A novel coronavirus disease brought on by the SARS-CoV-2 virus had first emerged in China in the month of December, 2019. The World Health Organisation (WHO) declared the coronavirus pneumonia outbreak as a “public health emergency of international concern” on January 30, 2020. On 11^th of February, 2020, the disease was termed as COVID-19 (the abbreviation of “Coronavirus Disease 2019”). The disease had a devastating effect on the entire world due to the quick spread and difficulty in the detection of silent infections and mild cases. Even if the virus can be totally eradicated from the community, the transfer from the host to the human remains unclear due to the population’s general susceptibility.^1,2 Several COVID-19 complicacies include respiratory failure, myocardial injury, stroke, thromboembolic complications, neurological complications (movement disorders and ataxia), inflammatory complications (Guillain-Barre syndrome and elevated inflammatory markers), and secondary infections.³ By December 31, 2021, there had been 5.94 million documented fatalities attributed to COVID-19, with a mortality rate of 9.22 per 100,000 people worldwide.⁴ Around 242 vaccine candidates and a total of 821 clinical trials are underway in which around 80 countries are participating in vaccine trials. About 50 vaccines have been approved so far and 66 vaccine candidates undergoing phase I trials, 72 in phase II trials, and 92 in phase III trials, as per the information provided in a publicly accessible COVID-19 vaccine tracker website (Data was last updated on 2nd December 2022).⁵ Some prominent vaccines like Pfizer-BioNTech BNT162b2, Moderna’s mRNA-1273, Oxford-AstraZeneca, Johnson & Johnson, Sinopharm-Beijing, Sinovac, Sputnik V, Novavax, and Covaxin vaccines are some of the vaccines that were approved for use.⁶

Mechanism of action
SARS-CoV-2 virus consists of several structural and non-structural proteins. The structural proteins are named as Spike (S) protein, envelope (E) protein, membrane/matrix (M) protein, and nucleocapsid (N) protein (Figure).⁷ Infection results from the binding of S proteins to certain receptors. The S protein is the most crucial target antigen for the development of vaccines against this virus since it can activate the T-cell immune response. Besides, the M and N proteins stimulate the body to create a powerful cellular immunological response. Upon its entry, the virus binds to a receptor called angiotensin-converting enzyme 2 (ACE2). Every organ expresses ACE2, but the lungs, brain, and gut express more of it than other organs.⁸ The virus spreads widely after this binding, and it can even harm tissues beyond the respiratory system. In various circumstances, the distribution of ACE2 causes alterations in the symptoms.^1,2,9

The S protein has two subunits such as S1 and S2. The S1 being the receptor-binding domain of the virus, attaches to the host making it a target for pharmaceutical applications. To initiate the infection inside the body, the S2 component encourages viral fusion with cells. The main goal of the vaccine’s design is to produce antibodies that would attach to the S protein’s epitope and potentially neutralise and stop viral intercellular propagation.¹⁰

Types of vaccines
The following Table 1 includes different categories of vaccines currently in development. Each type of vaccine has its own characteristic features, mechanism of action, advantages and disadvantages which have been discussed here.

Table (1):
Various types of vaccines with their mechanism of action, advantages, and disadvantages

Vaccination status
A total of 5,33,574 (1.18%) deaths were reported out of the total 4,50,35,573
COVID patients, and 4,45,01,431 patients were discharged, with a recovery rate of 98.81% (Statistical data obtained on April 14, 2024, from the website of Government of India). A total of 93,58,79,465 people have been tested positive for COVID-19 till date. About 2,20,68,93,569 vaccine doses were reported to have been administered as of April 14, 2024.²⁴ Nearly 67% of total population worldwide, have been administered with the primary dose of COVID-19 vaccine and 32% of them with at least one booster dose given. Globally, 13.59 billion doses have been administered.⁶ According to The New York Times, as of March 13, 2023, 72.3% of the world’s population is immunised, with 67% of those vaccinations being complete. Out of 100 people, 35 had taken an additional dose.²⁵

On 22 July 2022, the first COVID-19 vaccine product was introduced.⁶ According to statistics recorded on November 30, 2022, the vaccines being utilised in various nations include as given in Table 2.²⁵

Table (2):
Different COVID-19 vaccines used in various countries (as of November 30, 2022)

