5. Coronavirus disease (COVID-19)

Coronavirus disease 2019 (COVID‑19) is caused by the SARS-CoV-2 virus, which infects the respiratory tract and is transmitted human to human primarily through respiratory droplets and aerosols. Documented transmission has also occurred through direct contact and rarely fomites (objects or materials that can carry infection).

The symptoms of COVID 19 range widely from asymptomatic infection or from a mild to severe respiratory tract infection and pneumonia, which can lead to severe inflammatory disease and respiratory failure. The most common symptoms of COVID-19 are like those of other common respiratory illnesses and include a new or worsening dry cough, sneezing and rhinorrhoea or nasal congestion, fever, sore throat, shortness of breath and fatigue. Unlike other respiratory viral infections, COVID 19 is frequently associated with a temporary loss of smell or altered sense of taste. Some cases have reported gastrointestinal symptoms including nausea, diarrhoea, vomiting and abdominal pain, headache, muscle aches, malaise, chest pain, joint pain, and confusion or irritability; these symptoms almost always occur with one or more of the common symptoms. For most cases COVID 19 is a mild disease, but some can develop more severe disease or exacerbation of comorbidities. As for influenza and other respiratory viruses, some of those with laboratory-confirmed infection remain asymptomatic.

In the early stages, it is difficult to distinguish COVID 19 symptoms from other common viral infections. The most reliable common diagnostic test has been detection of viral mRNA from a nasopharyngeal swab, using PCR assay and rapid antigen tests (RATs).

The incubation period is typically around two to five days (up to 14 days). Individuals may be infectious from up to two days before becoming symptomatic.[4] Unlike previous coronavirus outbreaks (SARS and MERS), transmission of SARS-CoV-2 can also occur before the onset of symptoms or from asymptomatic individuals.[5] Viral loads and infectiousness are highest immediately after symptom onset, and most transmission occurs in household settings.[6, 7]

It is currently unclear what level and duration of protection is provided by infection with SARS-CoV-2. Early in the pandemic, neutralising antibodies were shown to remain relatively stable between eight to 11 months after primary infection.[8, 9] Frequently, reinfection occurs due to exposure to different variants of SARS-CoV-2 that are better able to evade the immune response and when inadequately matched neutralising antibody immunity has waned. The risk of reinfection is less in recently vaccinated individuals, and hybrid immunity, from both infection and vaccine, reduces the risk of COVID-19 hospitalisation.[10, 11] The degree of protection is highly variable depending on individual risk for severe disease. To maintain effective neutralising antibody levels, additional COVID-19 vaccination with a variant-matched vaccine is recommended, particularly for high-risk groups.

Overall, the incidence of severe or fatal disease in children is significantly lower than in adults, with fewer hospitalisations and shorter hospital stays. The incidence is less for the Omicron variants than the previous variants.[11,12] Children at highest risk of more severe disease are predominantly those living with pre-existing significant health conditions and those living in areas with highest levels of deprivation.[13] Pre-existing conditions in children associated with increased risk from COVID-19 include obesity, diabetes, cardiac and pulmonary diseases, immune disorders, metabolic disease, cancer, neurological, neurodevelopmental (in particular, Down syndrome [trisomy 21]) and neuromuscular conditions.[14, 15] Although these risk factors are prevalent in New Zealand children, particularly for some Māori and Pacific children,[16, 17] during the first wave of sustained Omicron transmission in New Zealand, hospitalisations of predominantly COVID-19-naïve children were of short duration (0-2 days) with few intensive care admissions.[18]

Paediatric multisystem inflammatory syndrome

Paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 (PIMS-TS or MIS-C) is a rare, delayed complication of COVID-19 following largely asymptomatic SARS-CoV-2 infection in children and adolescents.[11, 19] Surveillance in England has found that, despite the very high numbers of COVID-19 cases associated with the Omicron variants, the risk of PIMS-TS is extremely low due to most children having immunity to SARS-CoV-2 through previous infection and vaccination.[20]

Risk factors for severe disease include older age, male, smoking,[21] obesity and chronic medical conditions, including diabetes,[22] cancer, chronic respiratory disease, cardiovascular disease, chronic kidney disease, hypertension, immunocompromise[23] and pregnancy (see below). Increased incidence is well documented in some ethnic groups but seems primarily related to prevalence of the risk factors listed above. Increasing age is the most important risk factor for severe disease, due to declining immune function and high prevalence of comorbidities. The highest risk group for severe illness and mortality is those aged over 70 years[24], although Māori and Pacific populations experience age-related risk at a younger age than other ethnicities.

Pregnancy

With high vaccine uptake and widespread infection since 2022 in New Zealand, most people have good immunity against SARS-CoV-2. Individuals who are healthy with immunity to SARS-CoV-2 face a lower risk of severe illness in pregnancy than non-immune individuals earlier in the pandemic. Despite this, some individuals remain at increased risk of severe COVID-19 complications when pregnant, particularly when infection exacerbates underlying conditions or in high-risk pregnancy, for example those with gestational diabetes, hypertension, thrombosis risk factors, obesity or of an older age.[25]

Although considerably lower than during the start of the pandemic and during Delta variant period, pregnancy remained associated with an increased risk of moderate to severe COVID-19 complications when Omicron variants became predominant, particularly for unvaccinated people.[26,27] One international study found that the risk for referral to ICU or death was increased by 20 times for unvaccinated pregnant women with symptomatic Omicron COVID-19.[28] 

