No 2a - 2021

COVID-19 vaccination - COVID-19 mRNA vaccine from Moderna

COVID-19 vaccination - COVID-19 mRNA vaccine from Moderna

On 6 January 2021, a second COVID-19 vaccine was recommended for authorisation by the European Medicines Authority (EMA) and subsequently authorised by the EU Commission. The vaccine is manufactured by the Modena corporation and was coined “COVID-19 Vaccine Moderna” or ”the COVID-19 mRNA vaccine”. Below, we use the first of the two terms.

The first shipment of COVID-19 Vaccine Moderna® consisted of 480 vials containing a total of 4,800 doses, which arrived at Statens Serum Institut (SSI) on Tuesday morning (week 2, 2021). The Danish Health Authority has decided that the first shipment will be forwarded to the Region of Southern Denmark. We expect that the vaccines will arrive to the Region of Southern Denmark by Wednesday afternoon. An additional three shipments are expected in weeks to come (weeks 4, 5 and 7) containing 6,000, 16,000 and 48,000 doses, respectively.

The vaccines are released for distribution from the SSI and will form part of the ongoing vaccination programme on the same terms as the Comirnaty® vaccine from Pfizer/BioNTech. The vaccination schedule, including its various phases and the handling of vaccination against COVID-19, is described in detail (in Danish language) in the following publications by the Danish Health Authority: Organisation of the COVID-19 vaccination efforts (Danish language) and Guidelines on the handling of COVID-19 vaccination (Danish language).

The COVID-19 vaccine Moderna® has been granted a conditional marketing authorisation for the EU. This means that Moderna is required continuously to report collected data to the EMA, and that the vaccine is monitored just like the Comirnaty® vaccine - read more about this topic in EPI-NEWS 51/52b 2020. To achieve a standard marketing authorisation, the manufacturer must continuously report data from the clinical phase-three trial. This trial, along with others, is to produce information about the duration of the protection achieved, how effectively the vaccine protects against severe COVID-19, and how well it protects immuno-compromised persons, if it may be administered safely to children and child-bearing women and if it prevents asymptomatic cases and transmission from such cases.

Information about the basis for the authorisation, product information, patient information leaflets, etc. is available at the website of the Danish Medicines Agency (Danish language).

About the COVID-19 Vaccine Moderna®

The vaccine is a messenger-RNA (mRNA) vaccine approved for persons aged 18 years or more. An mRNA vaccine is a non-infectious vaccine that contains neither active nor inactive virus.

Therefore, vaccination carries no risk of infection. Read more about how an mRNA vaccine induces immunity in EPI-NEWS 51/52b 2020.

The vaccine is provided ready for use and must therefore not be diluted. Each vial includes a minimum of ten 0.5 mL doses, and each dose contains 100 micrograms vaccine antigen.

The vaccination schedule for COVID-19 Vaccine Moderna® consists of two 0.5 mL doses administered at a 28-day interval. The summary of product characteristics does not stipulate a grace period, but in the phase-three trial, 98% of the subjects received the second dose 25-35 days after their first dose, corresponding to -3 to +7 days around the 28-day interval. An interval of no less than 25 days between the two doses should therefore be acceptable. If the second dose is not administered on day 28, it should be given as soon as possible thereafter and should not be planned for administration after day 43. If the vaccination series is initiated using COVID-19 Vaccine Moderna®, it should be completed using the same vaccine type, as experience with the interchangeability of COVID-19 vaccines is lacking.

The efficacy of the vaccine

The COVID-19 Vaccine Moderna® has, among others, been tested in a clinical phase-three trial. In this trial, following randomisation, approx. 28,000 people aged 18 years or above (mean: 53 years) received two injections with either the vaccine or placebo at a 28-day interval. The primary endpoint was protection against clinical COVID-19 infection.

The vaccine was shown to have an overall efficacy against COVID-19 of 94.1% (95% CI: 89.3-96.8). In real numbers that corresponds to 11 COVID-19 cases in the group of fully vaccinated and 185 cases in the placebo group - corresponding to an incidence of 3.3 and 56.5, respectively, per 1,000 person years. During the trial, 30 cases of severe COVID-19 and one death occurred, all in the placebo group.

If the trial group is stratified by age, the vaccine was effective in 95.6% (95% CI: 90.6-97.9) in persons aged 18-64 years, and 86.4% (95% CI: 61.4-95.2) in persons aged 65 years or above. Among the oldest participants aged 75 years or above, no COVID-19 cases were recorded among 630 vaccinated persons, and seven cases were recorded among 688 unvaccinated persons.
Vaccinated persons may not expect the vaccine to be fully effective until at least 14 days after they have received the second dose. The duration of the protection achieved by the vaccine currently remains unknown.

Who may receive the vaccine?