COVID-19 variants
Since its discovery, the SARS-CoV-2 virus transformed into several forms. As this S protein is bound to the angiotensin-converting enzyme 2 receptor, antigenic impact, cell entry transmissibility, virulence, evasion of host cell immunity, and mutations in the spike S protein (critical S mutation) have occurred. The humoral immune response against the virus produces neutralising antibodies that bind to the spike protein. The SARS-CoV-2 variations were categorised by the Centre for Disease Control and Prevention (CDC) into four categories which are mentioned below.^26,27

• Variants of concern (VOC)
• Variants being monitored (VBM)
• Variants of interest (VOI)
• De-escalated variants

Variants of Interest (VOI) and Variants of Concern (VOC)
Research findings showed that these variants have potential effects on causing the disease, based on genetic characteristics, epidemiological evidence, in-vitro evidence with major impact on immunity, transmissibility, and severity. Some of the VOIs and VOCs reported on the website of European Centre for Disease Prevention and Control are mentioned in Table 3.

Table (3):
Different variants of VOI and VOC

Deescalated variants
These variants (Table 4) are listed as de-escalated variants as they follow at least one of the criteria^26,27:

• Not a single case has been reported of the infection of this variant.
• The variant still being active for a long time without showing any noticeable effects.
• The analysis indicates that these strains do not exhibit any alarming characteristics.

Table (4):
Different types of de-escalated variants

Variants being monitored (VBM)
There are no variants currently meeting the criteria to be listed under the variants being monitored.

Currently available and approved COVID-19 vaccines
Since the outbreak of SARS-CoV-2, efforts have been made globally to undergo antiviral treatments and vaccine development. The therapeutic objectives were concentrated on actions that could reduce the length of hospitalisation and improve the survival of infected patients. It was essential to create effective vaccinations against SARS-CoV-2 due to its pandemic spread and its related effects, such as constrained ventilators and hospital capacity. Vaccines against COVID-19 have mostly been produced in five different forms such as inactivated, DNA-based, RNA-based, replicating and non-replicating vaccines, protein subunit, and virus-like particles (VLPs).²⁸ About 185 nations used the AstraZeneca vaccine, which according to the data analysed, is the most widely used vaccine. Pfizer-BioNTech, Moderna, and Johnson & Johnson administered the vaccines in 165, 114, and 103 countries, respectively.²⁵ The other vaccines being used are Sinopharm-Beijing, Sinovac, Gamaleya, Novavax, etc. Table 5 includes the details of the available COVID-19 vaccines, their efficacy, dosage and immunogenicity.

Table (5):
Currently available and approved COVID-19 vaccines with their properties

With the help of emerging techniques of biotechnology, the current vaccines are being developed to tackle the new variants. As mentioned above in the table some of the currently available vaccines are efficient against the new variants of SARS-CoV-2 such as omicron, and delta strains. The new FDA announcements made on June 14, 2024; the vaccines developed should consider the new variants which are responsible for most cases in a particular region. As mentioned in an announcement made on June 7, 2024, by FDA that the COVID-19 vaccines for the use in United states should be monovalent meaning that it should be closely related to the current circulating strains. With the help of new biotechnological advancements, the COVID-19 vaccines efficacy can be increased to tackle the new variants.^65,66

Adverse effects in recovered patients
Reports are there of many ill-effects of SARS-CoV-2 virus in recovered COVID-19 patients. The effects varied from mental illness to various other health issues. Many studies have been conducted to assess the effects of the virus in different regions of the world.

Study conducted by Ahuja et al. on fifty Indian patients recovered from COVID-19, observed that SARS-CoV-2 has the potential for neurotropism, affecting central and peripheral nervous system. The feet electrochemical skin conductance (FESC) sue to COVID-19 infection is more linked to the sensory and motor symptoms than to autonomic symptoms. This study also identified FESC as a biomarker for the prediction of peripheral neuropathy in patients infected with SARS-CoV-2 virus. The COVID-19 treatment groups were found to have several neurological manifestations including mild symptoms like headache, hypogeusia to more severe symptoms including peripheral neuropathy, and cerebrovascular stroke. It was also observed that the patients suffered from sweat dysfunction. The patients with sweat dysfunction were mostly belonged to older age and were treated at home with antiviral drugs. Reports are there of a patient suffering from acute dysautonomia during SARS-CoV-2 infection.^67,68

