‘Long-COVID’: study of persisting symptoms, biomarker and imaging abnormalities

1. Swapna Mandal1,
2. Joseph Barnett2,
3. Simon E Brill1,
4. http://orcid.org/0000-0002-5650-5361Jeremy S Brown3,4,
5. Emma K Denneny4,
6. Samanjit S Hare2,
7. Melissa Heightman4,
8. Toby E Hillman4,
9. Joseph Jacob5,6,
10. Hannah C Jarvis1,
11. http://orcid.org/0000-0001-7501-4448Marc C I Lipman1,3,
12. Sindhu B Naidu1,
13. Arjun Nair6,
14. http://orcid.org/0000-0002-7307-169XJoanna C Porter3,4,
15. Gillian S Tomlinson4,7,
16. http://orcid.org/0000-0002-7246-6040John R Hurst1,3
17. ARC Study Group

PDF: https://thorax.bmj.com/content/thoraxjnl/early/2020/11/09/thoraxjnl-2020-215818.full.pdf

Abstract

Large numbers of people are being discharged from hospital following COVID-19 without assessment of recovery. In 384 patients (mean age 59.9 years; 62% male) followed a median 54 days post discharge, 53% reported persistent breathlessness, 34% cough and 69% fatigue. 14.6% had depression. In those discharged with elevated biomarkers, 30.1% and 9.5% had persistently elevated d-dimer and C reactive protein, respectively. 38% of chest radiographs remained abnormal with 9% deteriorating. Systematic follow-up after hospitalisation with COVID-19 identifies the trajectory of physical and psychological symptom burden, recovery of blood biomarkers and imaging which could be used to inform the need for rehabilitation and/or further investigation.

This article is made freely available for use in accordance with BMJ’s website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by BMJ. You may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained.

https://bmj.com/coronavirus/usage

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http://dx.doi.org/10.1136/thoraxjnl-2020-215818

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Icer adds to Gilead's Veklury woes

In May the US drug pricing watchdog Icer said a 10-day course of Gilead’s Covid-19 antiviral Veklury would be cost-effective at up to $4,500. In June this was cut to $2,520-2,800. Yesterday the price for treating patients with moderate to severe disease shrank further, to $2,470, but the real problem for Gilead is the price Icer has benchmarked for patients hospitalised with milder disease: just $70. Having analysed four studies evaluating Veklury’s influence on mortality, Icer has concluded that there can be no assumption of survival benefit with the drug, saying further US-based data are needed to support or reject such a benefit. It did acknowledge that new data from a trial in the US healthcare system demonstrated that the treatment shortened hospital stays and reduced the number of patients with moderate to severe disease who require higher levels of respiratory support. But the slicing of the cost-effective price in mildly ill, though still hospitalised, patients, chimes with some brokers' recent forecast cuts for Veklury. Leerink has made huge cuts to its highly bullish numbers: in mid-July it forecast global 2024 Veklury sales of $7bn; at the end of October it put the figure at just $4.2bn. A more reasonable number comes from EvaluatePharma's consensus of sellside forecasts, which puts 2024 sales at $2.1bn.

https://www.evaluate.com/vantage/articles/news/snippets/icer-adds-gileads-veklury-woes

It’s official: Covid-19 vaccine trials rank among the largest

Drug developers are throwing everything at Covid-19, but it is the vaccine trials that are consuming the most resources. A look at some of the largest clinical trials undertaken with experimental agents in recent years puts these endeavours into context: of phase III trials registered in clinicaltrials.gov, Covid-19 vaccine studies count for five of the 10 most expansive, in terms of enrolment. Vaccines dominate the top 10, largely because these projects require vast pivotal programmes to identify low-frequency safety issues that might occur in broader swathes of the population. Another reason is to bestow sufficient power to detect a significant difference, between control and active arms, in events that happen rarely. For example, Pfizer and Biontech confirmed only 94 Covid-19 cases among the 43,538 participants enrolled in their trial of BNT162b2. A cardiovascular outcome study also features below. This is another type of trial that requires large numbers of subjects for sufficient statistical power; Evaluate Vantage identified 10 further CVOTs with enrolment above 20,000. Of course size does not equal success. Notable failures in this list include the flu vaccine that was canned by Glaxo in 2010, while anacetrapib was Merck’s contender in the ill-fated CETP inhibitor class.

Power hungry: the largest clinical trials run with experimental agents
Experimental Agent	Details	Enrolment	NCT ID
Rotateq (Merck & Co)	Rotavirus vaccine	69,274	NCT00090233
Rotarix (GlaxoSmithKline)	Rotavirus vaccine	63,227	NCT00140673
Ad26.COV2-S (Johnson & Johnson)	Covid-19 vaccine	60,000	NCT04505722
BNT162b2 (Pfizer/Biontech)	Covid-19 vaccine	43,998	NCT04368728
GSK2186877A (Glaxosmithkline)	Influenza vaccine (abandoned)	43,695	NCT00753272
Ad5-nCoV (CanSino Biologics)	Covid-19 vaccine	40,000	NCT04526990
Zostavax (Merck & Co)	Shingles vaccines	38,456	NCT00007501
Anacetrapib (Merck & Co)	CVOT for CETP inhibitor anacetrapib (abandoned)	30,449	NCT01252953
mRNA-1273 (Moderna)	Covid-19 vaccine	30,000	NCT04470427
AZD1222 (Astrazeneca)	Covid-19 vaccine	30,000	NCT04516746
Note: Pre-approval trials only. Excludes phase IV trials or studies conducted with drugs already on the market. Source: clinicaltrials.gov, EvaluatePharma.  https://www.evaluate.com/vantage/articles/news/snippets/its-official-covid-19-vaccine-trials-rank-among-largest

