Policy Paper on Vaccines

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MMSA Policy Document on Vaccines Proposed by: Enya Aquilina, Joseph Fenech, Mark Farrugia, Nathan Fenech, Rachel Muscat Baron, Laura Demicoli, Katya Zerafa, Catherine Gatt Place: Zoom AGM 2021 Date of Adoption: March 2021 Date of expiry: March 2024

Policy Statement In an age characterised by preventative medicine and especially within the context of the COVID-19 pandemic, vaccination has risen to the top of the global health agenda. Despite being the most efficacious and cost-effective public health measure put in place in the past century, much confusion and scepticism remains in the public‟s consciousness. Through this concise and approachable document, MMSA seeks to highlight key points such as vaccine efficacy, safety, hesitancy, access and socioeconomic impact. Special consideration has been afforded to COVID19 vaccines, providing the most up to date information as available at the time of writing.

Definitions ● Pathogen- a bacterium, virus, or other microorganism that can cause disease. ● Monovalent vaccine- contains a single strain of a single antigen (e.g. Varicella Vaccine). ● Polyvalent vaccine- contains two or more strains of the same antigen (e.g. Influenza vaccine). ● Immunity- the ability of an organism to resist a particular infection or toxin by the action of specific antibodies or sensitized white blood cells. ● Attenuated- having been reduced in force, effect, or value. ● Adjuvant-a substance which enhances the body's immune response to an antigen ● Misinformation-false or inaccurate information ● Disinformation- false information which is intended to mislead, especially propaganda issued by a government organization to a rival power or the media.

Background ORIGIN OF VACCINATION The first ever vaccine created was that for the smallpox virus. The idea behind this arose in 1796 when Dr Edward Jenner noticed that milkmaids infected by the cowpox virus did not show any symptoms of smallpox after having been exposed to it. The logic here was that exposing someone to a milder form of the smallpox virus, such as cowpox, would confer immunity against smallpox (“History of Smallpox | Smallpox | CDC,” 2021). Interestingly, a method known as variolation has been around for hundreds of years and originated in Africa and Asia (Plotkin, 2014). This applies the same basis of vaccination in a cruder manner. Variolation involves acquiring viral material from an already infected person and exposing a healthy person to it, either by scratching it into the skin or through inhalation. Variolation was performed for the smallpox virus and many other infections prior to the arrival of the smallpox vaccine (Plotkin, 2014).

Most commonly this resulted in the individual

developing mild symptoms compared to a typical infection however, the full-on smallpox infection was always a possibility, which had a very high mortality at the time, and it also led to the spread of the virus in some cases (“The chilling experiment which created the first vaccine BBC Future,” 2020). In 1802, Dr Jean de Carro insisted that governments should discourage inoculation methods such as variolation due to many inconsistencies and encourage vaccination due to its superior success rates (“Timeline | History of Vaccines, 2021). Building on the work done by pioneers in this field, vaccines have become a tool at the forefront of preventative medicine, curbing morbidity and mortality from communicable diseases in an unprecedented manner. As interest in the field increased, the medical and scientific community, law makers, businesses, and the general public have all become increasingly involved in vaccination.

VACCINE DEVELOPMENT, VARIANTS, EFFICACY & SAFETY There are 4 main types of vaccines, with each type being more effective against a particular pathogen. Furthermore, a vaccine may be either mono or polyvalent - which refers to cover against one strain or two or more strains of one particular pathogen respectively (“Vaccine Types | Vaccines, 2021). For example, the local flu vaccine is tetravalent, providing protection against 4 different strains of influenza virus (“Influenza,” 2020). To improve efficiency in the administration of vaccines, there are also combined vaccines - which provide immunity against multiple different pathogens - such as the MMR vaccine; which safeguards against measles, mumps and rubella (“Vaccine Types | Vaccines, 2021). 1. LIVE ATTENUATED Live attenuated vaccines make use of a weakened, whole, live pathogen. The main advantage of this type of vaccine is that the body mounts a strong and long-lasting immune response to the pathogen, which means that most live attenuated vaccines bring about life-long immunity. The strength of the immune response elicited means that it is not always possible to give this type of vaccine - for example to those who have a weakened immune system (immunocompromised). Common vaccines which are live attenuated include the MMR, varicella (chickenpox) and rotavirus vaccines (Marin et al., 2016). 2. INACTIVATED WHOLE Inactivated vaccines make use of a pathogen that is inactivated or killed with heat and/or chemicals. The immune response towards this inactivated form of the pathogen is often not as strong or long-lasting as the live attenuated, so booster shots are often required to supplement immunity. Common vaccines of this type include the polio and hepatitis A vaccine (CDC Pink Book - Principles of Vaccination, 2020).

