2.1 SARS-CoV-2

The novel beta-coronavirus (SARS-CoV-2) represents the wide domain of coronaviruses belonging to the family Coronaviridae [7], which has severely attacked humanity in the last two decades. These viruses have the potential to induce severe acute respiratory infection (SARI) in healthy individuals [8]. First coronaviral emergence was observed in human coronavirus-229E in 1965 [9]. In 2002, a similar resurgence of SARS [10] was observed in the Guangdong province of southern China due to SARS-CoV but was contained rapidly and never reappeared since 2004. Later in 2012, another member of this family, known as the Middle East Respiratory Syndrome (MERS) virus, was discovered in Saudi Arabia [11] caused by MERS-CoV. These coronaviruses have origin from animal sources. According to reports from the WHO, human transmission of SARS has taken place through direct or indirect contact with infected civet cats. Human transmission of MERS, on the other hand, has taken place from infected dromedary camels; however, there are no strong shreds of evidence supporting human transmission of nCoV-2. According to the findings that were reported on genetic data, it is presumed that nCoV-2 has evolved from the bat species [10, 12]. Salespeople in the meat and seafood industry were the patient zero to get the COVID-19 virus [13-15]. Since 2019, multiple peaks of the SARS-CoV-2 infection have emerged, mainly due to the emergence of new variants, including the Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Epsilon (B.1.427/B.1.429), Delta (B.1.617.2), Mu (B.1.621), and Lambda (C.37), each with a new set of mutations in the viral genome, leading to different pathogenicity, transmissibility, and morbidity [4]. The most recent and rapidly spreading variant of n-CoV-2 to appear was the Omicron (B.1.1.529) variation, which the WHO identified on November 26, 2021 [16].

2.2 Transmission

Confirmation of cross-species transmission to humans followed the advent of CoV illnesses with a zoonotic etiology [7, 17]. The transmission of the virus occurs when a healthy individual comes in direct/indirect contact with a COVID-19-infected person through handshakes, hugs, kisses, or any sort of physical contact, respiratory droplets from sneezing, and coughing [8]. Additionally, transmission through fomites and surrounding objects when they are exposed/used by an infected person was also confirmed. Besides that, nose, mouth, and eyes via conjunctival contamination are the principal routes of entrance into a healthy person, thus safeguarding these areas is crucial [7-11]. The virus can live on plastic and stainless steel for up to 72 h, on cardboard for up to 24 h, on copper for up to 4 h, and in the air for up to 3 h [12]. In recent findings, the plausible mode of microdroplet transmission is in the form of aerosols, which can be of very high risk in hospital-linked and dense demographic locations [12]. Yet, there is no proof that the disease may be spread through the air or by fecal–oral route [12, 13]. These are the steps in the transmission of the COVID was observed across various countries of the globe that led to a pandemic:

Stage I: Immigrants from countries where COVID-19 was prevalent, tested positive for the virus.

Stage II: The local transmission of disease from infected those who traveled abroad and came in contact with relatives or acquaintances and all the cases were traced back. (India quarantined itself in this stage to halt community transfer).

Stage III: From here, community transmission starts; infection was untraceable.

Stage IV: Entry into the epidemic, where it is impossible to stop or prevent the infection and the rise is exponential with increasing deaths. China, Italy, Spain, and the United States are examples of them.

Stage V: Emergence of pandemic (spread across 200+ countries).

2.3 Indications of COVID-19

The WHO database indicates that COVID-19 has variable effects among its sufferers. Children and young people were at low risk as compared to the elder senior citizens (age ≥60 years) and those who have already predisposed to different clinical ailments and comorbidities [14]. The majority of patients showed mild to moderate symptoms and recovered without taking intensive care treatment, but people with underlying health conditions and elder citizens were prone to develop severe diseases and also caused fatalities. The general symptoms shown after 2–14 days of incubation period [15] include high fever, fatigue, sore throat with cough, difficulty in breathing, severe body ache, and very few cases reported of diarrhea, nausea, and a running nose [14]. Later studies revealed the symptoms like loss of smell and taste [13], and pink eye [18] associated with it. The National Health Commission of the People's Republic of China released a special report in March 2021 detailing the identification of 1541 patients who tested positive for COVID-19 but displayed none of the aforementioned symptoms and instead served as carriers of the virus [18]. In contrast, pathological examinations of critically and fatally ill patients indicated dramatically decreased numbers of lymphocytes, T cell subsets, and eosinophils. When compared to survivors, nonsurvivors either had stable or increased neutrophil levels, whereas neutrophil counts, interleukin-6, procalcitonin, serum amyloid A protein, and C-reactive protein levels remained steady or decreased in survivors [19]. Meanwhile, the majority of COVID-19 patients with severe or fatal outcomes were seniors, especially those with pre-existing chronic illnesses. Age and underlying illnesses reduce immunity, making life more challenging for the aged, which can delay or even prevent infection clearance. Thus, the elderly are a crucial demographic for preventing the spread of COVID-19 [20].

