Medicines and Vaccines in Dealing with Covid-19

Xianyi Zheng

Li Po Chun United World College of Hong Kong, HKSAR, China

Keywords:

SARS-CoV-2, Covid-19, Medecines, Vaccines.

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)(Wikipedia 2021) has several components,

including spike protein and membrane protein, and has several variants. Currently, remdesivir and

dexamethasone are two common medicines that are used for treatments of the Covid-19 disease. It has been

shown that the recovery time for patients who were treated with these two drugs was much shorter than

patients who did not treat with them and the mortality of patients who were treated with them was lower than

patients who did not. Also, several vaccines, including vaccines produced by Moderna, vaccines produced by

BioNTech/ Pfizer, and vaccines produced by Oxford/ AstraZeneca have shown efficacies in preventing

infection of the virus. The efficacies of these three vaccines towards original SARS-CoV-2 were all above

70%, for which vaccine produced by Moderna, vaccine produced by BioNTech/ Pfizer was around 94.5%

(Moderna, Inc. 2020) and 95%)(Polack et al. 2020), and that of Oxford/ AstraZeneca was around

70%(NEEDHAM 2020). However, when dealing with SARS-CoV-2 variants, the efficacies of these three

vaccines decreased. In conclusion, although different medicines and vaccines have been used to prevent the

exacerbation of the Covid-19 pandemic, the emerge of SARS-CoV-2 variants is still a challenge as these

variants decrease the efficacies of vaccines and increase the infection rate.

1 INTRODUCTION

A new type of coronavirus (severe acute respiratory

syndrome coronavirus 2) was rapidly spread in

Wuhan, China, in late 2019. Although many

governments and non-government organizations put

a large number of financial resources into tackling the

pandemic, it is hard to observe the turning point of

this pandemic until now, and the future course of this

virus is still unknown. Many companies and

institutions have been trying to invent vaccines and

medicines based on the structure of COVID-19, and

some of them have major breakthroughs on vaccines

and medicines. This paper would illustrate the basic

structure of coronavirus and give a broad overview of

the current medicines and the development of

vaccines. Topics discussed in the paper give the

newest update to understand the current situation of

the pandemic, which is essential to the fundamental

development of different research.

https://orcid.org/0000-0003-1467-1342

2 STRUCTURE OF SARS-COV-2

SARS-CoV-2 is a single-stranded RNA-enveloped

virus (figure 1), and like other viruses, it cannot

survive without a host cell. This virus has been

reported that it has more than 95% homology with the

coronavirus in the bat’s body and more than 70%

similar to the SARS-CoV. RNA of the virus gives its

structure and enables it to replicate. It has structural

proteins, such as the S (Spike) protein, the E

(Envelope) protein, the M (Membrane), and N

(Nucleocapsid) proteins, and non-structural proteins,

such as 3-chymotrypsin-like protease, papain-like

protease, and RNA-dependent RNA

polymerase(Huang, Yang, Xu, Xu, and Liu 2020).

2.1 Spike Protein

The spike protein gives the virus a “corona” structure.

For spike protein (figure 1), it is responsible for a

virus to attach to the membrane of the host cell, and

it has two functional subunits (figure 2), which are S1

and S2. The S1 subunit consists of the N-terminal

Zheng, X.

Medicines and Vaccines in Dealing with Covid-19.

DOI: 10.5220/0011248000003443

In Proceedings of the 4th International Conference on Biomedical Engineering and Bioinformatics (ICBEB 2022), pages 601-611

ISBN: 978-989-758-595-1

601

domain (NTD) and receptor-binding domain (RBD)

(Huang, Yang, Xu, Xu, Liu 2020), which allows it to

bind to the host cell receptor. The S2 subunit

comprises of fusion peptide (FP), heptad repeat 1

(HR1), central helix (CH), connector domain (CD),

heptad repeat 2 (HR2), transmembrane domain (TM),

and cytoplasmic tail (CT) (Huang, Yang, Xu, Xu, and

Liu 2020) (Figure 3), which allows it to mediate the

fusion of viral and cellular membranes. The receptor-

binding domain (RBD) recognizes a specific receptor

called the ACE2 (angiotensin-converting enzyme

receptor 2). It has shown that the binding of ACE2

receptor with RBD is at least the same affinity and

potentially as much as 20 times greater affinity than

the SARS virus. Such high infinity could be one of

the explanations for the reasons why it spreads so

easily.

2.2 Membrane Protein

The membrane protein (figure 1) is the most abundant

protein on the viral surface and defines the shape of

the viral envelope. It likes a central organizer for

coronavirus assembly and interacts with the other

structural proteins on the viral membrane.

2.3 Other Components and

Nucleocapsid Protein

The viral envelope (figure 1), a fatty layer, is

underneath the surface proteins derived from the host

cell membrane. When it contacts with soap, it will

break down and die, which suggests that

handwashing with soap is essential to prevent the

spread of this virus.

Underneath this layer is a capsid, a protein shell

that encloses the virus’s genetic material. Inside this

capsid, nucleocapsid proteins (figure 1) can be found.

These proteins are bound to the virus’s single strand

of RNA, which is the place where genetic information

is held to allow the virus to replicate. Nucleocapsid

protein is multifunctional. It essentially inhibits a lot

of host cells defense mechanisms and assists the viral

RNA in replicating itself and, therefore, in creating

new viral particles.

Figure 1: (LubioScience 2020). Structure of SARS-CoV-2.

Figure 2: (Mansbach, Chakraborty, Nguyen, Montefiori,

Korber, Gnanakaran 2021). Structure of spike protein.

