A Systematic Review - Adverse Effect of Covid-19 Vaccine

 

Ashish Kumar, Alka Singh*, Bhaskar Kumar Gupta*

School of Pharmacy and Research, People’s University, Bhanpur, 462037 Bhopal, M.P, India.

*Corresponding Author E-mail: singhalka7160@gmail.com

 

ABSTRACT:

The COVID-19 pandemic has placed unexpected strains on all aspects of human life, necessitating the rapid evaluation of various approaches to achieving protective immunity. In response, significant efforts have been dedicated to developing an effective vaccine, leading to a global race for vaccine advancement. To combat COVID-19, nations must prioritize widespread vaccination with a safe and effective vaccine. However, concerns about potential long-term adverse effects have contributed to public apprehension regarding vaccine use. The safety profile of a vaccine plays a crucial role in public confidence and overall vaccine uptake. This article reviews the latest primary literature on the adverse effects of different COVID-19 vaccines worldwide.

 

KEYWORDS: Symptoms, Epidemiology, Adverse effects, Adverse events, Complications, COVID-19, Vaccine.

 

 


INTRODUCTION:

The human body encounters various infectious microorganisms, including viruses, bacteria, fungi, protozoa, and helminths, each of which causes tissue damage through distinct mechanisms. Among these, viruses stand out due to their ability to manipulate host-cell machinery uniquely. They continuously evolve, adapting to survive and thrive across different species.1

 

COVID-19 is an illness caused by the novel coronavirus SARS-CoV-2. The World Health Organization (WHO) was first notified of the virus on 31 December 2019, following reports of a cluster of viral pneumonia cases in Wuhan, China.2

 

Fig. 1: Structure of a coronavirus15

 

Since its emergence, the virus rapidly spread across China, leading to a global outbreak, raising significant public health concerns. On January 30, 2020, WHO declared COVID-19 a global public health emergency. In India, the first confirmed case was reported on January 27, 2020, in Kerala. Case detection varies across the country and is primarily based on SARS-CoV-2 antigen testing using Real-Time Reverse Transcription Polymerase Chain Reaction (RT-qPCR) or Rapid Antigen Test (RAT).3

 

Coronaviruses (CoVs) belong to a viral family that infects both mammals and birds. The novel coronavirus responsible for the pandemic was initially named "2019-nCoV" by WHO in Geneva, Switzerland. Due to its genetic similarity to the severe acute respiratory syndrome (SARS) virus, it was later renamed SARS-CoV-2. It falls under the subfamily Orthocoronavirinae within the Coronaviridae family, order Nidovirales, and realm Riboviria. Electron microscopy images of the virus reveal a crown-like structure surrounding the virions, inspiring the name "corona," which means "crown" or "halo" in Latin.4

 

SARS-CoV-2 is the third major coronavirus to pose a severe threat to human health. It followed the SARS outbreak in 2003, which affected 8,429 people across 29 countries and had a mortality rate of nearly 10%. Another deadly coronavirus, Middle East Respiratory Syndrome (MERS), emerged in 2012, proving even more lethal with the fatality rate of approximately 30%.4

 

History:

Coronaviruses are enveloped, positive-sense RNA viruses measuring between 60 nm and 140 nm in diameter. They feature spike-like projections on their surface, giving them a crown-like appearance under an electron microscope, which inspired the name "coronavirus”. Four coronaviruses—HKU1, NL63, 229E, and OC43—circulate in humans and typically cause mild respiratory illnesses. Over the past two decades, there have been two significant instances where animal beta coronaviruses crossed over to humans, leading to severe diseases. The first occurred in 2002–2003 when a novel β-genus coronavirus, originating in bats, was transmitted to humans through an intermediary host, the palm civet cat, in China’s Guangdong province. This virus, known as Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), infected 8,422 individuals, primarily in China and Hong Kong, resulting in 916 deaths—a mortality rate of 11%—before being contained. Nearly a decade later, in 2012, another bat-origin coronavirus, the Middle East Respiratory Syndrome Coronavirus (MERS-CoV), emerged in Saudi Arabia, with dromedary camels as the intermediate host. This virus infected 2,494 people and caused 858 deaths, with a fatality rate of 34%.5

 

Symptoms:

COVID-19 presents with a wide spectrum of symptoms, ranging from mild or moderate illness to severe, rapidly progressing, and even life-threatening disease. Symptoms are non-specific, and the disease can manifest in various ways, from asymptomatic cases to severe pneumonia. The incidence of asymptomatic infections varies between 1.6% and 51.7%. These individuals do not exhibit typical clinical symptoms or signs and show no apparent abnormalities in the lung computed tomography scans. The most common symptoms of COVID-19 include fever, cough, muscle pain (myalgia), and fatigue. Less typical symptoms may include sputum production, a headache, hemoptysis(coughing up blood), vomiting, and diarrhea. Some patients may experience a sore throat, runny nose (rhinorrhea), headache, and confusion in the days leading up to fever, suggesting that while fever is a key symptom, it may not always be the first sign of infection. Additionally, some individuals report a loss of smell (hyposmia) or taste (hypogeusia), which are now recognized as early warning signs of COVID-19 and indicators for self-isolation.6

 

The most common symptoms of COVID-19 are:

·       Fever.