2.4 Precautions and prevention

In an effort to educate the public and prevent the further spread of COVID-19 and its variations, WHO has issued multiple guidelines and launched online courses [21, 22]. Distancing oneself socially is the first line of defense against the spread of disease. According to the Indian Council of Medical Research (ICMR) stated research, a COVID-19-infected patient can infect 406 others if the patient does not practice social distancing for 30 days [23]. Other possible ways to stop the spread are to avoid direct or indirect physical contact, maintain good sanitary practices such as frequently wearing a mask, handwashing with soap or sanitizers, covering nose and mouth with a handkerchief/tissue while sneezing and coughing, avoid touching eyes–nose–mouth frequently, staying indoors to minimize public gatherings, and self-contamination [24]. Regular bathing with antiseptic soap and clean running water, ideally twice daily (morning and night), as well as frequent washing of clothing with detergents [25]. Safeguarding personal care by boosting host immunity should be our primary concern, doing regular exercise, yoga, and consuming fruits and vegetables enriched with Vitamin C and E, intake of warm water, and steam inhalation will be beneficial for respiratory health [26].

2.5 Diagnostic tools and tracing strategies

The glycoprotein enveloped spike (S) structure of nCoV-2 was discovered through molecular biology investigations and was of paramount importance in the production of therapeutic biological products such as diagnostic tests, vaccinations, and antibodies [27, 28]. N-CoV-2 has a positive single-stranded RNA virus with a genome length of 30 kb, which is the largest among RNA viruses [29, 30]. Its trimeric spikes [31] have a strong affinity toward the angiotensin-converting enzyme-2 receptor [32]; after binding, it enters into the host cell, and using host machinery, it replicates itself and compromises target immunity [33, 34] as illustrated in Figure 1. For corona-positive suspects with symptomatic/asymptomatic COVID-19, the WHO and the US Food and Drug Administration recommend using a nucleic acid amplification test such as real-time reverse transcriptase-polymerase chain reaction (RT-PCR) [35, 36] and serological antigen (Ag)–antibody-based assays [36]. SARS-CoV-2 protein Ag detection immunoassays are frequently used for diagnosis. Diagnostic results from lateral flow assays can be obtained in about 15 min, making them the gold standard for usage at the point of care [37]. It is evident that early therapy with neutralizing monoclonal antibodies is good for ambulatory patients. Its success in hospitalized COVID-19 patients has been variable, despite the substantial risk of catastrophic disease progression in people with mild or moderate disease [38]. Initially, chest X-ray cum peritoneum computed tomography scan imaging techniques and whole viral genomic RNA identification were used as diagnostic tools to find the viral genome in infected patients [39, 40]. Consequently, the evaluation of chest radiograph (CXR) was a subsequent diagnostic screening technique taken into consideration alongside RT-PCR [11, 41]. Portable devices can considerably reduce the danger of virus transmission, which made CXRs the favored method of screening during the pandemic; however, the shortage of competent radiologists to interpret imaging data was a significant barrier to CXR screening at the time [42]. A recent virology investigation found that the reverse transcription-loop-mediated isothermal amplification assay was an effective diagnostic tool for use in healthcare personnel [43].

