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Department of Pharmacy, Adina Institute of Pharmaceutical Sciences (AIPS).
Since the onset of 2019, marked by a severe outbreak in Wuhan, China, the COVID-19 pandemic has become a significant global narrative. We are discussing SARS-CoV-2, the virus that initiated the pandemic. The situation has been exceedingly challenging for all individuals worldwide, resulting in a global health crisis. SARS-CoV-2, a beta coronavirus, is a single-stranded RNA virus characterized by a crown-like morphology and is closely associated with the SARS virus. This paper offers an extensive analysis of COVID-19 transmission, existing treatment modalities, and prospective therapeutic approaches. We examine the modes of virus transmission, including direct person-to-person contact and the inhalation of contaminants from various surfaces. We are currently examining how this virus instructs the body and the symptoms exhibited by an ill individual. The current therapy landscape, encompassing antivirals, immunomodulators, and supportive care, is clearly delineated. Additionally, we investigate prospective treatment options, encompassing vaccine development, gene editing technologies, and novel antiviral methodologies. This study seeks to summarize the present situation and significant advancements of the COVID-19 pandemic, while also emphasizing the necessity of ongoing investment in research and development to provide more effective therapeutic strategies to combat this global health problem. We will endeavor to narrate this story in a straightforward and lucid manner that is easily comprehensible to the audience.
Coronavirus disease-2019 (COVID-19) is caused by SARS-CoV-2, a newly emergent coronavirus, that was first recognized in Wuhan, China, in December 2019. Genetic sequencing of the virus suggests that it is a beta coronavirus closely linked to the SARS virus. It is from the family of single-stranded RNA virus (+ss RNA) with a crown-like appearance under an electronic microscope, of approximately 60-140 nm diameter, and contains large widely spread club or petal-shaped spikes. Although high temperature decreases the replication of the virus, it can resist the cold temperature. It is sensitive to ultraviolet rays and is effectively inactivated by lipid solvents including ether (75 percent), ethanol, chlorine-containing disinfectants, peroxyacetic acid, and chloroform except for chlorhexidine (1). Mechanism of action SARS-COV-2 virus is defines in (Figure 1). The dynamics of SARS-CoV-2 are currently unknown, but it is speculated that it has an animal origin.
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Figure 1. Mechanism Of Action Of SARS-COV-2 Virus
Global Scenario
In late December 2019, investigation of a cluster of pneumonia cases of unknown origin in Wuhan, China, resulted in identification of a novel coronavirus. The virus is distinct from both severe acute respiratory syndrome (SARS) coronavirus and Middle East Respiratory Syndrome (MERS) coronavirus, although closely related. Early epidemiological findings suggest that the virus is more contagious than its predecessors. Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a newly identified pathogen and it is assumed that there is no existing human immunity to the virus. Everyone is susceptible, although there may be risk factors that increase an individual’s illness severity. The disease since its first detection in China, has now spread to over 220 countries/territories. COVID-19 was declared a Pandemic by WHO on 11th March 2020, resulting in shift of focus from China to Europe and North America and later on to the world. As such WHO advised countries to take a whole-of-government, whole-of-society approach, built around a comprehensive strategy to prevent disease, save lives and minimize the effect. Countries closed their borders against travel-related activities (by air, road, railway or sea), and the lockdown was imposed to minimize the public movement. The pandemic has taught the world that "the global problem requires global solution". International cooperation is the requirement of the day. Whether in the detection of virus or development of vaccines or action on economic and social fronts. COVID-19 has imposed many restrictions on our daily behavior whether it is social distancing or wearing masks. We have also discovered that work-from-home-study-from-home, and shop-from-home, no visit to malls and markets are workable concepts. E-commerce portals witnessed record traffic, which may become a permanent feature (2). When compared globally, India's cases per million population were amongst the lowest in the world. Like-wise the number of deaths per million was also one of the lowest. USA reported the highest number of cases and deaths.
In India, the first case of COVID-19 was reported on 30th January 2020 in Kerala. India currently has the largest number of confirmed cases in Asia. The outbreak of the disease was declared an epidemic and Epidemic Disease Act, 1897 was invoked leading to temporary closure of educational, religious, entertainment and commercial establishments. It was followed by gradual un-lockdown spread in 6 phases (one month each) upto 30th November 2020. A three-tier arrangement of health facilities was created for appropriate management of COVID-19 cases. [(i) COVID Care Centre with isolation beds for mild or pre-symptomatic cases; (ii) Dedicated COVID Health Centre (DCHC) with oxygen-supported isolation beds for moderate cases; and (iii) Dedicated COVID Hospital (DCH) with ICU beds for severe cases] has been implemented. Tertiary care hospitals under ESIC, Defence, Railways, paramilitary forces, Steel Ministry etc. have been leveraged for case management. The top five states contributing to over 80 per cent active cases are Kerala, Maharashtra, Tamil Nadu, West Bengal and Karnataka. In India, about 92 per cent of the reported cases were having mild disease, 5.8 per cent cases required oxygen therapy and about 1.7 per cent cases required intensive care (3).