·       Dry cough.

·       Fatigue.

 

Other symptoms:

·       Loss of taste or smell.

·       Nasal congestion.

·       Conjunctivitis

·       Sore throat.

·       Headache.

·       Muscle or joint pain.

·       Nausea and vomiting.

·       Diarrhea.

·       Chills or dizziness.

 

Symptoms of severe COVID-19 disease:

·       Shortness of breath

·       Loss of appetite.

·       Confusion.

·       Persistent pain

·       High temperature

More serious and uncommon neurological issues, including strokes, brain inflammation, delirium, and nerve damage.7

 

Fig. 2: Symptoms of COVID-1914

 

Individuals of all ages who develop fever and cough accompanied by difficulty breathing, shortness of breath, chest pain or pressure, or loss of speech or movement should seek medical attention immediately. If possible, contact a healthcare provider, hotline, or medical facility in advance for guidance on the appropriate clinic to visit.1

 

Epidemiology and pathogenesis:

People of all ages are susceptible to COVID-19. The infection primarily spreads through large respiratory droplets expelled by symptomatic individuals during coughing and sneezing. However, transmission can also occur from asymptomatic individuals and even before symptom onset.8

 

Research indicates that viral loads are higher in the nasal cavity compared to the throat, with no significant difference in viral burden between symptomatic and asymptomatic individuals. Patients can remain infectious throughout their symptoms and even after clinical recovery. Some individuals, known as "super spreaders," may transmit the virus to multiple people9. For example, a UK citizen who attended a conference in Singapore infected 11 others while staying at a resort in the French Alps before returning to the UK.10

 

Infected droplets can travel 1–2 meters and settle on surfaces, where the virus may remain viable for several days under favourable atmospheric conditions. However, common disinfectants like sodium hypochlorite and hydrogen peroxide can destroy it within minutes. Infection occurs either through inhalation of these droplets or by touching contaminated surfaces and then touching the nose, mouth, or eyes.11

 

Additionally, the virus has been detected in stool, leading to hypotheses about possible transmission through contaminated water and the fecal-oral route. However, current evidence does not confirm transplacental transmission from pregnant women to their fetuses, though neonatal infection due to postnatal exposure has been reported.12

 

The incubation period for COVID-19 ranges from 2 to 14 days, with a median of 5 days. Studies have identified angiotensin-converting enzyme 2 (ACE2) as the receptor through which the virus enters respiratory mucosal cells, facilitating infection.13

 

Transmission:

COVID-19 is primarily transmitted when individuals inhale air containing virus-laden droplets, aerosols, or small airborne particles. Infected individuals release these particles when they breathe, talk, cough, sneeze, or sing. The risk of transmission increases with proximity, though infection can also occur over longer distances, especially in indoor settings.16,17

The virus spreads through fluid particles expelled from the respiratory tract via the mouth and nose. Transmission occurs in three ways: droplet transmission and contact transmission, both involving larger droplets, and airborne transmission, which involves smaller droplets. Large droplets settle quickly and contaminate surrounding surfaces, whereas smaller droplets, typically under 100μm in diameter, evaporate faster than they settle, forming aerosols that remain airborne for extended periods and can travel significant distances.18

 

Infectivity can begin four to five days before symptom onset, and individuals can spread the virus even if they are pre-symptomatic or asymptomatic19. Viral load in the upper respiratory tract typically peaks around symptom onset and declines within the first week. Current evidence suggests that the virus remains infectious for up to ten days after symptoms appear in mild to moderate cases and up to 20 days in severe cases, including those affecting immunocompromised individuals.20

 

Infectious particles vary in size, ranging from aerosols that can remain airborne for long periods to larger droplets that quickly fall to the ground.21 The largest respiratory droplets do not travel far but can infect individuals through direct inhalation or contact with mucous membranes in the eyes, nose, or mouth. Aerosol concentration is highest when people are in close proximity, making transmission easier in such situations. However, airborne transmission is also possible over longer distances, particularly in poorly ventilated spaces, where small particles can remain suspended for minutes to hours.22,23

 

Fig. 3: Transmission of COVID‑1924

 

Diagnosis:

COVID-19 diagnostic testing is performed to determine if an individual is infected with the SARS-CoV-2 virus, which causes COVID-19. Your healthcare provider may recommend testing if:

·       You are experiencing symptoms of COVID-19, such as high fever, cough, shortness of breath, or extreme fatigue.