3 SYMPTONS OF DISEASE

3.1 Transmission of COVID-19

Infection

People of all ages can be infected by this virus.

Infection is transmitted through a droplet of saliva or

snivel generated during talking, coughing, or

sneezing of symptomatic patients but can also occur

from asymptomatic people. Also, contact surface

spread, which means that directly touching the

surface which has viruses on it, is possible for virus

transmission, and it has been reported that this type of

virus can be transmitted through the air.

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3.2 Symptoms

Typically, COVID-19 symptoms begin one to

fourteen days after exposure to the virus. On average,

it takes 5–6 days from when someone is infected with

the virus for symptoms to

Figure 3: (Mansbach, Chakraborty, Nguyen, Montefiori,

Korber, Gnanakaran 2021): Detail structure of spike

protein.

show; however, it can take up to 14 days. Around one

in five infected individuals do not develop any

symptoms. Most people have mild symptoms, and the

most common mild symptoms of COVID-19 are

fever, dry cough, and fatigue(Wikipedia 2021). Also,

other mild symptoms that are less common but still

can affect some people, including loss of taste or

smell, nasal congestion, conjunctivitis (also known as

red eyes), sore throat, headache, muscle or joint pain,

different types of skin rash, nausea or vomiting,

diarrhea, and chills or dizziness(World Health

Organization 2021). However, some may have severe

symptoms, including shortness of breath, loss of

appetite, confusion, persistent pain or pressure in the

chest, high temperature(above 38 °C) (World Health

Organization 2021). Other less common severe

symptoms include irritability, confusion, reduced

consciousness (sometimes associated with seizures),

anxiety, depression, sleep disorders, and more severe

and rare neurological complications such as strokes,

brain inflammation, delirium, and nerve damage

(Wikipedia 2021). Some people even develop acute

respiratory distress syndrome (ARDS). ARDS can be

precipitated by cytokine storms, multi-organ failure,

septic shock, and blood clots (Wikipedia 2021).

Longer-term damage to organs (in particular, the

lungs and heart) has been observed (Wikipedia 2021).

4 VARIANTS OF SARS-COV-2

Variants of SARS-CoV-2 are caused by the mutation

of the genetic sequence of the virus. The mutation of

the genetic sequence of a virus can affect its property,

such as transmissibility. Up to August 2021, there are

many variants of SARS-CoV-2, and four of them:

Alpha, Beta, Gamma, and Delta, are listed in

currently designated variants of concern according to

the World Health Organisation(World Health

Organization 2021). Apart from these four variants,

lambda variant, another variant of SARS-CoV-2, is

also under concern.

4.1 Alpha

The Alpha variant, also known as lineage B.1.1.7,

was first documented in the United Kingdom in

September 2020(World Health Organization 2021). It

has been found that the transmissibility of this variant

is around 29%, substantially higher than the original

one. One of the most important differences between

the original virus and the Alpha one is the amino acid

in position 501. In the Alpha variant, the amino acid

position 501 is tyrosine instead of asparagine. Such

changes in amino acids cause changes in the receptor-

binding domain (RBD), which changes the specificity

of the binding between human ACE2 receptors and

RBD(Wikipedia 2021). This allows viruses to

become more infectious.

4.2 Beta

The beta variant, also known as lineage B.1.351, was

first recorded in South Africa in May 2020 (World

Health Organization 2021). It has also been proved

that the transmission rate of this variant is higher than

the original one. There is a total of eight mutations in

the spike proteins in this virus, including K417N (a

change from lysine to asparagine in amino acid

position 417), E484K (a change from glutamic acid to

lysine in amino acid position 484), and N501Y (a

change from asparagine to tyrosine in amino acid

position 501) (Wikipedia 2021). Similar to the

situation in the alpha variant, these mutations cause

changes in the receptor-binding motif (RBM) of the

receptor-binding domain (RBD), which allows the

beta variants to spread faster.

4.3 Gamma

The gamma variant, known as lineage P.1, is one of

the variants of SRAS-CoV-2. It was first recorded in

Brazil in November 2020(World Health Organization

2021). This variant has ten amino acids mutations,

including N501Y (a change from asparagine to

tyrosine in amino acid position 501), E484K (a

change from glutamic acid to lysine in amino acid

position 484), and K417T (a change from lysine to

threonine in amino acid position 417) (Wikipedia

2021). It has been shown that the transmission rate is

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approximately 38%, which is higher than that of the

alpha variant.

4.4 Delta

The delta variant, known as lineage B.1.617.2, has the

highest transmissibility of all discovered variants. It

was first identified in India in October 2020

according to the WHO(World Health Organization

2021). Mutations, D614G (an aspartic acid-to-glycine

substitution at amino acid position 614), T478K (a

threonine-to-lysine substitution at amino acid

position 478), L452R (a leucine-to-arginine

substitution at amino acid position 452), and P681R

(a proline-to-arginine substitution at amino acid

position 681), are found in delta variants (Wikipedia

2021). The common symptoms of the delta variant

have changed. Headaches, sore throat, a runny nose,

and fever are common symptoms of this

variant(healthline 2021).

4.5 “Delta Plus”

“Delta plus” variant is a delta variant with K417N

mutation (a lysine-to-asparagine substitution at

amino acid position 417) (Wikipedia 2021).

4.6 Lambda

Lambda variant, known as lineage C.37, was first

detected in Peru in December 2020. G75V, T76I,

L452Q, F490S, D614G, and T859N mutations and a

7-amino-acid deletion in the NTD (RSYLTPGD246-

253N) were found in the spike protein of the lambda

variant(Kimura et al. 2021). It has been shown that

this variant is more infectious, and the deletion in

NTD is responsible for neutralizing antibiotics

(Kimura et al. 2021).

