INTRODUCTION
This review article attempts to provide an overview of the novel coronavirus COVID-19 based on the literature review of current evidence available in the public domain. This review provides an overview of the genetic nature of the novel coronavirus infection, method of infection, epidemiology, clinical symptoms, complications associated with it, diagnostic methods of detection, possible treatment options, prevention and control of the current situation. As the novel coronavirus infection originated around 2 years ago, scanty reports are available in the public domain for reference. Several studies and research are still ongoing to understand the nature and trend of the virus.
In December 2019, an unknown respiratory disease was identified in a wet market in China (Huanan Seafood) which was later called Covid-19 caused by the virus severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). The coronavirus was new and its infection in humans has not been reported previously. This disease which originated in China quickly infected all the countries worldwide.[1,2,3]
The primary clusters of infected patients with unknown pneumonia were reported to be associated with the Huannan Seafood market.[4] The COVID disease is highly contagious in nature.[5] On March 11, 2020, the WHO declared the disease as a global pandemic.[6]
The reason for the fast and rapid spread of the disease from China throughout the world is still not confirmed or reported.
As per evidence, it was stated that the virus might have originated in bats in China. It spread in almost all the countries of the world within 2 months. SARS-CoV-2 belongs to the beta coronavirus and is a single-stranded, enveloped RNA virus.[7]
Previously two other coronaviruses were reported which were SARS and Middle East Respiratory Syndrome (MERS) in 2003 and 2012, respectively.[2]
The fatality of the COVID-19 virus is 2%–3%, which is less than that of SARS which was 10%.[8] The virus possibly originated in bats and got transmitted to humans through some intermediate animals.[9,10]
The number of cases of COVID-19 as on October 8, 2022, is presented in below Table 1.
;)
Table 1: Current number of COVID-19 cases reported as on 8th October 2022
Significant number of cases for COVID-19 is not being reported. The Government of India launched the Arogya Setu mobile App to connect the citizens of India with essential health-care workers to fight the coronavirus. It alerts a person using the App if coming in close proximity to a suspected or infected individual.
SYSTEMATIC SEARCH STRATEGY
Online electronic databases PubMed, Science Direct, Medline, Embase, Cochrane library, and general Google search was done with keywords such as articles and reviews on COVID-19, novel coronavirus, pregnancy and COVID, psychological effect of COVID, myths associated with covid, vaccines against COVID and treatment methods for COVID. Searches were done from September 10 to October 5, 2022. A total of 51 articles have been referred to in this article which seems to be adequate at the current point of time.
GENOME OF COVID-19
The COVID-19 has a better genome sequence identity compared to the SARS and MERS coronaviruses. The amino acid sequence of the virus differs from the other coronaviruses based on surface glycoprotein or S-protein.[11]
The virus is also claimed to be a mutated form of the SARS and MERS viruses.[12]
There are four subgroups of coronaviruses namely α, β, γ, and δ.[8]
The virus is an RNA-enveloped beta coronavirus.[13,14]
The genome showed similarity to that of the bat SARS coronavirus.[5]
Ninety-three patterns of genetic mutation were observed in the SARS-Cov-2 virus. Mutation in surface glycoprotein may result in changing the conformation which finally leads to a change in antigenicity. This may result in the difference in the severity of infection among individuals affected by the virus.[20]
MECHANISM OF INFECTION
The steps involved for the novel coronavirus infection involve attachment, penetration, biosynthesis, and maturation followed by release. On binding to the host cells, the virus enters the cells through endocytosis or penetration. The viral RNA then enters the nucleus for replication. mNA is used for the biosynthesis of viral proteins. The formed matured viral particles are then released.[15]
EPIDEMIOLOGY
People among all age groups are vulnerable to get infected with this novel coronavirus infection. The infection spreads when a symptomatic patient coughs or sneezes via droplets which can spread between 1 and 2 meters and deposit on common surfaces. The infection spreads by inhaling the viruses or touching contaminated surfaces followed by touching of mouth nose and eyes. It is hypothesized that the virus may spread through stool.