·       You have pre-existing health conditions like asthma or heart disease and notice a sudden worsening of symptoms.

·       You have recently been in close contact with someone who tested positive for COVID-19.

·       You are a healthcare worker operating in a hospital or high-risk environment.

·       You require hospitalization for treatment or surgery related to an existing medical condition.25

 

Different laboratory tests are available to diagnose COVID 19:

There are two primary types of diagnostic tests for COVID-19: antigen (rapid) tests and molecular (PCR) tests.

·       Antigen tests are commonly used as point-of-care tests. They are more affordable and provide results within minutes. However, they have a higher likelihood of false-negative results compared to molecular tests.

·       Molecular (PCR) tests are more accurate and reliable but take longer to process due to the need for laboratory analysis.25

·       A complete blood count can provide important prognostic indicators for COVID-19 severity. Lymphopenia, eosinopenia, and a neutrophil-to-lymphocyte ratio (NLR) of ≥3.13 are associated with increased disease severity and a poorer prognosis. Thrombocytopenia has been linked to a higher risk of myocardial damage and worse outcomes. Lymphopenia results from multiple factors, including the cytopathic effects of the virus, apoptosis induction, IL-1-mediated proptosis, and bone marrow suppression caused by inflammatory cytokines.26

 

Prevention:

Preventive measures are the primary approach to controlling the spread of COVID-19. Early screening, diagnosis, isolation, and treatment are essential in limiting transmission. Prevention strategies emphasize patient isolation and strict infection control protocols, ensuring proper precautions during diagnosis and clinical care.27

 

Key COVID-19 prevention and control measures in the community include:

·       Early Detection: Screening and testing to identify cases promptly.

·       Isolation and Quarantine: Separating infected individuals and close contacts.

·       Infection Control: Implementing hygiene protocols in healthcare settings.

·       Public Health Guidelines: Promoting mask-wearing, social distancing, and hand hygiene.

·       Vaccination: Ensuring widespread immunization to reduce disease severity and transmission.

Table 1: COVID-19 prevention and control measures in community.28

Quarantine

Other Measures

Voluntary quarantine (self-quarantine)

Avoiding crowding

Mandatory quarantine

Hand hygiene

Private residence

Isolation

Hospital

Personal protective equipment

Public institution

School measures/closures

Others (cruise ships, etc)

Social distancing

Workplace measures/closures

 

Treatment:

Initially, early in the pandemic, the understanding of COVID-19 and its therapeutic management was limited, creating an urgency to mitigate this new viral illness with experimental therapies and drug repurposing. Since then, due to the intense efforts of clinical researchers globally, significant progress has been made, which has led to a better understanding of not only COVID-19 and its management but also has resulted in the development of novel therapeutics and vaccines.29

 

Vaccine Strategies:

While the COVID-19 pandemic has caused significant morbidity and mortality, the emergence of new variants such as Delta and Omicron has further emphasized the need for continued control measures. Vaccination remains the most effective strategy to protect people worldwide, as SARS-CoV-2 is highly infectious and has impacted populations globally.30

 

A vaccine is a biological product that stimulates an immune response, providing protection when a pathogen enters the body, while vaccination refers to the process of administering the vaccine.31,32 The primary goal of vaccination is to prevent disease and reduce mortality or disability, though it may not always prevent infection entirely. Traditionally, vaccine development is a complex process that takes around 15 years, but advances in genomic sequencing and technology have significantly accelerated the development of COVID-19 vaccines. Due to the adaptability and efficiency of different vaccine technologies, vaccines were developed and deployed at an unprecedented speed.33

 

According to Bartsch et al., a vaccine must have at least 70% efficacy to control an epidemic and 80% efficacy to eliminate it. Beyond efficacy, factors such as delivery method, community acceptance, infection reduction, duration of protection, and safety must also be considered. COVID-19 vaccine candidates primarily target the SARS-CoV-2 spike protein (S1 subunit) to stimulate neutralizing antibodies and protective immunity.34,35

 

There are several types of COVID-19 vaccines, including:36

·       Inactivated virus vaccines

·       mRNA-based vaccines

·       Live-attenuated vaccines

·       DNA vaccines

·       Viral-vector-based vaccines

·       Protein subunit vaccines

 

Each vaccine platform has distinct characteristics that influence its efficacy, duration of protection, and safety profile. According to the WHO COVID-19 vaccine tracker, as of February 2022, there were 146 vaccines in clinical development and 195 in preclinical development. Additionally, the WHO COVID-19

 

Dashboard reported that 10.7 billion vaccine doses had been administered globally by February 28, 2022.37

 

Understanding the type and duration of immune response following vaccination is crucial for identifying the immunological mechanisms responsible for protection against COVID-19. If any side effects occur after vaccination, individuals should seek immediate medical assistance.

