COVID (SARS-COV-2) Vaccine


Continuing Education Activity

COVID-19 vaccines (tozinameran (BNT162b2) and mRNA-1273 SARS-CoV-2) received FDA emergency use authorized (EUA) to prevent COVID-19 caused by the SARS-CoV-2 virus. This activity reviews the indications, administration, and contraindications for COVID-19 vaccines: tozinameran (BNT162b2) and mRNA-1273 SARS-CoV-2. This activity will also highlight the mechanism of action, adverse event profile, and other key elements of the COVID-19 vaccines in the clinical setting for the interprofessional team members when vaccinating individuals to prevent COVID-19 and its related conditions sequelae.

Objectives:

  • Identify the mechanism of action of COVID-19 vaccines.
  • Describe indications for COVID-19 vaccines.
  • Review the adverse effects of tozinameran (BNT162b2) and mRNA-1273 SARS-CoV-2.
  • Outline some interprofessional strategies that the healthcare team can employ to optimize SARS COVID-19 vaccine deployment and improve public health outcomes.

Indications

The COVID-19 (SARS-CoV-2) vaccine is indicated for the prevention of coronavirus 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus.[1][2][3] The SARS-CoV-2 virus first surfaced in Wuhan, China, in December 2019. The virus was announced as a public health emergency of International Concern on January 30, 2020, by the World Health Organization (WHO).[4] Since then, the lethal virus had spread rapidly, affecting various countries worldwide. On March 11, 2020,  the global COVID-19 occurrence was declared a pandemic by the WHO.[5][6]

The virus's transmission mode is mainly through respiratory droplets, from coughing or sneezing, of infected individuals[4]. SARS-CoV-2 invades its host cells by binding its viral spike (S) protein - constituted of S1 and S2 spike glycoprotein subunits and located on its surface, to the human angiotensin-converting enzyme 2 (ACE2) receptors expressed on the surface epithelium of various organs (lungs, heart, CNS) and transmembrane protease, serine 2 (TMPRSS2) receptors.[7][8][9]

The COVID-19 disease can have various manifestations, with increased susceptibility in individuals with comorbidities and immunosuppression.[10][4] Individuals with underlying comorbid ailments are reported to have increased ACE2 expression.[11] Although the SARS-CoV-2 virus is predominantly a respiratory illness, extrapulmonary manifestations have been reported. The symptoms may present two to fourteen days (mean ∼5 days) after exposure.[6][10] The individual may exhibit mild to no symptoms or present with severe disease affecting multiple organs and mortality. Mild to moderate characteristics include; fever, headache, chills, dry cough, shortness of breath, sore throat, nasal congestion, malaise, myalgia, body aches, nausea, and vomiting.

Organ system manifestations include:

Respiratory[6][10]

  • Mild to severe pneumonia
  • Acute respiratory distress syndrome (ARDS)

Central Nervous System[12]

  • Headache
  • Dizziness
  • Meningitis
  • Encephalitis
  • Encephalopathy
  • Cerebrovascular event
  • Chemosensory dysfunction (altered taste and smell)

Cardiovascular[13][14]

  • Myocarditis
  • Dysrhythmias
  • Coronary heart disease
  • Cardiomyopathy

Renal[15][16]

  • Acute Kidney Injury 

Gastrointestinal[17][18]

  • Moderate to severe diarrhea 

Since the onset of the pandemic, the mainstay of treatment has been supportive measures - with over one hundred vaccine candidates in different phases of their clinical trials to prevent COVID-19. Vaccine candidate types currently in development include mRNA vaccines, replication-defective adenoviral vectors vaccines, sub-unit/protein-based vaccines, DNA vaccines, and inactivated vaccines.[19][20] To expedite the process, many vaccine candidates had combined phase 2/3 trials. mRNA vaccine candidates tozinameran (BNT162b2) and mRNA-1273 SARS-CoV-2 had shown promising data during the phases of their clinical trials. Tozinameran demonstrated 95% effectiveness seven days after the second dosage during their international, placebo-controlled, observer-blinded clinical trials.[1][3] Comparatively, the mRNA-1273 SARS-CoV-2 demonstrated 94.1% efficacy during their randomized phase 3, placebo-controlled, observer-blinded clinical trial following the two-dose series.

