Post by Nadica (She/Her) on Jun 25, 2024 2:34:45 GMT
SARS-CoV-2 Omicron Variant Sub-Lineages BA.4 and BA.5: Evidence and Risk Assessment - Public Health Ontario - Published July 8, 2022
Introduction
This evidence brief includes evidence that has emerged since the previous Public Health Ontario (PHO)
BA.4 and BA.5 Evidence and Risk Assessment.
Key Messages
• The proportion of whole genome sequencing (WGS) samples identified as BA.5 continues to
increase in Ontario, from 14.8% (June 5-11, 2022) to 25.7% (June 12-18, 2022), with a weekly
growth rate 3.11 (95% confidence interval [CI]: 2.89-3.34) times that of BA.2. The proportion of
BA.4 had a slight increase in Ontario, from 6.2% (June 5-11, 2022) to 6.9% (June 12-18, 2022),
with a weekly growth rate 2.48 (2.27-2.71) times that of BA.2.
• Using Nowcast modelling, the proportions of BA.5 and BA.4 in Ontario are projected to reach
66.3% (95% CI: 58.3%-73.5%) and 9.7% (95% CI: 6.5%-14.0%), respectively, by July 6, 2022.
Hospitalizations and mortality are likely to increase due to the rise in volume of cases, but there
is uncertainty about the extent of the increase since evidence on severity of BA4 and BA.5 is
uncertain.
• Based on those eligible for molecular testing in Ontario, Coronavirus Disease 2019 (COVID-19)
cases and percent positivity are increasing after a period of gradual decline. Hospital occupancy
shows early signs of potential plateau or increase, and the province-wide wastewater signal
continues to increase. Together, these epidemiological trends indicate increasing community
transmission.
• Evidence continues to show that BA.4 and BA.5 are highly transmissible, at least in part due to
neutralizing antibody titers against BA.4 and BA.5 being reduced as compared to other variants.
BA.4/5 could lead to high levels of community transmission in the absence of public health measures.
• For previous sub-lineages of Omicron, a complete primary series and for those eligible, the
recommended booster dose(s), provide optimal protection against severe outcomes.
SARS-CoV-2 Omicron Variant Sub-Lineages BA.4 and BA.5: Evidence and Risk Assessment
• Evidence shows that SARS-CoV-2 reinfection adds risk of all-cause mortality, hospitalization and
adverse health outcomes during acute and post-acute SARS-CoV-2 reinfection, and that the risk
and burden may increase in a graded manner according to the number of infections. The
evidence that SARS-CoV-2 can cause immune dysregulation is increasing. Reducing the risk of
SARS-CoV-2 infection and reinfection could reduce overall burden of death and disease in
Ontario during the pandemic and longer-term.
• To minimize morbidity and mortality in Ontario, as well as societal disruption, current public
health efforts could be augmented in response to the increasing epidemiological trends. Based
on evidence of significant immune evasion by BA.4/5 and waning immunity following
vaccination, use of public health measures will be the most effective way to reduce the risk of
SARS-CoV-2 transmission, and includes: wearing a well-fitted high quality mask whenever
feasible in indoor spaces, crowded places (including outdoors) and close contact settings (e.g.,
public transit), staying home when sick or with symptoms of COVID-19, optimizing ventilation,
and use of outdoor spaces.
Issue and Research Question
There are multiple PANGO sub-lineages associated with the B.1.1.529 (Omicron) variant of concern
(VOC). The main BA.1, BA.2, BA.3, BA.4, and BA.5 sub-lineages may also have their own sub-lineages
(e.g., BA.1.1, BA.2.12, BA.2.12.1, BA.2.3, BA. 2.20, BA.2.9, BA.5.1). Considering the possible changes to
transmissibility, severity, and/or vaccine effectiveness (VE) of these sub-lineages compared to other
VOCs, it is important to monitor the potential impact they might have in Ontario’s context.