Infants born to mothers with severe COVID‑19 are at increased risk of preterm birth and requiring neonatal ICU admission, primarily due to early induction of labour.[29,30] Early studies do not suggest intrauterine transmission, but perinatal transmission was shown in around 3 percent of neonates.[31] Most neonatal infections are asymptomatic or mild, but around 12 percent experience severe disease with dyspnoea and fever as the most commonly reported signs.[32] Transfer of maternal antibody across the placenta provides passive protective antibody for newborn infants, which can be enhanced by a dose of COVID-19 vaccine in pregnancy.[33]

Post-acute COVID-19 sequelae or commonly called ‘long COVID’ is characterised by persistent symptoms lasting for more than three months and appears to affect around 10 percent of those infected, particularly those with at least five symptoms in the first week of illness.[34, 35,36] Post-acute manifestations include cardiovascular, pulmonary and neurological effects, including chronic fatigue, dyspnoea, specific organ dysfunction and depression.[11]

Long COVID-19 is not well described in children, and although WHO formally agreed an international clinical case definition in February 2023, it was very broad.[11] In the UK in 2023, according to national statistics, the difference in prevalence of the most common persistent symptoms of long COVID-19 in children was 0.2 percent in 2-11 year olds and 1.0 percent in 12-16 year-olds between cases and controls.[37] Unfortunately, the broadly inclusive criteria for post-COVID-19 conditions fail to identify children who genuinely experience adverse complications of SARS-CoV-2 infection, such as chronic fatigue, respiratory compromise and cognitive difficulties.[38]

For further information see the Health NZ webpage on long COVID. (external link)

SARS-CoV-2 was first identified in January 2020 following clusters of distinctive pneumonia cases observed in Wuhan, China during December 2019. This virus has genetic and clinical similarity to the coronavirus causing the severe acute respiratory syndrome (SARS) epidemic from 2002 to 2004. A public health emergency of international concern (PHEIC) was announced in late January 2020. By the time the COVID‑19 pandemic was declared by the World Health Organization (WHO) on 11 March 2020, there were 118,000 reported COVID‑19 cases and 4,291 associated deaths in 114 countries. The global death toll surpassed one million by late September 2020. Case numbers and death continued to increase, with a rapid peak in cases at the end of December 2021 due to the more infectious omicron variant. As of 8 November 2022, WHO reported over 6.5 million cumulative COVID-19 deaths.

See the WHO Coronavirus Disease (COVID‑19) Dashboard (external link) for the latest official data. Actual rates are expected to be considerably higher than officially reported rates, especially since milder infections may not be reported.

The infection-fatality rate, while still high particularly in the older age groups, has reduced since the start of the pandemic, partly due to changes in the prevalent variants but also due to public health measures that include vaccination, improved clinical recognition and management and the use of therapies of demonstrated value, such as dexamethasone and antiviral medications such as nirmatrelvir with ritonavir.

The use of vaccines has reduced the global burden of COVID‑19 significantly. The first phase I clinical trial for a COVID‑19 vaccine commenced in March 2020 and the first public vaccination dose was administered in the United Kingdom on 8 December 2020. By late 2022, 11 COVID-19 vaccines had been granted emergency use listing or approval by the WHO.

In May 2023, the WHO declared an end to the PHEIC and moved forward to update its Strategic Preparedness and Response plan for 2023-2025 to transition from the emergency response to longer-term sustained COVID-19 protection, control and management.[39]

The first case of COVID‑19 was reported in New Zealand on 28 February 2020. Border restrictions were implemented on 16 March 2020 as cases numbers increased and clusters of transmission were identified. On 25 March 2020, New Zealand entered a nationwide lockdown (‘Alert level four’). With rapid contact tracing and the public health COVID-19 protection framework, the spread of SARS-CoV-2 was restricted during 2020 and 2021. Only 19 percent of the introductions of virus in 2020 resulted in ongoing transmission or more than one additional case.[39] Prior to the outbreak of the Delta variant in August 2021, most of the reported cases during 2021 were imported from overseas (over 95 percent from 1 January to 9 August 2021).

From 16 August 2021, the number of cases in New Zealand began to increase sharply due initially to the highly infectious Delta variant. From January 2022, when the more infectious Omicron variant entered the community, case numbers rose sharply but at this stage around 90 percent of the population aged from 12 years had been vaccinated with at least two doses of COVID-19 vaccine. In late February 2023, almost three years after the first reported case, there were over 2.2 million cases recorded, over 26,000 hospitalisations, and 711 ICU admissions for COVID-19. There were 1,599 deaths coded with COVID-19 as the underlying cause, and the vast majority (96 percent) were aged over 59 years.

The COVID-19 Mortality Report in published September 2022 found that although COVID-19-attributed mortality was highest in older age groups, based on age-adjusted estimates, the risk of mortality for those aged under 60 years was 3.7 times higher for those Māori and 3.9 times higher for those of Pacific ethnicities than of European and Other ethnicities.[40] Comorbidity in those under the age of 60 years significantly increased the risk of mortality by 78 times, and explained 59 percent of the increased risk for Māori and 69 percent for Pacific ethnicities. Vaccination was shown to have a strong protective effect: after adjusting for age, sex, comorbidities and vaccination status (>2 doses), mortality risk was lowered but still 1.7 times higher in Māori and 1.9 times higher for Pacific compared with European/Other ethnicities.[41]

Emergence of new variants is monitored in New Zealand by ESR through whole genome sequencing of specimens taken from hospitalised cases and wastewater sampling (see the ESR digital library (external link)). For current details on case demographics see COVID-19: Data and statistics and for the 2022 mortality report see COVID-19 Mortality in Aotearoa New Zealand: Inequities in Risk (external link).