Many case studies related to the adverse effects of coronavirus in recovered patients revealed the mental illnesses like insomnia, depression, anxiety, and post-traumatic stress. This might be due to the lifestyle during the COVID-19 pandemic being inside the house without any physical activities and interaction with other people. A study in Milan, on the recovered patients at one month follow up after hospital treatment, observed various neurological disorders as mentioned here. About 28% of the people suffered from post-traumatic stress disorder (PTSD), 31% with depression, 42% with anxiety, 20% with obsessive compulsive symptoms, and 40% with insomnia. The results were collected from the patients through a questionnaire designed to access the mental state of a person. It was clear from these case reports that SARS-CoV-2 induced significant immunological responses and affected the central nervous system, which may lead to the development of neuropsychiatric symptoms. It was concluded that sociodemographic and environmental factors play vital role in the development of COVID-19 related neuropsychiatric syndromes. Some symptoms of this condition were observed to be delusion, depression, emotional disorder, and loss of memory.^69,70

The data taken by a healthcare team in all population and age groups in Australia, revealed the insights into the effects of SARS-CoV-2 infection. Cardiac manifestations were observed and children with the infection recovered well, but a small population developed Kawasaki-like illness, and multisystem inflammatory syndrome temporarily associated with the SARS-CoV-2 infection. It was also seen that the pandemic has affected paediatric population with physical deconditioning and psychological harm.⁷¹

A study conducted to assess the post COVID-19 fitness, had shown a change in the lung computed tomography (CT). The CT observed were of glass ground opacities and fibrotic changes. This case study comprised of 43 occupational and recreational divers. It was observed that thirteen divers were restrained from further diving due to the changes in lung CT results. The results from fitness to dive (FTD) assessment showed that there were chances of air trapping regardless the severity of the disease. The CT results have shown hypo- and hyper-inflated zones, bronchiectasis and reticulations which were associated with pulmonary fibrosis and attributed to small airway disease and air trapping. The case study included 35 males and 8 females which were assessed post COVID-19 recovery. It was seen that a total of 5 subjects (4 male, 1 female) have shown cardiovascular disease, 3 subjects (3 males) have shown the symptoms of lung disease and 3 subjects (3 male) have shown the symptoms of diabetes. The study population consisted of divers with asymptomatic SARS-CoV-2 infected cases along with symptomatic infected cases. The common findings from this study were that post COVID-19 divers showed the symptoms of ground glass opacities (GGO), fibrotic changes, alveolar consolidation, and emphysematous changes.^72,73

A patient got admitted in a hospital of Portugal with a condition of rhabdomyolysis 3 days after being administered the first dose of Pfizer coronavirus vaccine Comirnaty® and it was found that the disease onset might be related to the vaccine administration. Following the immunization of the vaccine a total of 69 reports of rhabdomyolysis were reported in Europe, as stated by European Medicines Agency in 2021. The other causes of rhabdomyolysis were excluded as there were no abnormal levels of myoglobin and creatinine kinase (CK) before. The patient had a history of ischemic heart disease with electrocardiographic abnormality, cerebrovascular disease, and interstitial lung diseases medicated with nintedanib. The medication of nintedanib was started recently and showed no effects of the drug during the hospital stay which was same with the drug statin. The patient after being treated with more than one medication of rhabdomyolysis, it was seen that the disease onset has links with the vaccination by Comirnaty® vaccine. This case provided the insights into the effects of Pfizer coronavirus vaccine Comirnaty® with the onset of the disease rhabdomyolysis.^74,75

A study conducted in China to assess the effects of SARS-CoV-2 virus in recovered pregnant women and their foetus growth, comprised a total of 12 pregnant women recovered from COVID-19 prior to pregnancy termination. The study was conducted to provide clinical references for other countries with regard to the effects of COVID-19 in pregnant women. In this study group, two women chose labour induction (due to worries of SARS-CoV-2 infection), eight of them gave birth by caesarean and two by vaginal delivery. This study concluded that there were no effects of COVID-19 in pregnant women and their foetal growth. There were some cases of women undergoing abortion due to the anxiety of COVID-19 treatment. The conclusions were supported with placental pathological examination results, which was observed to be consistent in all the subjects studied. The results were supported by the finding that the foetus was protected from the infection of SARS-CoV-2 by the placenta after the mothers were cured with COVID-19 treatment.^76,77