3. SUB-UNIT As opposed to live attenuated or inactivated vaccines which contain whole organisms, subunit vaccines are composed of only a part of the pathogen – known as the antigen (Moyle and Toth, 2013). A reason for choosing to develop this kind of vaccine over live attenuated and inactivated vaccines (Moyle and Toth, 2008) is that safety is a major hurdle when it comes to developing live vaccines, especially for the immunocompromised group. Furthermore, sub-unit vaccines are a possible alternative to the failed live attenuated or inactivated approaches of certain vaccines such as HIV (Das et al., 2010). Apart from their safety and novelty, these vaccines are also advantageous since they are more stable, making storage and transportation easier (WHO Module 2; Types of Vaccines and Adverse Reactions, 2021). A current disadvantage of subunit vaccines is that the subunit alone often does not have the same effectiveness as inactivated or live-attenuated vaccines due to not containing as many immune system stimulating components and therefore requires the use of adjuvants and booster shots (Pulendran and Ahmed, 2011). Common vaccines of this type include the Haemophilus in-fluenzae type b (Hib), Pneumococcal (PCV-7, PCV-10, PCV-13) and Hepatitis B (HepB) vaccines (WHO - Module 2; Types of Vaccines and Adverse Reactions, 2021). 4. TOXOID The mechanism behind toxoid vaccines is somewhat unique when compared to the previous three. This type of vaccine consists of a toxin produced by the pathogen and stimulates an immune response against the toxin specifically. So, with this type of vaccine the body is being primed to recognise and dispose of the harmful products of the pathogen rather than the pathogen itself (“Vaccine Types | Vaccines, 2021). These vaccines also require adjuvants such as calcium and aluminium salts as well as booster shots to maintain long-term immunity. Vaccines of this type include Tetanus toxoid and Diphtheria toxoid (WHO - Module 2; Types of Vaccines and Adverse Reactions, 2021).

5. MRNA VACCINES Historically, designing vaccines to target coronaviruses has always been difficult. The best method for protein sub-unit vaccines has been the use of the S-protein (spike protein) found on the surface of all coronavirus strains (Roper and Rehm, 2009). At the time of writing, the main 3 vaccine types being developed for the SARS-CoV-2 virus (which causes COVID-19) that have been authorised for use by certain regulatory authorities (“Coronavirus disease (COVID-19): Vaccines, 2020) are: 

Protein Subunit Vaccines

Protein subunit vaccines for COVID-19 work in the same manner as the subunit vaccines mentioned in the previous section. The spike proteins from the SAR-CoV-2 virus are injected to trigger an immune response which will then prevent severe subsequent infections (“Coronavirus disease (COVID-19): Vaccines,” 2020). The “Vector State Research Centre of Virology and Biotechnology” is currently developing a peptide antigen vaccine (WHO Guidance Document, 2021). 

Nucleic Acid (DNA, RNA or mRNA) Vaccines

Nucleic acid vaccines are a relatively novel form of vaccine. They work by introducing a piece of genetic material via a lipid nano-particle into cells. This is taken up by cells and used as a blueprint to produce the S-protein, against which our body mounts an immune response (Koirala et al., 2020). Thus, the major difference between these vaccines and subunit vaccines is not the method by which our body generates an immune response, but rather the site at which the antigen is generated. With subunit vaccines, the antigen is produced in labs, whereas with nucleic acid vaccines, the antigen is produced within the body (Khan, 2013).

Currently, Pfizer-BioNTech (“Information about the Pfizer-BioNTech COVID-19 Vaccine | CDC,” 2021) and Moderna (CDC - Information about the Moderna COVID-19 Vaccine, 2019) have developed mRNA vaccines

and Inovio is developing a DNA vaccine (“The first

coronavirus vaccines have arrived. Here‟s where the rest stand. | BioPharma Dive,” 2021). 

Viral Vector Vaccines

At the time of writing, the main 3 vaccine types being developed for the SARS-CoV-2 virus (which causes COVID-19) that have been authorised for use by certain regulatory authorities are: Subunit vaccines, Nucleic acid vaccines and recombinant vaccines. The Oxford/Astrazeneca vaccine is an example of a viral vector vaccine.

THE EFFECT OF VACCINE HESITANCY ON MORBIDITY & MORTALITY OF VACCINE-PREVENTABLE DISEASES Vaccines are known to be the most significant and successful public health intervention (Shen and Dubey, 2019). The development of vaccines has made morbidity and mortality from communicable disease much less common, with smallpox and polio being eradicated in the Western world (Shen and Dubey, 2019). Wherever and whenever there are lapses in vaccination, preventable infections and mortality occur (Hussain et al., 2018; Phadke et al., 2016).