1.2. Aarogya Setu APP
The Aarogya Setu App was launched by the Government of India on 2nd April 2020 and is available in 11 languages, including Hindi and English. It is one of the many location-based surveillance apps that lets users check whether they have been in contact with infected people by using location and Bluetooth data from smartphones. The app is available on both Android and iOS devices. It asks a set of questions to the user to identify whether they are at risk of the coronavirus infection.
SARS-CoV-2 is primarily transmitted through respiratory droplets, but emerging evidence has also confirmed other modes of transmission.
1. Respiratory Droplets and Aerosols
2. Direct Contact
3. Fomite Transmission
4. Airborne Transmission
5. Asymptomatic and Presymptomatic Transmission
2.1. Period of Communicability
Knowing when an infected person can spread COVID-19 is important. Evidence suggests that COVID-19 can be detected in people 1-3 days before their symptoms appear, with the highest viral loads as measured by RT-PCR, observed around the day of symptom onset, followed by a gradual decline over time. The duration of RT-PCR positivity generally appears to be 1-2 weeks for asymptomatic persons, and up to 3 weeks or more for patients with mild to moderate disease. In patients with severe COVID-19 disease, it can be longer (8). A study of the first patients in the Republic of Korea showed that 9-13 secondary cases occurred among household contacts Govt. of India (2020).
3.2 Symptoms of post-COVID conditions
People with post-COVID conditions may experience many symptoms. The most common symptoms are as follows:
1. General symptoms: (a) Tiredness or fatigue that interferes with daily life; (b) Symptoms that get worse after physical or mental effort (also known as "post-exertional malaise"); and (c) Fever.
2. Respiratory and heart symptoms: (a) Difficulty in breathing or shortness of breath; (b) Cough; (c) Chest pain; and (d) Fast-beating or pounding heart (also known as heart palpitations).
3. Neurological symptoms: (a) Difficulty in thinking or concentrating (sometimes referred to as "brain fog"); (b) Headache; (c) Sleep problems; (d) Dizziness when you stand up (light-headedness); (e) Pins-and-needles feelings; (f) Change in smell or taste; and (g) Depression or anxiety diagnosis test of covid-19 is described in (TABLE 1).
4. Digestive symptoms: Diarrhoea and stomach pain.
5. Other symptoms Joint or muscle pain, rash, and changes in menstrual cycles.
4. Diagnosis Test Of Covid -19
(Table 1).
|
Category |
Details |
|
Testing Strategies |
Diagnostic Testing – for symptomatic or exposed individuals. |
|
Molecular Test Sample Collection |
Lower Respiratory Tract: Bronchoalveolar lavage, tracheal aspirate, sputum. |
|
NAAT (RT-PCR) |
Gold standard. Detects viral RNA. |
|
Antigen Testing |
Detects viral antigens. |
|
Serologic Testing |
Detects IgM/IgG antibodies. |
|
Chest Imaging |
X-ray: Limited early sensitivity, used in advanced stages. |
|
Laboratory Findings |
- Lymphopenia (poor prognosis). |
|
Current Treatment Approaches |
Mild-Moderate: Supportive care, antivirals (Paxlovid, Molnupiravir), monoclonal antibodies. |
Table 2. Future Therapeutic Strategies
|
S. No. |
Therapeutic Strategy |
Description |
|
1 |
Next-Generation Antivirals |
• Broad-spectrum antivirals targeting viral proteases and RNA polymerases are under development. • Ensitrelvir, a novel oral antiviral, is in advanced clinical trials (Shiraki & Daikoku, 2024). |
|
2 |
Therapeutic Monoclonal Antibodies |
• Modified monoclonal antibodies with enhanced affinity and longer half-lives are being designed to combat emerging variants. |
|
3 |
Host-Directed Therapies |
• Drugs targeting host pathways involved in viral replication, such as TMPRSS2 inhibitors, are in experimental stages (Hoffmann et al., 2020). |
|
4 |
mRNA and Viral Vector Therapies |
• mRNA therapeutics are being explored for both prevention and treatment, with adaptable platforms for variant-specific formulations. |
|
5 |
CRISPR and Gene-Editing Approaches |
• CRISPR-Cas13 systems targeting viral RNA have shown potential in preclinical models to directly degrade SARS-CoV-2 genomes (Abbott et al., 2020). |
|
6 |
Long COVID Management |
• Therapeutic trials are exploring anti-inflammatory agents, antivirals, and autonomic nervous system regulators to manage long-term symptoms. |
Research into COVID-19 treatments is ongoing, with several innovative approaches showing promise.