5 CURRENT MEDICINES

Two common medicines – remdesivir and

dexamethasone -- that are used for the covid-19

treatment would be discussed below.

5.1 Remdesivir

Remdesivir is one of the most common medicines

that is used for the treatment of COVID-19 because it

has been shown in research that it is efficacious.

Remdesivir is an intravenous nucleotide prodrug of

an adenosine analog. Remdesivir binds to the viral

RNA-dependent RNA polymerase, inhibiting viral

replication through premature termination of RNA

transcription(NIH 2021).

5.1.1 Analysis of the Research of Remdesivir

In the research, there were 1114 patients who were

assessed for eligibility: 1062 of them underwent

randomization; 541 of them were allocated to the

remdesivir group, and 521 were placed to the placebo

group(Beigel et al. 2020). The primary analysis was a

stratified log-rank test of the time to recovery with

remdesivir as compared with placebo, with

stratification by disease severity(Beigel et al. 2020).

5.1.2 Primary Outcome

Patients in the remdesivir group (median: 10 days;

rate ratio of recovery: 1.29) recovered faster than

patients in the placebo group (median: 15 days)

(Beigel et al. 2020). The 95% confidence interval (CI)

and the probability of extreme cases were 1.12-1.49

and <0.001 (Beigel et al. 2020). Among patients who

were hospitalized and required any supplementary

oxygen, the rate ratio for recovery was 1.45 (95% CI,

1.18 to 1.79) (Beigel et al. 2020); among patients who

were hospitalized and did not require any

supplementary oxygen but required ongoing medical

care and those who were hospitalized and required

noninvasive ventilation or use of high-flow oxygen

devices, the rate ratio of recovery were 1.29 (95% CI,

0.91 to 1.83) and 1.09 (95% CI, 0.76 to 1.57),

respectively(Beigel et al. 2020). The rate ratio for

recovery was 0.98 (95% CI, 0.70 to 1.36) for those

receiving mechanical ventilation or ECMO at

enrollment(Beigel et al. 2020). Patients who

underwent randomization during the first 10 days

after the onset of symptoms had a rate ratio for

recovery of 1.37 (95% CI, 1.14 to 1.64), which was

higher than that of those who underwent

randomization more than ten days after the onset of

symptoms (1.20; 95% CI, 0.94 to 1.52) (Beigel et al.

2020). P value in this experiment is very small, which

means that the probability of extreme cases in this

research is very small. Also, high confidence interval

(CI), 95% (Beigel et al. 2020), ensures the accuracy

of the primary outcome in the research of remdesivir.

5.1.3 Key Secondary Outcome

Mortality of patients in the remdesivir group was

numerically lowered than those in the placebo group,

but the difference was not significant (hazard ratio,

0.55; 95% CI, 0.36 to 0.83) (Beigel et al. 2020). The

mortality by 14 days was 6.7% and 11.9% in the

remdesivir and placebo groups, respectively(Beigel et

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al. 2020). The mortality rate by day 29 was estimated

to be 11.4% in remdesivir group and 15.2 in placebo

group, respectively (hazard ratio, 0.73; 95% CI, 0.52

to 1.03) (Beigel et al. 2020). Patients in the remdesivir

group (24.6%) who had serious adverse events were

lower than those in the placebo group (31.6%);

patients in the remdesivir group who suffered from

serious respiratory failure (8.8%) were lower than

those in the placebo group (15.5%)(Beigel et al.

2020). However, patients in the remdesivir group who

suffered from pyrexia were higher than those in the

placebo group. Other comparisons of safety outcomes

are shown in Table 1. Therefore, it can be observed

that the possibility of serious adverse events occurred

in the remdesivir group is much less than that in the

placebo group.

5.2 Dexamethasone

Dexamethasone is a corticosteroid that has been

recommended by the National Health Service in the

UK and the National Institutes of Health (NIH) in the

US for the treatment of the Covid-19. It is used to treat

those who are very ill, and it has been shown that

patients who were treated with dexamethasone

recovered faster because dexamethasone can

modulate inflammation-mediated lung injury caused

by the SRAS-CoV-2 and thereby reduce progression

to respiratory failure and death(Engl 2021).

Table 1: A Table showing the negative effects of

remdesivir. All the data is collected from Remdesivir for

the Treatment of Covid-19 — Final Report (Beigel et al.

2020).

Events Remdesivir

group

Placebo group

Total serious

adverse event

occurred

131 out of 531

patients

(24.6%)

163 out of 516

patients (31.6%)

Serious respiratory

failure adverse

events

47 patients

(8.8%)

80 patients

(15.5%)

Acute respiratory

failure,

hypotension, viral

pneumonia, and

acute kidney injury

Less common More common

Death related to

treatment

assignmen

No No

Anemia or

decreased

hemoglobin

43 events

(7.9%)

47 events (9.0%)

Acute kidney

injury, decreased

estimated

glomerular

filtration rate or

creatinine

40 events

(7.4%)

38 events (7.3%)

clearance, or

increased blood

creatinine

Pyrexia 27 events

(5.0%)

17 events (3.3%)

Hyperglycemia or

increased blood

glucose level

22 events

(4.1%)

17 events (3.3%)

Increased

aminotransferase

levels including

alanine

aminotransferase,

aspartate

aminotransferase,

or both

22 events

(4.1%)

31 vents

(5.9%)

5.2.1 Samples of the Research of

Dexamethasone

In this research, a total of 6425 patients underwent

randomization, where 2104 of them were assigned to

receive dexamethasone, and 4321 of them received

usual care(Engl 2021). The mean age of the patients

in this research was 66.1±15.7 years(Engl 2021). 36%

of them were female, and 18% were Black, Asian, or

from a minority ethnic group(Engl 2021).