Clinical trials for COVID‑19 vaccine candidates began shortly after the pandemic was announced in March 2020. Between October to December 2020, the New Zealand Government signed advanced purchase agreements for four vaccine candidates, with purchase dependent on approval for use from the New Zealand Medicines and Medical Devices Safety Authority (Medsafe). This is an ongoing process and, therefore, the availability and eligibility for these different vaccines may change.

Medsafe continues to review for each COVID-19 vaccine candidate, examining clinical trial and post-marketing surveillance data. Provisional consent imposes conditions on these vaccines to restrict their use by health professionals according to the available data at time of approval. This approval status allows New Zealanders early access to medicines with significant unmet clinical need under the Medicines Act.

Funded vaccines

The mRNA-CV, Comirnaty, consists of messenger ribonucleic acid (mRNA) encoding the full-length spike glycoprotein of the SARS-CoV-2 virus, inside a lipid nanoparticle. The spike protein mRNA has an adjuvant effect, so no additional adjuvant is included. The original version was designated BNT162b2 in clinical trials conducted by Pfizer and BioNTech. This mRNA vaccine delivers the instructions for human cells to build the viral antigen, SARS-CoV-2 spike protein. The mRNA is temporarily protected from degradation by the lipid nanoparticle that also facilitates fusion with the recipient’s cell wall.[42,43]

This section of the COVID-19 chapter reflects the development of the COVID-19 vaccines and the changing behaviour and variants of the SARS-CoV-2 infection during the COVID-19 pandemic. Further data is emerging. There is much heterogeneity in the immunity of different populations, many people have hybrid immunity to the wild-type infection as well as a range of booster doses, which make effectiveness measures challenging. Overall, COVID-19 vaccines continue to perform very well against severe disease and mortality, and in the short term can help to prevent symptomatic illness and infection.

mRNA COVID 19 vaccine – Comirnaty (Pfizer/BioNTech)

Immunogenicity

Compared with convalescent sera from those who had SARS-CoV-2 infection (original variant), the only group with lower antibody responses were older people (aged 55 – 85 years) but they had higher average neutralising antibody levels.[44] Clinical studies continued to assess immunogenicity in each age group in which the vaccines were used.[45,46] As SARS-CoV-2 variants evolved to become more immune evasive, higher levels of neutralising antibody were required to prevent infection. This was particularly evident in older people and those with comorbidities that affected the immune response. This was circumvented by offering booster doses and adapting the vaccine to better match circulating variants (ie bivalent and XBB.1.5 vaccines).

Efficacy – clinical trial data

Early in the pandemic, efficacy studies were straightforward as most individuals were naïve of SARS-CoV-2 vaccine. Efficacy of mRNA-CV 30 µg (BNT162b2) was first assessed during 2020 in the phase III component of a large, clinical trial. A total of 43,448 participants aged 16–85 years across six countries were randomised to receive vaccine or saline placebo, with a primary series of two doses given 21 days apart.[43] Interim data, based on the early SARS-CoV-2 variants, indicated a very high efficacy against symptomatic PCR-confirmed COVID-19 of 94.8 percent (95% CI: 89.8–97.6 percent) and consistent across all subgroups (defined by age, sex, race, ethnicity, baseline BMI and presence of co-existing conditions).[44] Efficacy in younger age groups was also high. For adolescents aged 12-15 years vaccinated with two doses of mRNA-CV (30 µg) efficacy of 100 percent (95% CI 75.3–100) was observed against symptomatic COVID-19 in 2020/2021.[45] A lower dose vaccine, mRNA-CV (10 µg) showed efficacy of 90.7 percent (95% CI 67.7–98.3) against symptomatic COVID-19 from seven days after dose two in 1,305 children aged 5–11 years.[47] Due to few cases in young children aged under 5 years, efficacy of mRNA-CV (3µg) was less well established. Combined for children aged 6-23 months and 2-4 years, vaccine efficacy of 80.4 percent (14.1–96.7 percent) was reported during a period of Omicron prevalence in the US.[48,49]

As the pandemic progressed, more hybrid immunity (with infection and vaccination) developed making placebo-controlled efficacy trials obsolete.

Effectiveness of primary course – real-world experience

At the start of the COVID-19 immunisation programmes in late 2020/early 2021, mRNA-CV (30 µg) was highly effective at preventing severe COVID-19 and COVID-19-related death, in line with efficacy observed during clinical trials.[50]

As the Delta variant emerged from mid-2021, effectiveness against symptomatic COVID-19 reduced (ranging from around 78–93 percent),[51] but the vaccine remained highly effective against hospitalisation (73–94 percent), severe disease and death (80-97 percent) in a range of groups in the UK.[52] With time following the two-dose primary series, the waning antibody levels were less effective against the Omicron variant and booster doses were required to help prevent symptomatic infection and reinfection (see below).

Vaccination with mRNA-CV in pregnancy reduces the risk of severe COVID-19 and provides passive immunity to the infant for the first few months of life.[53,54,55] During Delta, systematic review showed 70 percent reduction in SARS-CoV-2 infection in infants of vaccinated mothers for up to 6 months; vaccine effectiveness was much lower for omicron variants and the numbers of infants infected were very low.[56,57,58]

Duration of immunity and additional doses

A decline in vaccine effectiveness was observed after the primary course against SARS-CoV-2 infection and mild disease, particularly with emerging Omicron variants, but protection against severe disease has been maintained and enhanced with the use of additional doses for around 6–9 months, at least.[59,60] It is unclear how long-lived immunity is following immunisation or natural infection. Many people now have hybrid immunity from both vaccination and infection. 

