Congruence of influenza and COVID-19 vaccination

With the winter season approaching and recommencement of international travel in 2022, influenza and COVID-19 vaccination will be crucial for protecting individuals from infection and reducing healthcare burden. Current Australian guidelines recommend influenza and COVID-19 vaccines
can be coadministered, highlighting an important opportunity for disease prevention by GPs.

Influenza and COVID-19 prevention during the pandemic

The emergence of the SARS-CoV-2 virus in late 2019 and the global COVID-19 pandemic, which was declared in March 2020, saw the deployment of public health restrictions not seen since the H1N1 influenza A (Spanish flu) pandemic of 1918/1919.¹ Before the start of the COVID-19 pandemic, Australia experienced seasonal influenza epidemics annually during the winter months. These seasonal influenza epidemics are believed to be primarily introduced into Australia by international travellers from the northern hemisphere. In 2020 and 2021, with the introduction of border restrictions and quarantine, as well as other public health measures to control COVID-19, there were no seasonal influenza epidemics in Australia.² 

Reported coverage of annual influenza vaccination in Australia increased in 2020 compared with 2019 in both children and adults.³ However, vaccine coverage dropped in 2021 compared with 2020, likely because of the lack of influenza virus circulation and the COVID-19 vaccine program rollout.⁴

The period of peak influenza circulation is typically June to September in most parts of Australia. However, influenza epidemiology may be atypical in 2022, particularly in the context of the return of international travel but also due to two years without the usual seasonal circulation of influenza in the community.^1,5 To minimise these impacts, influenza and COVID-19 vaccination for eligible people should be encouraged as this will be crucial to both increasing individual protection against severe disease, as well as reducing the wider public healthcare burden in a year with ongoing COVID-19 infections, hospitalisations and related social impacts. 

Differences between COVID-19 and Influenza

Both COVID-19 and influenza disease result from RNA viruses, causing primary respiratory infections; however, their virology, pathophysiology and epidemiology are notably different.⁶ Although initial clinical presentations of COVID-19 and influenza infections are similar, with predominately respiratory and febrile symptoms, disease progression can differ. Influenza symptoms generally appear one to four days after infection compared with two to 14 days for COVID-19, although some studies suggest a shorter incubation period with disease caused by new coronavirus variants.^7,8 Anosmia (loss of sense of smell) and ageusia (loss of taste) have also been commonly observed with acute COVID-19 infection but rarely seen with influenza. Additionally, severe disease and post-infection complications are more common with COVID-19.⁹ A recent French study showed that patients hospitalised with COVID-19 in 2020 were more likely to experience acute respiratory failure, pulmonary embolism and septic shock than patients hospitalised with influenza between 2018 and 2019.¹⁰ Compared with patients with influenza, patients with COVID-19 were more likely to require ICU admission (16.3% vs 10.8%) and mechanical ventilation (9.7% vs 4.0%) and to die during hospitalisation (16.9% vs 5.8%).¹⁰ Although the current COVID-19-dominant variant Omicron is associated with lower severity of disease and risk of mortality, infection can still cause hospitalisation and death, especially among unvaccinated and at-risk populations.¹¹

COVID-19 complications

Although post-viral syndromes are rarely experienced with seasonal influenza infections, post-acute sequelae of COVID-19, or ‘long COVID’, is often observed in patients after acute COVID-19 infections (5 to 35% of COVID-19 cases).^12,13 Symptoms of long COVID, including fatigue, persistent cough, shortness of breath, mental health problems and cognition issues (i.e. ‘brain fog’) can persist for months after acute infection, representing a significant public health and potential economic burden. 

Children generally experience lower rates of severe COVID-19 and ‘long COVID’ than adults.¹⁴ However, COVID-19 can cause paediatric inflammatory multisystem syndrome (PIMS-TS). PIMS-TS is characterised by persistent fever, rash, tachycardia and abdominal pain, and can escalate to a serious shock-like state with myocardial dysfunction, pericarditis, valvulitis or coronary abnormalities.¹⁵ COVID-19 vaccination has been shown to be protective against long COVID and PIMS-TS, further highlighting the importance of vaccination in adults and children.^16,17 

COVID-19 and influenza coinfection

Currently, data on the interaction between SARS-CoV-2 and influenza viruses are limited. Coinfection of SARS-CoV-2 and influenza viruses has been observed at varying low rates globally during the COVID-19 pandemic, with 0.8% (ranging between 0.4 and 4.5%) of COVID-19 patients additionally testing positive for an influenza virus.¹⁸ An evaluation of diagnostic testing for SARS-CoV-2 and influenza in England between January and April 2020 showed that people with influenza had a 58% lower risk of testing positive for SARS-CoV-2 than those without influenza.¹⁹ However, those with coinfection were more than twice as likely to die (odds ratio, 2.27; 95% confidence interval, 1.23 to 4.19) compared with those infected with SARS-CoV-2 alone.¹⁹