The first emergency use authorization (EUA) was granted in the UK on December 2, 2020, by the UK's Medicines and Healthcare products Regulatory Agency (MHRA) to the BNT162b2 vaccine candidate.[21][22][23] Canada became the second nation, giving EUA to the  BNT162b2 vaccine on December 9, 2020, and mRNA-1273 SARS-CoV-2 vaccine on December 23, 2020, weeks after that. The Tozinameran vaccine is freighted in distinctive containers with dry ice in frigid temperatures and stored at approximately –70°C. Upon delivery, it may be stored in a refrigerator for five days[22]. Twenty-one million frontline medical care workers, including care home staff, are reported to receive the BNT162b2 vaccine first.[22]

U.S. Food and Drug Administration (FDA)

On December 11, 2020, emergency use EUA was granted by the U.S. Food and Drug Administration (FDA) to the BNT162b2 vaccine to prevent the 2019 COVID-19 with vaccine distribution in the US 48 hours later. Soon after, the second vaccine, mRNA-1273 SARS-CoV-2, was granted emergency use authorization on December 18, 2020.[24][25] Both mRNA vaccines are designated for active immunization for the prevention of COVID-19, caused by SARS-CoV-2.[1]

FDA Emergency Use Authorization (EUA):

  • Tozinameran (BNT162b2)
  • mRNA-1273 SARS-CoV-2

Mechanism of Action

mRNA Vaccines

The mRNA class of vaccines' rapid evolution and advancements are from the mRNA capabilities to imitate the antigen structure and expression comparable to those occurring during the SARS-CoV-2 infection.[19] The mRNA class of the vaccine does not pose a risk of infection or insertional mutagenesis. The mRNA eludes the anti-vector immunity permitting repeated vaccinations. The mRNA's ability to produce an undesired immune response within the body can be reduced, and modifications can be arranged to improve the mRNA vaccines' determination.[20]

Tozinameran (BNT162b2)

The tozinameran (BNT162b2) is a nucleoside-modified messenger RNA (modRNA) expressed in lipid nanoparticles (LNP), encoding the spike (S) protein for the SARS-CoV-2 virus - the main site for neutralizing antibodies.[26][27] The lipid particles allow the transfer of the RNA into host cells, resulting in the SARS-CoV-2 S antigens' expression.[19] The immunogenicity and antibody response to SARS-CoV-2 S antigens further confers protection against COVID-19. 

mRNA-1273 SARS-CoV-2

The mRNA-1273 vaccine comprises of a lipid nanoparticle (LNP) encapsulating nucleoside-modified messenger RNA (modRNA), encoding the perfusion stabilized spike (S) protein of the SARS-CoV-2 virus and an S1-S2 cleavage site, which includes a transmembrane component. The S-2P antigen present on its surface allows entrance into the host cell. This further transfers the RNA into host cells, resulting in the expression of the SARS-CoV-2 S antigens. The immunogenicity and antibody response to SARS-CoV-2 S antigens also confers protection against COVID-19.[27][19]

Administration

Tozinameran (BNT162b2) 

  • The vaccine is administered intramuscularly (into a muscle of the upper arm) as a series of two doses (0.3 ml each) 3 weeks apart.

The tozinameran (BNT162b2) vaccine can be administered to individuals 16 years of age and older for the prevention of COVID-19.