Methods
PHO Library Services conducted daily searches of primary and preprint literature using the MEDLINE
database (search strategies available upon request). Preprints are research papers that have not
undergone peer-review but are made publicly available to provide the latest data relevant to the rapidly
evolving COVID-19 pandemic. Formal critical appraisal of published and preprint COVID-19 literature is
out of scope for this PHO risk assessment. PHO performed grey literature searches daily using various
news feeds and custom search engines. English-language peer-reviewed and preprint records that
described COVID-19 variants were included. Sections from prior risk assessments for which there is no
new literature of note are removed from the current update.
Risk Assesment
The current risk of BA.4 and BA.5 transmissibility in Ontario is high with a low degree of uncertainty. The
risk of severe disease is low with a high degree of uncertainty. The risk of reinfection is high with a low
degree of uncertainty. The risks of lowered VE and breakthrough infection are high with a moderate
degree of uncertainty. The risk of impact on testing is low with a moderate degree of uncertainty. The
overall risk assessment may change as new evidence emerges (see Table 1).
SARS-CoV-2 Omicron Variant Sub-Lineages BA.4 and BA.5: Evidence and Risk Assessment 3
Additional Considerations
• Post-acute COVID-19 syndrome (PACS or “long-COVID”) is not included in the risk assessment
table, but several reviews report that the sequelae and their incidence vary.2-12 Preventing high
levels of COVID-19 community transmission may mitigate the incidence of post-COVID-19
sequelae and its long term impacts at the individual and population levels.
• Emerging evidence indicates that reinfection adds risk of all-cause mortality, hospitalization
and adverse health outcomes during acute and post-acute SARS-CoV-2 reinfection.
Additionally, the risk and burden may increase in a graded manner according to the
number of infections, which suggests preventing reinfection could reduce overall SARSCoV-2 burden of death and disease.12 Current COVID-19 vaccines and previous SARS-CoV-2
infection do not provide sterilizing immunity (i.e., full protection from infection or
reinfection), therefore public health measures have a considerable role to play in the
current pandemic response.
• There is increasing evidence that SARS-CoV-2 infection can cause immune dysregulation.2-9
Although all outcomes and the scale of immune dysregulation remain unclear, a potential
increase in acquired impaired immunity in the Ontario population could have significant impact
on the incidence and associated burden of infectious diseases (e.g., high viral loads, increased
antibiotic use and resistance) and other conditions in the longer-term.
• Even if BA.4 or BA.5 are found to be no more severe than BA.1 and BA.2, the increased
transmissibility of BA.4 and BA.5 suggests that the total number of cases (and therefore the total
number of severe cases) would be expected to rise. Early evidence suggests several monoclonal
antibodies approved for clinical use, exhibit substantial loss of activity in vitro against BA.4/5.14
High vaccine uptake, partial immunity from previous infections, and having additional public
health measures in place may attenuate an increase in cases from BA.4 and BA.5, and their
impact in Ontario.
• COVID-19 hospitalizations are no longer declining in Ontario (see below). Health care worker
absences, shortages, and impacts to scheduled care, could be yet more challenging in the
context of BA.4 and/or BA.5 community transmission. Transmission of other communicable
diseases (e.g., influenza, monkeypox) is another consideration for health care system recovery
and capacity planning in Ontario.
• Although summers have been lower transmission periods for COVID-19 in Ontario during the
past two years, and people can gather outdoors which lowers the risk of transmission events,
key considerations for increased risk in Ontario at this time include (in no particular order): first,
SARS-CoV-2 VE against infection has been waning in individuals last vaccinated more than four
months ago, and more so in individuals who received two doses compared to three doses (based
on studies from earlier Omicron waves); second, BA.4 and BA.5 are more transmissible than
earlier sub-lineages and their proportional representation in Ontario is increasing according to
WGS surveillance; third, although strains may share a common ancestor and sub-lineage, there
can be significant point mutations and antigenic changes between evolving strains of the same
sub-lineage (e.g., BA.2.12 versus BA.2.12.1, BA.2 versus BA.4/5), resulting in variable antibody
cross-neutralization after an infection. As a result, reinfections and breakthrough infections can
result in a resurgence of COVID-19, which the current Ontario context may reflect.