The incubation period of the virus ranges between 2 and 14 days from the day of the first infection.[1]
The novel virus is reported to use Angiotensin Converting Enzyme (ACE2) as the cell receptor for humans. It first causes interstitial damage of the lungs followed by parenchyma changes.[16]
The postulated mechanism for organ damage is cytokine storm or cytokine cascade. The virus activates the body's immune cells and facilitates the inflammatory cytokines and chemokines secretion into the pulmonary vascular endothelial cells.[3]
Coronavirus may spread through animals such as dogs, cats, cows, pigs, and turkeys.[17]
CLINICAL SYMPTOMS
The symptoms of the novel coronavirus appear in individuals after an incubation period of about 5.2 days.[1,2]
In patients dying due to the infection, the duration between onset and death ranged between 6 and 41 days. This time span was shorter in patients who were >70 years of age compared to those under 70 years. Elderly patients have a greater risk in developing the severity of the infection.[1]
The reported clinical symptoms of COVID-19 are fever, body pain, myalgia, runny nose, congestion of nose, sore throat, dry cough, fatigue, feeling tired, loss of taste or smell, production of sputum, nausea, vomiting, headache, chill, hemoptysis, palpitation, tightness of chest, diarrhea, and dyspnea.[1,2]
The symptoms which are initially reported after getting the infection are fever and cough, headache, production of sputum, diarrhea, hemoptysis, myalgia, fatigue, and dyspnea.[3]
The severity of the COVID-19 infection ranges from very mild having no symptoms in 30% of cases to severe symptoms in 10% of cases and critical symptoms in 5% of cases.[1]
Generally, the disease causes flu-like symptoms which may cause severe clinical manifestations in people with underlying risk factors.[18]
The symptoms may be classified based on the severity of the infection as follows:
Mild disease
Patients with mild disease may experience symptoms of upper respiratory tract infection such as fever, dry cough, sore throat, headache, malaise, and nasal congestion. Dyspnea may be absent. They may develop severe cases later though.
Moderate disease
Patients in this category may have shortness of breath, cough, and tachypnea. Symptoms of severe disease may be absent.
Severe disease
Patients in this category may have severe pneumonia, acute respiratory distress syndrome, shock and/or sepsis.[19]
TYPES OF COVID-19 VARIANTS
Variants of interest
Variants having specific markers which change binding to receptors, reduce neutralization of antibodies developed by prior vaccine or infection, reduced treatment efficacy, and rise in transmission and disease severity. P. 2., B.1.525, and B.1.526 are examples of variants of this category.
Variants of concern
This includes variants having a high transmission rate of disease, raised severity causing death and hospitalization, reduction in the neutralization of antibodies, reduced treatment efficacy, and detection failure by diagnostic tools. B.1.429, B.1.427, B.1.1.7, and B.1.351 are examples of variants in this category.[21]
The Omicron variant was responsible for the third wave of the pandemic in India. More than 325 million cases of infection were reported in the nation seconding the United States of America.[22]
Omicron was considered a variant of concern as it surpassed immunity caused by vaccines and had mutations in the RBD region of the spike protein. It had a great degree of infectivity and spread to more than 77 countries in the world.[23]
COMPLICATIONS
The complications reported in hospitalized COVID-19 patients were acute respiratory distress syndrome, cardiac injury, sepsis and secondary infections, kidney injury, secondary hemophagocytic lymph histiocytosis, and multi-organ failure.[1]
The virus infection can cause damage to the central nervous system by mechanisms of immune-mediated damage and hypoxic brain injury.[11]
Patients having preexisting disease conditions such as tumor surgeries, hypertension, heart disease, cirrhosis, and Parkinson's disease are more prone to death.[24]
Adverse conditions due to COVID have also been related to alcohol abuse and smoking.[14]
Diabetes is known as a triggering factor to cause the severity of COVID-19 infection and mortality. Several studies have reported that patients having diabetes are more prone to develop COVID-19 disease and complications such as acute respiratory distress syndrome and death. Increased patient care should be provided to diabetic patients to prevent complications and deaths.[12]
Geriatric and immunocompromised patients are at greater risk of fatality.[19]
AS PER WHO, THE FOLLOWING ARE THE CLASSES OF COVID CASES
Suspect case
A patient having any respiratory illness like cough or shortness of breath along with fever along with a history of travel to a COVID infection country before 14 days of development of the symptoms; or a patient having respiratory illness who has been in contact with a confirmed or likely COVID-19 case before 14 days of development of symptoms or a patient having a severe respiratory illness like cough, shortness of breath accompanied with fever requiring inpatient hospitalization.