Although neutralising antibody levels wane,[61] and lower levels are less effective against the emerging variants such as Omicron lineages, T cell responses and memory are maintained in vaccine recipients (for mRNA-CV and rCV),[62,63] and this is likely to correspond to the observed the rate of disease being reduced. The greatest waning in immunity is observed in those aged over 65 years and those aged 40–64 years with underlying medical conditions compared with healthy adults.[64]

Across all age groups, at least three exposures to SARS-CoV-2 spike protein through vaccination and infection (hybrid immunity), provide significant protection against Omicron-associated hospitalisation and death. Further doses help to maintain a high level of immunity in elderly adults, particularly if they have exposed through infection previous. A Canadian cohort study of people with previous exposure to Omicron (BA.1 and BA.2 predominance) estimated protection at one to two months post vaccination to be 96 percent (95% CI 92-98) after a fourth dose of vaccine.[61]

Booster dose programmes were accelerated following the emergence of the Omicron variant from late 2021, including in New Zealand. Variant specific vaccines, including Omicron variant vaccines (eg BA.4/5 and XBB.1.5), are being used as additional doses to enhance protection against more immune-evasive omicron variants.[65,66]

mRNA COVID-19 vaccine – additional doses 

A range of cohort studies in the US has demonstrated a relative improvement in effectiveness of booster doses against severe COVID-19, especially for previously well-vaccinated older adults, when bivalent mRNA-CV was given.[67,68,69] Due to varying exposures to SARS-CoV-2 variants, timing since vaccine doses and in different populations, comparison between these studies is not possible and they did not provide evidence comparing monovalent original vaccine with the bivalent one.

Data from the Netherlands during October 2023 to January 2024 estimated effectiveness of the XBB.1.5 mRNA-CV (30 µg) vaccine to be around 41 percent against Omicron infection for those aged 18-59 years and 50 percent for ages 60-85 years who had received at least one previous booster.[70]  Earlier data, from October 2023 to December 2023 in the Netherlands, found XBB.1.5 mRNA-CV (30 µg) vaccine to be around 70 percent effective against hospitalisation and ICU admission (95% CI 67-74 percent and 42-88 percent, respectively) within the first two months of vaccination in adults aged 60 years and over.[70] In the US, the overall VE against symptomatic infection was 58 percent (48-65 percent) up to 59 days after vaccination and 49 percent (36-58 percent from 60-119 days after vaccination).[71] Since the XBB.1.5 vaccine formulations were created, Omicron variants have evolved but the vaccines are still demonstrating effectiveness against symptomatic disease and inducing a good neutralising antibody response against these newer variants, including BA.2.86 and JN.1.[63,72]

mRNA COVID 19 vaccines – Comirnaty (3 µg, 10 µg and 30 µg)

These vaccines require storage at ultra-low temperatures (-90°C to -60°C) and at this temperature has a shelf-life of 18 months. Store unopened single (10µg and 30µg) or multidose (3µg) vials at +2°C to 8°C for up to 10 weeks within the 18 months shelf-life. Do not freeze.

Transport according to the National Standards for Vaccine Storage and Transportation for Immunisation Providers 2017 (2nd edition).

For mRNA-CV (3µg), multidose vials require dilution prior to use (see Table 5.1): Once an undiluted vial is taken out of the refrigerator (fridge), allow a few minutes for the vaccine to reach room temperature prior to dilution.  Store diluted vaccine in vials (ie punctured vial) at +2°C to 8°C for a maximum of 12 hours, or store vaccine drawn-up in syringe for a maximum of six hours at +2°C to 30°C. Discard any vaccine exceeding these times, accordingly. 

For further details, see also the IMAC COVID-19 information and factsheets available from immune.org.nz (external link).

mRNA COVID‑19 vaccine – Comirnaty (Pfizer/BioNTech)

JN.1 mRNA-CV (30 µg) for ages from 12 years (grey cap)

Individuals from the age of 12 years who have not previously received any doses of COVID-19 vaccine are recommended to receive a single dose of mRNA-CV (30 µg). For additional primary doses for severely immunocompromised, see section 5.5.2.

All individuals aged from 16 years can be offered a single dose, after receiving a primary dose(s) of any COVID-19 vaccine, given at least three months later. See section 5.5.3 for additional dose recommendations.

Individuals who have started but not completed a primary course.

Individuals aged 12 years and over who started but did not complete a primary course of any COVID-19 vaccine, including original mRNA-CV (30 µg), and have received no additional doses can be offered a dose of JN.1 mRNA-CV (30 µg), given from six months after the first dose.

JN.1 mRNA-CV (10 µg) for ages 5 to 11 years (blue cap)

Individuals from the age of 5 years who have not previously received any doses of COVID-19 vaccine can have a single dose of mRNA-CV (10 µg) and, if eligible, a further dose given at least three months later. See section 5.5.2 for primary course recommendations for those who are severely immunocompromised. For additional doses see section 5.5.3.

Individuals aged 5 years to 11 years who started but did not complete a primary course of any COVID-19 vaccine, including original mRNA-CV (10 µg), and have received no additional doses can be offered a dose of JN.1 mRNA-CV (10 µg), given from six months after the first dose.

For children who are severely immunocompromised and eligible for three primary doses (as described in section 5.5.2), who turn 12 years after their first or second dose, continue with the same dose of paediatric vaccine (ie, mRNA-CV (10 µg)) for subsequent doses, if it is less than three months since previous dose. If it is longer than 3 months, give age-appropriate vaccine (ie. mRNA-CV (30µg)). Give an additional dose mRNA-CV (30µg) 6 months later.

