Effective post-exposure prophylaxis of Covid-19 is associated with use of hydroxychloroquine

 

Prospective re-analysis of a public dataset incorporating novel data

 View ORCID ProfileDavid M Wiseman,  View ORCID ProfilePierre Kory,  View ORCID ProfileSamir A Saidi,  View ORCID ProfileDan Mazzucco

doi: https://doi.org/10.1101/2020.11.29.20235218

This article is a preprint and has not been certified by peer review [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

PDF: https://www.medrxiv.org/content/10.1101/2020.11.29.20235218v1.full.pdf

Abstract

BACKGROUND: A recent trial (NCT04308668) found that post-exposure prophylaxis with hydroxychloroquine (HCQ) was associated with a reduced incidence of Covid-19 by 17% overall; 36% in younger subjects, 31% in household contacts and 49% given within one day. To understand these trends, we prospectively re-analyzed the released dataset. METHODS: Our protocol conformed to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT). We compared the incidence of Covid-19 after HCQ or placebo, stratifying primarily by time to drug receipt, age and gender. RESULTS: Requesting additional data, we found that 52% of subjects received medication 1-2 days after the intended overnight delivery; 19% of them outside the intended four-day window from exposure. After re-analysis, there was a reduced incidence of Covid-19 associated with HCQ compared with placebo (9.6% vs. 16.5%) when received up to 3 days (Early) after exposure (RR 0.58, 95%CI 0.35 - 0.97; p=0.044; NNT 14.5) but not later (Late) (RR 1.22, 95%CI 0.72 - 2.04). We found a significant HCQ-associated reduction in subjects 18 to 45 years old associated with Early (RR 0.53, 95%CI 0.29-0.97; p=0.0448, NNT 11.5) but not Late (RR 1.02, 95%CI 0.55-1.89) prophylaxis, attenuated in older subjects (RR 0.75, 95%CI 0-27-2.05) and by co-morbidities. There were reductions associated with Early prophylaxis in household contacts (RR 0.35, 95%CI 0.13-0.89; p=0.025, NNT 5.7) and Health Care Workers (RR 0.74, 95%CI 0.4-1.38). We did not detect effects of gender, folate, zinc, or ascorbic acid. CONCLUSIONS: Using novel data with a prospective post hoc re-analysis, hydroxychloroquine, in an age-dependent manner, was associated with reduced illness compatible with Covid-19 or confirmed infection when supplied for post-exposure prophylaxis between 1 and 3 days after high-risk or moderate-risk exposure. This finding warrants prospective confirmation. Registered with the Open Science Framework (last revised September 27, 2020, osf.io/fqtnw).

Competing Interest Statement

The authors have declared no competing interest.

Clinical Trial

NCT04308668

Clinical Protocols

https://osf.io/hyp8k/

https://www.medrxiv.org/content/10.1101/2020.08.19.20178376v2

Funding Statement

There is no external support for this study.

https://www.medrxiv.org/content/10.1101/2020.11.29.20235218v1

Janssen in Rolling Submission for Single-dose COVID-19 Vaccine Candidate to European Medicines Agency

Janssen-Cilag International N.V., part of the Janssen Pharmaceutical Companies of Johnson & Johnson, has initiated a rolling submission with the European Medicines Agency (EMA) for its investigational single-dose vaccine candidate for the prevention of COVID-19.

The EMA’s Committee for Medicinal Products for Human Use (CHMP) enabled a rolling review of the investigational single-dose Janssen COVID-19 vaccine candidate based principally on positive non-clinical data showing that the vaccine candidate elicits a robust immune response, as demonstrated by neutralising antibodies. 