5.2.2 Primary Outcome and Secondary

Outcome

At 28 days, mortality of those who received treatment

of dexamethasone (22.9%) was lower than that of

those who received usual treatments (25.7%) (rate

ratio, 0.83; 95% confidence interval [CI], 0.75 to

0.93; P<0.001) (Engl 2021). Among patients

receiving invasive mechanical ventilation, the

incidence of death in the dexamethasone group

(29.3%) was lower than that in the usual care group

(41.4%) (rate ratio, 0.64; 95% CI, 0.51 to 0.81) (Engl

2021). However, no obvious effect of dexamethasone

could be seen among patients who were not receiving

any respiratory support at randomization(Engl 2021).

5.2.3 Secondary Outcome and Other

Prespecribe Clinical Outcomes

Patients who received dexamethasone as treatment

(median: 12 days) had a shorter duration of

hospitalization than those who received usual care

(median: 13days) and had a greater probability of

discharging alive(Engl 2021). The percentage of

patients who received Invasive mechanical

ventilation or died in the dexamethasone group (26%)

was lower than that of those in the usual group

(27.6%) (rate ratio: 0.93; 95% CI, 0.85–1.01) (Engl

2021). The percentage of patients who were not

receiving invasive mechanical ventilation at

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randomization and progressed to received invasive

mechanical ventilation later was lower in the

dexamethasone group than in the usual care group

(risk ratio, 0.79; 95% CI, 0.64 to 0.97) (Engl 2021).

The percentage of those who were receiving invasive

mechanical ventilation at randomization and did not

require invasive mechanical ventilation later was

higher in the dexamethasone group than in the usual

care group (rate ratio, 1.47; 95% CI, 1.20 to 1.78)

(Engl 2021). The percentage of the patients who were

not receiving renal- replacement therapy (renal

dialysis or hemofiltration) at randomization and had

to use later within 28 days was lower in the

dexamethasone group than in the usual care group

(risk ratio, 0.61; 95% CI, 0.48 to 0.76) (Engl 2021).

6 VACCINES

There are many covid-19 vaccines in the market, and

this paper will focus on three vaccines developed by

three renowned institutions -- Moderna, Pfizer/

BioNTech, and Oxford/ AstraZeneca. These

companies all had major breakthroughs in COVID-19

vaccine development in 2020. Vaccines developed by

these institutions have already been purchased by

different governments and used in different countries.

They all showed high efficacies for the prevention of

original SRAS-CoV-2. However, due to the

development of the pandemic and the evolvement of

different variants, the efficacies of these vaccines are

challenged.

6.1 Vaccine Produced by Moderna

Moderna, a biotechnology company, specializes in

the mRNA vaccine for COVID-19. It shows that a

total of 30,000 people in the United States have

participated in its COVID-19 vaccine clinical trial,

for which 79.4% are White, 10% are African

American, 5% are Asian, and <5% other

races/ethnicities (CDC 2021). For the age and sex

breakdown of those people, 52.6% are male, 47.4%

are female, 25% are 65 years and older, and 75% of

people are between 18-64 years old(CDC 2021).

According to data published by CDC, most people

who participated in the trials (82%) were considered

to have an occupational risk of exposure, with 25% of

them being healthcare workers(CDC 2021). People in

the clinical trials, 22.3% had at least one high-risk

condition, which included lung disease, heart disease,

obesity, diabetes, liver disease, or HIV

infection(CDC 2021). Four percent (4%) of

participants had two or more high-risk

conditions(CDC 2021). Of the 15,000 vaccinated

volunteers, only 11 were infected with the virus, and

no one developed severe symptoms(Moderna, Inc.

2020). Among the 15,000 placebo-vaccinated

volunteers, 185 were infected with the virus, of which

30 developed into severely ill patients, and one died

because of the disease(Moderna, Inc. 2020). It is

pointed out in the Moderna’s latest vaccine phase III

clinical trial data submitted to the FDA that the

vaccine efficacy is 94.5% (P<0.0001) (Moderna, Inc.

2020) in preventing infection with Covid-19 and can

prevent 100% of the severe symptoms of Covid-19.

By using the genetic information of COVID-19,

the sequence of spike proteins in the virus is identified

and encoded into mRNA. When humans received the

vaccines, the mRNA is taken into immune cells.

When mRNA is inside immune cells, the cells use it

to make the protein. After the protein is made, the

cells break down the mRNA. Next, the cells display

these protein pieces on their surface, which allows the

immune systems to recognize these proteins and

begin building an immune response by making

antibodies. These antibodies can prevent the body

from getting an infection in the future. The benefit of

mRNA vaccines, like all vaccines, is those vaccinated

gain this protection without ever having to risk the

serious consequences of getting sick with COVID-19.

(Figure 4)

6.2 General Information about the

Injection of Vaccine Produced by

Moderna

People receive vaccines in the muscle of the upper

arm. Normally they receive two doses, the time of

which was a month (28 days) apart (CDC 2021). The

vaccine also does not contain eggs, preservatives, and

latex(CDC 2021). The vaccine is recommended for

people who are more than or equal to 18-year-old

(CDC 2021). Also, pain, swelling, and redness were

the most common side effects in the arm where

people got the injection, and chills, tiredness, and

headache frequently happened throughout the rest of

the body (CDC 2021). These side effects usually start

within the first two days after getting the vaccine

(CDC 2021). They might feel like flu symptoms and

might even affect people's ability to do daily

activities, but normally they will go away in a few

days (CDC 2021).