 

Vaccine Strategies Classified into:

a.     mRNA-Based Vaccines

b.     Viral Vector-Based Vaccines

c.     Inactivated Virus Vaccines

d.     DNA-Based Vaccines

 

Fig. 4: Classification of Vaccine


 

Table 2: Comparison of different COVID-19 vaccines.41-100

Vaccine name

Manu-Facturer

Preparation

Dosage

AGE

% Efficacy

Side Effects

Comirnaty®

Pfizer and BioNTech

S-Protein (SARS-CoV2) + P2S LNP

2 doses, 0.3mL each 21 days apart

12 and older

95%

Headache, Fatigue, chills, Muscle and joint pain

mRNA-1273

Moderna

S-Protein LNP

2doses, 0.5mL each 28 days apart

18 and older

94.1%

Fatigue, Myalgia, Arthralgia, Headache

CoronaVac

Sinovac

Inactivated virus created from African greenmon key kidney cells (Vero cells)

2 doses, 0.5ML each 28 days apart

18 and above

83.5%

Headache, Fatigue, Muscle pain, Vomiting

BBIBP-CorV

Sinopharm

ß-propiolactone (inactivate COV) + adjuvant (Al (OH)3) + Verocell

2 doses, 0.5mL each 21days apart

18–59

79%

Pain at the injection site, Fatigue, Lethargy, Headache, Tenderness

Covaxin

Bharat Biotech

Whole-virion inactivated SARSCoV-2 antigen

2 doses, 0.5mL each 28 days apart

18 and above

77.8%

Injection site pain, Itching Headache, Fever, body ache, Nausea, Vomiting

Covishield

AstraZeneca/ University of Oxford

S-protein (SARS-CoV-2) + chimpanzee adenovirus vector

2 doses, 0.5mL each 3 months apart

18 and older

90%

Headache, Fever, Dizziness Nausea Vomiting, Myalgia.

Sputnik V

Gamaleya

rAd26and rAd5-bothcarry thegenefor S-protein (SARS-CoV-2)

2 doses, 0.5mL each 21days apart

18 and above

91.6%

Body pain, Injection site pain, Headache and Fatigue

Janssen Vaccines

Janssen

Non-replicating adenovirus serotype 26 +S-protein (SARS-CoV-2)

1dose 0.5mL

18 and older

66.9%

Fatigue, Headache, Myalgia, Fever, Chills, Nausea, Diarrhoea

Nuvaxovid

Novavax

LongS-Protein (SARS-CoV-2) + Madjuvant

2 doses, 0.5mL each 21 days apart

18and above

89.7%

Injection-site tenderness, Fatigue, Headache, Muscle pain

ZyCoV-D

Cadila Healthcare

S-protein (SARS-CoV-2)+ pVAX1

3 doses, 0.5mL each 28 days apart

12andabove

66.6%

Bodyache Nausea Vomiting, Fever, Chills


CONCLUSIONS:

The global response to the COVID-19 pandemic has highlighted the critical role of vaccines in controlling infectious diseases. With the emergence of new variants such as Delta and Omicron, continued vigilance and adaptation of vaccine strategies are essential. The unprecedented speed at which COVID-19 vaccines were developed. Various vaccine platforms—including mRNA-based, inactivated virus, viral vector-based, protein subunit, and DNA-based vaccines—have been deployed worldwide, each with distinct advantages and limitations. mRNA vaccines, like Pfizer-BioNTech and Moderna, have demonstrated high efficacy and rapid immune response, while inactivated vaccines such as CoronaVac and Covaxin offer easier storage and distribution. Viral vector vaccines like Covishield and Sputnik V have shown strong protection using recombinant technologies, and newer platforms like protein subunit and DNA vaccines contribute to the growing diversity and adaptability of vaccine strategies.

Key factors influencing vaccine effectiveness include efficacy, storage requirements, side effect profiles, community acceptance, and the duration of protection. Booster doses and heterologous vaccination strategies have further enhanced immunity against evolving variants.

 

Ultimately, the development and global distribution of COVID-19 vaccines underscore the power of science and innovation in combating pandemics.

 

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Received on 16.04.2025      Revised on 05.05.2025

Accepted on 22.05.2025      Published on 19.06.2025

Available online from June 23, 2025

Asian J. Research Chem.2025; 18(3):194-202.

DOI: 10.52711/0974-4150.2025.00031

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