Covid-19: Vaccine candidate may be more than 90% effective, interim results indicate
BMJ 2020; 371 doi: https://doi.org/10.1136/bmj.m4347 (Published 09 November 2020) Cite this as: BMJ 2020;371:m4347Read our latest coverage of the coronavirus outbreak
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Dear Editor,
Mass vaccination offers the best exit strategy from the COVID-19 pandemic. Pfizer/BioNTech's recent announcement, therefore, is encouraging.[1] Their vaccine candidate was more than 90% effective in preventing COVID-19 infection in participants without prior infection. Being an mRNA vaccine, mass production is cheaper and more straightforward than with other vaccine formulations.
mRNA vaccines effect coded protein production in the recipient’s body. In the case of COVID-19, inert spike (S) antigen proteins are produced. Normally, these enable SARS-CoV-2 coronavirus particles to enter host cells, but therapeutically, inoculation triggers humoral (antibody-mediated) acquired immunity.
Severe/fatal cases of COVID-19 are associated with immune hyperactivation and excessive cytokine release, leading to multiorgan failure. A broad range of mechanisms (with a final common pathway) appear to be involved. However, it has been suggested that molecular mimicry may contribute to this problem, with antibodies to SARS-CoV-2 spike glycoproteins cross-reacting with structurally similar host heptapeptide protein sequences (for example, in interleukin 7 and alveolar surfactant proteins), and raising an acute (auto)immune response against them.[2] Autoinflammatory dysregulation in genetically susceptible individuals, and other autoimmune mechanisms such as epitope spreading and bystander activation, might also contribute to acute but also chronic autoimmunity during and after COVID-19. [3]
In the understandable socioeconomic rush towards mass vaccination without longer-term safety testing, it would seem that an essential stage in any vaccine licensing process should involve careful analysis of the human proteome against vaccine peptide sequences. This should minimize the risks both of acute autoimmune reactions to inoculation and future chronic autoimmune pathology.
References
1. Mahane E. Covid-19: Vaccine candidate may be more than 90% effective, interim results indicate. BMJ 2020;371:m4347.
2. Ehrenfeld M, Tincani A, Andreoli L, et al. Covid-19 and autoimmunity. Autoimmun Rev 2020;19:102597.
3. Caso F, Costa L, Ruscitti P. Could Sars-coronavirus-2 trigger autoimmune and / or autoinflammatory mechanisms in genetically predisposed subjects? Autoimmun Rev 2020;19:102524.
Competing interests: No competing interests
Dr Azra Ghani is incorrect to say that Pfizer/Biontech only followed up patients for 7 days after the second dose of vaccine. The 7 days referred to in their press release actually refers to the point at which their analysis starts collecting data on Covid infections among the study participants. It is clear in the press release that the analysis was done when 94 cases had been diagnosed.
Competing interests: No competing interests
Important editorial notice for readers: This is a rapid response (online comment by a third party) and not an article in The BMJ. It is attributed in a misleading way on certain websites and social media. The Editor, 14/01/2021.
Dear Editor
Pfizer’s vaccine “may be more than 90% effective.” (Mahase, BMJ 2020;371:m4347, November 9) Specific data are not given but it is easy enough to approximate the numbers involved, based on the 94 cases in a trial that has enrolled about 40,000 subjects: 8 cases in a vaccine group of 20,000 and 86 cases in a placebo group of 20,000. This yields a Covid-19 attack rate of 0.0004 in the vaccine group and 0.0043 in the placebo group. Relative risk (RR) for vaccination = 0.093, which translates into a “vaccine effectiveness” of 90.7% [100(1-0.093)]. This sounds impressive, but the absolute risk reduction for an individual is only about 0.4% (0.0043-0.0004=0.0039). The Number Needed To Vaccinate (NNTV) = 256 (1/0.0039), which means that to prevent just 1 Covid-19 case 256 individuals must get the vaccine; the other 255 individuals derive no benefit, but are subject to vaccine adverse effects, whatever they may be and whenever we learn about them……We’ve already heard that an early effect of the vaccine is “like a hangover or the flu.” Will vaccinees who are later exposed to coronaviruses have more severe illness as a result of antibody-dependent enhancement of infection (ADEI), a known hazard of coronavirus vaccines? Is there squalene in the Pfizer vaccine? If so, will vaccinees be subject to autoimmune diseases, like Gulf War Syndrome and narcolepsy that have been associated with the adjuvant?
We already know that current Covid-19 vaccine trials are unlikely to show a reduction in severe illness or deaths. (Doshi, BMJ 2020;371:m4037, October 21) Will they be like seasonal influenza vaccines, which have not proved to be lifesavers, and may even have increased overall mortality in the elderly? (Anderson et al, Ann Intern Med 2020;172:445) We need a lot more time and a lot more data, especially in view of massive uncertainties about Covid-19 case definitions and statistics.
ALLAN S. CUNNINGHAM 13 November 2020
Competing interests: No competing interests
Dear Editor
The PR Press release by Pfizer concerning their Cov-19 vaccine being 90% effective is very misleading. They do not show any supporting evidence in the form of a peer reviewed publication in which the clinical trial data can be closely scrutinised.