A study conducted to assess the clinical course and outcomes of liver transplant recipients with hepatic cirrhosis, who have recovered from the infection of coronavirus and underwent liver transplant from dead donors. This study focused to determine the management, timing, and safety of liver transplant in the COVID-19 recovered patients. The study was conducted at Shiraz Transplant Center in Iran during the COVID-19 pandemic. It was concluded that the liver from the deceased can be transplanted into patients recovered from COVID-19, especially in those with increasing Model for End-Stage Liver Disease (MELD) scores and deteriorating clinical status. It was also discussed that the liver transplant can be performed in cases where patients have worsening clinical conditions. It was found that the reverse transcriptase polymerase chain reaction (RT-PCR) results were positive for SARS-CoV-2 after the liver transplantation in patients who had been previously infected with COVID-19. Further studies are required to find the implications of positive RT-PCR results post-transplantation and the long-term outcomes of such patients.^78,79

A study in which the data from the European Renal Association COVID-19 database (ERACODA) was analysed to compare the outcomes between peritoneal dialysis (PD) and haemodialysis (HD) patients with COVID-19. The study consisted of adult patients with kidney failure who were treated with dialysis and developed COVID-19. The study was mainly focused on finding the mortality rates, functional and mental health status among the survivors, and to compare the outcomes with HD and PD patients with COVID-19. The study was conducted to determine the effect of COVID-19 on kidney failure patients treated with dialysis, so that potential strategies can be designed for improving care and clinical outcomes of the patients during the COVID-19 pandemic. It was observed that the mortality rate of PD patients was higher as compared to HD patients. It was concluded that special attention and specialized care should be provided to the PD patients who were at higher mortality risk due to COVID-19 infection. The main insights of this study were the importance of specialised care for the vulnerable group and the need for proactive strategies to enhance the clinical outcomes of the population at risk by lowering the mortality rates of the vulnerable patients.^80,81

A study comprising the patients with both coronavirus infected and non-infected groups who have undergone total hip arthroplasty (THA) or total knee arthroplasty (TKA), was conducted to evaluate the complications associated with COVID-19. The results of this study revealed that the patients diagnosed with COVID-19 within 90 days of surgery had higher rates of readmission, pneumonia, deep vein thrombosis (DVT), kidney failure and acute respiratory distress syndrome as compared to the COVID-19 negative group. The potential reasons for the complications were combined risk of thromboembolism from COVID-19 and total joint arthroplasty (TJA), residual symptoms like fatigue, dyspnea, joint pain and chest pain, pulmonary complications such as acute respiratory distress syndrome (ARDS) which showed inflammation-mediated necrosis of the alveolar-capillary endothelium and epithelium along with interstitial and intra-alveolar edema.^82,83

A study was performed to determine the safety of surgery on patients recovered from COVID-19 and the challenges in the preoperative evaluation of the COVID-19 recovered patients. It was discussed that the surgeries are recommended to be postponed whenever possible and the surgeries should be performed based on the clinical status of the patients. It was observed that there is lung damage due to COVID-19 infection caused by the SARS-CoV-2 virus which increases the risks of pulmonary complications in COVID-19 recovered patients. It was suggested to use protective mechanical ventilation during and after the surgery to prevent the pulmonary complications. It also discussed the parameters to operate the protective mechanical ventilation for use during and after the surgery of recovered COVID-19 patients.^84,85

Since the outbreak of COVID-19 there has been a concern that the infection may adversely affect the patients due to immune thrombocytopenia (ITP). A study conducted on 52 ITP patients after administered with COVID vaccine, was able to provide insights into the effects of COVID-19 in the patients. The study revealed that 73% of the subjects had no new symptoms and no decline in the platelet count. However, 12% of the patients had an average platelet drop of 96% within 2-5 days from the day of vaccine administration. The results were related to the vaccines which were produced by dead bacteria or viruses which are the simulators of the immune system of the body. Some of the subjects have shown the same symptoms before when vaccinated for Neisseria meningitis and Streptococcus pneumoniae.^86,87

Remdesivir was one of the drugs used to treat COVID-19 infection at earlier stages before the vaccines were prepared. This drug was seen to decrease the time for recovery from the infection in adults. The effects of this drug were not known in the children as very few studies were conducted till then. The study included 77 SARS-CoV-2 infection cases who were administered with remdesivir drug. It was concluded that among the 77 cases most had recovered, and few adverse effects were observed. The side effects reported with the use of this drug include serious allergic reactions including infusion-related reaction and anaphylaxis. This study also evaluated the safety, quality, pharmacokinetics, and efficacy of the drug with the help of a control arm.^88,89