Probable case
A suspect case having inconclusive evidence of COVID-19 testing.
Confirmed case: A patient having confirmed laboratory testing of COVID-19 infection irrespective of the signs or symptoms.[1]
VIRUS DETECTION
Two methods which are currently used for the detection of SARS-CoV-2 are real-time quantitative polymerase chain reaction and high throughput sequencing. The WHO recommends the use of the former method which involves the collection of respiratory samples from both upper respiratory tract like naso and oropharyngeal and lower respiratory tract such as sputum expectorated, endotracheal aspirate, and bronchoalveolar lavage. Virus blood culture followed by high throughput sequencing of genes may also be used for the detection of SARS-CoV-2.[1,2,6]
The real-time reverse transcriptase polymerase chain reaction helps in the quick detection of corona virus-associated infection. It is very sensitive and helps in specific detection of SARS-Cov viruses.[25]
Chest computed tomography may be used for asymptomatic cases and false negative results in real-time reverse transcriptase polymerase chain reaction.[16,26]
Enzyme Linked Immunosorbent Assay and Western blots may detect specific proteins of COVID-19.[11]
Positive polymerase chain reaction results are generally found in the early days of symptoms. Hence, the time of testing is a major concern for virus detection. Early detection of the virus helps in the proper management of the disease and may prevent the occurrence of severe conditions.[6]
As per a published literature, it was concluded by the authors that real-time Reverse Polymerase Chain Reaction results may be falsely negative. The tests should be repeated in patient's indicative of computed tomography findings.[27]
Collection of the right specimen at the right time from the correct anatomic site is essential for the prompt and appropriate diagnosis of COVID-19 infection. Nasopharyngeal and oropharyngeal swabs are mostly preferred for testing the infection. Sputum samples and bronchoalveolar lavage should be used for collecting samples from the lower respiratory tract. Rapid antigen immunoassays are used for COVID diagnosis due to low cost and quicker results; however, they are less sensitive to detection of the virus.[28]
Antibody tests exhibit very low sensitivity for virus detection in the 1st week of COVID infection, however, they may be used to detect earlier infections.[29]
Rapid kits which are easy to use are being used which detects COVID-19 proteins in respiratory samples like swab of throat and sputum or antibodies detection in blood or serum of humans. The sensitivity of rapid antigen kits varies between 34% and 80% which depends on the timing of illness, specimen quality, and processing. The WHO does not recommend the use of rapid antigen test kits for the detection of the novel coronavirus.[49]
As per a published article, virus transmission may occur upto 8 days of the appearance of symptoms. Following several weeks of symptom remission, the patient may still be positive for the novel coronavirus.[18]
COVID AND PREGNANCY
As per a published case report, neonatal vertical transmission from a COVID-19 positive mother occurred to her baby.[30]
As per another published article, sufficient evidence for intrauterine transmission of COVID-19 infection from pregnant mothers to their fetuses is not available. Among the infected pregnant women who gave births to babies, none of them tested positive for the novel coronavirus infection. However, COVID-infected mothers are more prone to developing severe respiratory complications. Moreover, infected mothers can transmit the virus by means of respiratory droplets during breastfeeding.[31]
It has been reported that pregnant women are more prone to contracting the novel coronavirus as their immune system is weakened. The COVID-19 infection reduces the number of lymphocytes and raises selected pro-inflammatory cytokines, thereby affecting the immune system.[32]
COVID IN PAEDIATRICS
It has been reported that children <10 years old and up to 19 years were less vulnerable to the COVID infection. The percentage of infected individuals among children for asymptomatic, mild, moderate, and severe were 4.4%, 50.9%, 38.8%, and 5.9%, respectively.[15]
Pediatric patients experience milder symptoms compared to adults.[15]
PSYCHOLOGICAL IMPACT OF COVID-19
Psychological disturbances among people have been reported during the COVID-19 situation. These include anxiety, depression, stress, fear, boredom, frustration, uncertainty and even suicidal tendency. Apart from this isolation is also reported during periods of quarantine.[34]
COVID-19 has also caused hysteria, economic burden, and losses financially. Mass fear of the novel corona virus is called as “coronaphobia.” Fear of getting the infection, anxiety, and rise in substance dependence has been reported to occur.[30]
Due to the rapid number of cases of COVID infection measures such as social distancing, working from home, isolation of school and college-going students may impact the mentality of the general population.
