Thinking beyond behavioural change as an explanation for increased COVID post vaccination
Dear Editor,
As well as the papers cited by the authors, other studies have shown a similar effect. A Danish study showed a 40% increase in infections in the first two weeks after Pfizer-BioNTech vaccination, despite not vaccinating in homes with recent outbreaks.[1] Indeed, the original Pfizer trial demonstrated a statistically significant 40% increase in ‘suspected COVID’, with 409 cases in the vaccination arm in the first week of the trial, compared with 287 in the placebo arm.[2] Other publications have omitted mention of the period immediately after vaccination.[3] [4] There is substantial anecdotal evidence of people who had tested negative prior to vaccination, becoming infected shortly afterwards, invariably attributed to exposure just before vaccination.[5] Others have raised concerns about this.[6]
The REACT study of prevalence in January showed that the odds ratio of having a positive swab was 1.48 in healthcare and care home workers and 1.38 in other key workers (when compared to all workers).[7] It seems highly unlikely that behavioural change alone (in the over 80s) could account for an increase in the risk of infection of a similar magnitude to that assumed by being in high-risk employment.
The ONS study quoted does show that over 40% of vaccinated over 80 year-olds met with someone outside of their household or bubble during some unspecified period after vaccination, but there was no data collection for behaviour prior to vaccination with which to compare that figure.[8] No specific dates were given for when the meetings had taken place. It is therefore impossible to conclude that there has been any change in behaviour, let alone one specifically related to the week or two after vaccination.
The ONS has reported that the proportion of adults who had no contact at all with over 70 year-olds rose from 83% prior to vaccine rollout to 90% during vaccine rollout, from the beginning of December to 8th February.[9] By 8th February 90% of the over 70s had been vaccinated.[10] It is hard to reconcile fewer people visiting the over 70 year-olds prior to 8th February with more over 80 year-olds having contact with others.
If the elderly were in fact shielding more after vaccination, as the ONS data suggests, then what could be the cause of the higher risk? Could the COVID vaccination clinics themselves have been superspreader events? It cannot be ruled out as a possibility: shielding elderly ventured out, sometimes for the first time in months, and were kept indoors for several hours with many others, none of whom were tested in advance.
The real puzzle though is the care home residents. No one is suggesting there was a change of behaviour within care homes, except for inviting people in to carry out the vaccinations. However, care homes in every corner of the country saw outbreaks from December. What changed?
Over time, as expected, the likelihood of a healthcare worker being an index case had been falling as immunity developed. However, after vaccination this figure started to rise.[11]
The Pfizer vaccination causes a transient fall in lymphocytes for the first three days after vaccination.[12], The phase 2 trials of AstraZeneca similarly showed a fall in neutrophils.[13] Post vaccination neutrophil depletion[14] and lymphocyte depletion[15] has been shown for other vaccines and the latter has been known about since 1981.[16] There is conflicting literature on whether this effect results in susceptibility to viral infections but there is certainly evidence suggesting that is the case in children.[17] Given the evidence of white cell depletion after COVID vaccination and the evidence of increased COVID infection rates shortly after vaccination, the possibility that the two are causally related needs urgent investigation.
This response is only referring to susceptibility to COVID in the first two weeks of vaccination; it is not commenting on the efficacy of vaccines after this period.
A genuine increased risk of contracting infection post vaccination is important to understand, both for evaluating the vaccination programmes as well as planning the best time of year to carry such programmes out.
1 Moustsen-Helms IR, Emborg H-D, Nielsen J, et al. Vaccine effectiveness after 1st and 2nd dose of the BNT162b2 mRNA Covid-19 Vaccine in long-term care facility residents and healthcare workers – a Danish cohort study. bioRxiv. 2021. doi:10.1101/2021.03.08.21252200
2 U.S. Food and Drug Administration. Emergency Use Authorization (EUA) for an Unapproved Product Review Memorandum. https://www.fda.gov/media/144416/download
3 Chodick G, Tene L, Patalon T, et al. The effectiveness of the first dose of BNT162b2 vaccine in reducing SARS-CoV-2 infection 13-24 days after immunization: real-world evidence. bioRxiv. 2021. doi:10.1101/2021.01.27.21250612
4 Voysey M, Clemens SAC, Madhi SA, et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet 2021;397:99–111. doi:10.1016/S0140-6736(20)32661-1
5 HM Government of Gibraltar. https://www.facebook.com/gibraltargovernment/posts/3958089680902965 (accessed 25 Mar 2021).
6 Re: Will covid-19 vaccines save lives? Current trials aren’t designed to tell us. Published Online First: 23 March 2021.https://www.bmj.com/content/371/bmj.m4037/rr-20 (accessed 26 Mar 2021).
