Diabetes & COVID-19, Vaccine Testing, Drug Pricing and more, COVID-19 Science News: Wk 29/06

6 min readJul 4, 2020

Breaking News

Many vaccine efforts around the world are well underway. Derek Lowe from In The Pipeline has done a fantastic job summarising all the news on this, for a general overview I suggest you read his article. [1]

The vaccine candidate from CanSino (a Chinese company) has apparently been approved for use in the Chinese military, on the basis of promising results in Phase II which have yet to be published. [2]

In Phase I, this vaccine was generally well tolerated. The vaccine uses a harmless virus (adenovirus 5; Ad5) to present a part (spike protein) of SARS-CoV-2 to the immune system which causes production of antibodies. Not all patients developed antibodies against SARS-CoV-2 however, due to some of them having antibodies against the carrier Ad5. So far we have no information as to how the company has or plans to overcome this limitation. [3]

Pfizer and BioNTech have released the Phase I data of their mRNA vaccine candidate called BNT162b1. This is one of four mRNA vaccine programs this collaboration is developing. Specifically, BNT162b1 is a base-modified mRNA, coding for a trimeric RBD domain of the spike protein, with unnatural 1-methylpseudouridine incorporated,which increases protein production in cells and dampens the immune response to the vaccine. [4]

In general, most patients reported some side-effect, mainly soreness and mild or moderate headaches. Overall, the vaccine seems very safe and typically well tolerated. Levels of antibodies higher than patients who recovered from COVID-19 were developed for all doses of the vaccine after the second administration. The results indicate a promising outlook for this candidate. [5]

Antibody response for the patients administered the BNT162b1 vaccine candidate developed by Pfizer and BioNTech, compared to antibody levels of patients that recovered from COVID-19. Credit: see source [4].

The RECOVERY trial in the UK has announced via press release that the combination of lopinavir-ritonavir (an anti-HIV medication) did not show a reduction in mortality, no reduction in length of hospital stay nor in probability of progression to mechanical ventilation. [6]

This is in line with a Chinese study on the drug published in May, which also did not show any clinical benefit. [7]

Temporal variation of improvement rate and viral load of patient groups receiving lopinavir-ritonavir *vs. standard of care. Credit: Cao et al. NJEM, 2020, 382, 19, 1787–1799 see also [7].*

Clearing Up Misconceptions

A lot of noise has been generated around the pricing of remdesivir, Gilead’s medicine that has shown some effectiveness for mild patients with COVID-19, both for reduced mortality and for faster time to recovery. [8]

The price has been set to $390 per vial for developed countries, which works out to $2,340 per patient (government insurance in the US) for a full treatment. In developing countries, the price has not been set yet, but in India for example the treatment is expected to cost ~$80. [9,10]

This represents the absolute cost of the treatment and does not reflect the cost directly incurred by the patient, since insurance is involved in most cases. Here, only the figures relating to the development are presented.

The cost of a clinical trial in the US for assessing effectiveness of medicines against SARS-CoV-2 is between $88 m and $92 m. Gilead has run one such trial in the US, with $70 m being provided by the US government. [11,12]

Remdesivir was originally developed as a treatment for Ebola and accordingly underwent phase I and II trials against this disease. Phase I was successful but phase II was not. [13]

The manufacture of remdesivir is expensive, laborious and challenging and is constantly being improved. [14,15]

Gilead has announced that an additional $1 bn will be spent in 2020 on remdesivir. It also donated the entire available stock (1.5 m doses) of remdesivir back in May when the positive trial results were announced. [16]

The Institute for Clinical and Economic Review (ICER) has estimated that the price for a course of treatment to recover the costs of 2020 would be ~$1000; this does not include costs of all pre-clinical R&D (5–10 years typical), phase I and phase II trials for Ebola. When considering the savings made by healthcare facilities for early discharge associated with remdesivir (~$12k per patient) and the new standard of care in the absence of remdesivir (assumed to be dexamethasone), ICER estimates that the lowest cost-effectiveness price range for remdesivir is $2,520–2800 (cf. $2,340 announced price). [17,18]

Notably, the full development (concept to launch) of a drug is estimated to cost between $1 bn and $2 bn on average and the failure rate in clinical trials is ~90 %. [19]

There have been reports of a “flu virus with pandemic potential” circulating. [20]
Here is an attempt to clarify some things about the paper which triggered these headlines.

The study is published in PNAS by researchers in China and the UK. A summary of some excellent breakdowns seen in sources 22 and 23 is provided here.
In short, the virus in question has been around for 5 years and no human to human transmission has been observed. The virus did not cause symptoms to the workers who contracted it. Overall, a paper like this would not raise eyebrows in normal circumstances, as the research itself is not particularly sensationalist. It points out something that should be monitored but not something that is an immediate threat. [21–23]

The US National Bereau of Economic Research has conducted a study of the overall effect of BLM protests in the US on the number of COVID-19 cases. The analysis does not investigate the number of diagnosed COVID-19 cases in conjuction with the percentage of test that are positive. The study presents data which shows that the net effect of the protests actually increased social distancing and did not affect COVID-19 diagnoses. This is a result of two competing effects. Protest attendees did not follow social distancing and most likely spread SARS-CoV-2 between them at a much higher rate. However, large portions of the population did not attend the protests stayed at home more than did the general population in areas that did not see protests, resulting in less transmission overall. It should be noted that the analysis cannot determine how much the latter effect was influenced by the warnings by public health officials that protests will increase the incidence of COVID-19. [24]

Disease Physiology

Physicians have observed that some patients with COVID-19 have been showing signs of diabetes without having this as a pre-existing condition. SARS-CoV-1 was observed to cause acute (short-term) diabetes in some patients. [25,26]

The protein that SARS-CoV-2 interacts with to enter cells (ACE2) is highly expressed in key tissues related to diabetes and viral ketosis-prone diabetes has been established in the past. Therefore, clinicians seek to investigate the very worrying possibility that COVID-19 may cause diabetes. Whether this is indeed happening and whether the diabetes is type I, type II, a different type, chronic or acute is still to be determined. [27,28]

A systematic review of serological tests for antibodies against SARS-CoV-2 finds that non-laboratory based tests are extremely unreliable and in need of much further development. [29]

Immunity to a disease may be mediated either by antibodies or by T-cells. Antibody responses to SARS-CoV-2 have been relatively well studied so far. Some new research from France looks at T-cell responses. The researchers find that some symptomatic patients do not produce antibodies against SARS-CoV-2, however they recover from COVID-19 and do show a T-cell response. This means that it is possible to mount an immune response against SARS-CoV-2 without raising free antibodies in the serum. [30]

This could also help to explain the fact that some asymptomatic patients do not seroconvert. It is possible that these people do not experience symptoms and do not produce antibodies, showing instead a T-cell based immune response. Therefore, it is possible that some patients do not show symptoms or antibodies but are in fact still immune (for how long?) to the virus. The specifics of T-cell responses have been shown to be highly important to disease progression. [31]

References

Diabetes & COVID-19, Vaccine Testing, Drug Pricing and more, COVID-19 Science News: Wk 29/06

Written by Michael Bogdos