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6.3 Vaccine Produced by Pfizer/

BioNTech

BioNTech is another company that specialized in the

mRNA vaccine for COVID-19. About 82% of people

who participated in the research are White, 9.8% are

African American, 4.4% are Asian, and <3% other

races/ethnicities (CDC 2021). For the age and sex

breakdown, 50.6% of the people are male, 49.4% are

female, and 21.4% are 65 years and older (CDC

2021). Also, the most frequent underlying medical

conditions for those people were obesity (35.1%),

diabetes (8.4%), and pulmonary disease (7.8%) (CDC

2021). Among 36,523 participants who had no

evidence of existing or prior SARS-CoV-2 infection,

8 cases of Covid-19 with onset at least seven days

after the second dose were observed among vaccine

recipients and 162 among placebo recipients. This

case split corresponds to 95.0% vaccine efficacy

(95% confidence interval [CI], 90.3 to 97.6) (Polack

et al. 2020). Among participants with and those

without evidence of prior SARS CoV-2 infection, 9

cases of Covid-19 at least seven days after the second

dose were observed among vaccine recipients and

169 among placebo recipients, corresponding to

94.6% vaccine efficacy (95% CI, 89.9 to 97.3)

(Polack et al. 2020). In general, local reactions were

mostly mild-to-moderate in severity and resolved

within 1 to 2 days. No deaths were considered by the

investigators to be related to the vaccine(CDC 2021).

By using the genetic information of COVID-19,

the sequence of spike protein in the virus is identified.

This sequence is encoded into mRNA. mRNA

formulated in LNP enters the cell. When the whole

things enter the cell, mRNA is released. Then, spike

protein is made and processed. APCs present spike

protein fragments, and these can activate the

formation of T cells and B cells. The CD8+ cytotoxic

T cells can eliminate virus-infected cells and

potentially increase the length of protection. The B

cells will become virus-neutralizing antibodies.

These can bind spike proteins and prevent virus

infection of human cells. In addition, the memory T

and B cells provide immune memory to ensure long-

term protection against the virus.

6.4 General Information about the

Injection of Vaccine Produced by

Pfizer/ BioNTech

People receive vaccines in the muscle of the upper

arm. Normally, they receive two doses, the time of

which was 21 days apart. The vaccine does not

contain eggs, preservatives, and latex(CDC 2021).

This vaccine is available for people aged 12 years

older (CDC 2021). The side effects of this vaccine are

similar to those produced by Moderna.

6.5 Information about People Who

Cannot Receive mRNA Vaccines,

Both Vaccines Produced by

Moderna or Pfizer/ BioNTech

People who have severe allergic reactions

(anaphylaxis) or an immediate allergic reaction to any

ingredient in an mRNA COVID-19 vaccine should

not get this mRNA vaccine (CDC 2021). Also, people

who have severe or immediate allergic reactions

(anaphylaxis) after getting the first dose of the

vaccine should not get another dose of this mRNA

COVID-19 vaccine (CDC 2021). In both situations

mentioned above, a reaction within 4 hours of getting

vaccinated, including symptoms such as hives,

swelling, or wheezing (respiratory distress), is

regarded as an immediate allergic reaction (CDC

2021). In addition, people who are allergic to PEG or

polysorbate should not get an mRNA COVID-19

vaccine (CDC 2021). Although polysorbate is not an

ingredient in either mRNA COVID-19 vaccine, it is

closely related to PEG, which is in the vaccines

(CDC 2021). (Figure 4)

6.6 Vaccine Produced by Oxford/

AstraZeneca

The vaccine produced by Oxford/ AstraZeneca is a

viral vector vaccine. It is announced that the vaccines

had average effectiveness of 70.4 percent, which

splits into 90 percent in one dosing regimen and 62

percent in the other (NEEDHAM 2020). This came

after clinical trials enrolled over 24,000 participants

from across the UK, Brazil, and South Africa. Further

trials will include 60,000 participants from the United

States, Kenya, Japan, and India (NEEDHAM 2020).

Viral vector-based vaccines use the body’s own cells

to produce antigens. In the case of SRAS-CoV-2,

spike proteins are antigens. Modified viruses (the

vector) are used to deliver genetic code for antigen,

so spike proteins found on the surface of the virus are

delivered into human cells to instruct the body’s own

cells to make spike proteins. Then, an immune

response can be triggered by producing immune T

cells and B cells as the immune system identifies that

spike proteins do not belong to the human body. This

can prevent the body from being infected in the

future.

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6.7 Advantages and Disadvantages of

Different Vaccines

First of all, for safety, all three vaccines mentioned

above are safe, which means that these vaccines are

non-infectious because the real viruses are not

injected into human bodies, and only the formation of

spike protein stimulates the response of the immune

system.

Figure 4: (Worldometer 2022). How do mRNA vaccines

work.

For the efficacy, vaccines produced by Moderna

and Pfizer/ BioNTech have higher efficacy towards

original SRAS-CoV-2, both of which are around

95%(Asipilin 42195 2020) shown in the clinical trial,

compared to vaccines produced by Oxford/

AstraZeneca (around 70.4% (Asipilin 42195 2020).