The vaccine is distributed as a frozen suspension in a multiple-dose vial, containing a volume of 0.45 ml, that does not contain a preservative. After dilution with 1.8 ml of 0.9% sodium chloride injection, each vial contains up to 6 dosages of 0.3 ml. Vial labels and cartoons may state that after dilution, a vial contains 5 doses of 0.3 ml. Each 0.3 ml dose contains 30 mcg of a modRNA, expressed in lipid nanoparticles encoding the spike (S) protein for the SARS-CoV-2 virus.

mRNA-1273 SARS-CoV-2

  • The vaccine is administered intramuscularly as a series of two doses (0.5 ml each) 4 weeks apart.

The mRNA-1273 SARS-CoV-2 vaccine can be administered to individuals 18 years of age and older for the prevention of COVID-19. The vaccine is given in 2 doses, one month apart, by intramuscular injection. 

The vaccine is distributed in 0.20 mg/ml white to off-white suspension rendered in vials containing 10 doses of 0.5 ml. Each vial dosage carries 100 micrograms of mRNA. 

Management for severe allergic reaction should be on hand in the event of anaphylaxis occurring following the vaccine regime. Epinephrine, antihistamines, stethoscopes, and blood pressure cuffs should be readily available at the vaccination site. Data on co-administration or interchangeability of COVID-19 vaccinations have been reported or analyzed. Individuals receiving vaccinations should complete the two-dose series with the same one administered as the first dosage.

Individuals receiving either vaccine will also obtain a vaccination card indicating which vaccine they had received. The vaccination card will include their first and last name, date of birth, dates of their first and second vaccination, and where they received the two-dose regime.[22]

Adverse Effects

Tozinameran (BNT162b2)[28][3][23][3]

  • Injection site tenderness/pain (84.1%)
  • Injection site swelling (10.5%)
  • Redness at the injection site (9.5%)
  • Fever (14.2%)
  • Fatigue (62.9%)
  • Headache (55.1%)
  • Muscle pain (38.3%)
  • Chills (31.9%)
  • Joint pain (23.6%)
  • Nausea (1.1%)
  • Malaise (0.5%)
  • Lymphadenopathy (0.3%)
  • Severe allergic reaction (rare)
  • Temporary one-sided facial drooping (rare)

Four serious adverse events related to the BNT162b2 vaccination during clinical trials were reported. Serious adverse events include lymphadenopathy - localized to the right axillary, paroxysmal ventricular arrhythmia, right lower limb paresthesia, and shoulder injury associated with vaccine injection.[3] Mortality was seen in two BNT162b2 vaccine recipients but was not considered to be associated with the vaccination as per investigators. These deaths were deemed to have been from arteriosclerosis and cardiac arrest. Mortality linked to Covid-19 following vaccine administration was not seen.

mRNA-1273 SARS-CoV-2[2]

  • Injection site tenderness/pain (92.0%)
  • Injection site swelling (14.7%)
  • Injection site redness (10.0%)
  • Fever (15.5%)
  • Fatigue (70.0%)
  • Headache (64.7%)
  • Muscle pain (61.5%)
  • Chills (45.4%)
  • Joint pain (46.4%)
  • Swollen lymph nodes on injection site arm (1.1%)
  • Nausea/vomiting (23.0%)
  • Hypersensitivity (1.5%)

Serious adverse effects had occurred in 1% of recipients of the mRNA-1273 SARS-CoV-2 during the clinical trials. Three cases (<0.1%) of Bell's palsy were also reported during the clinical trials of mRNA-1273 SARS-CoV-2.[2]

Contraindications

Tozinameran (BNT162b2)

The tozinameran (BNT162b2) vaccine is not recommended for individuals with a known history of severe allergic reactions to any vaccine's components.[29] The use of this vaccine in children under the age of 16 is not recommended. Pregnant or breast-feeding women have to consult with the doctor or pharmacist before receiving this vaccine.

mRNA-1273 SARS-CoV-2

The mRNA-1273 SARS-CoV-2 vaccine is not recommended for individuals with a known history of severe allergic reactions to any vaccine's components. Data of its use in pregnancy has not been studied, and its associated risks are yet to be determined. Its uses in individuals under the age of 18 have not yet been analyzed.