Introduction
This evidence brief includes evidence that has emerged since the previous Public Health Ontario (PHO)
BA.4 and BA.5 Evidence and Risk Assessment.
Key Messages
• The proportion of whole genome sequencing (WGS) samples identified as BA.5 continues to
increase in Ontario, from 14.8% (June 5-11, 2022) to 25.7% (June 12-18, 2022), with a weekly
growth rate 3.11 (95% confidence interval [CI]: 2.89-3.34) times that of BA.2. The proportion of
BA.4 had a slight increase in Ontario, from 6.2% (June 5-11, 2022) to 6.9% (June 12-18, 2022),
with a weekly growth rate 2.48 (2.27-2.71) times that of BA.2.
• Using Nowcast modelling, the proportions of BA.5 and BA.4 in Ontario are projected to reach
66.3% (95% CI: 58.3%-73.5%) and 9.7% (95% CI: 6.5%-14.0%), respectively, by July 6, 2022.
Hospitalizations and mortality are likely to increase due to the rise in volume of cases, but there
is uncertainty about the extent of the increase since evidence on severity of BA4 and BA.5 is
uncertain.
• Based on those eligible for molecular testing in Ontario, Coronavirus Disease 2019 (COVID-19)
cases and percent positivity are increasing after a period of gradual decline. Hospital occupancy
shows early signs of potential plateau or increase, and the province-wide wastewater signal
continues to increase. Together, these epidemiological trends indicate increasing community
transmission.
• Evidence continues to show that BA.4 and BA.5 are highly transmissible, at least in part due to
neutralizing antibody titers against BA.4 and BA.5 being reduced as compared to other variants.
BA.4/5 could lead to high levels of community transmission in the absence of public health measures.
• For previous sub-lineages of Omicron, a complete primary series and for those eligible, the
recommended booster dose(s), provide optimal protection against severe outcomes.
SARS-CoV-2 Omicron Variant Sub-Lineages BA.4 and BA.5: Evidence and Risk Assessment
• Evidence shows that SARS-CoV-2 reinfection adds risk of all-cause mortality, hospitalization and
adverse health outcomes during acute and post-acute SARS-CoV-2 reinfection, and that the risk
and burden may increase in a graded manner according to the number of infections. The
evidence that SARS-CoV-2 can cause immune dysregulation is increasing. Reducing the risk of
SARS-CoV-2 infection and reinfection could reduce overall burden of death and disease in
Ontario during the pandemic and longer-term.
• To minimize morbidity and mortality in Ontario, as well as societal disruption, current public
health efforts could be augmented in response to the increasing epidemiological trends. Based
on evidence of significant immune evasion by BA.4/5 and waning immunity following
vaccination, use of public health measures will be the most effective way to reduce the risk of
SARS-CoV-2 transmission, and includes: wearing a well-fitted high quality mask whenever
feasible in indoor spaces, crowded places (including outdoors) and close contact settings (e.g.,
public transit), staying home when sick or with symptoms of COVID-19, optimizing ventilation,
and use of outdoor spaces.
Issue and Research Question
There are multiple PANGO sub-lineages associated with the B.1.1.529 (Omicron) variant of concern
(VOC). The main BA.1, BA.2, BA.3, BA.4, and BA.5 sub-lineages may also have their own sub-lineages
(e.g., BA.1.1, BA.2.12, BA.2.12.1, BA.2.3, BA. 2.20, BA.2.9, BA.5.1). Considering the possible changes to
transmissibility, severity, and/or vaccine effectiveness (VE) of these sub-lineages compared to other
VOCs, it is important to monitor the potential impact they might have in Ontario’s context.