In terms of the efficacy towards different variants,

patients who have received a second dose of the

vaccines, be it vaccines produced by

Pfizer/BioNTech, Moderna, or Oxford/ AstraZeneca,

have a higher percentage of preventing infection of

the virus (Table 2, Table 3, and Table 4). Vaccines

produced by Pfizer/BioNTech (above 90%) and

Moderna (around 90%) have higher efficacy towards

alpha variant; Moderna’s vaccines have higher

efficacy when dealing with the beta variant and

gamma variant; Oxford’s / AstraZeneca’s vaccines

have lower efficacy when dealing with delta variant

compared to that of Pfizer/BioNTech. Other data can

refer to Table 2, Table 3, and Table 4 below.

For the production of vaccines, all of them can be

produced faster than conventional vaccines because

the time to cultivate the virus can be saved. In terms

of the distribution of vaccines, vaccines produced by

Pfizer/ BioNTech can only store in a fright, which is

2-8°C for five days(Asipilin 42195 2020). However,

vaccines produced by Moderna and Oxford/

AstraZeneca can be stored in a fright which is 2-8°C

for a long time, which are one month and six months

respectively . Normally, the storage temperature for

vaccines produced by Pfizer/ BioNTech is -70°C and

this for vaccines produced by Moderna is -20°C, and

this for vaccines produced by Oxford/ AstraZeneca is

2.22-7.78°C (Asipilin 42195 2020).

In addition, for the price of different vaccines,

vaccines produced by Oxford/ AstraZeneca are the

cheapest, costing only 3.5USD per dose (Asipilin

42195 2020). Also, vaccines produced by Moderna

and Pfizer/ BioNTech cost 35USD and 20USD per

dose. It is obvious that vaccines produced by Pfizer/

BioNTech are the most expensive ones (Asipilin

42195 2020).

6.8 Other Types of Vaccines

There are two other common types of vaccines in the

world: inactivated vaccine and protein subunit

vaccine. For inactivated vaccine, the inactivated virus

can no longer replicate or reproduce (Johns Hopkins

University 2020). The immune system is exposed to

viral proteins, but the inactivated virus does not cause

disease. Inactivated viruses stimulate the body's

immune system to produce antibodies, so when

people are exposed to natural viruses, antibodies

work to fight the virus (Johns Hopkins University

2020). The production of inactivated vaccines

requires the ability to cultivate or breed a large

number of viruses. Since the virus cannot replicate

outside the host cell, the vaccine virus needs to be

cultured in a continuous cell line or tissue (Johns

Hopkins University 2020). Several inactivated

vaccines are currently widely used, including

vaccines against influenza, polio, hepatitis A and

rabies viruses. The inactivated virus can no longer

replicate or reproduce (Johns Hopkins University

2020). Bharat Biotech is one of the companies which

is developing this type of vaccine for COVID-19.

For subunit vaccine, it contains fragments of

protein from the pathogen. The protein selected must

be likely to produce a strong and effective immune

response. In the case of SRAS-CoV-2, spike proteins

on the surface are always selected. When these

fragments enter our body, the immune system can try

to produce immune cells and antibodies to defend

ICBEB 2022 - The International Conference on Biomedical Engineering and Bioinformatics

608

these fragments. As these fragments are incapable of

causing diseases, some side effects can be minimized.

However, a disadvantage of this vaccine is that the

antigens used to elicit an immune response may lack

pathogen-associated molecular patterns(Gavi 2021).

These patterns can be read by immune cells and

recognized as danger signals, so their absence may

result in a weaker immune response (Gavi 2021).

Also, because the antigens do not infect cells, subunit

vaccines mainly only trigger antibody-mediated

immune responses, which means the immune

response may be weaker than with other types of

vaccines (Johns Hopkins University 2020). To deal

with this problem, subunit vaccines are sometimes

delivered alongside adjuvants, and another booster

dose may be required (Gavi 2021). There are also

upsides to this type of vaccine. They are cheaper to

produce and more stable.

7 CURRENT SITUATION OF THE

PANDEMIC

Although people can be vaccinated to prevent the

SARS-CoV-2, there is no downward trend of the

covid cases and death cases indicating the alleviation

of the problem. This is due to the emerging of new

variants, and the covid vaccines are developed by

targeting the original unmutated virus. However,

different governments have encouraged residents to

get vaccines and have imposed strict policies to

prevent the spread of the virus. These actions can

potentially lower the risk of being infected.

8 CONCLUSION

In conclusion, the spike protein in the SARS-CoV-2

virus is responsible for the transmission of the virus,

and different variants arisen because of the mutation

of this protein. Also, remdesivir and dexamethasone

are the two medicines that are currently used in the

treatment, which shows efficacies in shortening the

recovery time and lowering the mortality rate. In

terms of the covid vaccines, it is clear that all three

vaccines are recorded drops in their efficacies

because of the emerging of different variants.

Therefore, the development of vaccines to deal with

different covid variants and prevention of further

mutation of the virus are vitally important to fight the

virus.

Table 2: A table showing the efficacy of vaccines produced by Pfizer/BioNTech.