MYTHS ASSOCIATED WITH COVID-19
It is reported that several myths and superstitions have been associated with COVID like the virus cannot survive in hot temperatures. As per WHO, COVID-19 infection can occur in hot and humid conditions. False beliefs like eating nonvegetarian food cause risk of infection, cow dung, and urine can prevent Indian people from getting corona infection are also prevalent in India.[35]
Unpublished reports claim that a myth is being followed by some people that hard vaccination of small pox prevents the infection of the novel corona virus.
Drinking alcohol do not help corona infection. Most of the people infected with corona virus generally recover without major clinical consequences. Adding pepper in diet do not prevent COVID infection. Thermal scanners help in detecting elevated body temperatures but cannot detect COVID infection.[49]
TREATMENT
Infected patients should be asked to be quarantined and isolated to prevent the virus transmission to others. Patients having mild symptoms should be asked to self-manage at home with proper nutrition and adequate hydration, however reporting any severe signs to health authorities. Hypoxic patients should be managed with oxygen via nasal prongs, face mask, high flow nasal cannula or ventilation. Mechanical ventilation or extra corporeal membrane oxygen may be required in cases of severe pulmonary dysfunction. Patients having co-infections, antibiotics and antifungals may be used based on requirement.[1]
For the treatment of SARS-2-Cov, protease inhibitors like Lopinavir and Ritonavir or combination with Ribavirin showed some efficacy in reported cases. Nebula of interferons-α, antibiotics having broad spectrum, and antiviral drugs are used to reduce the viral load. The drug Remdesivir has shown some results in treating the virus infection.[1]
The drugs Lopinavir and Ritonavir combination, infusion of Vitamin C, Remdesivir, Darunavir, and Cobicistat are claimed to be useful for the treatment of the novel coronavirus infection.[2]
Remdesivir is considered a promising antiviral agent. It acts by inhibiting the actions of RNA dependent RNA polymerase. Hydroxychloroquine along with Azithromycin should have proper clinical efficacy in a clinical trial conducted on Chinese COVID-19 patients.[32]
Hydroxychloroquine may be used for the treatment of pneumonia associated with COVID-19 disease.[2,4]
As per the WHO, the drugs Hydroxychloroquine and Chloroquine are used as antimalarial drugs and cannot be used for the clinical treatment of COVID infection. Till date, there are no drugs licensed for the treatment of the COVID infection. The coronavirus infection is caused by a virus and not bacteria, hence antibiotic use will not help in treating the disease.[49]
Some Chinese herbal medications are also being used for the treatment of COVID-19 infection. However, rigorous clinical trials should be conducted to test the safety and efficacy of these herbal treatments.[36]
VACCINE
There were no vaccines initially to curb the spread of the disease. During the first wave of the pandemic, there was an urgent need for a quick development of a vaccine for public use.[1]
The novel virus belongs to the class of SARS-related coronavirus. The rate of transmission to the various geographical areas of the world and rising number of cases per day indicated that it was much more potent that the SARS and MERS. The experience gained during the research work of vaccine development of previous coronavirus infections may be implemented during the vaccine development of the current coronavirus.[36,37]
Even countries having state-of-the-art health facilities found it difficult to prevent the viral infections, managing and reducing the number of deaths caused by it. However, some rich countries were able to keep the situation under control. This infection seemed mild in children and provided good immunity, however, transmission had to be prevented. Pregnant women might develop a severe form of the infection if infected by SARS-CoV-2. Vaccination might develop immunity for them.[38]
