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COVID-19 Vaccines a Literature Analysis of the Three First Approved COVID-19 Vaccines in the EU

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COVID-19 Vaccines a Literature Analysis of the Three First Approved COVID-19 Vaccines in the EU COVID-19 Vaccines A literature analysis of the three first approved COVID-19 Vaccines in the EU Morgan Persson Bachelor thesis, 15 hp Pharmacist program, 300 hp Report approved: Spring 2021 Supervisor: Martin Bäckström. Examinor: Maria Sjölander Abstract The SARS-CoV-2 virus, more famously known as Coronavirus disease 2019 (“Covid-19”), has claimed over 3.4 million lives worldwide. The virus, belonging to the RNA coronavirus family, emerged from China during the end of 2019 and was declared a global pandemic by the World Health Organization (WHO) in March 2020. The SARS-CoV-2 genome sequence was published and available on January 11th, 2020. Thereafter multiple pharmaceutical companies began researching on a vaccine. The objective of this literature study was to evaluate the efficacy and safety profiles of the three first approved SARS-CoV-2 vaccines in the EU. This literature study was primarily built on original articles on the three first approved SARS-CoV-2 vaccines in the EU. Two main methods were used to find relevant articles. The primary method was by using the PubMed database and sorting out relevant articles as seen in Table 1 and 4. The focus was randomized control trials for efficacy and safety and/or articles researching efficacy and/or safety. PubMed was used for its robust and large database of articles. The secondary method of finding articles was by searching in The New England Journal of Medicine (NEJM) found in table 2 or in The Lancet, found in table 3. These journals were used primarily for the reason being that papers on the vaccines were originally published in these journals and a lot of other articles regarding the vaccine’s efficacy were published there as well. Articles from NEJM and The Lancet were sorted for relevancy in a similar manner as searches done in PubMed. All vaccines showcased good protection against severe Covid-19. Zero participants in the trial arm of any of the vaccines died from severe Covid-19. Likewise, all vaccines in their respective trials showcased overall high safety with reactogenicity being mild in all trials. Most common local reactions across all vaccines were post-injection pain, tenderness, and redness. All 0f whom lasted a few days. Likewise, systemic reactions were overall mild to moderate in nature with the most common reactions being fatigue, myalgia (or “muscle pain”), headache(s) and arthralgia (or “joint pain”), these too lasted a few days. In general, the odds of receiving any reaction were high; but the reactions themselves were of modest nature, indicating the vaccines were well-tolerable compared to placebo and/or active control. Despite its limitations and disadvantages, this paper can showcase that the three first Covid-19 vaccines approved in the EU (BNT162b2; mRNA-1273 and AZD1222) present overall high efficacy and safety for their approved ages. Future research is needed to assess efficacy for Covid-19 variants of concern and efficacy and safety for adolescents Keywords: COVID-19, COVID-19 Vaccines, SARS-CoV-2, Corona. Abbreviations and definitions ACE2 = Angiotensin-Converting Enzyme 2 APCs = Antigen-Presenting Cells ARR = Absolute Risk Reduction CI = Confidence Interval Covid-19 = Coronavirus Disease 2019 dsDNA = double stranded Deoxyribonucleic Acid EMA = European Medicines Agency FDA = Food and Drug Administration HIV = Human Immunodeficiency Viruses IL-6 = Interleukin-6 IL-8 = Interleukin-8 MERS-CoV = Middle East Respiratory Syndrome Coronavirus MHC1 = Major Histocompatibility Complex 1 MHC2 = Major Histocompatibility Complex 2 MHRA = Medicines and Healthcare products Regulatory Agency NIAID = National Institute of Allergy and Infectious Diseases NIH = National Institutes of Health NNT = Number Needed to Treat NNV = Number Needed to Vaccinate PAMPs = Pathogen-Associated Molecular Patterns ORF = Open Reading Frames RBD = Receptor Binding Domain RRR = Relative Risk Reduction SARS-CoV = Severe Acute Respiratory Syndrome Coronavirus SARS-CoV-2 = Severe Acute Respiratory Syndrome Coronavirus 2 ssRNA = single stranded Ribonucleic Acid TMPRSS2 = Transmembrane protease, serine 2 URT = Upper Respiratory Tract Table of Contents Abstract……………………………………………………………………………………………………………………I Abbreviations………………………………………………………………………………………………………….II 1. Introduction………………………………………………………………………………………………………….1 1.1. The immune system…………………………………………………………………………………………1 1.2. SARS-CoV-2…………………………………………………………………………………………………..1 1.2.1. Origins…………………………………………………………………………………………………….1 1.2.2. Taxonomy……………………………………………………………………………………………….1 1.2.3. Transmission………………………………………………………………………………..…………1 1.2.4. Pathology………………………………………………………………………..