Doses Severity of illness Alpha varian

Beta Varian

Gamma Variant Delta varian

1 Asymptomatic 38% (29–45%)

(Wikipedia 2021)

17% (10–23%)

(Wikipedia 2021)

Not found 30% (17–41%)

(Wikipedia 2021)

1 Symptomatic 27% (13–39%)

(Wikipedia 2021)

43% (22–59%)

[(Wikipedia 2021)

43% (22–59%)

(Wikipedia 2021)

33% (15–47%)

(Wikipedia 2021)

1 Hospitalization 83% (62–93%)

(Wikipedia 2021)

0% (0–19%)

(Wikipedia 2021)

56% (−9 to 82%)

(Wikipedia 2021)]

94% (46–99%)

(Wikipedia 2021)

2 Asymptomatic 92% (90–93%)

(Wikipedia 2021)

75% (71–79%)

(Wikipedia 2021)

Not found 79% (75–82%)

(Wikipedia 2021)

2 Symptomatic 92% (90–93%)

(Wikipedia 2021)

88% (61–96%)

[(Wikipedia 2021)

88% (61–96%)

(Wikipedia 2021)

83% (78–87%)

(Wikipedia 2021)

2 Hospitalization 95% (78–99%)

(Wikipedia 2021)

100% (74–100%)

(Wikipedia 2021)

100% (74–100%)

(Wikipedia 2021)

96% (86–99%)

(Wikipedia 2021)

Table 3: A table showing the efficacy of vaccines produced by Moderna.

Doses Severity of illness Alpha varian

Beta Varian

Gamma Variant Delta varian

1 Asymptomatic Not foun

Not foun

1 Symptomatic 61% (56–66%)

(Wikipedia 2021)

43% (22–59%)

(Wikipedia 2021)]

43% (22–59%)

(Wikipedia 2021)

Not found

1 Hospitalization 59% (39–73%)

(Wikipedia 2021)

56% (−9 to 82%)

(Wikipedia 2021)

56% (−9 to 82%)

(Wikipedia 2021)

Not found

2 Asymptomatic Not foun

Not foun

2 Symptomatic 90% (85–94%)

(Wikipedia 2021)

88% (61–96%)

(Wikipedia 2021)

88% (61–96%)

(Wikipedia 2021)

Not found

2 Hospitalization 94% (59–99%)

(Wikipedia 2021)

100% (Wikipedia

2021)

100% (Wikipedia

2021)

Not found

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Table 4: A table showing the efficacy of vaccines produced by Oxford/ AstraZeneca.

Doses Severity of illness Alpha varian

Beta Varian

Gamma Variant Delta varian

1 Asymptomatic 37% (32–42%)

(Wikipedia 2021)

Not found Not found 18% (9–25%)

(Wikipedia 2021)

1 Symptomatic 39% (32–45%)

(Wikipedia 2021)

Not found 33% (26–40%)

(Wikipedia 2021)

33% (23–41%)

(Wikipedia 2021)

1 Hospitalization 76% (61–85%)

(Wikipedia 2021)

Not found 55% (47–62%)

(Wikipedia 2021)

71% (51–83%)

(Wikipedia 2021)

2 Asymptomatic 73% (66–78%)

(Wikipedia 2021)

Not found Not found 60% (53–66%)

(Wikipedia 2021)

2 Symptomatic 81% (72–87%)

(Wikipedia 2021)

10% (−77 to 55%)

(Wikipedia 2021)

78% (69–84%)

(Wikipedia 2021)

61% (51–70%)

(Wikipedia 2021)

2 Hospitalization 86% (53–96%)

(Wikipedia 2021)

Not found 88% (78–93%)

(Wikipedia 2021)

92% (75–97%)

(Wikipedia 2021)

REFERENCES

Asipilin 42195: Comparisons of different advantages and

disadvantages of vaccines [Chinese]. Available from:

http://mp.weixin.qq.com/s?__biz=MzUzMzkxOTc4N

A==&mid=2247485529&idx=1&sn=5ea5d4c26f8ff2d

5e7c066f64eb4ab91&chksm=fa9de91ecdea60082b9ab

81e29dc34be0b1c53cf6a89dc0973137bd71c224e5992

c53bf73f9b#rd (accessed Aug. 18, 2021).

“COVID-19,” Wikipedia. Aug. 01, 2021. Accessed: Aug.

18, 2021. [Online]. Available:

https://en.wikipedia.org/w/index.php?title=COVID-

19&oldid=1036654407

CDC, “Information about the Pfizer-BioNTech COVID-19

Vaccine,” Centers for Disease Control and Prevention,

Jun. 24, 2021. https://www.cdc.gov/coronavirus/2019-

ncov/vaccines/different-vaccines/Pfizer-

BioNTech.html (accessed Aug. 13, 2021).

“COVID-19 Delta Variant: What You Need to Know.”

https://www.healthline.com/health-news/the-covid-19-

delta-variant-heres-everything-you-need-to-

know#What-symptoms-does-the-Delta-variant-cause?

(accessed Aug. 05, 2021).

CDC, “Information about the Moderna COVID-19

Vaccine,” Centers for Disease Control and Prevention,

Jun. 11, 2021. https://www.cdc.gov/coronavirus/2019-

ncov/vaccines/different-vaccines/Moderna.html

(accessed Aug. 12, 2021).

CDC, “Understanding mRNA COVID-19 Vaccines,”

Centers for Disease Control and Prevention, Mar. 04,

2021. https://www.cdc.gov/coronavirus/2019-

ncov/vaccines/different-vaccines/mrna.html (accessed

Aug. 12, 2021).

“COVID Live Update: 206,980,203 Cases and 4,358,550

Deaths from the Coronavirus - Worldometer.”

https://www.worldometers.info/coronavirus/ (accessed

Aug. 14, 2021).

“Dexamethasone in Hospitalized Patients with Covid-19,”

N. Engl. J. Med., vol. 384, no. 8, pp. 693–704, Feb.

2021, doi: 10.1056/NEJMoa2021436.

I. Kimura et al., “SARS-CoV-2 Lambda variant exhibits

higher infectivity and immune resistance,” bioRxiv, p.