JN.1 mRNA-CV (3 µg) for ages 6 months to 4 years (yellow)

A paediatric formulation, mRNA-CV (3µg), is available for use for certain children aged 6 months to 4 years in New Zealand. Three doses are given for the primary series individuals aged 6 months to under 5 years. Dose two is administered at least three weeks after dose one followed by dose three at least eight weeks after dose two.

The use of this vaccine is limited to young children who are at highest risk of severe disease if they were to catch COVID-19 such as those with severe immunocompromise (see section 5.5.2) or with complex and/or multiple health conditions (see the Starship website (external link)).

Children who started the three-dose primary course with a previous mRNA-CV (3 µg) vaccine formulation (ie original (tozinameran) or XBB.1.5 (raxtozinameran) vaccines) can complete the three-dose series with JN.1 mRNA-CV (3 µg).

Children who start their primary course aged under 5 years need three doses even if they turn 5 years part way through the course. For children who turn 5 years after their first or second dose, continue with the same dose of paediatric vaccine (ie, mRNA-CV (3 µg)) for subsequent primary doses, if it is less than three months since previous dose: dose two is given at least three weeks after first dose and dose three is given at least 8 weeks after previous dose. If it is longer than 3 months between their primary doses, give an age-appropriate vaccine (ie. mRNA-CV (10µg)).

There are no safety concerns around administering mRNA-CV to individuals who are immunocompromised and/or receiving immunosuppressive agents. As with other non-live vaccines, the antibody response to these vaccines may be reduced and protection may be suboptimal but, it is likely to be adequate to protect against severe disease. It is recommended to discuss the optimal timing for vaccination with a specialist before the vaccine appointment for those who are severely immunocompromised. Ideally, vaccination should be conducted prior to any planned immunosuppression (see section ‎4.3.6).

It is important that all household members and other close contacts of immunocompromised individuals aged from 5 years are up to date with immunisations. Close contacts aged from 16 years should also receive an additional dose at least six months after any previous doses or SARS-CoV-2 infection. For additional doses, see section ‎5.5.3.

Individuals who are severely immunocompromised

Severely immunocompromised individuals aged 5 years and over

Three primary doses of mRNA-CV (10 µg or 30 µg, as age-appropriate) are indicated for certain individuals aged from 5 years who are severely immunocompromised who are likely to have not responded adequately to the first doses (for children younger than 5 years, see note below). Serology is not recommended. A second and third primary dose is distinct from a booster dose or additional doses (for additional doses see section ‎5.5.3).

Preferably, a second dose is given eight weeks after dose one, and a third dose given a further at least eight weeks after the second dose. However, the timing also needs to consider current or planned immunosuppressive therapies. Consider vaccination during a treatment ‘holiday’ or at a nadir of immunosuppression between doses of treatment. If the period of least immunosuppression is less than eight weeks, vaccine doses can be given any time from three weeks apart.

For children who turn 12 years after their first or second dose, continue with the same dose of paediatric vaccine (ie, mRNA-CV (10 µg)) for subsequent doses, if it is less than three months since the previous dose. If the spacing is greater than 3 months, complete the primary course with an age-appropriate vaccine (ie mRNA-CV (30 µg). Give an additional dose mRNA-CV (30µg) 6 months later.

If a significant adverse reaction to mRNA-CV has occurred, it is recommended to seek advice from IMAC to determine whether further doses are contraindicated.

Children aged 6 months to 4 years with severe immunocompromise or complex or multiple health conditions

Note: For children aged 6 months to 4 years, three doses of mRNA-CV (3 µg) is available for those who are severely immunocompromised, including those given in Table 5.4, and for those who have complex or multiple health conditions that increase their risk from COVID-19 (see the Starship website (external link)), such as:

• chronic lung disease including bronchiectasis, cystic fibrosis, BiPAP for obstructive sleep apnoea (not asthma)
• complex congenital heart disease, acquired heart disease or congestive heart failure
• diabetes (insulin-dependent)
• chronic kidney disease (GFR <15 ml/min/1.73m²)
• severe cerebral palsy (or severe neurodisability including neuromuscular disorders)
• complex genetic, liver, metabolic disease or multiple congenital anomalies for example trisomy 21/Down Syndrome
• primary or acquired immunodeficiency, including HIV infection
• haematological malignancy and/or post-transplant (solid organ or HSCT in last 24 months)
• on immunosuppressive treatment including chemotherapy, high-dose corticosteroids, biologic agents or DMARDS.

Examples of severe immunocompromising conditions recommended three primary doses

Table 5.4 provides guidance on types of immunocompromise for which three primary doses are recommended for those aged from 5 years, and for children aged 6 months to 4 years with immunocompromise eligible for mRNA-CV (3 µg). For further information on corticosteroid indicative dosages and examples of non-corticosteroid agents considered immunosuppressive, see section below.

Vaccination should be offered regardless of an individual’s history of symptomatic or asymptomatic SARS-CoV-2 infection. As the duration of protection post infection alone, is currently unknown, vaccination is recommended. Hybrid immunity from at least three exposures to both vaccination and infection provides longer lasting protection against hospitalisation and death than vaccine or infection alone.[73] Although, there are no specific safety concerns around giving mRNA-CV to individuals with a history of symptomatic COVID-19 or asymptomatic SARS-CoV-2 infection, those who have had recent infection can experience more systemic reactogenicity after the first dose of mRNA-CV (see section 5.7.1).[27] Viral or serological testing is not required before vaccination.