My impression on reading their press release was that it was timed for the benefit of share holders and the stock market and the election of a new US President.
It is very doubtful that this vaccine will in fact be 90% effective on deployment. Its storage at -70C poses logistics problems, making it impractical for UK wide use, also it is a two shot vaccine. By the time it passes regulatory approval the Sars-cov-2 virus will have mutated again, reducing its efficacy still further.
It still has not gone through rigorous clinical safety trials and evaluation necessary to comply with UK and EU pharmaceutical legislation; remember, if used in UK it will still be under the control of European Medicine's Agency, whose office in London cannot close until 2039!
Competing interests: No competing interests
Dear Editor,
Preliminary reports of SARS-CoV-2 immunisations with 90% efficacy are a rightful source of hope(1), and bring into focus decisions regarding prioritisation of delivery. In addition to the simple, and justified, prioritisation of SARS-CoV-2 immunisation by age and comorbidities that forms the foundation of the approach outlined by the government(2), we should also consider highly targeted approaches that optimise the efficiency of healthcare provision particularly in contexts where COVID related disruptions have been most keenly felt.
As has been widely reported, disruptions to healthcare for non-COVID illnesses have been, and continue to be, widespread(3), and already lengthy elective surgery waiting lists have increased dramatically due to cancelations and delays(4). Targeted immunisation delivered in pre-op clinics, combined with the already established prioritisation of healthcare workers, could mitigate some of these ongoing negative impacts, through facilitating the return of elective surgical capacity. Equally, antenatal appointment immunisations of birth partners could facilitate their full presence during childbirth, whose restricted access over the last year has been a considerable source of distress. Other situations where targeted approaches may be relevant include palliative care, as the fear of dying alone due to COVID related restrictions in healthcare settings is a major concern for many people(5).
Decisions regarding immunisation prioritisation are challenging, and simplicity is vital. However, targeted approaches for specific groups could expedite returning capacity to care delivery, and in doing so, mitigate some of the broader negative health impacts resulting from COVID related care disruption.
1. Mahase E, Covid-19: Vaccine candidate may be more than 90% effective, interim results indicate. BMJ. 2020.
2. Department Of Health and Social Care. JCVI: updated interim advice on priority groups for COVID-19 vaccination. 2020.
3. Philip K, Cumella A, Farrington-Douglas J, Laffan M, Hopkinson N. Respiratory patient experience of measures to reduce risk of COVID-19: findings from a descriptive cross-sectional UK wide survey. BMJ open. 2020;10(9):e040951.
4. Griffin S. Covid-19: Waiting times in England reach record highs. BMJ. 2020.
5. Philip K, Lonergan, B., Cumella, A., Farrington-Douglas, J., Laffan, M., Hopkinson, NS.,. COVID-19 related concerns of people with long-term respiratory conditions: A qualitative study. 2020.
Competing interests: No competing interests
Dear Editor
According to Peter Hotez, quoted MedPage Today (5 November):
"Even as the first vaccines become more widely available they may be only partially protective to reduce severity of illness and won't stop transmission anyway...”
But at Downing Street briefing las night we were being exhorted that everyone needed to get the vaccine presumably to prevent transmission. What’s right?
https://www.medpagetoday.com/infectiousdisease/covid19/89512
Competing interests: AgeofAutism.com, an on-line daily journal, concerns itself with the potential environmental sources for the proliferation of autism, neurological impairment, immune dysfunction and chronic disease. I receive no payment as UK Editor
Re: Covid-19: Vaccine candidate may be more than 90% effective, interim results indicate
Dear Editor,
I read the analysis of NNTV provided on 13th November by Dr Allan S. Cunningham. Although the numbers appear correct, the applicability of the analysis appears to rely on the permanently living under lockdown conditions.
The basis for the argument that 90.7 % efficacy provides little value is based on the attack rate for the placebo group of 0.0043 and for the vaccinated group 0.0004. This represents a factor of 10.75 or 90.7 % effectiveness. Dr Cunningham then subtracts the two percentages to claim that the reduction in attack rate is just 0.0004 reducing the absolute attack rate to 0.0039. From this he concludes that it would be necessary to vaccinate 1/0.0039 = 256 to avoid one infection and claims this means the vaccine adds almost no value. I find this conclusion very troubling.
Absolute attack rates during lockdown are probably around 0.005 and do not represent normal living conditions. The absolute impact fo a virus when in lockdown will scale with the attack rate. Without mitigation, the attack rate would be similar or higher than other airborne viruses like the flu. If we pick 50 % as an attack rate in an unguarded society and assume a 2% mortality rate then in a population of 330 million, the expected deaths would be 3.3 million. If that population had all been vaccinated using a 90.7 % effective vaccine then the death figure would drop to 306,900.
If we now repeat the trick of subtracting attack percentages, the figures are now 50 % and 4.65 %, with the difference being 45.35 %. I.e. one infection saved for every two people vaccinated. That is a far more realistic analysis of the impact of a vaccine with 90.7 % efficacy than the 1 in 256 calculated by Dr Cunningham which is an accurate figure for a lockdown but not how we want to live the rest of our lives.
Regards,
Moray Rumney
moray@rumneytelecom.com
Competing interests: No competing interests