2021.07.28.454085, Jul. 2021, doi:

10.1101/2021.07.28.454085.

J. H. Beigel et al., “Remdesivir for the Treatment of Covid-

19 — Final Report,” N. Engl. J. Med., vol. 383, no. 19,

pp. 1813–1826, Nov. 2020, doi:

10.1056/NEJMoa2007764.

Johns Hopkins University: Detailed explanation of the

types, advantages and disadvantages of the COVID-19

vaccines. [Chinese]. 3 December 2020. Available from:

https://mp.weixin.qq.com/s/hWZ0YBL4tgpyB6BaQe

VSXQ

“Moderna’s COVID-19 Vaccine Candidate Meets its

Primary Efficacy Endpoint in the First Interim Analysis

of the Phase 3 COVE Study | Moderna, Inc.”

https://investors.modernatx.com/news-releases/news-

release-details/modernas-covid-19-vaccine-candidate-

meets-its-primary-efficacy/ (accessed Aug. 08, 2021).

“Moderna COVID-19 vaccine,” Wikipedia. Aug. 12, 2021.

Accessed: Aug. 14, 2021. [Online]. Available:

https://en.wikipedia.org/w/index.php?title=Moderna_

COVID-19_vaccine&oldid=1038439218

“Oxford–AstraZeneca COVID-19 vaccine,” Wikipedia.

Aug. 13, 2021. Accessed: Aug. 14, 2021. [Online].

Available:

https://en.wikipedia.org/w/index.php?title=Oxford%E

2%80%93AstraZeneca_COVID-

19_vaccine&oldid=1038621367

“Page not found (404),” LubioScience.

https://www.lubio.ch/blog/neutralizing-antibodies.

(accessed Aug. 18, 2021).

“Pfizer–BioNTech COVID-19 vaccine,” Wikipedia. Aug.

13, 2021. Accessed: Aug. 14, 2021. [Online].

Available:

https://en.wikipedia.org/w/index.php?title=Pfizer%E2

%80%93BioNTech_COVID-

19_vaccine&oldid=1038650584

R. A. Mansbach, S. Chakraborty, K. Nguyen, D. C.

Montefiori, B. Korber, and S. Gnanakaran, “The

SARS-CoV-2 Spike variant D614G favors an open

conformational state,” Sci. Adv., vol. 7, no. 16, p.

eabf3671, Apr. 2021, doi: 10.1126/sciadv.abf3671.

“Runtime Error.” https://www.who.int/news-room/q-a-

detail/coronavirus-disease-covid-19. (accessed Aug.

18, 2021).

ICBEB 2022 - The International Conference on Biomedical Engineering and Bioinformatics

610

“Remdesivir,” COVID-19 Treatment Guidelines.

https://www.covid19treatmentguidelines.nih.gov/thera

pies/antiviral-therapy/remdesivir/ (accessed Aug. 06,

2021).

“SARS-CoV-2 Alpha variant,” Wikipedia. Jul. 29, 2021.

Accessed: Aug. 04, 2021. [Online]. Available:

https://en.wikipedia.org/w/index.php?title=SARS-

CoV-2_Alpha_variant&oldid=1036066787

“SARS-CoV-2 Beta variant,” Wikipedia. Jul. 28, 2021.

Accessed: Aug. 04, 2021. [Online]. Available:

https://en.wikipedia.org/w/index.php?title=SARS-

CoV-2_Beta_variant&oldid=1035925918

“SARS-CoV-2 Gamma variant,” Wikipedia. Jul. 28, 2021.

Accessed: Aug. 04, 2021. [Online]. Available:

https://en.wikipedia.org/w/index.php?title=SARS-

CoV-2_Gamma_variant&oldid=1035998057

“SARS-CoV-2 Delta variant,” Wikipedia. Aug. 04, 2021.

Accessed: Aug. 04, 2021. [Online]. Available:

https://en.wikipedia.org/w/index.php?title=SARS-

CoV-2_Delta_variant&oldid=1037048949

“Safety and Efficacy of the BNT162b2 mRNA Covid-19

Vaccine | NEJM.”

https://www.nejm.org/doi/full/10.1056/NEJMoa20345

77?fbclid=IwAR1YoOCQ3DNr0GjMQv4hFXVvu4L

8SI0fAMkbJdJdh-

AfrLOHBmSVSbo7oTM#.X9QvTNjPnRc.facebook

(accessed Aug. 08, 2021).

“Tracking SARS-CoV-2 variants.”

https://www.who.int/emergencies/emergency-health-

kits/trauma-emergency-surgery-kit-who-tesk-

2019/tracking-SARS-CoV-2-variants (accessed Aug.

18, 2021).

“The top five coronavirus vaccine candidates explained |

WIRED UK.”

https://www.wired.co.uk/article/coronavirus-vaccines-

frontrunners (accessed Aug. 08, 2021).

“What are protein subunit vaccines and how could they be

used against COVID-19?”

https://www.gavi.org/vaccineswork/what-are-protein-

subunit-vaccines-and-how-could-they-be-used-

against-covid-19 (accessed Aug. 14, 2021).

Y. Huang, C. Yang, X. Xu, W. Xu, and S. Liu, “Structural

and functional properties of SARS-CoV-2 spike

protein: potential antivirus drug development for

COVID-19,” Acta Pharmacol. Sin., vol. 41, no. 9, pp.

1141–1149, Sep. 2020, doi: 10.1038/s41401-020-0485-

Medicines and Vaccines in Dealing with Covid-19

611