The vaccines that were undergoing various clinical trials mostly act by inducing neutralizing antibodies against spike protein (S). The resulting antibodies would prevent uptake via the ACE-2 receptor in humans. This would result in preventing the entry of the virus. At present, more than 230 vaccines are under development. Quite a number of them have received approval in <1 year since the first occurrence of SARS-C0V-2 virus.[39]
Some of the vaccines that are under various phases of clinical trials include Oxford/AstraZeneca AZD 1222, CoronaVac of Sinovac and mRNA-1273 of Moderna.[40]
Although vaccines are an effective tool, none of them are 100% effective in preventing illness. A small percentage of fully vaccinated population can still get sick to many degrees by the vaccine due to breakthrough cases. People having the viral RNA or antigen detected on a biological sample within 14 days of vaccination might be good candidates for breakthrough cases. Not much studies with the vaccines have been conducted for pregnant and breastfeeding females and immunocompromised patients. Some people are reluctant about getting vaccinated. Equal distribution of the vaccine, cost and storage condition requirements can impact vaccination all over the world.[21]
Covaxin developed by Bharat Biotech Limited and the Indian Council of Medical Research has been approved in India against COVID-19. Whole virion inactivated Vero cell-derived technology and alhydroxiquim II was used as an adjuvant. Thoi saws were authorized for emergency use in India on January 16, 2021. Antibodies induced by the vaccine also neutralized variants such as B.1.1.28, B.1.1.7, B.1351, B.1.617, B.1.617.2, and SARS-CoV-2 virus.[41]
As per the Ministry of Health and Welfare, more than 21 crores of Indians have been vaccinated against the virus.[50]
MEANS OF PREVENTION AND PROTECTION
It is truly said that prevention is better than cure. The novel coronavirus is very new and scanty literatures and articles are available in the public domain.
Drugs such as remdesivir, hydroxychloroquine, monoclonal antibodies, nucleoside analogs, and herbal medicine of China are some of the available treatment options for COVID-19. These drugs and remedies act by inhibiting viral interaction with RNA-dependent RNA polymerase, ACE-2 cell receptors, replication of RNA, and virus packaging. Chloroquine and hydroxychloroquine were found to be effective for treating COVID-19 and improved the recovery of patients. Chinese herbal medicines reduced mortality and relieved the viral symptoms in clinical trials. This is also considered to be safe and less toxic compared to conventional drug treatment.[42]
As per the WHO recommendation, confirmed and suspected cases having even mild symptoms should be quarantined or under home isolation. Patients and caregivers should be asked to wear a mask all times and follow respiratory hygiene. Patients having respiratory symptoms should wear masks to prevent the spread of droplet infection to others and surfaces.[1,2]
Health-care workers should be provided with respirators, protective shields, and goggles. Infected patients should be kept together in separate rooms. Common surfaces and equipment should be sanitized using sodium hypochlorite.[1,2]
Efficient hand hygiene should be practiced.[43]
Hands should be sanitized using alcohol-based hand sanitizers containing 60%–80% alcohol. Hands should be washed with soap and water repeatedly times in a day.[2]
People should be advised not to touch their hands, mouth, and nose without washing their hands.[19]
Strict travel restrictions should be implemented for both domestic and international travelers from the point of travel to the destination. All passengers should be isolated for minimum of 2 weeks even if asymptomatic and COVID-19 testing should be done. People who come in contact with any COVID-19 suspect or confirmed cases should undergo mandatory COVID testing.[1,2]
Inconclusive evidence are present regarding the more parts of the body being linked to better protection from the novel coronavirus infection.[44]
As per a Cochrane review, quarantine is an excellent method to prevent the incidence and mortality associated with COVID-19 infection.[37]
Social distancing and telework are recommended to prevent the spread of the coronavirus.[37]
Few countries such as China, Britain, and India have implemented lockdowns in specific containment areas in order to prevent the transmission of the virus infection from the infected people.