Decline in polio infection after the introduction of the vaccine in the early 1960s (“Polio - Our World in Data,” 2017)

(“How bad is the measles comeback? Here‟s 70 years of data | PBS NewsHour,” 2019) Vaccine hesitancy, defined by the WHO as the “delay in acceptance or refusal of vaccines despite availability of vaccination services,” has led to underimmunisation or no immunisation and has widely contributed to the resurgence of diseases previously considered almost eradicated (Sansonetti, 2018). The causes of vaccine hesitancy include fear of harm caused by the vaccine, lack of information and knowledge regarding the vaccine-preventable disease and lack of trust in pharmaceutical companies (Salmon et al., 2015). The major factor which resulted in the decline of immunisation of measles was the emergence of the unfounded and discredited study released in 1998 by the former physician Andrew Wakefield in The Lancet. This study claimed a correlation between the MMR vaccine and autism (Rao and Andrade, 2011). Multiple studies since then have refuted the link made between the two along

with the retraction of the initial study due to proof of falsified data (Edwards, 2001). The consequences of this event resulted in outbreaks of the infection (Sansonetti, 2018). Vaccine hesitancy has spread quicker through the use of social media platforms where unvetted information is accessible to all (Hussain et al. 2018). In that, misinformation and disinformation can run rampant. Misinformation is the unintentional spread of incorrect information based on conclusions made from false facts. This can be addressed by the provision of evidence-based research and information. However, disinformation, which is the intentional spread of incorrect information for a particular agenda, requires a more strategic plan (Wilson and Wiysonge 2020). Studies have shown that combating social media disinformation will be essential to decrease vaccine hesitation whilst also outreaching and providing the public with the necessary information of the importance of vaccines (Wilson and Wiysonge 2020). During this current time, much research worldwide has focused on the development of the COVID-19 vaccine. Surveys carried out have shown the main reasons for not wanting the vaccine report concern about the side effects, the effectiveness and COVID-19 not posing a large enough risk. In order to reduce the number of cases of the virus and the burdens of morbidity and mortality of the disease, a sufficient number of people need to be inoculated in order to attain widespread immunity (Grech et al. 2020). Vaccine hesitancy could be one of the biggest barriers in reaching herd immunity, however, by boosting the public‟s vaccine confidence, the required amount of global immunity can be reached (Randolph and Barreiro 2020).

LEGISLATION, ACCESS & EQUITY Mandatory Vaccination Through the Vaccination Act of 1853, the UK became the first country to make vaccination mandatory. This piece of legislation enforced smallpox vaccination of all infants within the first 3 months of life through fines or imprisonment for abstaining parents (“Timeline | History of Vaccines,”, 2021). Since then, 105 countries have enacted some form of mandatory vaccination legislation and 59% of such legislation contains penalties for non-compliance (Gravagna et al., 2020). Penalties vary widely from country to country and vaccine to vaccine however the most prevalent are educational penalties, such as barring the child from attending school until vaccinated, at 69% (Gravagna et al., 2020). Whereas the vast majority of countries are actively promoting taking the COVID-19 vaccine, no country has made it compulsory (Marta Rodriguez Martinez, 2020), instead opting to organise large-scale, educational campaigns to encourage uptake. Furthermore, it is yet unclear whether companies, including healthcare providing ones, can make COVID-19 vaccination mandatory for their employees (“Can US employers order workers to get the coronavirus vaccine? | Coronavirus | The Guardian,” 2020) or even customers, especially in the case of airlines (“Airports reject vaccine requirement as travel debate intensifies | Reuters,” 2020; “Covid: Vaccination will be required to fly, says Qantas chief - BBC News,” 2020). Access & Equity In developed countries, potentially life-saving vaccines are widely available, the most fundamental of which being offered at no cost. Despite this, ensuring global access remains a pressing issue. In 2012 the WHO endorsed the Global Vaccine Action Plan 2011–2020 (GVAP), a global framework which set more ambitious vaccination goals and outlined various strategies and support systems to reach these goals (“Ensuring access to immunization,” 2020; “The global vaccine action plan 2011-2020: review and lessons learned: strategic advisory group of experts on immunization,” 2020).

