Webinar Series on COVID-19 vaccine: Jointly organized by Malaysian Society of Infection Control and Infectious Diseases (MyICID) & Institute for Clinical Research (ICR), NIH Speaker: Dr. Low Lee Lee, Infectious Disease Physician at the Hospital Sultanah Bahiyah, Ministry of Health Malaysia.

1. COVID-19 vaccines :
Side Effects and
Concerns
DR. LOW LEE LEE
INFECTIOUS DISEASE PHYSICIAN
HOSPITAL SULTANAH BAHIYAH

2. Disclaimers
•This slide was prepared for the Webinar Series on
COVID-19 session on 21st April 2021, by Dr.Low
Lee Lee, Infectious Disease Physician, Hospital
Sultanah Bahiyah, Malaysia.
•This is intended to share within healthcare
professionals, not for public.
•Kindly acknowledge “Clinical Updates in COVID-19
http://www.nih.gov.my/covid-19” should you plan to
share the information obtained from this slide with
your colleagues.
Jointly organized by Malaysian Society of Infection Control and Infectious Diseases (MyICID) & Institute for Clinical Research, NIH

3. COVID-19 : Fearing the disease
or the vaccine
Vaccine
acceptance
Severity of
disease
Vaccine
efficacy
Safety of
vaccine
Impact to
yourself
and family
Kartlson et al, Personality and individual differences 2021

4. Outline
•Different types of covid-19 vaccines
•Side effects / Adverse events : local and
systemic
•Adverse events of interest
•Pre-vaccination assessment (PVA)

5. mRNA vaccine
Vaccine Doses Vaccine efficacy Real world
effectiveness
Comirnaty
Pfizer
BioNtech
BNT162b2 2 Phase III trial
Efficacy 95 %
92-94%
Moderna mRNA-1273 2 Phase III trial
Efficacy 94%
---

6. BNT162b2 mRNA Covid-19 Vaccine
in a Nationwide Mass Vaccination
Setting ( Israel )
Noa Dagan et al , NEJM Feb 2021

7. Inactivated vaccine
Vaccine Dose Vaccine efficacy Effectiveness
CoronaVac
(SinoVac)
------- 2 50.4 – 91.25 % 94.9% seroconversion
rate in a Phase I/II clinical
trial
Phase III
50.7%
Sinopharm BBIBP-CoV 2 Efficacy 86% --

8. Viral vector vaccine
Vaccine Dose Vaccine efficacy
Cansino Ad5-nCoV 1 Human adenovirus Ad5 carrying
mRNA for the spike protein
65.7%
Janssen &
Janssen
Ad26COVs1 1 Human adenovirus Ad26 carrying
mRNA for the spike protein
United States: 72%
Latin American
countries: 66%
South Africa: 57%
Gamaleya
(Russia)
Sputnik V 2 Two human adenovirus : Ad5 and
Ad6 , carrying the mRNA for spike
protein
91.6%
Astra Zeneca ChAdOx1 2 Chimpanzee adenovirus carrying
mRNA for the spike protein
UK + Brazil
70%

9. Adverse event following
vaccination ( AEFI)
Solicited
• Localised adverse event
• Systemic adverse event
Unsolicited
• Adverse event of interest
Unsolicited
• Severe adverse event

10. Severe adverse events :
coincidence or causality
Pre-existing illness and risk factors
Background rates in unvaccinated population
Placebo arm

11. Comirnaty ( Pfizer ) : local and systemic AE 2nd
dose > 1st
dose

12. 12
Systemic AE more
common in < 55
years old

13. In summary : Comirnaty ( Pfizer)
Solicited local and systemic
reactions
•Local reaction more intense after second dose
•Local reaction is self-limiting ; peak at 24 hours then
resolving by 48-72H
•Systemic reaction is more common in people < 55 years
old

14. Case report
• A 59-year-old woman with current metastatic squamous cell lung
cancer (stage IV). post chemotherapy and radiation, presented for
routine surveillance 18F-fluorodeoxyglucose (FDG) PET/CT.
• Chest CT demonstrated new left axillary lymphadenopathy, with
moderate to intense uptake on FDG PET. In the right middle lobe, at
the site of primary malignancy, nodularity was identified along the area
of radiation fibrosis. There was interval progression of a right eighth
posterolateral rib lytic metastasis .
• The patient had received the second dose of the Pfizer-BioNTech
COVID-19 vaccination in the left deltoid muscle 5 days before imaging.
• Given recent COVID-19 vaccination, the left axillary lymph nodes were
assessed as likely reactive.