Since vaccination is not a guarantee to combat the disease, precautionary methods like practicing hand and respiratory hygiene, using masks, quarantine, early detection and identification of variants, prevention of viral mutation, and replications will continue to remain the action plans to combat the pandemic situation.[21]
EFFECT OF THE PANDEMIC ON INDIA
During the first wave of COVID-19 in India, the country had declared lockdown and social distancing rules which impacted the economy negatively. However, less pollution due to reduced traffic had a positive impact on the environment.[45]
The 21-day lockdown during the first wave pressured down the growth of the nation. Due to the suspension of supplies of products from China, the pharmaceutical companies of India faced a tremendous shortage of the active pharmaceutical ingredients. This caused a spike in the process of Over-the-counter medicines such as penicillin, vitamins, and paracetamol. Visa restrictions were implemented for countries having a high number of COVID-19 cases. Asymptomatic travelers to India from international countries were advised to be home quarantined.[46]
As per a published literature, the actual number of COVID-19-related deaths was more compared to the reported ones.[22]
Negative impact was observed in a study conducted on Indian adolescents during the lockdown. Females were more tensed about physical health and academics compare to males. However, a greater number of males were tensed about recreational and social activities.[42]
Precautionary steps and required actions are being taken by the Ministry of Health and Family Welfare of India like raising awareness and mean to prevent the transmission of the virus. A 24 × 7 helpline had been created to manage the diseases, surveil it, collect samples, transport, discharge of confirmed or suspected cases, and control and prevent the infections. People traveling to the country from China and other international countries exhibiting COVID symptoms like fever, cough, breathlessness, difficult breathing, and sore throat were advised to visit hospitals for support and treatment. The ministry of AYUSH and ICMR have also provided guidelines for using conventional treatment and prevention systems to help increase immunity against the novel corona virus. India has specialized medical and pharmaceutical industries having adequate production facilities that helped the government to accelerate the production of low-cost vaccines and rapid diagnostic test kits. Serum Institute of India has also started the development of a vaccine against the SARS-CoV-2 infection.[48]
CONCLUSION
The novel SARS-Cov-2 infection may be asymptomatic in few patients and may cause mild to moderate infection in others. Fever, cough, sore throat, and myalgia are thought to be indicators of the disease. Oxygen saturation and lung auscultation results may be used for diagnostic purpose.[39]
There have been previous epidemics of SARS and MERS but the WHO has declared the COVID infection as a pandemic affecting globally for the first time. It is unknown how the disease which originated in China spread globally in a short span of time. It is not yet evident why some individuals are asymptomatic and require mild-to-moderate treatment while some individuals need to be hospitalized and need critical treatment. The symptoms, treatment, and recovery show no correlation with age, gender, or race. Several research works are ongoing presently on the novel coronavirus. The final outcome of the current COVID situation is difficult to be predicted at this point of time. India has seen three waves of the COVID-19 infection as of the end of 2022. Adequate precautionary and preventive measures were taken by the Ministry of health and welfare and AYUSH during the pandemic. Free meals were served during lockdown by the Government of India under the “PM care” scheme to support poor people and daily wage laborers who were impacted the most during the lockdown phase in the country.
Since majority of the population has been vaccinated, currently there are very less cases of active infections of the novel coronavirus. The Government of India has uplifted norms and restrictions of mask and sanitizer usage. It has been unofficially reported that there might be no other waves of the virus in India. Indians might have developed her immunity since most of them have been infected at least once and majority of them are vaccinated with two doses of either Covaxin or Coveshield and a booster dose of the same. However, this is subject to the emergence of another mutated form of the virus.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
Acknowledgment
We are thankful to Gitam University to allow us to carry out the current review work.
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