Sanofi more confident about its coronavirus vaccines

Sanofi’s confidence in its coronavirus vaccine candidates has increased this summer as the French drugmaker prepares to start clinical trials, its chief executive told Reuters.

The company is working on two of the more than 150 potential vaccines being developed across the world to tackle the COVID-19 pandemic, which has claimed more than 831,000 lives and sparked economic chaos.

One candidate, to be manufactured on the back of an existing platform that develops vaccines to treat flu, will use an adjuvant made by Britain’s GlaxoSmithKline (GSK) to boost its efficacy.

The other, being developed with U.S. company Translate Bio, relies on a different technology known as mRNA.

“The early data is saying that we’re on the right track and that we have a vaccine,” Paul Hudson said in an interview on Friday, referring to the vaccine being developed with GSK.

That vaccine is set to start clinical trials next month.

Around 30 experimental coronavirus shots are already in human trials. But Hudson said in June the probability of Sanofi obtaining a vaccine with an efficacy of more than 70% was higher than for rivals, in part due to its experience in vaccines.

“Our confidence has increased. We have work to do like everybody on manufacturing in large volumes. But we will have one, maybe two vaccines next year,” Hudson said.

Translate Bio said on Tuesday the mRNA vaccine had induced an immune response in non-human studies, with trials in humans expected to start in November.

Sanofi has secured deals for the vaccine-plus-adjuvant with the United States and Britain, and is in advanced talks with the European Union to supply it with up to 300 million doses.

But the EU is offering only partial protection to vaccine makers against legal risks from side-effects of their potential shots, European officials said earlier this week, in a move that is hampering deals and contrasts with U.S. policy.

“I think with the level of protection, we have reached an ‘agreed level’. And I think that has allowed us to go forward and sign. But I am aware there are different positions on how strong that is,” Hudson said.

With vaccines being developed at record speed during the pandemic, there is potentially a greater risk they may have unexpected consequences or may not be effective.

The financial coverage of these liabilities is a key feature of drugmakers’ talks with governments keen to secure vaccine shots in advance.

There is so far no approved coronavirus vaccine, except one authorised in Russia before large-scale trials.

https://www.marketscreener.com/quote/stock/SANOFI-4698/news/Exclusive-Sanofi-more-confident-about-its-coronavirus-vaccines-31196215/

COVID-19 studies top 3,100 globally in race for treatments and vaccines

A good indicator of the substantial global effort to develop treatments and vaccines against COVID-19 can be found in ClinicalTrials.gov. A beta version of a new feature shows that there are 3,136 registered clinical trials worldwide evaluating some aspect of treating or preventing COVID-19. The studies are planned or are being conducted across 115 countries.

21.6% (n=677/3136) of the trials include at least one U.S. location and 2.5% (n=77/3136) are supported, at least in part, by U.S. federal funding.

There are 1,042 studies assessing at least one drug intervention and number of “mapped drug names” (standardized drug names assigned by the National Library of Medicine). Of these, 29.8% (n=310/1042) include at least one U.S. location and 2.4% (n=25/1042) are supported by funding from the feds.

There are 24 studies involving Gilead Sciences’ (NASDAQ:GILD) remdesivir (GS-5734), still the only drug approved in the U.S. for emergency use to treat COVID-19.

There are 48 studies involving antiretroviral ritonavir, an HIV protease inhibitor marketed as Norvir by AbbVie (NYSE:ABBV) and 47 studies involving tocilizumab, an interleukin-6 receptor antagonist, sold by Roche (OTCQX:RHHBY) as Actemra (approved for arthritis, giant cell arteritis and cytokine release syndrome).

Leading the pack is malaria med hydroxychloroquine, involved in 184 studies, despite showing no benefit in earlier trials, followed by antibiotic azithromycin, involved in 69 studies (used to treat lung infections among others). 

https://seekingalpha.com/news/3609464-covidminus-19-studies-top-3100-globally-in-race-for-treatments-and-vaccines

Does convalescent plasma help COVID-19 patients? Studies will answer

Investors in convalescent plasma players have experienced a bit of volatility of late related to the FDA emergency use nod to treat COVID-19 patients.

Shares sold off on August 19 on a delay in approval to allow the agency to review additional trial data. It finally signed off on emergency use earlier this week.

Efficacy has been challenging to prove. A study in the Netherlands was stopped after investigators saw no difference from placebo in mortality, length of hospital stay or disease severity.

Recent results from the largest study to date, run by the Mayo Clinic, showed a lower mortality rate if convalescent plasma was administered early, within three days of diagnosis, compared to later but the study has no control group so the treatment effect cannot be definitively confirmed.

At least 10 randomized trials in the U.S. are struggling to recruit participants since severe infections are waning.

Per ClinicalTrials.gov, there are 96 registered studies that are recruiting, enrolling by invitation or active not recruiting, including 19 Phase 3s.