Janssen will continue to work in close collaboration with the EMA’s CHMP to complete the rolling review process and to facilitate a conditional Marketing Authorisation Application (MAA) when appropriate. In addition to the EMA, Janssen is in discussions with other regulatory authorities worldwide, as it prepares to initiate regulatory review processes for use of its investigational single-dose COVID-19 vaccine candidate during the pandemic response period.

https://www.janssen.com/emea/sites/www_janssen_com_emea/files/jj_announces_initiation_of_rolling_submission_for_its_single_dose_janssen_covid19_vaccine_candidate_with_the_ema.pdf

Fauci apologizes for casting doubt over UK's approval of Pfizer vaccine

 Anthony Fauci, the top U.S. infectious diseases expert, apologized on Thursday after casting doubt over the rigor of the British regulators who approved the Pfizer vaccine against COVID-19 and said he had faith in their work.

“There really has been a misunderstanding, and for that I’m sorry, and I apologize for that,” Fauci said in an interview with BBC television, after his earlier comments on CBS were broadcast in Britain and received prominent coverage.

“I do have great faith in both the scientific community and the regulatory community in the UK,” Fauci said.

“I did not mean to apply any sloppiness (to the UK regulatory process) even though it came out that way,” he said. “So if it did, I just want to set the record straight. I have a great deal of confidence in what the UK does both scientifically and from a regulatory standpoint.”

https://www.reuters.com/article/us-health-coronavirus-britain-fauci-apol/fauci-apologizes-for-casting-doubt-over-uks-approval-of-pfizer-vaccine-idUSKBN28D3AH

Britain to cover COVID-19 vaccine side-effects under damages scheme

 Britain will pay individuals who suffer any severe side-effects from COVID-19 vaccines under an existing programme, the government said on Thursday, ahead of a rollout of Pfizer and BioNTech’s vaccine in the country following emergency approval.

COVID-19 will be added as a "precautionary step" to the list of diseases covered for potential liabilities under the Vaccine Damage Payments Scheme (VDPS), the Department of Health and Social Care said. It added that vaccines would be deployed only after stringent checks. (bit.ly/3mEuZ3I)

Compensation for any possible side-effects from a COVID-19 vaccine has been the subject of much debate in recent months, as drugmakers and governments around the world have worked in record time to develop and approve vaccines against the illness which has created havoc worldwide.

Britain's VDPS was set up in 1979 and covers victims of side-effects caused by common vaccines, such as those against measles, influenza, smallpox and tetanus. In 2009 the vaccine against the H1N1 swine flu was also briefly added to the list.

Under the scheme, individuals are entitled to a lump sum capped at 120,000 pounds ($161,676) if they can prove to have been seriously disabled as a result of a vaccination.

The scheme is meant to dissuade people from seeking compensation through lengthy and costly court proceedings, but has been criticised for the cap and its restrictive conditions.

“The current scheme is not really adequate for the current situation. If adverse events occur, the route to compensation is too complicated. It would be much better if the government set up a bespoke scheme for COVID-19,” said Duncan Fairgrieve, of the British Institute of International and Comparative Law.

Britain said it would continue to monitor the safety of Pfizer and BioNTech’s vaccine after the country on Wednesday became the first in the Western world to approve a COVID-19 vaccine.

The emergency use authorisation does not include liabilities, however, unlike a conditional approval granted by the European Union.

https://www.reuters.com/article/us-health-coronavirus-britain-vaccines/britain-to-cover-covid-19-vaccine-side-effects-under-damages-scheme-idUSKBN28D2WF

Amgen to host investor event on BiTE platform December 8

 

• Following ASH 2020, Amgen (NASDAQ:AMGN) will host a webcast for investors on Tuesday, December 8, at 4:00 pm ET on its oncology and hematology programs with a particular focus on its BiTE platform, including late-stage pediatric data on Blincyto (blinatumomab) and the first clinical results on AMG 701.
• https://seekingalpha.com/news/3641518-amgen-to-host-investor-event-on-bite-platform-december-8

Pfizer vaccine supply cut wipes out S&P 500 gains, stimulus optimism

 

