CME INDIA Presentation by Dr Rajeev Jayadevan, Dr Ramesh Shenoy, Ms. Anithadevi TS.

Fear of the unknown is a driver of vaccine hesitancy.

By describing what to expect, the findings of this study will be reassuring to those who are fearful of the new vaccine. The fact that post-vaccination symptoms were mild, predictable and short-lived will help reduce vaccine hesitancy.

Results of survey on post-vaccination symptoms in India: Experience of 5396 healthcare workers.

By Dr Rajeev Jayadevan¹, Dr Ramesh Shenoy², Ms. Anithadevi TS³ ; Dated: 9 February 2021.

1. Dr Rajeev Jayadevan, MBBS and MD General Medicine. Board Certification in Medicine and Gastroenterology (Fellowship) from New York Medical College. Consultant Gastroenterologist, department of Gastroenterology at Sunrise Hospital, Cochin.

2. Dr. Ramesh Shenoy, DMRD, MBBS, Radiology, Consultant at Lisie Hospital, Kochi.

3. Biostatistician,‎ Sunrise hospital, Kakkanad, Kochi.

This information is important for everyone

• We had done a survey on the immediate post-vaccination experience among healthcare workers.
• We wish to thank those who enthusiastically responded.
• Here we have summarised the large amount of data we received from 5396 individuals.
• All the data were obtained exclusively through the online survey.
• Conclusions of this survey are important for everyone.

Why was the survey done?

• Although the protective efficacy is frequently discussed, not much is known about the real-world post-vaccination experience outside of clinical trial conditions.
• Knowledge about what to expect after vaccination will help educate the public, dispel misinformation and reduce vaccine hesitancy.

How many people responded?

• A total of 5396 people responded to the online survey over a one-week period from 29 January to 4 February.
• Among those who responded to the survey, the majority were doctors (85.8%), followed by nurses (6.2%), technicians (1.1%) and others. This does not necessarily reflect the relative proportion of those who received the vaccine.
• 56% of the respondents were male, 44% were female.

What vaccine did they receive?

• 5128 (95%) respondents received Covishield (Astra-Oxford vaccine manufactured by Serum Institute, India), 180 (3.3%) received Covaxin (Bharat Biotech, India), while 44 (0.8%) each had received Pfizer-Biotech and Sino pharm vaccine from other nations.
• Majority (98.3%) of the respondents had received either Covaxin or Covishield.

How many developed symptoms?

What were the symptoms?

• Overall, 66 % of respondents reported at least one post-vaccination symptom. Tiredness (45%), myalgia (44%), fever (34%), headache (28%), local pain at injection site (27%), joint pain (12%), nausea (8%) and diarrhoea (3%) were the most prevalent symptoms.
• All other symptoms were 1% or less.
• See graph below

Were any of the symptoms serious?

• None of the symptoms reported in the survey were serious or required hospitalization

How did the symptoms differ by age group? Was it safe in people over 60?

• 947 out of the 5396 respondents were over the age of 60.
• There were no serious outcomes.
• In fact, the chance of having symptoms decreased with advancing age.
• Older people also had later onset of symptoms, occurring at an average of 13.4 hours (70-79 years), compared to 10 hours in younger age groups (20-29 years) following vaccination. (P<0.001)

What was the age distribution?

Did the symptoms affect your work the next day?

How soon did the symptoms appear after the injection?

How long did the symptoms last?

Were the symptoms more common among women?

• Yes.
• Post-vaccination symptoms were more likely to be reported by women (74.7%) compared to men (58.6%) (p < 0.001), this observation was consistent across all age groups.
• Women were more likely to report symptoms severe enough to prevent working for a day (27% vs. 15%) and the need to take pain relievers (70% vs. 51%).
• Women developed symptoms slightly earlier (10 hours) than men (12 hours) (p < 0.001). Women had slightly longer duration of symptoms (30 hours vs. 28.5 hours, p = 0.01) (See table below).

Did past history of COVID-19 make any difference to the symptoms?

• No.
• 472 out of 5396 (8.7%) reported past history of COVID-19. Their symptom profile was not different to those who did not have a past history.

Is it possible to calculate the efficacy of the vaccine from this study?

• Protection from a vaccine becomes fully active only two weeks following the booster (second) dose. This study was done soon after the first dose, to look at immediate symptoms.
• Long-term efficacy can only be determined by careful long-term observation of groups of people who received the vaccine and comparing their disease rates with those who did not receive vaccine.

Final Message

• Two-thirds of healthcare professionals who completed the survey reported mild and short-lived post-vaccination symptoms.
• Tiredness, myalgia (muscle pains) and fever were most commonly reported.
• These symptoms were consistent with an immune response commonly associated with vaccines, and correlated with the findings from previously published phase 2/3 trials.
• In 90% cases, the symptoms were either milder than expected or meeting the expectation of the vaccine recipient. No serious events were reported.
• Symptoms were more common among younger individuals.
• There was no difference in symptoms among those who had a past history of COVID-19.