Methods
PHO Library Services conducted daily searches of primary and preprint literature using the MEDLINE
database (search strategies available upon request). Preprints are research papers that have not
undergone peer-review but are made publicly available to provide the latest data relevant to the rapidly
evolving COVID-19 pandemic. Formal critical appraisal of published and preprint COVID-19 literature is
out of scope for this PHO risk assessment. PHO performed grey literature searches daily using various
news feeds and custom search engines. English-language peer-reviewed and preprint records that
described COVID-19 variants were included. Sections from prior risk assessments for which there is no
new literature of note are removed from the current update.
Risk Assesment
The current risk of BA.4 and BA.5 transmissibility in Ontario is high with a low degree of uncertainty. The
risk of severe disease is low with a high degree of uncertainty. The risk of reinfection is high with a low
degree of uncertainty. The risks of lowered VE and breakthrough infection are high with a moderate
degree of uncertainty. The risk of impact on testing is low with a moderate degree of uncertainty. The
overall risk assessment may change as new evidence emerges (see Table 1).
SARS-CoV-2 Omicron Variant Sub-Lineages BA.4 and BA.5: Evidence and Risk Assessment 3
Additional Considerations
• Post-acute COVID-19 syndrome (PACS or “long-COVID”) is not included in the risk assessment
table, but several reviews report that the sequelae and their incidence vary.2-12 Preventing high
levels of COVID-19 community transmission may mitigate the incidence of post-COVID-19
sequelae and its long term impacts at the individual and population levels.
• Emerging evidence indicates that reinfection adds risk of all-cause mortality, hospitalization
and adverse health outcomes during acute and post-acute SARS-CoV-2 reinfection.
Additionally, the risk and burden may increase in a graded manner according to the
number of infections, which suggests preventing reinfection could reduce overall SARSCoV-2 burden of death and disease.12 Current COVID-19 vaccines and previous SARS-CoV-2
infection do not provide sterilizing immunity (i.e., full protection from infection or
reinfection), therefore public health measures have a considerable role to play in the
current pandemic response.
• There is increasing evidence that SARS-CoV-2 infection can cause immune dysregulation.2-9
Although all outcomes and the scale of immune dysregulation remain unclear, a potential
increase in acquired impaired immunity in the Ontario population could have significant impact
on the incidence and associated burden of infectious diseases (e.g., high viral loads, increased
antibiotic use and resistance) and other conditions in the longer-term.
• Even if BA.4 or BA.5 are found to be no more severe than BA.1 and BA.2, the increased
transmissibility of BA.4 and BA.5 suggests that the total number of cases (and therefore the total
number of severe cases) would be expected to rise. Early evidence suggests several monoclonal
antibodies approved for clinical use, exhibit substantial loss of activity in vitro against BA.4/5.14
High vaccine uptake, partial immunity from previous infections, and having additional public
health measures in place may attenuate an increase in cases from BA.4 and BA.5, and their
impact in Ontario.
• COVID-19 hospitalizations are no longer declining in Ontario (see below). Health care worker
absences, shortages, and impacts to scheduled care, could be yet more challenging in the
context of BA.4 and/or BA.5 community transmission. Transmission of other communicable
diseases (e.g., influenza, monkeypox) is another consideration for health care system recovery
and capacity planning in Ontario.
• Although summers have been lower transmission periods for COVID-19 in Ontario during the
past two years, and people can gather outdoors which lowers the risk of transmission events,
key considerations for increased risk in Ontario at this time include (in no particular order): first,
SARS-CoV-2 VE against infection has been waning in individuals last vaccinated more than four
months ago, and more so in individuals who received two doses compared to three doses (based
on studies from earlier Omicron waves); second, BA.4 and BA.5 are more transmissible than
earlier sub-lineages and their proportional representation in Ontario is increasing according to
WGS surveillance; third, although strains may share a common ancestor and sub-lineage, there
can be significant point mutations and antigenic changes between evolving strains of the same
sub-lineage (e.g., BA.2.12 versus BA.2.12.1, BA.2 versus BA.4/5), resulting in variable antibody
cross-neutralization after an infection. As a result, reinfections and breakthrough infections can
result in a resurgence of COVID-19, which the current Ontario context may reflect.