Influenza and COVID-19 virology and vaccines

Influenza A and B viruses are responsible for seasonal influenza epidemics previously seen in Australia.²⁰ Between seasonal epidemics, influenza virus surface proteins mutate in a process called antigenic drift, and allows the virus to evade immune protection provided by previous influenza infections and vaccinations. Antigenic drift is the primary reason why annual influenza vaccination is needed, and updated vaccine composition is based on predicted influenza strains.²¹ 

Since the emergence of the SARS-CoV-2 virus, numerous variants have been identified with differing genomic and clinical profiles, including five variants of concern (Alpha, Beta, Gamma, Delta and Omicron).²² COVID-19 variants arise from random mutations in viral replication during infection, some of which result in viruses with increased evolutionary fitness. These variants of concern have conferred increases in transmissibility, infectivity and immune evasion, and can have increased disease severity compared with the ancestral strain.²³ Current COVID-19 vaccines are based on ancestral virus-like spike proteins and, as such, lead to reduced levels of neutralisation antibodies in vaccinated individuals and reduced vaccine effectiveness against variants of concern (particularly Omicron).²⁴ However, a third mRNA vaccine dose after a primary course produces a robust T-cell response and increased vaccine effectiveness against severe disease compared with a primary course alone.²⁵ COVID-19 vaccines with updated and multiple spike protein types are currently in development to increase vaccine efficacy and infection prevention. 

Influenza and COVID-19 vaccine delivery

At the time of writing, the Australian Technical Advisory Group on Immunisation (ATAGI) advises that the coadministration of current COVID-19 and influenza vaccinations (i.e. during the same appointment) is acceptable. Studies have shown both safety and immunogenicity with coadministration of these vaccines.⁴ Therefore, if a patient is concurrently eligible for both vaccines, they can be given at the same visit. No additional contraindications for coadministration of COVID-19 and influenza vaccines are recognised outside of the known contraindications for each vaccine. 

Highlighting the importance of and encouraging patients to receive both COVID-19 and influenza vaccinations before the start of the winter months in Australia will be vital to assist disease prevention this year. This is especially important as increased virus exposure and severity of infection are likely to result from: 

• the recommencement of international travel
• the lifting of many public health and social restrictions
• lower levels of influenza vaccine uptake in 2021
• current levels of COVID-19 infections within the community. 

GPs have an important role in delivering both vaccines to the community and in communicating the rationale for these recommendations to patients. Considering the large social and health focus on COVID-19 over the past three years, highlighting the severity of influenza disease and the need for influenza vaccination to patients will also be important. Resources have been developed to address common patient concerns, including the safety of coadministering COVID-19 and influenza vaccines, and should be used to assist in conversations with patients (https://ncirs.org.au/influenza-vaccination-2022).

Vaccination in vulnerable groups 

GPs also have a vital role in the promotion and delivery of COVID-19 and influenza vaccines to vulnerable groups, including young children, immunocompromised patients, pregnant women, Aboriginal and Torres Strait Islander (Indigenous) people and those at increased risk of infection due to comorbidities. Influenza and COVID-19 vaccines are both strongly recommended and provided for free to these populations because of the increased risk for severe disease. Co-ordination with the patient’s specialist physicians is crucial to identify specific clinical concerns associated with coadministration, deliver appropriate recommendations and address specific concerns raised by patients. 

Influenza vaccine coverage in children with comorbidities is typically low; however, recommendation to receive influenza vaccination by a child’s hospital-based physician has been shown to be associated with greater vaccine uptake.²⁶ Despite these findings, hospital specialists express difficulty in directly delivering influenza vaccination to paediatric patients with comorbidities because of limitations in clinical capacity and on-site vaccine availability.²⁷ These and other similar barriers are likely to also be present for other vulnerable populations, highlighting the key role for GPs in vaccine delivery. 

Conclusion

Against the backdrop of the ongoing COVID-19 pandemic, the potential for increased disease burden and strain on Australia’s healthcare system in the approaching 2022 winter season underscores the need for increased COVID-19 and influenza vaccine uptake. GPs will be fundamental in delivering these vaccines, and the capacity for coadministration of COVID-19 and influenza vaccines highlights an opportunity for increased vaccination.     MT

COMPETING INTERESTS: None.

References