With the plan‟s timeframe drawing to a close some notable achievements include the eradication of wild poliovirus Types 2 and 3 and a decrease by 24% in global child mortality between 2010 and 2017 (“The global vaccine action plan 2011-2020: review and lessons learned: strategic advisory group of experts on immunization,” 2020). Despite good progress, none of the goals set in 2012 were reached by the end of 2020, a notable cause being resurgences in deaths from vaccine-preventable causes due to increased hesitancy (“The global vaccine action plan 20112020: review and lessons learned: strategic advisory group of experts on immunization,” 2020). In the context of the COVID-19 vaccine, the issue of equity is extremely pertinent. To ensure that countries, regardless of their wealth, were guaranteed rapid and fair access to a vaccine, COVAX was set up. COVAX is the vaccination pillar of the Access to COVID-19 Tools (ACT) Accelerator and is co-led by the WHO, the Centre for Epidemic Preparedness (CEPI) and Gavithe Vaccine Alliance (“COVAX explained | Gavi, the Vaccine Alliance,” 2020). COVAX is built on the idea of equitable access, bringing together the largest group of research teams, investment and manufacturing capabilities (Seth Berkley, 2020). COVAX is on track to accomplish its initial goal of 2 billion doses by the end of 2021, which would be sufficient to cover all front line workers and the most vulnerable, the world over (“COVAX ANNOUNCES ADDITIONAL DEALS TO ACCESS PROMISING COVID-19 VACCINE CANDIDATES; PLANS GLOBAL ROLLOUT STARTING Q1 2021,” 2020; “COVAX explained | Gavi, the Vaccine Alliance,” 2020). THE ECONOMIC BENEFITS OF VACCINATION The benefits of vaccines can be classified into health, social, and economic. Whilst the health benefits are well established, less focus is put on the economic benefits of vaccines, with much left to be done to ensure there is the necessary financial support, provision, distribution and administration of vaccines globally (Rodrigues and Plotkin 2020). The cost effectiveness analyses of vaccination programmes demonstrate that they are overwhelmingly worth the investment. The financial advantages of vaccination are important both to industrialised nations as well as to LMIC (Low- and Middle-Income Countries). The

United States has a net economic benefit of $69 billion from vaccination and investment of $34 billion in 94 LMIC resulted in savings of $586 billion from costs of direct illness (Orenstein and Ahmed, 2017; Rodrigues and Plotkin, 2020). Vaccines have contributed to a significant decrease in the burden of communicable diseases (“The economic value of vaccination: why prevention is wealth.,” 2015). The reduction in morbidity and mortality associated with successful vaccine programmes, through a combination of direct and indirect protection, has led to a decrease in incidence of diseases, their respective treatment and healthcare costs (Deogaonkar et al., 2012). Consequently, less money is spent on medical tests, procedures, treatment and less time off work by patients and/or their caregivers, whilst strengthening the sustainability of the healthcare systems (Bonanni et al., 2015). Health officials within governments are required to perform systematic economic analyses of vaccination programmes to justify the various costs, such as, vaccine purchase, infrastructure to maintain the programme, cold chain and the training and compensation of healthcare and administration personnel (“The economic value of vaccination: why prevention is wealth.,” 2015). An often less considered economic saving from vaccination programs is from the prevention of long-term morbidities following acute infections, such as hearing impairment following pneumococcal meningitis or limb amputation following meningococcal diseases (Rodrigues and Plotkin 2020). Also of significance are the broader productivity gains that could be made by the prevention of these morbidities; more people would be able to work jobs which these morbidities would make impossible (Deogaonkar et al. 2012). Much light has been shed onto the economic effects of COVID-19. As the pandemic developed, many industries were forced to a halt in order to mitigate dissemination of the virus. This led to productivity losses and an overall downturn in the global economy. These aforementioned economic effects are projected to be long lasting and far reaching. This makes vaccination against COVID-19 an evermore pertinent and urgent issue, in order to be able to safely mobilise significant amounts of workforce back into industry.

At the time of survey, 18.9% of the general population in 7 European countries indicated that they were unsure whether they would be taking a COVID-19 vaccine, hence a greater concerted effort is required on the advocacy front (Roope et al. 2020).