Moderna surpasses target cases for first data readout from pivotal vax study

• Citing a spike in COVID-19 cases across clinical sites, Moderna (NASDAQ:MRNA) announces that the first interim analysis of results from the large-scale pivotal study, COVE, of vaccine candidate mRNA-1273 will include "substantially more" that the 53 cases it was expecting (the higher the number the better). Case accrual has been completed for the readout. The dataset is being prepared for submission to the independent Data Safety Monitoring Board.
• Enrollment was completed on October 22.
• The company remains blinded to the data.
• The efficacy bar has been set by Pfizer (NYSE:PFE) and BioNTech (NASDAQ:BNTX). Their candidate, BNT162b2, showed 90% efficacy based on 94 confirmed cases.
• https://seekingalpha.com/news/3635185-moderna-surpasses-target-cases-for-first-data-readout-from-pivotal-study-of-covidminus-19
  

Nektar immuno-oncology candidates show positive action in early-stage studies

Nektar Therapeutics (NKTR +1.5%) announces updated data from studies on several of its immuno-oncology (I-O) candidates. The results were presented at the SITC annual meeting.

Bempegaldesleukin (bempeg) (NKTR-214) plus Bristol Myers Squibb's (BMY -1.9%) Opdivo (nivolumab): Results from the treatment-naive melanoma cohort in the Phase 1/2 PIVOT-02 study showed an overall response rate (ORR) of 53% (n=20/38) in evaluable patients, including 13 (34%) complete responders. 47% (n=18/38) achieved 100% reduction in RECIST target lesions while 80% (n=16/20) had ongoing responses. Median duration of response was not reached at the month 29 time point. Median progression-free survival (PFS) was 30.9 months. Median overall survival (OS) was not reached. No new safety signals were observed. Phase 3 studies are in process.

NKTR-262 + bempeg: Results from the Phase 1/2 REVEAL study in patients with solid tumors showed induced systemic activation of T cells and natural killer (NK) cells demonstrating immune system engagement. Maximum tolerated dose (NKTR-262 only) was not reached. Early signs of clinical activity with an acceptable safety profile in heavily pretreated melanoma patients.

NKTR-255: Data from a Phase 1 study in blood cancer patients showed consistent expansion of lymphocytes and sustained increased in NK and CD8+ T cells. It was well-tolerated with low-grade cytokine-related adverse events that were transient and easily managed. The half-life was long with no evidence of accumulation.

https://seekingalpha.com/news/3635108-nektar-therapeutics-immuno-oncology-candidates-show-positive-action-in-early-stage-studies

Qiagen launches portable rapid SARS-CoV-2 antigen test

• QIAGEN (NYSE:QGEN) commences the U.S. commercialization of its portable digital QIAreach SARS-CoV-2 Antigen Test that, it says, can generate results in 2-15 minutes and can process over 30 samples per hour.
• It expects to file a CE Mark application as early as year-end.
• https://seekingalpha.com/news/3635147-qiagen-launches-portable-rapid-sars-covminus-2-antigen-test
  

Moderna could begin analyzing COVID-19 vaccine data within days: Fauci

Moderna Inc MRNA.O could have data from a large trial of its experimental COVID-19 vaccine anywhere between "a couple of days" to "a little more than a week", the top U.S. infectious disease expert said on Wednesday.

A high degree of effectiveness for the vaccine would make sense as it was “almost identical” to the Pfizer shot, Anthony Fauci, director of the U.S. National Institute of Allergy and Infectious Diseases, said at a conference organized by the Financial Times.

“It may not be 95%, it might be 90%, or 96%, or 89%, but it is going to be up there,” he said.

Hopes of the world soon getting an effective vaccine against the virus that has killed over a million people were raised on Monday after Pfizer Inc PFE.N said its COVID-19 vaccine was more than 90% effective based on interim trial results.

Moderna, which uses a technology similar to Pfizer’s, said earlier on Wednesday that its November timeline for initial data was on track.

It did not immediately respond to a Reuters request for comment on when it would disclose the data, though the company has said it would publish the data as soon as it is available.

The company would still have to wait for two-month follow up data on safety, which is expected in the second half of this month, before applying for U.S. emergency use authorization.

Earlier in the day, Chief Executive Officer Stephane Bancel said at a Credit Suisse conference the world would have to wait for more data to understand whether the use of a particular vaccine would be more widespread.

There are no vaccines that have gained global approval yet, although a handful, including Moderna’s, are in late-stage studies.

https://www.reuters.com/article/us-health-coronavirus-moderna/moderna-could-begin-analyzing-covid-19-vaccine-data-within-days-says-fauci-idUSKBN27R1SO