extensive NPIs were in place throughout this study period. Also worth bearing in mind that the predominate variant in Israel right now is B.1.1.7. Preprint due shortly.

מחקר ענק של כללית: יעילות החיסון במניעת מחלה - 94%

המחקר הגדול ביותר על החיסונים עד כה: מניתוח נתונים של 1.2 מיליון מבוטחי כללית, שמחציתם חוסנו, עולה כי בקרב המתחסנים נרשמה גם ירידה של 92% במניעת מחלה קשה. פרופ' בליצר: "חד-משמעית - החיסון יעיל ביותר בחיים האמיתיים, בדיוק כפי שנמצא במחקר המקורי". יותר מ-2.5 מיליון כבר התחסנו בשתי מנות. שיעור...

www.ynet.co.il

A second healthcare provider reports 544 cases, 15 requiring hospitalisation, 4 severe, no deaths, from 523k fully vaccinated (two doses of BNT162b2). This is reported as a 93% effectiveness rate. Note that NPIs were and are still in effect.

It works: 0 deaths, only 4 severe cases among 523,000 fully vaccinated Israelis

HMO data a week after 2nd dose shows 93% effectiveness, ‘unequivocally' proving vaccine's success and leaving ‘no doubt’ it’s saved many Israeli lives, says Maccabi official

www.timesofisrael.com

 

[2hats]

This study (600 participants) indicates that mRNA-1273 vaccine doses at both 50μg and 100μg appear to elicit similarly robust immune responses in younger (18-55 yr) and older (≥55 yr) adults. It may be possible to half dosing each time and thereby immediately double the inventory. T cell responses still need to be profiled.

DOI: 10.1016/j.vaccine.2021.02.007.

 

[2hats]

A bumper set of studies (not yet peer reviewed) into the effectiveness of vaccine sera with respect to various variants of concern. All tell a similar story.

Here early measurements for P.1 and P.2, as well as B.1.1.7 and B.1.351 (plus a few other) performed with BNT162b2 (and with fewer participants, mRNA-1273) vaccine sera on lentivirus based pseudoviruses. B.1.1.7 ("UK"/"Kent"), B.1.1.298 ("Danish" 'mink') and B.1.1.298 ("Californian") all neutralised to a similar degree to earlier wild types (though the 'mink' variant has a small degree of resistance). P.1/P.2 ("Brazilian") variants noticeably more resilient whilst a significant reduction in neutralisation is seen with B.1.351. Just waiting for the preprint to drop (e2a: preprint now available).

A second study along similar lines, here using a vesicular stomatitis pseudovirus (exhibits similar dynamics to SARS-CoV-2 with respect to ACE2 and TMPRSS2) and BNT162b2 vaccine sera. "Our results await confirmation with authentic SARS-CoV-2. However, the data available at present suggest that the South Africa and Brazil variants constitute an elevated threat to human health and that containment of these variants by non-pharmaceutic interventions is an important task". Earlier D614G wild type, B.1.1.7, B.1.351 and P.1 are compared, with ever decreasing neutralisation seen between B.1.1.7 v P.1 v B.1.351 in both convalescent and vaccine sera.

DOI: 10.1101/2021.02.11.430787.

Finally, a third study focussed on B.1.1.7 with/without E484K (another pseudovirus to mimic the behaviour currently being observed in some regions of the UK) versus the performance of BNT162b2 mediated sera and convalescent sera. Again B.1.1.7 reduces the effectiveness of neutralisation, but B.1.1.7 with a E484K mutation noticeably reduces the neutralisation ability of both sera. The need for a second dose to maximise immune antibody response is underlined. Here the 'fold change' of titres required to achieve the same outcome is plotted (essentially read inverted compared to the previous two plots).

DOI: 10.1101/2021.01.19.21249840.
An investigation of vaccine mediated T-cell immunity compared to that naturally acquired appears warranted. In particular as most leading vaccines currently focus on the spike proteins and it is quite likely that convalescent T-cell immunity is also gained from the nucleocapsid and perhaps membrane proteins too.

 

[Badgers]

Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials

The results of this primary analysis of two doses of ChAdOx1 nCoV-19 were consistent with those seen in the interim analysis of the trials and confirm that the vaccine is efficacious, with results varying by dose interval in exploratory analyses. A 3-month dose interval might have advantages...

www.thelancet.com

 

[elbows]

Good news in this study, although it is worth paying attention to the caveats.