Monitoring

Immunocompromised recipients of the vaccination may not have a prominent immune response and should be routinely monitored. Recipients of the vaccines should periodically monitor any new and unusual adverse effects and report them to their vaccination provider.

Pregnant women planning to be vaccinated by the mRNA-1273 vaccine are encouraged to register in the pregnancy exposure registry. The registry monitors outcomes in pregnant women exposed to the mRNA-1273 vaccine.

Toxicity

Insufficient data have been reported on the toxicity of tozinameran (BNT162b2) and mRNA-1273 SARS-CoV-2 vaccines.

Enhancing Healthcare Team Outcomes

The COVID-19 vaccine is intended for its use in the prevention of the COVID-19 disease caused by the SARS-CoV- 2 virus. The vaccine is not FDA-approved but has been granted emergency use authorization (EUA) by the U.S. FDA following an HHS public health emergency declaration supporting its emergency use during the pandemic. An interprofessional team that provides a holistic and integrated approach to preventing COVID-19 can help achieve the best possible outcomes per person and population. COVID-19 is a public health emergency that may manifest from mild symptoms to severe multi-system effects in all age groups.

Two vaccines, tozinameran (BNT162b2) and mRNA-1273 SARS-CoV-2, are now available for use in various nations. Healthcare professionals providing the COVID-19 vaccination should thoroughly communicate and educate the vaccination recipients on the information presented in “Fact Sheet for Recipients and Caregivers” before receiving the vaccination. The healthcare provider should give a CDC vaccination card to each person receiving the vaccine with a return date to complete the two-dose series.

The healthcare team should inform the recipients on the V-safe information sheet, a smartphone app that identifies possible adverse effects following the COVID-19 vaccination through texting, and a website survey. The provider should also register in the federal COVID-19 vaccination program and report any unusual or severe adverse effects to Vaccine Adverse Event Reporting System (VAERS). The vaccination information must be included in a proper state or local jurisdictions' preferred system, such as the Immunization Information System (IIS), by the healthcare professional providing the vaccine.

The healthcare team should be prepared for immediate allergic reactions and have the equipment and treatment such as; epinephrine, antihistamines, stethoscopes, and blood pressure cuffs, on hand in case anaphylaxis occurs following vaccine administration. Providers should also be aware of the limited data on vaccines' interchangeability and complete the two-dose series with the same vaccination given as the first dose. The healthcare team should also communicate the vaccinations' effectiveness and advise that receiving a vaccine does not ensure protection to all recipients.

The vaccine provider should also inform pregnant women of the lack of sufficient data on vaccination use during pregnancy and its associated risks. Pregnant women planning to be vaccinated by the mRNA-1273 vaccine should also be informed and encouraged to register in the pregnancy exposure registry, which monitors their outcomes.

The healthcare team should also be aware of the age limit of vaccine recipients -  tozinameran (BNT162b2) age 16 and older and mRNA-1273 SARS-CoV-2 age 18 and older, and should not be administered to any individuals below these age groups as clinical studies are limited.

Interprofessional communication is vital for establishing patient rapport and increasing public health measures, so the spread of the virus and disease is best controlled within communities. Patients should be counseled on handwashing, wearing a mask, maintaining a distance of 6 feet, and 14-day quarantine after suspected exposure to limit the spread of the virus. Individual, collective, and preventative measures can help stop the further spread of COVID-19.