Seven of the late-stage studies should wind up this year, followed by 10 next year and two in 2022. Only five are based in the U.S. All are still recruiting patients, only one (Stanford University) by invitation.

The largest is a 15,000-subject trial led by the University of Oxford that also includes lopinavir/ritonavir, azithromycin, tocilizumab and hydroxychloroquine. Its primary completion date is December of next year.

Selected tickers: Kamada (NASDAQ:KMDA), Grifols (NASDAQ:GRFS), XBiotech (NASDAQ:XBIT), Cerus (NASDAQ:CERS), ADMA Biologics (NASDAQ:ADMA)

https://seekingalpha.com/news/3609798-convalescent-plasma-help-covidminus-19-patients-studies-will-answer

Hydroxychloroquine in treatment of outpatients with mildly symptomatic COVID-19

View ORCID ProfileAndrew Ip, View ORCID ProfileJaeil Ahn, Yizhao Zhou, View ORCID ProfileAndre H Goy, Eric Hansen, View ORCID ProfileAndrew L Pecora, Brittany A Sinclaire, Urszula Bednarz, Michael Marafelias, Shivam Mathura, Ihor S Sawczuk, View ORCID ProfileJoseph P Underwood III, David M Walker, Rajiv Prasad, Robert L Sweeney, Marie G Ponce, Samuel LaCapra, Frank J Cunningham, Arthur G Calise, Bradley L Pulver, Dominic Ruocco, Greggory E Mojares, Michael P Eagan, Kristy L Ziontz, Paul Mastrokyriakos, View ORCID ProfileStuart L Goldberg

doi: https://doi.org/10.1101/2020.08.20.20178772

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/10.1101/2020.08.20.20178772v1.full.pdf

Abstract

Background: Hydroxychloroquine has not been associated with improved survival among hospitalized COVID-19 patients in the majority of observational studies and similarly was not identified as an effective prophylaxis following exposure in a prospective randomized trial. We aimed to explore the role of hydroxychloroquine therapy in mildly symptomatic patients diagnosed in the outpatient setting. Methods: We examined the association between outpatient hydroxychloroquine exposure and the subsequent progression of disease among mildly symptomatic non-hospitalized patients with documented SARS-CoV-2 infection. The primary outcome assessed was requirement of hospitalization. Data was obtained from a retrospective review of electronic health records within a New Jersey USA multi-hospital network. We compared outcomes in patients who received hydroxychloroquine with those who did not applying a multivariable logistic model with propensity matching. Results: Among 1274 outpatients with documented SARS-CoV-2 infection 7.6% were prescribed hydroxychloroquine. In a 1067 patient propensity matched cohort, 21.6% with outpatient exposure to hydroxychloroquine were hospitalized, and 31.4% without exposure were hospitalized. In the primary multivariable logistic regression analysis with propensity matching there was an association between exposure to hydroxychloroquine and a decreased rate of hospitalization from COVID-19 (OR 0.53; 95% CI, 0.29, 0.95). Sensitivity analyses revealed similar associations. QTc prolongation events occurred in 2% of patients prescribed hydroxychloroquine with no reported arrhythmia events among those with data available. Conclusions: In this retrospective observational study of SARS-CoV-2 infected non-hospitalized patients hydroxychloroquine exposure was associated with a decreased rate of subsequent hospitalization. Additional exploration of hydroxychloroquine in this mildly symptomatic outpatient population is warranted.

Competing Interest Statement

All authors have completed the ICMJE uniform disclosure form at http://www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted work; AHG reports being a study investigator for Genentech-Hoffman La Roche, during the conduct of the study; research funding as study investigator from Acerta, AstraZeneca, Celgene, Kite Pharma, Elsevier’s PracticeUpdate Oncology, Gilead, Medscape, MJH Associates, OncLive Peer Exchange, Physicians Education Resource, and Xcenda, outside the submitted work, and research funding as a study investigator for Constellation, Infinity, Infinity Verastem, Janssen, Karyopharm, and Pharmacyclics, outside of the submitted work. EH and SM report consulting for Regional Cancer Care Associates and Hackensack Meridian Health, outside the submitted work. ALP and SLG report having equity ownership in COTA, outside the submitted work. No other relationships or activities that could appear to have influenced the submitted work.