Common Misconceptions about Vaccination 1. Misconception - Vaccines don’t work Vaccines work, and there‟s plenty of evidence for it. On May 8th 1980, the World Health Assembly declared the world free of smallpox, the eradication of which is considered the biggest achievement in international public health. Among the many conditions necessary for eradication of a disease is high vaccine coverage, as was the case for smallpox. The last person to die of smallpox was Janet Parker, in 1978. (Institute of Medicine (US) Forum on Emerging Infections et al., 2002) One argument that is used to push the idea that vaccines don‟t work is that getting vaccinated made them sick. Symptoms often reported are fever and pain at the injection site. Vaccines work by prompting the immune system to produce its first response towards an unfamiliar pathogen or molecules derived from it. This creates immunological memory, meaning the creation of cells that in the future will recognise that pathogen and be able to mount an effective second response when the person comes across it. This second response should both prevent disease in the vaccinated individual and prevent transmission of the pathogen to others. The first response that a person has towards a vaccine is similar to but milder than being infected. (Stratton et al., 2011) ● The influenza vaccine does not work („I took the influenza vaccine and still got influenza‟) The influenza vaccine‟s effectiveness is annually estimated to be at 25-60%. This is due to a number of reasons: -

Strains of the pathogen that are unaccounted for in the vaccine.


Immunosenescence and the inability for immunological memory in the elderly. Children are more likely to spread influenza and other upper respiratory tract infections, such as pneumococcal infection. This is seen in the figures; 20% of unvaccinated children get influenza, compared to the 10% of unvaccinated adults, annually (Grech and Borg, 2020)

Influenza has multiple strains which are of varying contagiosity and cause symptoms and systemic stress of varying severity. WHO predicts the strains which will be most prevalent and which will produce the worst pathology. However the vaccine does not include all of the active strains and therefore non-included strains can instead become prevalent themselves and become widespread. Since the non-included strains are not accounted for in the vaccine, an individual who has been vaccinated for influenza can still become infected by these strains. Thus, total immunity against influenza can never be achieved, as a vaccinated individual could come across a strain of influenza which was not accounted for in the vaccine. The influenza vaccine induces immunity after about 2 weeks post-vaccination. In the period between vaccination and becoming immune, a person who comes across influenza may still be able to become infected.

2. Misconception: Vaccine contain a number of toxic compounds

Along with the components that work directly towards providing immunity against a particular disease, vaccines contain a number of other ingredients that are frequently miscited as cause for alarm. These include preservatives such as thimerosal found in the flu vaccine, adjuvants such as aluminum salts as well as ingredients that make up part of the production process of a vaccine, like formaldehyde. Thimerosal contains a form of mercury called ethylmercury (which differs from the mercury found in fish that is toxic in large amounts, methylmercury). Thimerosal prevents bacterial and fungal contamination. This compound is only used in minute amounts and studies have shown that there is no link between the ethylmercury used in vaccines and any evidence of harmful effects (Center for Disease Control and Prevention 2013). Furthermore, it is worth noting that thimerosal is only used in a few vaccines (which are stored as multi-dose vials) like the influenza vaccine - so the great majority of vaccines do not even have thimerosal in them (Center for Disease Control and Prevention 2013). Adjuvants help increase the body‟s immune response and so contribute to the efficacy of many vaccines. Aluminum salts are a type of adjuvant - but the amount of aluminum used in vaccines is so small that, even immediately after injection, it is hard to notice an increase from the baseline amount usually found in our blood, let alone be linked to the conditions associated with chronic exposure to far higher amounts. Formaldehyde is used during the production process of some vaccines to inactivate potentially harmful toxins. The maximal amount of formaldehyde that makes its way into a vaccine, per dose, is 0.02mg - which is significantly less than that found in a pear. As is the case with almost everything around us, the potential for harm depends on the dose. This is negligible in all three of the above ingredients which really help serve to make vaccines safer, longer-lasting and more effective.

3. Misconception: Influenza vaccine given in early pregnancy increases the risk of complications a) Safety There are two kinds of influenza vaccines that are widely available to the public. The inactivated influenza vaccine (IIV); which is the flu vaccine we are most accustomed to, is administered as an intramuscular shot for persons aged 6 months and older. The other is the live attenuated influenza vaccine (LAIV) which is less commonly given. This vaccine is administered as a nasal spray and is only approved for those aged 2-49 years old without any underlying health conditions. Nowadays it is common knowledge that live vaccines should not be given to pregnant women. This is important as the LAIV is a live attenuated vaccine and hence contraindicated. Unfortunately, many also think that flu vaccines in general are unsafe for pregnant women and other susceptible groups, which is simply not true as the inactivated formulation is not only safe for pregnant women but encouraged to be taken during pregnancy by the CDC and WHO. During the 2000-2003 influenza season in the USA, around 2 million pregnant women were given the vaccine. Out of all these women only a very small proportion reported having adverse effects such as muscle pains and headaches, which seem trivial compared to the effects of a fullblown influenza infection on a pregnancy (Iskander et al. 2006). b) Efficacy A general concern surrounding pregnant women and the influenza vaccine is that the vaccine does not achieve the same effectiveness in this group and is hence not worth administering. This has been disproved since the 1970s by studies showing how pregnant and non-pregnant women achieved similar responses to the vaccine (Sakala et al. 2016). It is also known that the influenza vaccine given during pregnancy not only protects the mother but also the newborn; as evidenced by increased presence of antibodies in both groups (Englund 2003).