Covid vaccines - 'spectacular' impact on serious illness

First evidence from the UK's vaccine programme shows a reduction in hospital admissions in Scotland.

www.bbc.co.uk

 

[2hats]

Good news in this study, although it is worth paying attention to the caveats.

Covid vaccines - 'spectacular' impact on serious illness

First evidence from the UK's vaccine programme shows a reduction in hospital admissions in Scotland.

www.bbc.co.uk

Preprint here. A prospective cohort study of 1,137,775 first dose recipients. Caution: they estimated vaccine effects against COVID-19 related hospital admission. Other outcomes (A&E/ICU admission and deaths) were not considered. The cohort was somewhat stratified with respect to age by vaccine type (proportionally higher AZD1222(ChAdOx1) uptake in 80+, higher BNT162b2 uptake in under 65s).

Findings: The first dose of the BNT162b2 vaccine was associated with a vaccine effect of 85% (95%CI 76 to 91) for COVID-19 related hospitalisation at 28-34 days post-vaccination. Vaccine effect at the same time interval for the ChAdOx1 vaccine was 94% (95%CI 73 to 99). Results of combined vaccine effect for prevention of COVID-19 related hospitalisation were comparable when restricting the analysis to those aged ≥80 years (81%; 95%CI 65 to 90 at 28-34 days post-vaccination).

Interpretation: A single dose of the BNT162b2 mRNA and ChAdOx1 vaccines resulted in substantial reductions in the risk of COVID-19 related hospitalisation in Scotland.

 

[Wilf]

Good news in this study, although it is worth paying attention to the caveats.

Covid vaccines - 'spectacular' impact on serious illness

First evidence from the UK's vaccine programme shows a reduction in hospital admissions in Scotland.

www.bbc.co.uk

Good news certainly, though the piece could have been clearer. Were they discounting hospitalisations that occurred less than 4 after vaccination - I'm guessing they were. Also, I'm not sure how the study ran up to 15 Feb, as many of those vaccinations wouldn't yet be up to 4 weeks. But good news is good news and anything like this kicks back at the anti-vaxx twats.

The preliminary data from the EAVE II project covers 1.14 million vaccinations given in Scotland between 8 December and 15 February.
The study looked at the numbers being admitted to hospital with Covid among this population and compared it to those admitted who were not vaccinated.
In total, there were just over 8,000 people who ended up in hospital, but only 58 were among the vaccinated group after the four-week mark.

 

[souljacker]

My antibody blood test for the Convalescent Plasma Donor Eligibility Test came back today and I scored 98.4 U/mL. Anyone know what that means? They want my blood though so I'll book an appointment. I'd be interested to know if that is considered a low or high amount though. I was hardly affected by the disease so I was expecting a low result.

 

[Supine]

My antibody blood test for the Convalescent Plasma Donor Eligibility Test came back today and I scored 98.4 U/mL. Anyone know what that means? They want my blood though so I'll book an appointment. I'd be interested to know if that is considered a low or high amount though. I was hardly affected by the disease so I was expecting a low result.

I don't know about the value but I know there is a shortage of plasma in the supply chain. So good work on donating

 

[2hats]

Yet two more studies looking at immune responses after one dose (here both BNT162b2) in seropositives, compared to seronegatives.

The first study, amongst (51) healthcare workers, found that previously infected individuals exhibited a neutralising response to the spike (at 21-29 days post dose) of up to two orders of magnitude greater than the uninfected (who after one dose exhibited a response similar to that of the previously infected prior to their first dose).

DOI: 10.1016/S0140-6736(21)00501-8.

The second study, again of (72) healthcare workers, likewise found a huge immune response to a first dose amongst seropositives (samples taken just prior to first dose and then 21-25 days later). This was seen in both antibody and T-cell responses. Notably, a poor response to first dose amongst older (>50 years) seronegatives was seen (a correlation not seen in seropositives). Previously uninfected also exhibited a poor T-cell response to first dose across all ages, half of them with barely any response at all. This highlights the importance of a timely second dose for the previously uninfected, in particular ages 50+, and the need for them to continue NPIs.

DOI: 10.1016/S0140-6736(21)00502-X.