7 REACT-1: real-time assessment of community transmission of coronavirus (COVID-19) in January 2021. https://www.gov.uk/government/publications/react-1-study-of-coronavirus-... (accessed 25 Mar 2021).
8 Littleboy K. Coronavirus and vaccine attitudes and behaviours in England - Office for National Statistics. 2021.https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/... (accessed 25 Mar 2021).
9 All data related to Coronavirus (COVID-19) Infection Survey: characteristics of people testing positive for COVID-19 in England, September 2020. https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/... (accessed 25 Mar 2021).
10 Public Health England. National flu and COVID-19 surveillance reports. 2020.https://www.gov.uk/government/statistics/national-flu-and-covid-19-surve... (accessed 25 Mar 2021).
11 Scientific Advisory Group for Emergencies. EMG: COVID-19 risk by occupation and workplace, 11 February 2021. 2021.https://www.gov.uk/government/publications/emg-covid-19-risk-by-occupati... (accessed 25 Mar 2021).
12 Walsh EE, Frenck RW Jr, Falsey AR, et al. Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates. N Engl J Med 2020;383:2439–50. doi:10.1056/NEJMoa2027906
13 Folegatti PM, Ewer KJ, Aley PK, et al. Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial. Lancet 2020;396:467–78. doi:10.1016/S0140-6736(20)31604-4
14 Muturi-Kioi V, Lewis D, Launay O, et al. Neutropenia as an Adverse Event following Vaccination: Results from Randomized Clinical Trials in Healthy Adults and Systematic Review. PLoS One 2016;11:e0157385. doi:10.1371/journal.pone.0157385
15 Munyer TP, Mangi RJ, Dolan T, et al. Depressed lymphocyte function after measles-mumps-rubella vaccination. J Infect Dis 1975;132:75–8. doi:10.1093/infdis/132.1.75
16 Faguet GB. The effect of killed influenza virus vaccine on the kinetics of normal human lymphocytes. J Infect Dis 1981;143:252–8. doi:10.1093/infdis/143.2.252
17 Rikin S, Jia H, Vargas CY, et al. Assessment of temporally-related acute respiratory illness following influenza vaccination. Vaccine 2018;36:1958–64. doi:10.1016/j.vaccine.2018.02.105
Rapid Response:
Thinking beyond behavioural change as an explanation for increased COVID post vaccination
Dear Editor,
As well as the papers cited by the authors, other studies have shown a similar effect. A Danish study showed a 40% increase in infections in the first two weeks after Pfizer-BioNTech vaccination, despite not vaccinating in homes with recent outbreaks.[1] Indeed, the original Pfizer trial demonstrated a statistically significant 40% increase in ‘suspected COVID’, with 409 cases in the vaccination arm in the first week of the trial, compared with 287 in the placebo arm.[2] Other publications have omitted mention of the period immediately after vaccination.[3] [4] There is substantial anecdotal evidence of people who had tested negative prior to vaccination, becoming infected shortly afterwards, invariably attributed to exposure just before vaccination.[5] Others have raised concerns about this.[6]
The REACT study of prevalence in January showed that the odds ratio of having a positive swab was 1.48 in healthcare and care home workers and 1.38 in other key workers (when compared to all workers).[7] It seems highly unlikely that behavioural change alone (in the over 80s) could account for an increase in the risk of infection of a similar magnitude to that assumed by being in high-risk employment.
The ONS study quoted does show that over 40% of vaccinated over 80 year-olds met with someone outside of their household or bubble during some unspecified period after vaccination, but there was no data collection for behaviour prior to vaccination with which to compare that figure.[8] No specific dates were given for when the meetings had taken place. It is therefore impossible to conclude that there has been any change in behaviour, let alone one specifically related to the week or two after vaccination.
The ONS has reported that the proportion of adults who had no contact at all with over 70 year-olds rose from 83% prior to vaccine rollout to 90% during vaccine rollout, from the beginning of December to 8th February.[9] By 8th February 90% of the over 70s had been vaccinated.[10] It is hard to reconcile fewer people visiting the over 70 year-olds prior to 8th February with more over 80 year-olds having contact with others.
If the elderly were in fact shielding more after vaccination, as the ONS data suggests, then what could be the cause of the higher risk? Could the COVID vaccination clinics themselves have been superspreader events? It cannot be ruled out as a possibility: shielding elderly ventured out, sometimes for the first time in months, and were kept indoors for several hours with many others, none of whom were tested in advance.
The real puzzle though is the care home residents. No one is suggesting there was a change of behaviour within care homes, except for inviting people in to carry out the vaccinations. However, care homes in every corner of the country saw outbreaks from December. What changed?