For most healthy, previously vaccinated people under the age of 50 years, SARS-CoV-2 infection can boost their immunity to a level like that following a dose of vaccine and are unlikely to require further vaccine doses for at least 12 months after infection.[74]

A person aged from 5 years (or from age 6 months for special groups) who has had prior SARS-CoV-2 infection, and is at increased risk of complications, is recommended to complete the recommended course of mRNA-CV (or another COVID-19 vaccine, as available). Individuals are generally advised to wait 6 months after SARS-CoV-2 infection (after recovery from acute illness with a confirmed positive test) before receiving a recommended dose of COVID-19 vaccine. When the individual is at increased risk of severe disease from reinfection and has not completed the recommended doses, vaccination can be given sooner than 6 months after SARS-CoV-2 infection, at clinical discretion and once the individual has recovered from the acute illness.

For all other vaccines, vaccination can commence as soon as the individual is no longer acutely unwell.

Pregnancy can increase the risk of an adverse outcomes from COVID-19 infection, particularly for those with underlying conditions, when compared to age-matched non-pregnant adults (see section 5.2.2).[75]

JN.1 mRNA-CV (30 µg) vaccine can be used in pregnancy and while breastfeeding.

• If previously unvaccinated, a single primary dose of JN.1 mRNA-CV (30 µg) can be given at any stage during the pregnancy.
• For those who have been previously immunised, a dose of JN.1 mRNA-CV (30 µg) is recommended during pregnancy for those who are at increased risk from severe COVID-19. This includes anyone who is pregnant with:
  • a high-risk pregnancy (eg gestation diabetes, hypertension, thrombosis, obesity with BMI >35 kg/m2 or with a history of pregnancy complications)
  • with underlying medical conditions or meet other eligibility criteria (given above in section 5.5.3)
  • of older age (usually considered those aged 35 years and older).
• Anyone who is pregnant is eligible for mRNA-CV, to be given from 6 months after a previous COVID-19 vaccination or acute, confirmed COVID-19 infection.
• JN.1 mRNA-CV can be given at the same time as influenza vaccine and pertussis (Tdap) vaccine, or separately.

International evidence from large quantities of safety surveillance has found no safety concerns with administering mRNA-CV in any stage of pregnancy for the mother or her infant. [53,76,77,78,79] There is also evidence of antibody transfer in cord blood and breast milk that can offer protection to infants through passive immunity.[80,81,82,83] Infants born to those vaccinated in pregnancy have some protection from COVID-19-associated hospitalisation for up six months.[46]

People who are trying to become pregnant do not need to avoid pregnancy after receiving mRNA-CV. 

Although there is limited data available yet for the use of the JN.1 mRNA-CV (30 µg) formulation in pregnancy, the safety of JN.1 mRNA-CV in pregnancy is inferred from the large quantity of reassuring data from the use of the original (30µg) and variant-matched (BA.4/5 and XBB.1.5) mRNA-CVs in pregnant people. Observational data for these vaccines show no increased risk of adverse pregnancy outcomes or increased risk of miscarriage in first trimester. The safety profile of additional doses of original mRNA COVID-19 vaccines given in pregnancy is as seen with the primary course.[77] During use in clinical trials and in real-world use from the age of 12 years, no clinically meaningful difference in safety profiles has been shown between the monovalent and the bivalent mRNA COVID-19 vaccines. There is no theoretically plausible reason for there to be any increased risk in pregnancy because the differences between these vaccine formulations are confined to mRNA spike protein sequences. 

As with all schedule vaccines, there are no safety concerns about giving mRNA-CV to those lactating.

It is recommended that all previously unvaccinated individuals from age 5 years to receive one dose of mRNA-CV (30 µg or 10 µg, as age appropriate). Pre-existing cardiac conditions, in general, are not regarded as precautions or contraindications to vaccination. This includes pre-existing rheumatic heart disease. Note that many cardiac conditions increase the risk from COVID-19 infection.

Individuals aged from 5 years with a history of pericarditis or myocarditis, unrelated to mRNA-CV, can have the vaccine once the condition is completely resolved, (ie, no symptoms and no evidence of ongoing cardiac inflammation).

Infants and young children aged from 6 months to 4 years with complex congenital heart disease, acquired heart disease or congestive heart failure are recommended to received three doses of mRNA-CV (3 µg), dose two given at least three weeks after dose one and dose three given at least eight weeks later. An additional dose can be considered at 6 months after the previous vaccine dose or SARS-CoV-2 infection. For young children with a history of inflammatory heart disease, discuss with cardiologist/specialist paediatrician.

For those with a history of myocarditis and pericarditis related to mRNA-CV, seek specialist immunisation advice on a case-by-case basis to consider appropriate vaccination options and timing of any further doses. See section 5.6.2 for those who have myocarditis associated with mRNA-CV.

Individuals from age 6 months who have undergone haematopoietic stem cell transplantation since their first course can be revaccinated with a three-dose primary course of a COVID-19 vaccine, plus additional doses as age appropriate (preferably with age-appropriate mRNA-CV).

Based on clinical discretion, if all scheduled doses have been completed prior to commencement of chemotherapy or solid organ transplant, a single further dose of mRNA-CV can be given.

Vaccination with mRNA-CV is contraindicated for individuals with a history of anaphylaxis to any component or previous dose the same vaccine.

A definite history of immediate allergic reaction to any other product is considered as a precaution but not a contraindication to vaccination with COVID-19 vaccines (mRNA-CV). A slightly increased risk of a severe allergic response in individuals who have had a previous anaphylaxis-type reaction needs to be balanced against the risk of SARS-CoV-2 exposure and severe COVID‑19. These individuals can still receive a COVID-19 vaccines, if not contraindicated, and observation extended to 30 minutes after vaccination in health care settings, where anaphylaxis can be immediately treated with adrenaline.