During pregnancy, the body undergoes a great number of changes ranging from hormonal changes, increased inflammation and even changes in the way the blood, heart and various other organs function (Kohlhepp et al. 2018). In accordance with this, a substantial number of pregnant women who do not get vaccinated and get infected by the influenza virus suffer more adverse effects than those who were vaccinated. Some additional vaccine side-effects observed in the pregnant population include: greater likelihood of requiring hospitalisation, preterm birth, low birth weight, pre-term diabetes mellitus and even a greater likelihood of stillbirth (Song et al. 2020). Another valid reason for pregnant women to get vaccinated is that there are currently no licensed influenza vaccines for children under the age of 6 months (this age is associated with greater rates of influenza infection), yet the simple influenza vaccine can provide passive immunity to the newborn by maternal antibodies that are produced in response to the vaccine (Nunes and Madhi 2018). Despite the potentially deadly effects of influenza infection during pregnancy listed previously, which are hardly exhaustive, the rates of influenza vaccine uptake in the pregnant population remain suboptimal. With rates of vaccine uptake in developed countries such as the US being as low as 49.1% (Kahn et al. 2018)

Misconceptions about COVID-19 Vaccine: 4. Misconception: Influenza is a common disease that passes quickly with no complications or long-term effects, so why would I go through the trouble of taking a vaccine? COVID-19 is very similar to the yearly flu. The yearly incidence of influenza is lower than that of the common cold however due to its

severity and potential complications it results in a far heavier burden on healthcare systems around the world. There are an estimated 3-5 million cases of severe illness and about 250,000 to 500,000 deaths worldwide per year (“What is the global incidence of influenza?,” 2020). It is difficult to compare the aforementioned incidence statistics to the ones for COVID-19 since data available is rather limited in light of the recent emergence of the disease. With respect to morbidity and mortality, COVID-19 is proving to be significantly more fatal than influenza, with over 1.83 million deaths worldwide in 2020. (“WHO Coronavirus Disease (COVID-19) Dashboard | WHO Coronavirus Disease (COVID-19) Dashboard,” 2021). Influenza is not the common cold and COVID-19 is not influenza- they are distinct diseases caused by different pathogens and with varying clinical signs and symptoms. The common cold is most often caused by viruses from the Rhinovirus class (Mäkelä et al., 1998) and influenza is caused by viruses from the class Orthomyxoviridae while COVID-19 is a member of the Coronavirus class. The common cold‟s effects are usually limited to the upper respiratory tract (“Rhinovirus (RV) Infection (Common Cold): Practice Essentials, Background, Pathophysiology,” 2019) while influenza is a systemic illness which affects several organ systems. COVID-19 is primarily a disease of the respiratory tract, however several short and long term effects in other organs have been reported. These effects include hypercoagulability (Liu et al., 2020), (Ackermann et al., 2020) other haematological complications (Kochi et al., 2020) and cardiovascular complications (Wang et al., 2020).

All three of these diseases are spread through contact, fomites (objects carrying infectious particles) and droplets (“Coronavirus disease (COVID-19): Similarities and differences with influenza,” 2020). A critical difference between Influenza and SARS COV-2 is that the latter seems to spread more easily than the flu. The increased transmissibility of COVID-19 has been attributed to the virus‟ longer incubation period (influenza: 12-72 hours (Lessler et al., 2009) & (“Rhinovirus (RV) Infection (Common Cold): Practice Essentials, Background,

Pathophysiology,” 2019); COVID: up to 14 days (Lauer et al., 2020) during which the patient may be asymptomatic but still contagious. Regarding symptomatology, the common cold is characterised by a sore throat and nasal sinus symptoms but doesn‟t typically present with fever. Contrastingly, fever and dry cough are common to both influenza and COVID-19 (Struyf et al., 2020). Shortness of breath (Xu et al., 2020) and a significant loss in sense of smell (Agyeman et al., 2020) have been more widely reported in COVID-19 infections. Whereas clinicians and researchers are familiar with the characteristics of the influenza virus, with COVID-19 the scientific and medical community is learning something new everyday. An influenza vaccine has been readily available to the public since the 1940s (CDC Influenza Historic Timeline), while vaccines for COVID-19 are only now starting to be approved and distributed. Effective treatments with antiviral drugs are available for severe influenza infections (Ison, 2017). In the case of COVID, currently-available treatment is predominantly supportive, there is no pharmacological cure (Esposito et al., 2020).