Article Details

Article Author

Inderbir Padda

Article Editor:

Mayur Parmar

Updated:

2/16/2021 7:36:18 PM

References

[1]

Joffe S, Evaluating SARS-CoV-2 Vaccines After Emergency Use Authorization or Licensing of Initial Candidate Vaccines. JAMA. 2020 Dec 14;     [PubMed PMID: 33315069]

[2]

Baden LR,El Sahly HM,Essink B,Kotloff K,Frey S,Novak R,Diemert D,Spector SA,Rouphael N,Creech CB,McGettigan J,Kehtan S,Segall N,Solis J,Brosz A,Fierro C,Schwartz H,Neuzil K,Corey L,Gilbert P,Janes H,Follmann D,Marovich M,Mascola J,Polakowski L,Ledgerwood J,Graham BS,Bennett H,Pajon R,Knightly C,Leav B,Deng W,Zhou H,Han S,Ivarsson M,Miller J,Zaks T, Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. The New England journal of medicine. 2020 Dec 30;     [PubMed PMID: 33378609]

[3]

Polack FP,Thomas SJ,Kitchin N,Absalon J,Gurtman A,Lockhart S,Perez JL,Pérez Marc G,Moreira ED,Zerbini C,Bailey R,Swanson KA,Roychoudhury S,Koury K,Li P,Kalina WV,Cooper D,Frenck RW Jr,Hammitt LL,Türeci Ö,Nell H,Schaefer A,Ünal S,Tresnan DB,Mather S,Dormitzer PR,┼×ahin U,Jansen KU,Gruber WC, Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. The New England journal of medicine. 2020 Dec 31;     [PubMed PMID: 33301246]

[4]

Guo YR,Cao QD,Hong ZS,Tan YY,Chen SD,Jin HJ,Tan KS,Wang DY,Yan Y, The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak - an update on the status. Military Medical Research. 2020 Mar 13;     [PubMed PMID: 32169119]

[5]

Cucinotta D,Vanelli M, WHO Declares COVID-19 a Pandemic. Acta bio-medica : Atenei Parmensis. 2020 Mar 19;     [PubMed PMID: 32191675]

[6]

Cascella M,Rajnik M,Cuomo A,Dulebohn SC,Di Napoli R, Features, Evaluation, and Treatment of Coronavirus 2020 Jan;     [PubMed PMID: 32150360]

[7]

Kuhn JH,Li W,Choe H,Farzan M, Angiotensin-converting enzyme 2: a functional receptor for SARS coronavirus. Cellular and molecular life sciences : CMLS. 2004 Nov;     [PubMed PMID: 15549175]

[8]

Zheng YY,Ma YT,Zhang JY,Xie X, COVID-19 and the cardiovascular system. Nature reviews. Cardiology. 2020 May;     [PubMed PMID: 32139904]

[9]

Dong M,Zhang J,Ma X,Tan J,Chen L,Liu S,Xin Y,Zhuang L, ACE2, TMPRSS2 distribution and extrapulmonary organ injury in patients with COVID-19. Biomedicine     [PubMed PMID: 32861070]

[10]

Sanyaolu A,Okorie C,Marinkovic A,Patidar R,Younis K,Desai P,Hosein Z,Padda I,Mangat J,Altaf M, Comorbidity and its Impact on Patients with COVID-19. SN comprehensive clinical medicine. 2020 Jun 25;     [PubMed PMID: 32838147]

[11]

Leung JM,Yang CX,Tam A,Shaipanich T,Hackett TL,Singhera GK,Dorscheid DR,Sin DD, ACE-2 expression in the small airway epithelia of smokers and COPD patients: implications for COVID-19. The European respiratory journal. 2020 May;     [PubMed PMID: 32269089]

[12]

Padda I,Khehra N,Jaferi U,Parmar MS, The Neurological Complexities and Prognosis of COVID-19. SN comprehensive clinical medicine. 2020 Sep 29;     [PubMed PMID: 33015552]

[13]

Babapoor-Farrokhran S,Gill D,Walker J,Rasekhi RT,Bozorgnia B,Amanullah A, Myocardial injury and COVID-19: Possible mechanisms. Life sciences. 2020 Jul 15;     [PubMed PMID: 32360126]