Clinical Trial

NCT04347993

Funding Statement

No external funding was received to support this research.

https://www.medrxiv.org/content/10.1101/2020.08.20.20178772v1

Risk of SARS-CoV-2 reinfection in an intense re-exposure setting

August 28, 2020

View ORCID ProfileLaith J Abu-Raddad, View ORCID ProfileHiam Chemaitelly, View ORCID ProfileHoussein H. Ayoub, View ORCID ProfileZaina Al Kanaani, Abdullatif Al Khal, Einas Al Kuwari, Adeel A Butt, Peter Coyle, Andrew Jeremijenko, Anvar Hassan Kaleeckal, Ali Nizar Latif, View ORCID ProfileHanan F Abdul Rahim, Mohamed Ghaith Al Kuwari, Hamad Eid Al Romaihi, Sheikh Mohammad Al Thani, Roberto Bertollini

doi: https://doi.org/10.1101/2020.08.24.20179457

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/10.1101/2020.08.24.20179457v1.full.pdf

Abstract

Background: Reinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a subject of debate. We aimed to assess the risk and incidence rate of documented SARS-CoV-2 reinfection in a large cohort of laboratory-confirmed cases in Qatar. Methods: All SARS-CoV-2 laboratory-confirmed cases with at least one PCR positive swab that is ≥45 days after a first positive swab were individually investigated for evidence of reinfection, and classified as showing strong, good, some, or weak/no evidence for reinfection. Risk and incidence rate of reinfection were estimated. Results: Out of 133,266 laboratory-confirmed SARS-CoV-2 cases, 243 persons (0.18%) had at least one subsequent positive swab ≥45 days after the first positive swab. Of these, 54 cases (22.2%) had strong or good evidence for reinfection. Median time between first and reinfection swab was 64.5 days (range: 45-129). Twenty-three of the 54 cases (42.6%) were diagnosed at a health facility suggesting presence of symptoms, while 31 (57.4%) were identified incidentally through random testing campaigns/surveys or contact tracing. Only one person was hospitalized at or following time of reinfection swab, but still had relatively mild infection. No deaths were recorded. Risk of reinfection was estimated at 0.04% (95% CI: 0.03-0.05%) and incidence rate of reinfection was estimated at 1.09 (95% CI: 0.84-1.42) per 10,000 person-weeks. Conclusions: SARS-CoV-2 reinfection appears to be a rare phenomenon suggestive of a strong protective immunity against reinfection that lasts for at least a few months post primary infection.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

The authors are grateful for support provided by the Ministry of Public Health, Hamad Medical Corporation, and the Biomedical Research Program and the Biostatistics, Epidemiology, and Biomathematics Research Core, both at Weill Cornell Medicine-Qatar. The statements made herein are solely the responsibility of the authors.

https://www.medrxiv.org/content/10.1101/2020.08.24.20179457v1

What is the evidence for physical distancing in covid-19?

BMJ 2020; 370 doi: https://doi.org/10.1136/bmj.m3223

1. Nicholas R Jones, 1 clinical researcher,  
2. Zeshan U Qureshi, clinical academic,2,  
3. Robert J Temple, medical student3,  
4. Jessica P J Larwood, medical student4,  
5. Trisha Greenhalgh, professor1,  
6. Lydia Bourouiba, professor5

Rigid safe distancing rules are an oversimplification based on outdated science and experiences of past viruses, argue Nicholas R Jones and colleagues

Physical distancing is an important part of measures to control covid-19, but exactly how far away and for how long contact is safe in different contexts is unclear. Rules that stipulate a single specific physical distance (1 or 2 metres) between individuals to reduce transmission of SARS-CoV-2, the virus causing covid-19, are based on an outdated, dichotomous notion of respiratory droplet size. This overlooks the physics of respiratory emissions, where droplets of all sizes are trapped and moved by the exhaled moist and hot turbulent gas cloud that keeps them concentrated as it carries them over metres in a few seconds.12 After the cloud slows sufficiently, ventilation, specific patterns of airflow, and type of activity become important. Viral load of the emitter, duration of exposure, and susceptibility of an individual to infection are also important.

Instead of single, fixed physical distance rules, we propose graded recommendations that better reflect the multiple factors that combine to determine risk. This would provide greater protection in the highest risk settings but also greater freedom in lower risk settings, potentially enabling a return towards normality in some aspects of social and economic life.

https://www.bmj.com/content/370/bmj.m3223

Preventing, Mitigating SARS-CoV-2 Transmission: 4 Camps, Maine, June–Aug. 2020

Laura L. Blaisdell, MD¹; Wendy Cohn, PhD²; Jeff R. Pavell, DO³; Dana S. Rubin, MD⁴; Jeffrey E. Vergales, MD⁵ (View author affiliations)

Summary

What is already known about this topic?

Nonpharmaceutical interventions (NPIs) have been shown to decrease spread of communicable disease. Data on the effectiveness of NPIs on the prevention and mitigation of SARS-CoV-2 transmission among children and adolescents in congregate settings are limited.

What is added by this report?

During the 2020 summer camp season, four Maine overnight camps with 1,022 attendees from 41 states and international locations implemented a multilayered prevention and mitigation strategy that was successful in identifying and isolating three asymptomatic COVID-19 cases and preventing secondary transmission.

What are the implications for public health practice?

Understanding successful interventions to prevent and mitigate SARS-CoV-2 transmission in overnight camps has important implications for similar congregate settings such as day camps and schools with the same age range.

https://www.cdc.gov/mmwr/volumes/69/wr/mm6935e1.htm?s_cid=mm6935e1_w