1. Next-Generation Antivirals
2. Therapeutic Monoclonal Antibodies
3. Host-Directed Therapies
4. mRNA and Viral Vector Therapies
5. CRISPR and Gene-Editing Approaches
6. Long COVID Management
7. Drug Interactions:
Chloroquine, hydroxychloroquine the two aminoquinolines, chloroquine (CQ) and hydroxychloroquine (HCQ) are used for malaria and rheumatic diseases. They showed the activity against COVID-19 in Vero E6 cells and recommended it as a primary treatment option for COVID-19 CQ and HCQ have weak diprotic features, and they could increase the pH of the endosome during the fusion of the virus to the host cell. Several clinical trials were preceded in China for CQ and HCQ on COVID-19-infected patients. One of them disclosed promising results in a reduction of the disease progression. One clinical trial was performed in France to find the efficacy of HCQ at different doses, along with azithromycin on COVID-19-infected patients. The clinical demonstration noticed that the treated rate was considerably higher in HCQ used in combination with azithromycin. Even though this study showed favorable results, extensive clinical data are required to confirm the efficacy and safety of HCQ with azithromycin.
8. Precautions:
Continue with COVID-19 appropriate behaviour-The most important thing to do post-vaccination is to continue wearing masks, regularly washing, or sanitizing your hands, maintaining physical distance, avoid crowded places, and avoid touching surfaces.
9. Covid-19 Vaccines
In the light of urgent need due to the COVID pandemic in the country, the Central Drugs Standard Control Organization (CDSCO) has granted permission to following six COVID-19 vaccines for restricted use in emergency situation:- Vaccines used for covid-19 are summerized in COVID-19 vaccines (TABLE 3).
Table 3. COVID-19 Vaccines
|
S. No. |
Vaccine Name |
Type |
Manufacturer / Importer |
|
1 |
Covishield |
ChAdOx1 nCoV-19 Corona Virus Vaccine (Recombinant) |
Serum Institute of India Pvt. Ltd., Pune |
|
2 |
Covaxin |
Whole Virion Inactivated Corona Virus Vaccine |
Bharat Biotech International Ltd., Hyderabad |
|
3 |
Sputnik V |
Gam-COVID-Vac Combined Vector Vaccine |
Dr. Reddy's Laboratories Ltd., Hyderabad (Importer) / Ra (Biologicals), Panacea Biotec Ltd., New Delhi (Manufacturer) |
|
4 |
Moderna (mRNA-1273) |
mRNA-based COVID-19 Vaccine |
Cipla Limited, Mumbai (Importer) |
|
5 |
Johnson & Johnson (Janssen/Ad26.COV2.S) |
Adenovirus Vector-Based COVID-19 Vaccine |
Johnson & Johnson |
|
6 |
ZyCoV-D |
DNA-Based COVID-19 Vaccine |
Zydus Cadila Ltd. |
Currently, three COVID-19 vaccines are being used under the vaccination program namely Covishield manufactured by M/s Serum Institute of India, Covaxin manufactured by M/s Bharat Biotech International Limited, and Sputnik V vaccine developed by Gamaleya Research Institute, Russia (imported by Dr Reddy's Lab and is being administered in few private hospitals, presently).
Persons who are temporarily not eligible to get the vaccine are (23):
(a) Persons showing active symptoms of SARS-CoV-2 infection;
(b) COVID-19 patients who have been given anti-SARS-CoV-2 monoclonal antibodies or convalescent plasma;
(c) The vaccine should be given with caution to persons with a history of any bleeding or coagulation disorder platelet disorder, clotting factor deficiency coagulopathy; and or
(d) Actually unwell and hospitalized patients (with or without intensive care) due to any illness.