15. Unsolicited adverse event :
post-vaccination lymphadenopathy
•Lymphadenopathy were imbalanced with 58 more cases in the
vaccine group (64) vs in the placebo group (6).
•Lymphadenopathy is plausibly related to the vaccine.
•Lymphadenopathy occurred in the arm and neck region and
was reported within 2 to 4 days after vaccination. The average
duration of lymphadenopathy was approximately 10 days.
Polack et al, NEJM Dec 2020

17. Characteristics of healthcare workers
with supraclavicular lymphadenopathy
after COVID-19 vaccination, Spain, 2021
(n = 20, all female)
•Onset of lymphadenopathy : 1- 9 days post vaccination
(10 cases within 1 day )
•Resolution of LN : 5 days to > 32 days
• 3 cases with concomitant infraclavicular LN
•19/20 cases involving left arm
•Conclusions: begin , self-limiting , associated with
high point injection

18. Recommendations for timing
of vaccination and imaging
• Management in this clinical context of a current cancer diagnosis is tailored to
the specific case, ideally with consultation between the oncology treatment
team and the radiologist
• Vaccination possibly in the thigh or contralateral arm according to the location
of the known cancer.
• Imaging for screening, routine surveillance, and staging , to schedule for at
least 6 weeks after final vaccination dose
• To postpone mammography screening until 4 to 6 weeks after the final
vaccination dose
• To postpone short-interval follow-up for 4 to 12 weeks after the final
vaccination dose
• Imaging should not be delayed when clinically indicated to be performed
Society of Breast Imaging Patient Care and Delivery Committee. American college of Radiology 2021

20. Efficacy and safety of a Covid-19 inactivated vaccine
in healthcare professionals in Brazil :The PROFISCOV
study
•Double blind phase 3 clinical trial , with 9,823 participants
received two doses .
•Efficacy to prevent symptomatic Covid-19 : 50.7% ( 95% CI
35.9-62.0)
•Efficacy to prevent scored 4 and above (Hospitalisation and
severe disease ) : 100% ( 95% 56.4-100.0)
Palacios et al , April 2021
https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3822780
CoronaVac ( SinoVac )

21. CoronaVac : Real World
experience in Chile

22. Systemic Adverse Event AE within 14 after 1st dose AE within 28 after 2nd dose
No of event % No of event %
Fever 8 0.1 3 0.1
Hypersensitivity 53 0.8 37 0.6
Rash 42 0.6 25 0.5
Diarrhoea 502 7.3 335 5.5
Impaired appetite 208 3.0 126 2.0
Vomiting 48 0.8 50 0.9
Nausea 464 0.8 304 4.8
Myalgia 686 9.8 526 8.0
Headache 2615 31.4 1957 24.7
Fatigue 1016 13.9 593 9.1
Arthralgia 331 4.7 229 3.4
Chills 274 4.1 185 3.0
Systemic
reaction more
common after
1st
Dose , less
common after
2nd dose

23. Safety profile of AZD1222 in phase I/ II Safety
• SAEs occurred in 168 participants (<1%)
• Solicited Adverse Events, the majority usually resolved within a few
days of vaccination.
• Reactogenicity; the most frequently reported AEs were mild to
moderate in severity including injection site tenderness (>60%);
injection site pain, headache, fatigue (>50%); myalgia, malaise
(>40%); pyrexia, chills (>30%); and arthralgia, nausea (>20%).
• Generally milder and reported less frequently after second dose and
in older adults (≥65 years old)
• Local and systemic reactions ~20% less frequent after the 2nd dose
Astra Zeneca Covid-19 vaccine

24. Signal assessment report on embolic and
thrombotic events with COVID-19
Vaccine (ChAdOx1-S -COVID-19Vaccine
AstraZeneca
•Of the 18 case Cerebral venous sinus thrombosis
(CVST)/Cerbral venous thrombosis (CVT)
•16/18 are women
•Age 20-59 yo
•The time-to-onset ranged from 1 to 14 days with a median of 8
days.
•Thrombocytopenia occurred in 12 cases (67%).
The risk of cerebral venous thrombosis after the
AstraZeneca vaccine is 5.0 (4.3 to 5.8) per million people.
In adults, the annual incidence of CVST is 2 to 5 cases per
million individuals, but it is likely to be underestimated
because of the lack of well-designed epidemiological
studies

25. Cerebral venous thrombosis: a retrospective
cohort study of 513,284 confirmed COVID-19
cases and a comparison with 489,871 people
receiving a COVID-19 mRNA vaccine
Taquet et la, Oxford university https://osf.io/a9jdq/
(pre-print non-peer review study)
Influenza
infection
Per million people
Covid-19 infection
Per million people
After receiving
mRNA covid-19
vaccine
Per million people
After receiving
AZ covid vaccine
EMA
Per million people
CVT 0.0
(95% CI 0.0–22.2)
39.0
(95% CI, 25.2–60.2)
4.1
( 95% CI 1.1–14.9 )
5.0
Portal VT 98.4 436.4 44.9 1.6
Thrombotic events following COVID-19 infection are significantly higher