Myocarditis or pericarditis

If myocarditis, myopericarditis or pericarditis occurs after a dose of COVID-19 vaccine (mRNA-CV or another COVID-19 vaccine) defer further doses of COVID-19 vaccination. Seek specialist immunisation advice, on a case-by-case basis, to consider an appropriate alternative vaccine or no further vaccination, and about timing for further doses. Vaccination is not recommended for anyone with current active cardiac inflammation.

The risk of myocarditis following vaccination is not thought to be greater in children aged 6 months to 4 years than any other group, acknowledging that background rates of myocarditis from any cause in infants (aged under 1 year) are generally higher than in older children. There is no current evidence of a safety concern with this vaccine in young children or infants, overall.

mRNA COVID 19 vaccine – Comirnaty (Pfizer/BioNTech)

Commonly reported responses to mRNA-CV (30 µg) are injection-site pain, headache, dizziness and fatigue; other responses included muscle aches, feeling generally unwell, chills, fever, chest discomfort, joint pain, nausea and axillar lymph node swelling. These occurred most often after dose two and in younger adults (aged 18–55 years), and within one or two days of vaccination. Most are mild or moderate in severity and are self-limiting.[84,85] According to Australian AusVaxSafety active surveillance data, the responses to XBB.1.5 mRNA-CV, given as a single primary dose or as an additional dose, are similar or milder than the previous mRNA-CV vaccines.[44] No new adverse reactions have been identified in clinical trials and real-world usage.[86] Analgesia, such as paracetamol or ibuprofen (as appropriate), can be taken for pain and discomfort following vaccination. It is advisable to limit vigorous exercise if feeling unwell.

Responses to the paediatric formulation mRNA-CV (10 µg) in children aged 5–11 years are similar to those seen for the adult formulation mRNA-CV (30 µg) in those age 16–25 years. During clinical trials, reactions were generally mild to moderate and short-lived. Pain at injection site was commonly reported (by over 70 percent) after dose one and two. Overall fewer children reported systemic reactions than seen after the 30 µg dose in adults, with fever, fatigue, headache, chills and muscle ache as the most common and more frequent after the second dose.[87] These responses were mirrored in reports to VAERS and V-safe after 8.7 million doses given routinely to children in the US.[88] As with adults, the responses to paediatric JN.1 mRNA-CV, given as a single primary dose or as an additional dose, are expected to be similar to the earlier mRNA-CV.

In clinical trials for paediatric mRNA-CV (3 µg), the most frequent responses seen in infants (aged 6–23 months) were irritability, decreased appetite, injection-site tenderness and redness, and fever; and in children aged 2–4 years, injection-site pain and redness, fatigue and fever. Less common responses included lymphadenopathy, diarrhoea, vomiting and nausea. Consistent with the clinical trial, systemic reactions were more frequently reported to V-safe in the US for infants (ages 6 months – 2 years) than those aged 3–5 years.[89]

See chapter 2 (section 2.3.3) for immunisation-stress related responses (ISRR).

Breast screening and CT scans

Transient unilateral axillary adenopathy, a known response to vaccination, was particularly noted following vaccination with mRNA-CV due to the scale of the roll-out and age groups being immunised. Early estimates suggest that 12–16 percent of vaccine recipients experience axillary adenopathy after vaccination with mRNA-CV, starting one or two days after vaccination and which can persist for several weeks.[88, 90] Lymphadenopathy has also been commonly reported after additional doses of mRNA-CV.[91]

When attending breast screening appointments, including MRI scans and mammography, it is recommended that individuals advise the radiographer or doctor that they have received a COVID-19 vaccine recently. It is advised to monitor any lymph node changes that persist for longer than six weeks after vaccination.[92]

Likewise, individuals undergoing FDG PET/CT or MRI scans for cancer screening are advised to inform the radiologist or their oncologist that they have been recently vaccinated, or, if possible, to have COVID-19 vaccination at least two weeks before a scheduled scan or as soon as possible afterwards. Treatment should not be delayed.

Adverse events following immunisation (AEFIs) with the COVID-19 vaccines are being closely monitored during clinical trials and by post marketing surveillance. A dedicated COVID-19 vaccine AEFI reporting tool is available online from CARM (see section 1.6.3). Medsafe reports weekly on the AEFI reported to CARM after COVID-19 vaccinations (see the Medsafe website (external link)).

A list of adverse events of special interest (AESIs), including those previously associated with immunisation in general and with the individual vaccine platforms, was created by Safety Platform for Emergency Vaccines (SPEAC) in collaboration with the Coalition for Epidemic Preparedness Innovations (CEPI) and based on existing and new Brighton Collaboration case definitions. For further information, see the Brighton Collaboration website (external link). Global pharmacovigilance and active safety monitoring systems continue to watch for both AESI and unexpected AEFI.

mRNA COVID 19 vaccine – Comirnaty (Pfizer/BioNTech)

Overall, no AESI signals were detected by the Vaccine Safety Datalink in the US up to 21 days after vaccination, following the administration of over 13 million doses of mRNA-CV (Comirnaty), however, subgroup analyses did find mRNA-CV to be associated with a slight increase in myocarditis and pericarditis in younger people (aged under 30 years).[46, 93]

Preliminary phase II/III clinical trial safety data reported lymphadenopathy in 64 (0.3%) vaccine recipients and six (<0.1%) placebo recipients (follow-up of up to 14 weeks after second dose of a subset of 18,860 participants who received at least one dose of mRNA-CV). Four vaccine-related adverse events were recorded (namely, shoulder injury related to vaccine administration, lymphadenopathy local to injection site, paroxysmal ventricular arrhythmia and right leg paraesthesia). No deaths were related to either the vaccine or the placebo.[94] During clinical trial follow-up to 1 February 2021, acute peripheral facial paralysis (Bell’s palsy) was reported by four vaccinated participants and none in the placebo group.[44] No safety signal has been detected for this condition as an AESI,[86] and safety monitoring is ongoing.