………………………1 1.2.5. Risk Factors…………………………………………………………………………………………….2 1.2.6. Genome…………………………………………………………………………………………………..2 1.3. Vaccines………………..………………………………………………………………………………………3 1.3.1. RNA Vaccines: Mechanism of action overview…………………………………………….3 1.3.2. RNA Vaccines: Historical overview……………………………………………………………4 1.3.3. BioNTech-Pfizer………………………………………………………………………………………4 1.3.4. Moderna…………………………………………………………………………………..…………….4 1.3.5. Viral Vector Vaccines: Mechanism of action overview………………………………….5 1.3.6. Viral Vector Vaccines: Historical overview………………………………………………….5 1.3.7. Oxford-AstraZeneca………………..………………………………………………………….……5 1.4. Objective……………………………………………………………………………………………………….6 2. Method……………………………………………………………………………………………………………..…7 3. Results……………………………………………………………………………………………………………….10 3.1. Pfizer: BNT162b2 Phase 2 / 3 trial methodology……………………………………………...10 3.1.1. BNT162b2 Phase 2 / 3 trial participant information…………………………………..10 3.1.2. BNT162b2 Safety……………………………………………………………………………..…….10 3.1.3. BNT162b2 Local reactogenicity…………………………………………………..…………..10 3.1.4. BNT162b2 Systemic reactogenicity………………………………………………….……….11 3.1.5. BNT162b2 Efficacy……………………..…………………………………………………………..11 3.1.6. Articles showcasing BNT162b2 against variants of concern…………………..……12 3.1.7. Adverse events from BNT162b2 seen in practice……………………..…………………12 3.2. Moderna: mRNA-1273 Phase 3 methodology…………………………………………………..12 3.2.1. mRNA-1273 Phase 3 participant information……………………………………………13 3.2.2. mRNA-1273 Safety…………………………………………………………………………………13 3.2.3. mRNA-1273 Local reactogenicity…………………………………………………….………13 3.2.4. mRNA-1273 Systemic reactogenicity…………………………………………….………….13 3.2.5. mRNA-1273 Efficacy………………………………………………………………………………14 3.2.6. Articles showcasing mRNA-1273 against variants of concern…………………..…14 3.2.7. Adverse events from mRNA-1273 seen in practice………………..……………………15 3.3. AstraZeneca: AZD1222 Trial methodology………………………………………………………15 3.3.1 AZD1222 Trials Participant information……………………………………………………16 3.3.2. AZD1222 Safety………………..……………………………………………………………..…….16 3.3.3 AZD1222 Local reactogenicity………………………………………………………………….17 3.3.4. AZD1222 Systemic reactogenicity…………………………………………………………….17 3.3.5. AZD1222 Efficacy…………………………………………………………………………………..18 3.3.6 AZD1222 against variants of concern………………………………………………………..19 3.3.7 Adverse events from AZD1222 seen in practice: Case series………………………..19 3.3.8 Adverse events from AZD1222 seen in practice: Cohort……………………………..19 4. Discussion………………………………………………………………………………………………………..…21 4.1. Result discussion…………………..………………………………………………………………………21 4.1.1. Prevention of Covid-19/severe Covid-19 vaccine efficacy………………..…………..21 4.1.2. Vaccine side effects……………………………..…………………………………………………22 4.1.3. Vaccine efficacy against SARS-CoV-2 variants of concern……………..…………..23 4.1.4. Future research……………………………………………………………………………………..24 4.1.5. Method discussion…………………………………………………………………………………24 4.2. Conclusion…………………………………………………………………………..………………………24 5. Acknowledgements……………………………………………………………………………………………..25 6. References…………………………………………………………………………………………………….……26 Appendix………………………………………………………………………………………………………….…….31 1. Introduction As of writing this paper the severe acute respiratory syndrome coronavirus 2, also known as SARS-CoV-2 virus and more famously as Coronavirus disease 2019 (“Covid-19”), has claimed over 3.4 million lives worldwide (1). The virus, belonging to the ssRNA (single stranded ribonucleic acid) coronavirus family, emerged from China during the end of 2019 (2) and was declared a global pandemic by the World Health Organization (WHO) in March 2020 (2,3). The coronavirus family, with their characteristic surface protein resembling a crown (Latin: corona for crown), were discovered during the 1960s in humans (4) and as of writing this paper there are seven known viruses within the coronavirus family that infect humans (4,5). Notable examples besides SARS-CoV-2 are MERS-CoV (Middle East Respiratory Syndrome Coronavirus) and SARS-CoV respectively (4,5). 1.1. The immune system When a pathogen enters the human body, it encounters the immune system. Our immune system is compromised of two primary components; the innate and adaptive immune system. Our innate immune system is basic in its function and is our first line of defense, primarily consisting of phagocytes (e.g., macrophages, neutrophils, and so forth). Its most basic function is to protect the human body regardless of invader. Whereas the adaptive immune system (composing of T-lymphocytes such as T-helper cells and Cytotoxic T- Cells or B-lymphocytes such as Clonal- and Memory B-cells) main function is to eliminate pathogens and remember them specifically and methodically. The latter of which is of great importance to vaccines given that they train the adaptive immune system to remember pathogens if the body encounters them in the future (6). 1.2. SARS-CoV-2 1.2.1. Origins SARS-CoV-2 emerged
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