THE LATEST ON THE COVID-19 GLOBAL SITUATION
& MONITORING VACCINE SAFETY
LAST UPDATE: 19 April 2021
CORONAVIRUS
UPDATE
57
3
* Data are incomplete for the current week. Cases depicted by bars; deaths depicted by line
Current global situation
CASES REPORTED TO WHO AS OF 18 APRIL 2021, 10:00 CEST
CHECK OUT THE LATEST
GLOBAL SITUATION
WHO
Coronavirus
Disease (COVID-19)
Dashboard
• Cases: > 140 million
• Deaths: > 3 million
Note: Data smoothed with 7-day moving average
4
COVID-19 vaccine administration worldwide
AS OF 19 April 2021
• > 792 million COVID-19 vaccine doses administered
Figure. WHO COVID-19 vaccines tracker on global distribution: % of population given at least 1 dose of COVID-19 vaccine as of 19April 2021
Source: Data retrieved from WHO dashboard on 19 April 2021, https://covid19.who.int/
61%
60%
47%
40%
39%
37%
35%
30%
29%
25%
0
10
20
30
40
50
60
70
Israel Bhutan U.K. Bahrain UAE Chile U.S. Hungary Malta Serbia
% of population given at least 1+ dose of COVID-19 vaccine
MONITORING VACCINE SAFETY
• A vaccine is approved after efficacy and safety data is
reviewed from controlled, randomized clinical trials
• These clinical trials are evaluating COVID-19 vaccines in
tens of thousands of study participants
• After approval, vaccines are used in the real world by a
much larger population than in clinical trials
• To safeguard public health, a strong pharmacovigilance
system is in place to continue to monitor for any adverse
events after deployment of vaccines
5
Monitoring the safety of COVID-19 vaccines
Source: CDC
MONITORING VACCINE SAFETY
• Safety of vaccines is studied from the first development stage through to use in real life
6
How vaccine safety is monitored during and after
the vaccine development process
Source: adapted from: https://www.ema.europa.eu/en/human-regulatory/overview/public-health-
threats/coronavirus-disease-covid-19/treatments-vaccines/vaccines-covid-19/covid-19-vaccines-development-
evaluation-approval-monitoring#monitoring-vaccine-safety-and-use-in-real-life-sec
Quality Toxicity Regulatory databases of suspected adverse reactions to medicines and vaccines
Extended clinical trials (phase IV)
Information from regulators worldwide
Medical literature
Safety studies
Reports from patients & healthcare professionals
Post-marketing safety monitoring
Pharmaceutical
quality
Non-clinical Clinical trials
Evaluation
& decision
Manufacturing
Vaccine in use
Vaccine development phase Safety monitoring
Figure. How vaccine safety is monitored
MONITORING VACCINE SAFETY
• Rigorous safety monitoring during clinical trials allows to estimate the frequency of
common side effects
• Follow up of trial participants and extended clinical trials will identify longer-term effects
7
The safety of COVID-19 vaccines is studied
before approval in pre-clinical and clinical trials
https://www.ema.europa.eu/en/documents/presentation/presentation-how-safety-new-covid-19-vaccines-will-be-monitored-sstraus-prac_en.pdf
Lab testing is used to
ensure that each batch of
vaccine is of good quality
Vaccines undergo
non-clinical studies to
exclude toxicity
Vaccines are being
studied in large clinical
trials, involving tens of
thousands of individuals
MONITORING VACCINE SAFETY
• Safety monitoring after approval is important to detect previously
unrecognized adverse events
• Vaccine safety monitoring after approval involves:
➢ Intensive analysis of reports of suspected adverse events from patients
and healthcare professionals through passive reporting
➢ Active surveillance systems in the countries
➢ Safety studies conducted by vaccine manufacturers
➢ Research studies to examine the safety of COVID-19 vaccines when they
are used in real life
➢ Sharing of information on COVID-19 vaccine safety between regulators
around the world
8
The safety of COVID-19 vaccines continues to be
monitored after approval
https://www.who.int/publications/i/item/10665338400
MONITORING VACCINE SAFETY
• An adverse event following immunization (AEFI) may
be any unintended sign, abnormal laboratory finding,
symptom or disease
• The presence of an adverse event does not necessarily
mean the vaccine has caused the reported adverse
event
• The assessment of adverse events establishes whether
or not there is a causal relationship between the
vaccine and the reported adverse event*
• An adverse event of special interest (AESI) is a pre-
specified medically-significant event that has the
potential to be causally associated with a vaccine
product that needs to be carefully monitored and
confirmed by further special studies
9
Vaccine safety monitoring can detect adverse events
* https://www.who.int/vaccine_safety/publications/gvs_aefi/en/
Causality