Persons aged 18 years or more with a view to active protection against SARS-CoV-2. For contraindications and precautions, please see below.

Side effects

The clinical trial established the safety profile of COVID-19 Vaccine Moderna®. The most frequently recorded side effects were swelling of the lymph nodes under the arm receiving the vaccination, headache, nausea and vomiting, muscle ache, joint ache, pain and swelling at the injection site, fatigue, chills and fever (seen in ≥1/10). Common side effects were rash, erythema and urticaria at the injection site (seen in ≥1/100 to <1/10). The only uncommon side effect was pruritis (seen in ≥1/1,000 to <1/100). Rare side effects were acute paralysis of the face and swelling of the face (seen in ≥1/10,000 to <1/1,000). Swelling of the face was observed in two persons who had a history of dermatologic fillers. The vaccine was also tested in 343 persons who were seropositive to SARS-CoV-2 at the time of their first vaccination, and here the safety profile was in line with the above description.

All vaccinations carry a small risk of a strong allergic reaction (anaphylaxis).

For the remaining reported side effects, please see the summary of product characteristics (SPC) for the vaccine and the published phase-three trial.

Special precautions and attention points

Anaphylaxis preparedness measures must be in place at all vaccination sites, and it falls upon the regional authorities to ensure this. After vaccination, at least 15 minutes of close monitoring is recommended. The second dose should not be given to people who have experienced anaphylaxis in connection with vaccination with the first dose of COVID-19 vaccine Moderna.

Vaccination should be postponed in case of severe acute febrile (≥38.0⁰C) illness.

Persons who have experienced an immediate anaphylactic reaction after receiving other vaccinations or after having another medicinal product injected should be assessed by a physician before being vaccinated with COVID-19 vaccines as they are at increased risk of experiencing an allergic reaction. These patients may be assessed by their GP, who may confer with a specialised allergy centre, as needed. Particular attention should be given to persons who may have an undiagnosed allergy to the ingredient polyethylene glycol (PEG).

It must be assessed if vaccination requires specially enhanced anaphylactic preparedness measures at a hospital department with relevant experience.
Persons with mastocytosis must be vaccinated in the specialised national treatment centre (The Dermatology Department I and the Allergy Centre at Odense University Hospital), which is responsible for contact to these patients.

In its “Guideline on the handling of COVID-19 vaccination” (Danish language), the Danish Health Authority assesses that vaccination should be given with caution to persons with thrombocytopenia and coagulation disorders, and special needles should be used (e.g. size 25-27 G) as haemorrhage may occur following intramuscular injection in this group of patients. Patients with severe or moderate haemophilia A or B or severe von Willebrand’s disease may be vaccinated intramuscularly if they have received prophylactic treatment with a factor product a few hours before their vaccination. Patients with milder haemophilia must contact their haemophilia centre to establish if they should receive prophylactic haemophilia medicine before being vaccinated. Standard anticoagulative (AC) treatment is not normally a contraindication to intramuscular injection, and therefore standard AC treatment is also not a contraindication to vaccination.

The efficacy of the vaccine may be reduced in persons with a reduced immune response, including people who are receiving immunosupressive treatment. The Danish Health Authority’s updated guideline (Danish language, published 12 January 2021) provides additional information about the timing of vaccination for patients who are receiving chemotherapy, patients receiving immuno-suppressants (e.g. anti-CD 20 antibodies) and patients who have received immune therapy (and who may have immune activation).

Clinical protection against SARS-CoV-2 cannot be guaranteed in all vaccinated persons, cf. the above section on the efficacy of the vaccine.

No data are available on vaccination with the COVID-19 Vaccine Moderna® in persons who have received partial or full vaccination with another COVID-19 vaccine. You should therefore strive to always conclude vaccination with the same COVID-19 vaccine as that which was given at the first vaccination.

Contraindications

For hypersensitivity to any of the vaccine’s ingredients or excipients, please see the summary of product characteristics.

Pregnancy and breast-feeding

Due to lacking safety data, the vaccine should not be given to pregnant women, and pregnancy should be excluded through pregnancy work-up before vaccinating women of fertile age. In case of amenorrhoea, the woman should be encouraged to take a pregnancy test before proceeding to vaccination, if relevant. If a woman has a non-acknowledged pregnancy at the time of her vaccination, termination of pregnancy is not recommended as the vaccine is not a live attenuated vaccine why no or only very limited foetal harm is expected.

It remains unknown if vaccine products may be found in breast milk. As a risk for the neonate cannot currently be excluded, the vaccine should not be given to breastfeeding women. Even so, if the mother is at risk of running a severe COVID-19 course, this should be considered as part of the overall risk assessment.

It remains unknown if the vaccine affects the fertility in men as well as women.