Persons with a past history of COVID-19 infection can be administered the vaccine. Persons with a history of chronic disease and comorbidities (cardiac, neurological, pulmonary, and metabolic) are eligible for the vaccine although efficiency of the vaccine may be less in these patients. Administration of vaccine to pregnant women should only be considered when the potential benefits outweigh any potential risks for the mother and foetus. According to recent guidelines, a pregnant woman who opts for vaccination can be vaccinated at any time during pregnancy. It is unknown whether the vaccine is secreted in human milk. However, the current guidelines of the Indian Government recommend COVID-19 vaccination for all lactating mothers. The vaccines are not interchangeable.
9.1 Covishield vaccine
Covishield vaccine is a recombinant chimpanzee adenovirus vector vaccine, administered intramuscularly in deltoid muscle. Given in two doses, 12-16 weeks apart. The protective level of antibodies are generally developed two weeks after the 2nd dose of the vaccine. The vaccine has been approved for individuals 18 years of age and above. To be stored at 2-8°C.
Side effects: The common side effects with the Covishield vaccine are: injection site pain and tenderness, headache, fatigue, myalgia, discomfort, pyrexia, chills and nausea. Very rare events of demyelination disorder have been reported following vaccine "without the causal relationship establishment".
Contraindications: 1. Vaccine should not be given if there is severe allergic reaction after the previous dose of this vaccine;
2. Had a severe allergic reaction to any ingredient of this Vaccine.
9.2 Sputnik V Vaccine
Sputnik V Vaccine (Gam-COVID-Vac) is manufactured by Gamaleya Research Institute, Russia. It is a non-replicating viral vector vaccine administered by intramuscular injection in two doses to people 18 years and above. The second dose is taken 21 days after the 1st dose. For both the Jabs, two different vectors are used (Adenovirus 26 and Adenovirus 5). The use of two varying serotypes is unique and provides long-lasting immunity. Vaccine can be stored at 2 to 8°C. Some people reported mild side effects such as pain, redness or swelling at the site of injection, Asthenia, fatigue, body and muscle pain, cough and sore throat, runny nose, fever and chills, nausea and vomiting, diarrhea, and headache (24). In India, vaccination is not mandatory. But if you choose to get vaccinated, you cannot choose which vaccine you will get. You will be vaccinated by the vaccine that is available at the site. 16th January 2021 is the historical day when India launched the vaccination drive.
9.3 Pfizer-BioNTech COVID-19 Vaccine
It is a messenger RNA vaccine with 95 percent efficacy. People 16 years and older are eligible for the vaccine, administered in two doses intramuscularly, 3 weeks apart. It is authorized for emergency use. It is not interchangeable. Storage is at -70°C.
Contraindications: (a) history of severe allergic reaction after the previous dose of this vaccine; (b) had a severe reaction to any ingredient of this vaccine. Before taking the vaccine the provider must know the medical history of the person any allergy, fever, bleeding disorder if any, or taking blood thinner, if the person is immunocompromised or on a medicine that affects immune system, pregnancy and breast-feeding, and have received another COVID-19 vaccine.
Side effects: Injection site pain, tiredness, headache, muscle pain, chills, joint pain, fever, injection site swelling and redness, nausea, feeling unwell, swollen lymph nodes. There are remote chances of severe allergic reaction (within a few minutes to one hour after getting the dose).
9.4 Moderna COVID-19 Vaccine
It is a messenger RNA vaccine, with an efficacy of about 94.1 percent, meant for people 18 years of age and above, two doses given intramuscularly 1 month apart. It should be stored between -25°C and -15°C temperature. The vaccine provider must know about the history of allergies, fever, bleeding disorders or history of taking blood thinner, pregnancy and breast-feeding in mothers, history of taking another COVID-19 vaccine and if the recipient is immunocompromised.
Side effects: Side effects reported are:
(a) injection site reactions are pain, redness, swelling, and tenderness;
(b) general side effects are fatigue, headache, muscle pain, joint pain, vomiting, and fever.
Severe side effects are difficulty in breathing, swelling of the face and throat, fast heartbeat, bad rash all over the body, dizziness, and weakness.
10. ACKNOWLEDGEMENT
The authors wish to thank the Head, Department of Pharmacy, Adina institute of pharmaceutical sciences Sagar (M.P.) India, for providing the required facilities to perform the research work.
11. Conflict Of Interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
REFERENCES
Vaishnavi Soni, Utkarsh Shrivastava, Talib Khan, Triloki Kurmi, Ritu Soni*, An Overview of Covid-19 Transmission, Current Treatment, And Future Therapeutic Strategies, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 4, 2203-2214 https://doi.org/10.5281/zenodo.15236690
10.5281/zenodo.15236690