CME INDIA Learning Points

(By Dr Rajeev Jayadevan)

• The remarkable linear correlation between age and post-vaccination symptoms suggests that vaccine reactogenicity declined with age.
• Vaccine reactogenicity is associated with elevation of inflammatory cytokines, but is not considered a reliable sign of immune response (1). In other words, lack of symptoms is not necessarily a disadvantage.
• Women were more likely to develop post-vaccination symptoms. This observation was consistent across all age groups.
• The findings of the survey correlated with results from published trials of vaccines. In the phase 2/3 trial of Astra-Oxford ChAdOx1 nCoV-19, at least one systemic symptom was reported following vaccination with the standard dose by 86% participants in the 18–55 years group, 77% in the 56–69 years group, and 65% in the 70 years and older group (2)
• While discussing post vaccination experience, it is noteworthy that placebo injections produce comparable symptoms. In the phase 3 trial of Pfizer-Biontech vaccine, the incidence of headache following vaccination was 42% in the vaccine group and 34% in those who received saline placebo (3). This has been termed the nocebo effect, which results from enhanced anticipation of negative outcomes from an intervention (4).
• This study did not measure post vaccination antibody response. Hence it is not possible to infer whether the muted post-vaccination symptoms among older people was a sign of immune senescence.
• Although symptoms are known to correlate with neutralising antibody levels in patients with COVID-19 (5), the presence of symptoms after vaccination does not reliably predict antibody response (6).
• The frequency of using paracetamol to reduce post vaccination symptoms decreased from 71% in the 20-29 age group to 16% in the 80-90 age group. This correlated with the symptom frequency in these subgroups. Although the use of paracetamol to alleviate post-vaccination discomfort is considered acceptable (7), routine prophylactic use of pain relievers is not recommended as there is evidence of blunted immune response as a result (7,8).
• Fear of the unknown is a driver of vaccine hesitancy.
• By describing what to expect, the findings of this study will be reassuring to those who are fearful of the new vaccine.
• The fact that post-vaccination symptoms were mild, predictable and short-lived will help reduce vaccine hesitancy.
• It is important to know the background rates of disease in a population while assessing the outcome of a vaccination program. Unrelated incidental illness correlating temporally with vaccination could easily get attributed to vaccine, and may require expert evaluation to tell the difference.
• Academic research papers always include a discussion on limitations. All research methods are tools to find the truth. However, each method has its own limitations. For instance, a survey is more likely to be taken by those with an interest in the topic. As a result, those who developed symptoms following vaccination might show greater interest in the survey. Greater awareness and anticipation of adverse effects among healthcare workers could also get reflected in the reporting rate. Hence, the reported 65% incidence of post-vaccination symptoms could be an overestimation.
• Survey questions were in English, which might have posed some difficulty among those with limited proficiency in that language. As the survey was done soon after initiation of vaccination, there was no scope for reporting delayed symptoms.
• The survey was done on trust; it was not possible to verify the I.D or information provided by each respondent. The relatively small number of respondents who took the Covaxin, Pfizer and Sino pharm vaccines makes it difficult to do a head-to-head comparison.

CME INDIA Tail Piece

• The vaccine hesitant are people who have reservations about being vaccinated, but are still open to being assured that the treatments are safe and reliable.
• Anti-vaxxers are a more concrete, organised movement of people who actively try and suppress vaccination as a practice and prevent people from getting vaccinated, and their minds are far harder to change.
• “If you were to address their arguments perfectly, they would come up with new ones. The arguments don’t matter. They have this fear of vaccines that’s driven by emotion and stories their neighbours and friends have told them, which they use to justify those beliefs.” – Berman
• Anti-vaxxers: a misinformed movement (From: https://pharma.nridigital.com/pharma_nov20/covid-19-vaccine-anti-vaxxers)

References

1. Hervé, C., Laupèze, B., Del Giudice, G. et al. The how’s and what’s of vaccine reactogenicity. npj Vaccines 4, 39, 2019 https://doi.org/10.1038/s41541-019-0132-6
2. Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a primeboost regimen in young and old adults(COV002): a single-blind, randomised, controlled, phase 2/3 trial Lancet 2020; 396: 1979–93 November 19, 2020 https://doi.org/10.1016/S0140-6736(20)32466-1
3. Polack FP et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine December 31, 2020. N Engl J Med 2020; 383:2603-2615 DOI: 10.1056/NEJMoa2034577
4. Colloca L, Miller FG. The nocebo effect and its relevance for clinical practice. Psychosom Med. 2011;73(7):598-603. doi:10.1097/PSY.0b013e3182294a50
5. Post N et al, Antibody response to SARS-CoV-2 infection in humans: A systematic review PlosOne December 31, 20. December 31, 2020 https://doi.org/10.1371/journal.pone.0244126
6. 6.Christian LM, Porter K, Karlsson E, Schultz-Cherry S. Proinflammatory cytokine responses correspond with subjective side effects after influenza virus vaccination. Vaccine. 2015;33(29):3360-3366. doi:10.1016/j.vaccine.2015.05.008
7. Jennifer S. Chen, Mia Madel Alfajaro, Ryan D. Chow, Jin Wei, Renata B. Filler, Stephanie C. Eisenbarth, Craig B. Wilen. Non-steroidal anti-inflammatory drugs dampen the cytokine and antibody response to SARS-CoV-2 infection. Journal of Virology Jan 2021, JVI.00014-21; doi: 10.1128/JVI.00014-21
8. Saleh E, Moody MA, Walter EB. Effect of antipyretic analgesics on immune responses to vaccination. Hum Vaccin Immunother. 2016;12(9):2391-2402. doi:10.1080/21645515.2016.118307720 https://doi.org/10.1371/journal.pone.0244126

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