No vaccine-related severe adverse events were seen during the phase II/III clinical trial of mRNA-CV (10 µg) and mRNA-CV (3 g). In 1,518 children aged 5–11 years, lymphadenopathy was reported in ten (0.9 percent) of mRNA-CV (10 µg) recipients. Rashes, with no consistent pattern, considered related to the vaccination were observed in four participants; these were mild and self-limiting with typical onset seven or more days after vaccination. No differences were apparent in vaccine safety between the children who had baseline evidence of previous SARS-CoV-2 infection.[85] Following administration of approximately 8.7 million doses of mRNA-CV (10 µg) in children aged 5–11 years in the US, the majority of reports to VAERS (97.6 percent) were non-serious and 2.4 percent were serious. The most common non-serious reports were due to vaccine administration errors. Of the serious reports, 11 verified cases of myocarditis were reported to VAERS but no chart-confirmed myocarditis cases were reported through the Vaccine Safety Datalink in this age group.[85] Post-licensure surveillance is ongoing internationally.

Variant-matched (BA.4/5 and XBB.1.5) mRNA COVID-19 vaccines

Safety monitoring in the US was evaluated following of use bivalent mRNA-CV as a booster dose (approximately 14.4 million doses bivalent Comirnaty and 8.2 million doses of bivalent Moderna) given to those who had received at least two doses of monovalent original mRNA-CV.[95] Of the 5,542 VAERS reports, 34% of events were vaccine administration and handling errors and 95% non-serious AEFI. V-safe reports, from almost 211,959 participants aged at least 12 years who received age-appropriate bivalent booster doses, were consistent with those reported following monovalent booster doses. Most people were receiving their fourth or fifth COVID-19 vaccine dose and 98.3 percent received influenza vaccine at the same visit. Adverse events were less common and less serious than the health impacts associated with COVID-19 illness.[95]

A Danish data linking study, covering a cohort of over one million adults aged 65 years and over (mean 74.7 years ± 7.4 years), reported no increased risk for 28 predetermined adverse events were observed within 28 days following XBB.1.5 mRNA-CV given as a fifth COVID-19 vaccine dose.[96] For example, incidence rate ratio of hospital contact was 0.96 (95% CI 0.87-1.07) for an ischaemic cardiac event, 0.87 (0.79-0.96) for cerebral infarction and 0.60 (0.14-2.66) for myocarditis.[97]

Myocarditis and pericarditis

A small increase in incidence of myocarditis, myopericarditis and pericarditis has been observed following the second dose of mRNA-CV vaccination (40.6 cases per million doses in young males and 4.2 cases per million in young females, aged 12–29 years, decreasing to 2.4 and 1.0 per million, respectively, in men and women aged over 30 years).[98] Very rarely, myocarditis has also been report in boys aged 5–11 years after dose two in the US (reporting rate of 2.2 cases per million doses).[99] Most cases occur within 14 days of vaccination typically with full recovery after standard treatment and rest.[99, 100] A review of clinical records in the US observed the median time to onset for myocarditis was 3.5 days (interquartile range 3.0–10.8 days) after vaccination and a median of 20 days (range 6.0–41 days) for pericarditis.[85] Wider spacing between doses (ie, eight weeks) has been shown to significantly lower the risk of myocarditis in young adults in Canada.[101] Following 22.6 million doses of bivalent mRNA-CV given to individuals aged from 12 years in the US, three out of five cases of myocarditis and four cases of pericarditis reported to VAERS were medically verified. These early data confirm that myocarditis and pericarditis post vaccine dose is an extremely rare event and suggests that this rate is the same or lower than after the primary doses.[102]

Myocarditis and pericarditis are uncommon conditions considered to be associated with viral infection, including COVID-19. Recently vaccinated individuals should seek immediate medical attention if they experience new onset of (acute and persisting) chest pain, shortness of breath or arrhythmia (palpitations). Diagnosis is based on elevated troponin, C-reactive protein and electrocardiogram and/or MRI findings. Report all suspected cases to CARM as Medsafe continues to monitor this AEFI closely. Defer further doses of mRNA-CV if myocarditis or pericarditis occurs after vaccination. Seek specialist immunisation advice, on a case-by-case basis, to consider an appropriate alternative vaccination option, and timing for further doses (see section 5.6.2).

Anaphylaxis

Following approval for use in the US, the VAERS detected 47 cases of anaphylaxis after administration of just under ten million doses (around five cases per million doses) mRNA-CV (Pfizer/BioNTech). The median interval to symptom onset was ten minutes (range <1–1140 minutes), almost 90 percent occurred within 30 minutes of vaccination.[102] All were successfully treated with adrenaline. See section 5.6 for contraindications and precautions.

A placebo-controlled trial evaluated the recurrence of systemic allergic reactions after a second or third dose of mRNA-CV in individuals who reported anaphylactic reactions after previous dose.[103] It found that immunisation stress-related (ISRR) responses were significantly more common (more than five times higher), including in the placebo group, than recurrent serious allergic reactions following revaccination. Increased levels of anxiety prior to vaccination were a risk factor for ISRR.[104]

See chapter 2 (section 2.3.3) for immunisation-stress related responses.

History of Guillain-Barré Syndrome

There is no evidence of a higher rate of reporting of Guillain-Barré syndrome (GBS) following COVID-19 vaccination in individuals who have previously had GBS. Vaccination with mRNA-CV is preferred.

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