assessment
Feedback AEFI
detection
Notification
Reporting
Investigation
Figure. AEFI surveillance circle
MONITORING VACCINE SAFETY
• Established analysis techniques are in place to assess whether
an adverse event is likely caused by the vaccine
• A systematic approach is undertaken to determine the causality
of an adverse event to the vaccine
➢ Findings are supported by
• Post-marketing safety monitoring
• Safety studies
• Information from regulators worldwide
• Medical literature
• If analysis concludes that a new adverse event is caused by a
vaccine, action is taken. This may include listing the adverse
event on the vaccine packaging or a medical alert
10
Causality assessment of adverse events
https://www.who.int/vaccine_safety/publications/gvs_aefi/en/
https://www.who.int/initiatives/the-global-vaccine-safety-initiative/investigation-of-safety-signals
© UNICEF/UN023959/Clark
MONITORING VACCINE SAFETY
• The Global Advisory Committee on Vaccine Safety is a group of experts
that provide independent guidance on vaccine safety issues of potential
global importance to WHO
• A WHO COVID-19 subcommittee of the Global Advisory Committee on
Vaccine Safety is established to assess the latest safety data for COVID-19
vaccines during weekly meetings
11
The role of the Global Advisory Committee on
Vaccine Safety
https://www.who.int/initiatives/the-global-vaccine-safety-initiative
https://www.who.int/news/item/17-03-2021-who-statement-on-astrazeneca-covid-19-vaccine-safety-signals
MONITORING VACCINE SAFETY
• A very rare new type of adverse event called Thrombosis with Thrombocytopenia Syndrome
(TTS), involving unusual and severe blood clotting events associated with low platelet counts, has
been reported after vaccination with AstraZeneca COVID-19 vaccines
• Thrombosis in specific sites such as the brain and abdomen appears to be a key feature of TTS
• Data from the UK suggest that the risk is approximately four cases per million adults (1 case per
250 000) who receive the vaccine, while the rate is estimated to be approximately 1 per 100 000 in
the European Union
• The TTS syndrome has not been linked to mRNA-based vaccines, such as the Pfizer and Moderna
COVID-19 vaccines
• Whilst we have some information on the Pfizer, Moderna and AstraZeneca vaccines, there is
limited post-market surveillance data on other COVID-19 vaccines and from low- and middle-
income countries
12
Blood clotting events associated with low platelet
counts have been reported after COVID-19 vaccination
https://www.who.int/news/item/16-04-2021-global-advisory-committee-on-vaccine-safety-(gacvs)-review-of-latest-evidence-of-rare-adverse-blood-coagulation-events-
with-astrazeneca-covid-19-vaccine-(vaxzevria-and-covishield)
MONITORING VACCINE SAFETY
• Clinicians should be alert to any new, severe, persistent headache
or other significant symptoms, such as severe abdominal pain and
shortness of breath, with an onset between 4 to 20 days after
adenovirus vectored COVID-19 vaccination
• At a minimum, countries should encourage clinicians to measure
platelet levels and conduct appropriate radiological imaging
studies as part of the investigation of thrombosis
• Clinicians should also be aware that although heparin is used to
treat blood clots in general, administration of heparin in TTS may
be dangerous, and alternative treatments such as
immunoglobulins and non-heparin anticoagulants should be
considered
13
Considerations for health workers in the
context of TTS
https://www.who.int/news/item/16-04-2021-global-advisory-committee-on-vaccine-safety-(gacvs)-review-of-latest-
evidence-of-rare-adverse-blood-coagulation-events-with-astrazeneca-covid-19-vaccine-(vaxzevria-and-covishield)
MONITORING VACCINE SAFETY
• Countries assessing the risk of TTS following COVID-19 vaccination should perform a
benefit-risk analysis that takes into account local epidemiology (including incidence and
mortality from COVID-19 disease), age groups targeted for vaccination and the availability
of alternative vaccines*
14
Considerations for countries in the context of TTS
* https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/976877/CovidStats_07-04-21-final.pdf
** https://brightoncollaboration.us/thrombosis-with-thrombocytopenia-syndrome-case-finding-definition/
• To support evidence-based recommendations, countries
should:
➢ review, report and investigate all cases of TTS following
COVID-19 vaccinations
➢ assess cases according to the presence of thrombosis with
thrombocytopenia and the time to onset following
vaccination using the Brighton Case Definition of TTS**
➢ provide data to their local authorities and to the WHO
global database of individual case safety reports.
