COVID-19 update: on hydroxychloroquine, an old vaccine and convalescent plasma

A belated and somewhat bitty update, due to illness over the past week (respiratory, although thankfully ticking very few of the COVID-19 boxes. Living in the UK, it might be 2025 before I get tested...).

While the FDA has granted emergency approval for the use of hydroxychloroquine and chloroquine in COVID-19 patients (with the EMA limiting use to clinical trials only), definitive evidence for benefit remains elusive. 

A (non-peer reviewed) study from Wuhan involving patients with mild to moderate COVID-19 symptoms suggests that hydroxychloroquine treatment may have shortened the time to clinical recovery[1]. A second study[2] from the French group which first claimed benefit from treatment with hydroxychloroquine in combination with the antibiotic azithromycin is proving as controversial as the first with respect to flaws in design and interpretation (I recommend Derek Lowe's incisive analysis as a place to start- "More on Chloroquine/Azithromycin. And On Dr. Raoult.. ", online 23rd March).

New vaccine candidates seem to appear every other day, with around 50 or so (most at early lab or even concept stage) now listed. The latest into the clinic, LV-SMENP-DC (Shenzhen Geno-Immune Medical Institute)[3]  borrows heavily from experimental cancer vaccines, using antigen-presenting dendritic cells genetically engineered to express a selection of COVID-19 antigens in combination with antigen-specific cytotoxic T cells. Primary read out is several years away. 

At the other end of the vaccine innovation spectrum, Australian researchers are about to kick off studies of the centenarian Bacillus Calmette–Guérin (BCG) tuberculosis vaccine among healthcare workers[4]. BCG is a powerful immunostimulant in its own right and the hope is that boosting the innate immune system, our first line of defence before specific (adaptive) immune responses develop, might induce some degree of early protection. 

The use of convalescent plasma is gathering pace, with the FDA now coordinating passive immunotherapy studies, with the Mayo Clinic taking point on clinical studies[5]. A second pilot study out of Wuhan appears to echo earlier encouraging results[6]. 

---

[1] Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial. Chen Z et al. https://tinyurl.com/s46woam

[2] Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: an observational study. Gautret P et al. https://tinyurl.com/rdsnhoq

[3] Immunity and Safety of Covid-19 Synthetic Minigene Vaccine. https://tinyurl.com/wmvn8es

[4] BCG Vaccination to Protect Healthcare Workers Against COVID-19 (BRACE). https://tinyurl.com/qndc9lm

[5] Coronavirus (COVID-19) Update: FDA Coordinates National Effort to Develop Blood-Related Therapies for COVID-19. Online April 3^rd 2020. https://tinyurl.com/s9x4qqy

[6] The feasibility of convalescent plasma therapy in severe COVID-19 patients: a pilot study. Duan, K et al. https://tinyurl.com/sbaqc25

COVID-19 drug study update: hydroxychloroquine a bust?

While there have been high (and certainly over-optimistic hopes) for the repurposed antimalarial drug, hydroxychloroquine, a small study (n=30, equal numbers in the test and control groups) conducted in Shanghai and reported today by Forbes did not find any benefit with time to viral  clearance over best standard of care. 

A real bust? Probably, but at this stage, even negative results are valuable if it helps redirect efforts towards more productive avenues. 

Hydroxychloroquine Is Ineffective In Treatment Of Patients Hospitalized With Covid-19, According To Small Controlled Trial From Shanghai. Haseltine WA Forbes online 25th March https://tinyurl.com/vjg75c4