5. Misconception: The COVID-19 Vaccine Development and Approval Process were rushed The emergence of a new vaccine on the market tends to cause fear and hesitancy amongst the general public due to concern of potential side effects and unknown contraindications of the vaccine (Sato and Fintan, 2020). However, fear tends to stem from the lack of knowledge of the safety evaluation, immunogenicity and efficacy of the approval process that each vaccine must go through. (Sato and Fintan, 2020) Pharmaceutical companies must follow the guidelines and regulations issued by the World Health Organisation (WHO), the European Medicines Agency (EMA) and Drug Administration (USFDA) (Singh and Mehta, 2016).

The main development process is split into the preclinical and clinical stages, whereby the former tests are carried out on animals whilst in the latter on human subjects. The main aspects of the preclinical stage include the exploratory stage whereby laboratory research and analysis of different antigens are identified and tested in vitro. Following this, the in vivo testing on animal models is used to test the proposed vaccine and its immunogenicity and safety. (Singh and Mehta, 2016) (Aban and George, 2015) (Rab et al., 2020)

The clinical trials are composed of three main phases whereby phase 1 includes a small group of healthy individuals. This stage is essential when determining the extent of the immune response. The second phase includes large groups of people with an increased risk of acquiring the disease, with the aim of determining the most efficacious dose. The final stage involves even larger groups, it aims to search for any signs of side effects and adverse events which may arise. (Rab et al., 2020) In reality, due to the extreme surveillance and scrutiny

that each product is subjected to, only 10% of vaccine candidates are transferred from phase 1 to phase 3. (Aban and George, 2015)

The last stage is the approval and licensure of the vaccine. Once the vaccine has been successful in all the previous stages, regulatory bodies must approve of the vaccine, reviewing the safety before manufacturing it. Post-distribution, the pharmaceutical companies continuously monitor the production and outcome of the vaccine which includes the postmarketing surveillance. This is known as Phase 4 of clinical studies. (Rab et al., 2020). In light of the current pandemic, many contemplate whether vaccines are being made at too fast a pace and therefore, certain preventative and safety measures may be bypassed. In actual fact, due to the unprecedented recruitment of volunteers, necessary for the clinical trials, vaccine testing is occuring at a much faster rate. Furthermore, the funding provided for the investment in the research for the vaccine has also been extensive. The overlapping research by multiple companies made researching the virus and the vaccine more efficient and still following and abiding with all the regulations and guidelines. (“COVID-19 vaccines: development, evaluation, approval and monitoring | European Medicines Agency,” 2021).

6. Misconception: The pneumococcal vaccine provides protection against COVID-19 The pneumococcal vaccines protect against infections of the bacterium Streptococcus pneumoniae, which is a prevalent and potentially fatal infection. There are two main vaccines which provide immune protection against pneumonia, the pneumococcal vaccine and Haemophilus influenzae type B vaccine. This respiratory infection has a high morbidity and mortality rate in children under the age of five, in the elderly above the age of 65 years, individuals suffering from chronic illnesses and pregnant women. (Licciardi and Papadatou, 2019; Wang et al., 2018) Although the pneumococcal, Haemophilus influenzae type B and influenza vaccines do not prevent one from acquiring the SARS-CoV-2 infection, it is recommended that individuals are immunised against these pathogens. The relevance of the uptake of the aforementioned vaccines in the COVID-19 context is that studies have shown co-infection can significantly worsen the outcome of SARS-CoV-2. Current evidence, also, suggests that the innate

immune response against SARS-CoV-2 can weaken the respiratory system‟s immune response against other pathogens. A higher proportion of patients in Intensive Therapy units had bacterial co-infections than patients housed in other wards. Moreover, it is important to note that one is not safe from coronavirus by having the pneumococcal vaccine and should still follow all preventative measures promoted by the Public Health department. (Lansbury et al., 2020; Toombs et al., 2021) Furthermore, it is important to take into consideration that due to the pandemic health-care systems across the world have been overwhelmed, and thus, it is critical to avoid further strain on the system and healthcare workers. (Cheong, 2020)