• The S&P (SP500) -0.1% went from highs to lows of the day, losing about 50 basis points, after the report that Pfizer would only be able to ship the COVID vaccines originally planned due to supply chain constraints.
• The Nasdaq (COMP) +0.2%, helped by software, and Dow (DJI) +0.3%, boosted by Boeing, fared better.
• The S&P had been rallying towards the close before the Pfizer news hit as the noises out of Washington indicated that a bipartisan $908B COVID relief bill might have a shot if it made it to the president's desk.
• Sen. Lindsey Graham said he supported the bill and had talked to President Trump "extensively" about it. But Sen. Mitch McConnell is still leading to a smaller targeted bill.
• The S&P sectors ended split, with six gaining and five declining.
• Energy (NYSEARCA:XLE) was the leader, with crude futures +0.8% edging up after OPEC+ agreed on a small production hike starting in January. Utilities (NYSEARCA:XLU) was the worst performer.
• Tesla was the lone megacap in the green.
• Rates also dropped on vaccine supply concerns. The 10-year Treasury yield was down four basis points to 0.91%
• https://seekingalpha.com/news/3641508-prizer-vaccine-supply-cut-wipes-out-s-and-p-500-gains-stimulus-optimism

Airports reject vaccine requirement as travel debate intensifies

 Aviation industry opposition to requiring mandatory COVID-19 vaccination for passengers has intensified as impending drug approvals trigger a debate over their role in air travel.

Airports Council International, which represents airports worldwide, joined most airlines in calling for a choice between testing or vaccination, fearing a blanket rule imposing pre-flight inoculation would be as disruptive as quarantines.

Qantas Airways triggered the debate last week when it said a COVID-19 vaccination would be necessary for passengers on its international flights, which remain largely idle because of Australia’s strict border controls.

But other airlines, and now global airports, are worried that waiting for vaccines would bar people from traveling until they are rolled out widely, crippling business in regions, such as Europe that have relatively small domestic aviation markets.

“Just as quarantine effectively halted the industry, a universal requirement for vaccines could do the same,” ACI World Director General Luis Felipe de Oliveira told Reuters.

“While we welcome the rapid development and deployment of vaccines, there will be a considerable period before they are widely available,” he added.

“The industry cannot wait till vaccination becomes available worldwide. During the transition period, tests and vaccines together will play a key role on the industry recovery.”

Australia has indicated people arriving from abroad will need to be vaccinated or to self-isolate in one of a limited number of hotels.

Qantas Chief Executive Alan Joyce said the policy could spread to other countries, noting proof of vaccination is already required for yellow fever for some destinations.

“Other governments are moving in that direction,” he told reporters on Thursday.

TESTING OR VACCINES?

But the head of airline trade group IATA, which last week downgraded its financial outlook for the sector as a second wave of COVID-19 cases swept Europe and the United States, believes making vaccines compulsory would not work globally.

Systematic testing is “more critical to reopening borders than the vaccine”, IATA Director General Alexandre de Juniac told Reuters.

Shukor Yusof, head of Malaysia-based aviation consultancy Endau Analytics, said Southeast Asian countries would take different approaches on vaccine requirements. Asian countries have some of the lowest case numbers of the novel coronavirus globally.

Taiwan Health Minister Chen Shih-chung said on Wednesday that COVID-19 “passports” to show inoculation and infection history are a good idea, but hard in practice.

Australian Prime Minister Scott Morrison called on Thursday for a common set of global recognitions for COVID-19 vaccines.

Some experts say vaccines will be difficult to mandate because of limited supply and a range of quality.

Dr David Freedman, a U.S. infectious diseases specialist, believes more countries will follow Britain’s lead and use testing to reduce quarantine times.

“For the majority of the world’s population, especially in the developing world, it’s going to be years before everybody that wants to fly even has the possibility of getting the vaccine,” said Freedman, a professor at University of Alabama at Birmingham.

As more countries develop vaccines, airlines and governments will need to decide which ones to clear.

“The other issue about mandatory vaccines is going to be well what vaccine did you get?” Freedman said. “Do we trust every vaccine that’s made in the world?”

https://www.reuters.com/article/us-health-coronavirus-airports/airports-reject-vaccine-requirement-as-travel-debate-intensifies-idUSKBN28D2TV