• There may be a geographic variation in the risk of these rare
adverse events. Therefore, it is important that all countries
evaluate potential cases of TTS
MONITORING VACCINE SAFETY
• A specific case definition for TTS is being developed by the Brighton Collaboration*
• The biological mechanism for this syndrome of TTS is still being investigated. At this stage, a
-vectored vaccines is not certain but
cannot be excluded
• Ongoing review of TTS cases and related research should include all vaccines using adenoviral
vector platforms
• Global Advisory Committee on Vaccine Safety (GACVS) recommends further epidemiological,
clinical and mechanistic studies to fully understand TTS including:
➢ an increased risk in younger adults
➢ gender-related risk (although more cases have been reported in women; it is important to
underscore that more women have been vaccinated and some TTS cases have also been
reported in men)
15
TTS after COVID-19 vaccination continues to be
investigated
* https://brightoncollaboration.us/thrombosis-with-thrombocytopenia-syndrome-case-finding-definition/
MONITORING VACCINE SAFETY
• Listen to the media and communities to understand the
main questions and concerns and any associated rumours
• Communicate clearly, proactively, early and frequently,
through trusted spokespeople. Demonstrate competence in
science, the systems and programme, with empathy,
honesty, transparency. Do not over-reassure. Put the data
in context. Visuals can help explain risk/benefit ratios
• Connect with your networks and identify and engage all the
various influencers, advocates, champions, who can be
trusted intermediaries and amplifiers to answer questions
and provide context
16
Informing the public about suspected adverse events
Source: WHO
MONITORING VACCINE SAFETY
• Avoid the use of numbers such as 1 in 2 million. These comparisons tend to be too abstract
for people to grasp the true meaning
• Instead, be visual by using familiar settings and items to show numbers. For example:
➢ one person in a large football stadium
➢ one grain of sand in a teaspoon
• Test the comparison of risk with the audiences that receive the information. Ensure that the
message intended is conveyed clearly
• Use empathy in referring to deaths and harm. Even one death may feel like too much for
something that people choose to do (e.g. vaccination)
• Emphasize the benefits over the risks of getting vaccinated
17
Communicate vaccine safety numbers visually and
recognizably for the public
SOCIAL MEDIA LISTENING
RISK OF THROMBOSIS: THE ASTRAZENECA VACCINE vs. THE
CONTRACEPTIVE PILL
•
contraceptive pill has a higher potential blood clot rate than the AstraZeneca
vaccine'
• The comparison has been resonating strongly on social media platforms. Users
expressed confusion and frustration over why the risk of thrombosis was
enough for authorities to allegedly take the AstraZeneca jab off the market in
some countries, whilst comparable levels of risk are seemingly deemed
acceptable for contraceptive products
VACCINE COMPARISONS (GLOBAL)
• Users have expressed confusion over why cases of blood clots have been
linked to the AstraZeneca vaccine in particular and not to other vaccines
18
Online mentions on blood clots & thrombosis in
relation to the AstraZeneca vaccine
17 MARCH to 06 APRIL 2021
European and North American countries were likely to
engage with the conversation the most. On the other hand,
Indian, Kenyan and Nigerian profiles that attracted most
engagement were most likely to share news reports of
deaths allegedly caused by vaccine-elicited blood clots.
Google search patterns around thrombosis, blood clots, and
AstraZeneca also saw an overrepresentation of European
countries, but Kenya, Uruguay, Australia and Namibia broke
the pattern.
Figure. Conversation on blood clots by country (top 10)
Figure. Online mentions of blood clots or thrombosis after the global peak*
(17 Mar - 6 Apr 2021)
+78%
Conversation on
up by
Blood clots
19
Additional resources
• COVID-19 vaccine introduction toolkit
The COVID-19 vaccine introduction toolbox equips all countries to
prepare for and implement COVID-19 vaccination by providing
guidance, tools, and training.
https://www.who.int/tools/covid-19-vaccine-introduction-toolkit
• WHO Coronavirus (COVID-19)
Dashboard
A global overview of confirmed COVID-19 cases, deaths and
vaccine doses administered.
https://covid19.who.int/
• Causality assessment of an adverse
event following immunization (AEFI)
User manual on causality assessment
https://www.who.int/vaccine_safety/publications/gvs_aefi/en/
• Vaccine safety surveillance
manual
vaccine safety surveillance manual for COVID-19
vaccines
https://www.who.int/publications/i/item/10665338400
• Investigation of safety signals
vaccine safety signal is information that indicates a potential
link between a vaccine and an event previously unknown or
incompletely documented, that could affect health.
https://www.who.int/initiatives/the-global-vaccine-safety-
initiative/investigation-of-safety-signals
• WHO statement on
AstraZeneca COVID-19 vaccine
safety signals
https://www.who.int/news/item/17-03-2021-who-statement-on-astrazeneca-
covid-19-vaccine-safety-signals
20
COVID-19 protective measures
Protect yourself & others
Cough & sneeze into
your elbow
Wear a mask
Keep your distance
Wash your hands
frequently
Ventilate or open
windows
www.who.int/epi-win