Over time, as expected, the likelihood of a healthcare worker being an index case had been falling as immunity developed. However, after vaccination this figure started to rise.[11]
The Pfizer vaccination causes a transient fall in lymphocytes for the first three days after vaccination.[12], The phase 2 trials of AstraZeneca similarly showed a fall in neutrophils.[13] Post vaccination neutrophil depletion[14] and lymphocyte depletion[15] has been shown for other vaccines and the latter has been known about since 1981.[16] There is conflicting literature on whether this effect results in susceptibility to viral infections but there is certainly evidence suggesting that is the case in children.[17] Given the evidence of white cell depletion after COVID vaccination and the evidence of increased COVID infection rates shortly after vaccination, the possibility that the two are causally related needs urgent investigation.
This response is only referring to susceptibility to COVID in the first two weeks of vaccination; it is not commenting on the efficacy of vaccines after this period.
A genuine increased risk of contracting infection post vaccination is important to understand, both for evaluating the vaccination programmes as well as planning the best time of year to carry such programmes out.
1 Moustsen-Helms IR, Emborg H-D, Nielsen J, et al. Vaccine effectiveness after 1st and 2nd dose of the BNT162b2 mRNA Covid-19 Vaccine in long-term care facility residents and healthcare workers – a Danish cohort study. bioRxiv. 2021. doi:10.1101/2021.03.08.21252200
2 U.S. Food and Drug Administration. Emergency Use Authorization (EUA) for an Unapproved Product Review Memorandum. https://www.fda.gov/media/144416/download
3 Chodick G, Tene L, Patalon T, et al. The effectiveness of the first dose of BNT162b2 vaccine in reducing SARS-CoV-2 infection 13-24 days after immunization: real-world evidence. bioRxiv. 2021. doi:10.1101/2021.01.27.21250612
4 Voysey M, Clemens SAC, Madhi SA, et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet 2021;397:99–111. doi:10.1016/S0140-6736(20)32661-1
5 HM Government of Gibraltar. https://www.facebook.com/gibraltargovernment/posts/3958089680902965 (accessed 25 Mar 2021).
6 Re: Will covid-19 vaccines save lives? Current trials aren’t designed to tell us. Published Online First: 23 March 2021.https://www.bmj.com/content/371/bmj.m4037/rr-20 (accessed 26 Mar 2021).
7 REACT-1: real-time assessment of community transmission of coronavirus (COVID-19) in January 2021. https://www.gov.uk/government/publications/react-1-study-of-coronavirus-... (accessed 25 Mar 2021).
8 Littleboy K. Coronavirus and vaccine attitudes and behaviours in England - Office for National Statistics. 2021.https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/... (accessed 25 Mar 2021).
9 All data related to Coronavirus (COVID-19) Infection Survey: characteristics of people testing positive for COVID-19 in England, September 2020. https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/... (accessed 25 Mar 2021).
10 Public Health England. National flu and COVID-19 surveillance reports. 2020.https://www.gov.uk/government/statistics/national-flu-and-covid-19-surve... (accessed 25 Mar 2021).
11 Scientific Advisory Group for Emergencies. EMG: COVID-19 risk by occupation and workplace, 11 February 2021. 2021.https://www.gov.uk/government/publications/emg-covid-19-risk-by-occupati... (accessed 25 Mar 2021).
12 Walsh EE, Frenck RW Jr, Falsey AR, et al. Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates. N Engl J Med 2020;383:2439–50. doi:10.1056/NEJMoa2027906
13 Folegatti PM, Ewer KJ, Aley PK, et al. Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial. Lancet 2020;396:467–78. doi:10.1016/S0140-6736(20)31604-4
14 Muturi-Kioi V, Lewis D, Launay O, et al. Neutropenia as an Adverse Event following Vaccination: Results from Randomized Clinical Trials in Healthy Adults and Systematic Review. PLoS One 2016;11:e0157385. doi:10.1371/journal.pone.0157385
15 Munyer TP, Mangi RJ, Dolan T, et al. Depressed lymphocyte function after measles-mumps-rubella vaccination. J Infect Dis 1975;132:75–8. doi:10.1093/infdis/132.1.75
16 Faguet GB. The effect of killed influenza virus vaccine on the kinetics of normal human lymphocytes. J Infect Dis 1981;143:252–8. doi:10.1093/infdis/143.2.252
17 Rikin S, Jia H, Vargas CY, et al. Assessment of temporally-related acute respiratory illness following influenza vaccination. Vaccine 2018;36:1958–64. doi:10.1016/j.vaccine.2018.02.105
Competing interests: No competing interests