26. The European Medicines Agency (EMA) has
said clotting should be listed as a very rare
vaccine side effect .

27. Sputnik V vaccine has shown no signs of
blood clots !
15 April 2021

28. After a study looking at 86 such cases in
the EU, the EMA concluded the benefits
of the vaccine outweighed the risks of the
virus - hospitalisation and death.
•Germany, Spain, Italy and Ireland, France , UK
•Australia
•Canada
•UK
To continue the rollout of AZ COVID-19
vaccination, BUT to avoid in certain individuals

29. Joint CDC and FDA Statement on
Johnson & Johnson COVID-19 Vaccine
(13 April 2021)
•Vaccine adverse event reports: a low level of platelets in the
blood in combination with a rare and severe type of blood clot
called cerebral venous sinus thrombosis (CVST) in individuals
who had received the Janssen COVID-19 Vaccine.
•All cases occurred in females ranging in age from 18-48 years.
•Onset : 3-13 days
•6 cases were detected in more than 6.8 million
doses

30. Capillary Leak Syndrome with
AZ Vaccine
•European Medicines Agency (EMA) press release – a
review of safety signal reports identify 5 cases of
capillary leak syndrome, characterized by leakage of
fluid to tissue with drop of BP
•Pharmacovigilance Risk Assessment Committee
(PRAC) is carrying out investigation

31. Post-vaccination anaphylactic
reaction :
•Trivalent inactivated influenza vaccine : 1.31 cases per million
vaccine doses (95% CI, 0.90– 1.84)
•Comirnaty mRNA covid vaccine : 4.7 cases per million doses
•Moderna : 2.5 cases per million doses
• CoronaVac ( SinoVac) : no anaphylaxis in trial ( 33620 cases)
• Convidicea (CanSino ) : no anaphylaxis in trial ( 40000 cases)
• Oxford/Astra Zeneca : no anaphylaxis in trial ( 10069 cases)
• Janssen : 1 case in 21895 doses
• Spuntnik : no anaphylaxis in trial ( 14964 cases)
https://www.janssencovid19vaccine.com/hcp/clinical-trial-data.html
MMWR report 2021
Turner et al. World Allergy Organization Journal (2021)

32. AEFI COVID-19 Vaccine Reporting

33. npra.gov.my/index.php/en/
health-professionals/repor
ting-adr.html
AEFI COVID-19 Vaccine Reporting

34. REPORTING OF AEFI
Adapted from: Clinical Guidelines on COVID-19 Vaccination In Malaysia (2nd Edition)

35. Pre-vaccination Assessment
• Link to download

36. Priority group in Phase 2
vaccination program
•Elderly
•Patient with underlying medical conditions that increase
risk of severe illness for Covid-19
Pre-vaccination assessment
Some may need PVA

37. Purpose of pre-vaccination
assessment
To decide whether:
1. Patient can receive vaccination at any time
2. Patient can receive vaccination but at later time (deferred)
3. Patient cannot receive vaccination at any time (absolute
contraindication)
To decide vaccination center : Hospital vs vaccination center in
community
To illicit history of severe allergy : eg allergic to PEG

38. 3 Groups of patients requiring PVA
Group
1 Immunocompromised host
- To discuss on the optimal timing for vaccination
- To inform with patient : insufficient data on vaccine efficacy
2 Patients with bleeding tendency or on medications which may make them
more prone to bleeding
- Hemostasis precaution
3 Patient with history of severe allergic reaction or allergic to multiple class of
drugs
- Allergic reaction precaution
4 Others : Frail elderly patient, mentally challenged , terminal illness but not
actively deteriorating; persons who need close observation after
vaccination

39. Timing for vaccination
• Acute illnesses that require admission to hospital- to defer vaccination till the
person recovers from the acute illness
• Persons who previously had SARS-CoV-2 infection and belong to the priority
group for vaccination : vaccination should be deferred until the person has
recovered from the acute illness (if symptomatic) and they have met criteria
to discontinue isolation, in order to prioritise people with no immunity ,
vaccination can be deferred for 3/12
• Persons being quarantined at quarantine centre or under HSO for being a
close contact : vaccination must be given once the persons have completed
10 days of quarantine/self-isolation, and remains /has become
asymptomatic .

40. •Recent immunisation with any other vaccines :Vaccination to
be deferred or postponed for at least after 2 weeks.
•Patients on anticoagulant nd antiplatelet agents :
if on warfarin with INR < 4 on their last scheduled visit can
receive IM vaccination without stopping the drug.
On the day of vaccination, warfarin/ DOAC/ LMWH should be
taken AFTER the vaccine injection
•Individuals who are receiving immunosuppressive or
immunomodulating biological therapy or with malignancy on
treatment : to discuss with patient’s health care provider
regarding the optimal spacing for vaccination

41. Please make your choice !

42. Vaccinations and the impact of
COVID-19 (ISREAL)

43. THANKYOU