RECOMMENDATIONS ● For the Public First and foremost, MMSA calls for the general public to place their trust in our dedicated health-care workers and scientists. It is easy for our judgement to become clouded by all the misguided information that is being spread on social media. While we want the public to remain up to date, we also want to emphasize the importance of using reputable sources. False knowledge is more dangerous than ignorance, and for this reason it is important to remain objective when trying to learn online, especially when it comes to novel topics such as COVID and vaccines in general which are in a continuous state of innovation. ● For Health Students MMSA calls for medical and other health students to remain up-to-date with developments on vaccination through the appropriate sources. Health students bear a degree of responsibility to the public to combat the spread of misinformation and disinformation. Whilst MMSA acknowledges that repetitive engagement on social media threads has a tendency to become tiresome, MMSA urges health students to continue to share the right information regarding vaccines, whether through social media or otherwise, to their immediate circles of friends and family. MMSA believes this combined action will have a strong impact on the fight against misinformation and disinformation. ● For Health Student Organisations MMSA commits itself to continuing its public campaigning for vaccine education and awareness through its social media channels.

Whilst MMSA‟s Standing Committee on Public Health (SCOPH) has taken a broad stance on vaccination education in recent years, MMSA commits itself to strengthen advocacy on the importance of equity in the access to vaccines, among target minority groups such as the HIV affected community, through efforts from the Standing Committee on Sexual and Reproductive Health (SCORA) as well as the Standing Committee on Human Rights and Peace (SCORP). MMSA recognizes the importance of taking a public stance on the encouragement of vaccine uptake in the light of the daily misinformation spread regarding vaccines especially in the local community. MMSA urges other local health student organizations to take up a similar stance. ● For the University of Malta Faculty of Medicine and Surgery MMSA calls on the Faculty of Medicine and Surgery at the University of Malta to increase vaccine education in the formal curriculum. Material could include types of vaccine technologies and the infrastructure in place/being developed to deal with rolling out new vaccines in normal and exceptional circumstances (such as COVID-19), vaccine hesitancy and how to combat the spread of vaccine-related misinformation. Vaccine hesitancy can be a topic if vaccines were to be ever introduced as a module. Much of this could be integrated into the infectious diseases module of 4th year, and there can also be an earlier introduction such as during the microbiology or ethics modules in preclinical years. ● For Healthcare Workers MMSA calls on healthcare workers to lead by example, by taking the yearly Influenza vaccine and currently, the COVID-19 vaccine, to decrease the spread of infection whilst protecting their patients and vulnerable members of society. Vaccine hesitancy does not only lie amongst the public, as noted in a recent study, a correlation with taking the COVID-19 vaccine has been made with the likelihood of healthcare workers taking the influenza vaccine, with 26% of healthcare workers participating in this study stating that it was „unlikely‟ that they would take the COVID-19 vaccine. (Grech et al. 2020)

Furthermore, hesitancy amongst Maltese healthcare workers‟ to the COVID-19 vaccine and influenza vaccine is also omnipresent. MMSA also calls upon healthcare workers to keep well informed on the current advances being made to be able to better inform and educate their patients, and thus fight against the spread of misinformation and disinformation. During this time, it is crucial that the public are informed and educated on the importance of vaccination to ensure adequate uptake of the COVID-19 vaccines. Moreover, the general public looks towards healthcare workers for guidance, therefore it is important to acknowledge this and be of example during such a critical time. It is essential that one is knowledgeable on the COVID-19 vaccines whilst continuing to research on the new advancements and understanding of the COVID-19 virus and the latest data gathered on the vaccine itself. ●

For National Government

MMSA commends the government‟s decisions in May and June 2020 to add the pneumococcal vaccine, the Meningitis ACWY Vaccine and Meningitis B Vaccine, respectively, onto the national immunisation schedule. Following from this, MMSA advocates for equitable access to immunisation through the inclusion of vaccines such as that against Varicella in the national immunisation schedule. Furthermore, MMSA urges the relevant authorities to regulate the prices of other vaccines in order to ensure that they are financially viable for all. The digitisation of vaccination records through MyHealth was a good step forward, MMSA believes that the next step is to fully integrate public and private vaccine records, to improve clarity and collaboration. Additionally, we appeal to government representatives to stay abreast and collaborate with the EU-wide strategy for the creation of a common vaccination card or passport for all EU citizens in line with the European Commission Recommendation made in 2018 (European Commission, 2019). This initiative would facilitate the free movement of people and information between member states and streamline healthcare systems across the EU.

MMSA commends the government‟s decision early on during the pandemic to make COVID-19 vaccines available for free for all. MMSA further commends the strategy chosen for prioritising front liners and vulnerable patients who live in long-term care facilities due to limited stocks. In the COVID context, MMSA urges that the government invest significantly in public education on vaccination to combat rising trends of misinformation and disinformation online. Finally, government officials are expected to safeguard the health of the people living in Malta by procuring the number of doses necessary to achieve herd immunity.

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