[14]

Shi S,Qin M,Cai Y,Liu T,Shen B,Yang F,Cao S,Liu X,Xiang Y,Zhao Q,Huang H,Yang B,Huang C, Characteristics and clinical significance of myocardial injury in patients with severe coronavirus disease 2019. European heart journal. 2020 Jun 7;     [PubMed PMID: 32391877]

[15]

Pei G,Zhang Z,Peng J,Liu L,Zhang C,Yu C,Ma Z,Huang Y,Liu W,Yao Y,Zeng R,Xu G, Renal Involvement and Early Prognosis in Patients with COVID-19 Pneumonia. Journal of the American Society of Nephrology : JASN. 2020 Jun;     [PubMed PMID: 32345702]

[16]

Raza A,Estepa A,Chan V,Jafar MS, Acute Renal Failure in Critically Ill COVID-19 Patients With a Focus on the Role of Renal Replacement Therapy: A Review of What We Know So Far. Cureus. 2020 Jun 3;     [PubMed PMID: 32642345]

[17]

Agarwal A,Chen A,Ravindran N,To C,Thuluvath PJ, Gastrointestinal and Liver Manifestations of COVID-19. Journal of clinical and experimental hepatology. 2020 May-Jun;     [PubMed PMID: 32405183]

[18]

Kopel J,Perisetti A,Gajendran M,Boregowda U,Goyal H, Clinical Insights into the Gastrointestinal Manifestations of COVID-19. Digestive diseases and sciences. 2020 Jul;     [PubMed PMID: 32447742]

[19]

Kaur SP,Gupta V, COVID-19 Vaccine: A comprehensive status report. Virus research. 2020 Oct 15;     [PubMed PMID: 32800805]

[20]

Ura T,Yamashita A,Mizuki N,Okuda K,Shimada M, New vaccine production platforms used in developing SARS-CoV-2 vaccine candidates. Vaccine. 2020 Nov 24;     [PubMed PMID: 33279318]

[21]

Ledford H,Cyranoski D,Van Noorden R, The UK has approved a COVID vaccine - here's what scientists now want to know. Nature. 2020 Dec;     [PubMed PMID: 33288887]

[22]

Mahase E, Covid-19: UK approves Pfizer and BioNTech vaccine with rollout due to start next week. BMJ (Clinical research ed.). 2020 Dec 2;     [PubMed PMID: 33268330]

[23]

Cabanillas B,Akdis C,Novak N, Allergic reactions to the first COVID-19 vaccine: a potential role of Polyethylene glycol? Allergy. 2020 Dec 15;     [PubMed PMID: 33320974]

[24]

Tanne JH, Covid-19: FDA panel votes to approve Pfizer BioNTech vaccine. BMJ (Clinical research ed.). 2020 Dec 11;     [PubMed PMID: 33310748]

[25]

Tanne JH, Covid-19: Pfizer-BioNTech vaccine is rolled out in US. BMJ (Clinical research ed.). 2020 Dec 14;     [PubMed PMID: 33318040]

[26]

Chien KR,Zangi L,Lui KO, Synthetic chemically modified mRNA (modRNA): toward a new technology platform for cardiovascular biology and medicine. Cold Spring Harbor perspectives in medicine. 2014 Oct 9;     [PubMed PMID: 25301935]

[27]

Heaton PM, The Covid-19 Vaccine-Development Multiverse. The New England journal of medicine. 2020 Nov 12;     [PubMed PMID: 32663910]

[28]

Choi KR, A Nursing Researcher's Experience in a COVID-19 Vaccine Trial. JAMA internal medicine. 2020 Dec 7;     [PubMed PMID: 33284328]

[29]

Mahase E, Covid-19: People with history of significant allergic reactions should not receive Pfizer vaccine, says regulator. BMJ (Clinical research ed.). 2020 Dec 10;     [PubMed PMID: 33303484]