Dispensing

At present, the vaccine is only supplied to the regional vaccination centres established as part of the initiation of the COVID-19 vaccination programme. The vaccine is stored frozen (-25 to -15°C) at the SSI, and freezing should be maintained until thawing immediately prior to use. Nevertheless, see below for information about shelf-life and thawing. Each pack contains ten vials each containing a minimum of ten doses.

Storage and handling

The COVID-19 Vaccine Moderna® is stored at -25°C to -15°C. At this temperature, the vaccine’s unopened shelf life is seven months. The vaccine may be thawed at room temperature (15-25oC) for one hour and in a refrigerator (2-8oC) for 2.5 hours. The thawed, unopened vaccine may be stored for up to 12 hours in darkness at 8-25°C or for up to 30 days in darkness at 2-8°C. Once the vial is opened, the vaccine is stored at 2-25°C, and all doses must be used within no more than six hours. Subsequently, the vial is discarded. Thawed vaccine cannot be re-frozen.

Store in the original package to protect from light.

Do not store on dry ice or at temperatures below -40°C.

Preparation

The thawed vaccine is heated to room temperature and maintained vertical with the bottom part pointing downwards. Carefully swirl the vial around (may not be shaken or turned). The vaccine should be a colourless-to-white solution, and visible white particles may be observed. 0.5 mL of vaccine is withdrawn into the syringe and injected. Changing the needle between withdrawal from the vial and injection is not necessary. Be sure to swirl the vaccine vial gently before withdrawing another vaccine dose. Also, be sure to leave the vial in an upright position while a vaccine dose is withdrawn. The SSI has prepared an infographic (Danish language).

According to the EU SPC, the vial will provide a minimum of ten 0.5 mL vaccine doses, and any unused diluted vaccine is discarded as usual and no more than six hours after its preparation (store at 2-25°C). State the date and time at which the preparation must be discarded on the vial to avoid adverse events.

Dosage and administration

COVID-19 Vaccine Moderna® is a ready-to-use multidose vial that should not be diluted. Each vial contains 6.3 mL vaccine, corresponding to a minimum of ten 0.5 mL doses, each containing 100 micrograms of vaccine antigen (mRNA-1273 embedded in lipid nanoparticles).

Two 0.5 mL doses of undiluted vaccine are administered at a 28-day interval. If the second vaccine is given a minimum of 25 days after the first vaccination, this may be accepted as valid vaccination.

Immunisation is done by intramuscular injection into the deltoid muscle. In case of contraindication to vaccination in the deltoid muscle, the vaccine may be administered to the central section of the lateral great muscle.

Observation

After vaccination, the Danish Health Authority recommends that the vaccinee remains in the waiting area for a minimum of 15 minutes.

Registration

All COVID-19 vaccines must be registered in the Danish Vaccination Register (DVR), either by rapid or standard registration. See separate instructions about this (Danish language).
We encourage that the vaccination is registered as quickly as possible after the time of the vaccination. To ensure quality in the monitoring of the vaccines, it is important to ensure correct registration of product name and batch number.

Information for the person receiving the vaccination

The vaccinee should receive the folder published by the Danish Health Authority and prepared in collaboration with the Danish Medicines Agency. The folder provides information about the most frequently occurring side effects and informs that you should see your doctor if you experience any serious side effects/symptoms after being vaccinated.
Phone advice is also available to the general public via the joint corona hotline of the Danish authorities at +45 7020 0233. Phone advice does not include advice about symptoms or medical assessments in relation to citizens; for these complaints, please refer to your general practitioner.

Additional vaccination to the person giving the vaccination

Vaccinators may find additional information about COVID-19 vaccination at the websites of the Danish Health Authority, the Danish Medicines Agency and Statens Serum Institut. At the SSI’s website, the following are available for download: the vaccine-specific descriptions and infographics about vaccine facts and about storage and reconstitution/injection of the vaccines. This material will also be enclosed with each batch of vaccines supplied by the SSI.

The SSI has prepared a questions and answers section about COVID-19 vaccination at our COVID-19 subsite for use by healthcare workers.

If the need arises for vaccination-related advice, healthcare workers may contact the Department of Infectious Disease Epidemiology and Prevention. We are open for phone-based advice at +45 3268 3037 from Monday to Friday 8.30-11.00 a.m., except for Wednesdays 12.30-3.00 p.m. Beyond these periods, the department can be contacted during daytime office hours on phone +45 3268 3038. You may also write to covidinfo@ssi.dk. On working days, we aim to respond within the day the request was made, but we cannot guarantee that this is possible in all cases. Outside normal office hours, the physician on call may be contacted for acute advice on phone +45 4131 7404.

(K.F. Nielsen, L.K. Knudsen, P. Valentiner-Branth, P.H. Andersen, Infection Epidemiology and Prevention)