2.6 Clinical management and pharmacotherapeutic treatment

The spread of disease can be halted by taking protective and preventative measures [44, 45]. Patients with a confirmed case of COVID-19 were treated according to their symptom severity, which was categorized as either mild, severe, or critical. In severe and critical cases, SARI is triggered by acute respiratory distress syndrome, organ dysfunction, and septic shocks with critical cardiac and kidney damage [46]. In a report, WHO mentioned that elderly people in the age group of >60 years can easily get the disease, and the mortality rate among them is also higher as compared to youngsters and children [47]; very rare cases are reported regarding the death of pediatric patients but they could have served as carriers [48]. Transmission of the virus through the amniotic fluid and breastfed milk of pregnant women was found negative and the fetus also tested negative [8, 49]. Therapeutic options include the combination of lopinavir and ritonavir (400/100 mg every 12 h), chloroquine (500 mg bis a day), and hydroxychloroquine (200 mg bis a day) with α-interferon (5 million units by inhalational aerosol bis a day) as one of the regimens for the treatment [50]. In an open-label nonrandomized clinical trial, it was reported that azithromycin and hydroxychloroquine were very effective for the treatment of COVID-19; reduction in pulmonary viral load was increased by the use of azithromycin [51]. Additionally, therapeutic repurposing of medicines with potential against COVID-19 and its novel variants have also been cited in numerous papers as being successful, for example, nirmatrelvir [52], baricitinib [53], lopinavir [54], ritonavir [54, 55], darunavir [56], favilavir, favipiravir [54, 57], remdesivir [58-60], ribavirin [39, 58, 61], galidesivir [40], arbidol [56], nitazoxanide [58], and ivermectin [62]. Other nutraceuticals that played an important role include hesperidin and Patanjali's Divya Swasari Coronil Kit for the management of COVID-19.

2.7 Post-COVID syndrome

The Department of Health and Human Services, in collaboration with the Center for Disease Control, has introduced the term “Post-COVID Conditions” (PCCs). This term refers to a phenomenon where individuals who have been infected with COVID-19 may continue to experience clinical symptoms for more than 4 weeks after the initial infection. Other names used to describe this condition include long COVID, long-haul COVID, postacute COVID-19, persistent post-COVID syndrome, and chronic COVID. Common clinical symptoms associated with PCCs include cough, fever, irregular breathing, fatigue or tiredness, headache, dizziness, persistent loss of taste or smell, depression or anxiety, and muscle and joint pain, among others [63, 64].

2.8 COVID-19 vaccinations

COVID-19 vaccination has substantially altered the course of the pandemic, saving tens of millions of lives globally [65]. The WHO published a statement in September 2022 reporting that 172 vaccines were in clinical development and another 199 were in preclinical testing. There were numerous pharmaceutical companies racing to develop a vaccine for COVID-19 before it was approved by the WHO to curb the pandemic including Pfizer, AstraZeneca, Johnson & Johnson, Bharat Biotech, Sinovac, and Moderna described in Table 1. These vaccines are designed using protein fragments, RNA, a nonreplicating viral vector, and inactivated viruses as their basis. Some countries now compel tourists, students, and migrant workers to show immunization documentation as a result of the vaccines' widespread impact. Free COVID-19 vaccination was the first step in what is being called the world's largest immunization program, and on January 16, 2021, the government of India asked all of its citizens to take part [44]. As per the data from daily media reports, India has supplied COVID-19 vaccines to many countries, including its neighbors such as Bhutan, Maldives, Nepal, Myanmar, and Bangladesh. India has shipped millions of COVID vaccine doses around the world. The Indian government has supplied over 22.9 million doses of COVID-19 vaccines to 25 countries on a commercial basis to date, and more are on the way. The vaccines supplied by India include Covishield (Oxford-AstraZeneca vaccine manufactured by Serum Institute of India), Covaxin (manufactured by Bharat Biotech), Sputnik V, and NVX-CoV2373 (Novavax) [66]. Modern science has also developed vaccines for administration via the nasal route, and many countries (including India and China) have begun to embrace this alternative to the intravenous approach [67]. Two other mucosal COVID-19 vaccines have been developed, although data on their effectiveness is scarce. More than 5000 doses of a COVID-19 nasal spray vaccine made by the Razi Vaccine and Serum Research Institute in Karaj were distributed to the public since the vaccine was licensed in Iran in October 2021. Meanwhile, Russian health ministry has approved an intranasal spray version of Sputnik V, the modified version of injectable COVID-19 vaccine [68]. The daily vaccination data is being updated by the Indian Ministry of Health and Family Welfare (MoHFW); as of March 23, 2023, the total number of Indians who have been vaccinated is 2,206,528,710 (Figure 2a) [69]. Adverse effects in vaccines were reported including drowsiness, muscular pain, headache, chills, joint pain, fever, and skin problems like pernio/chilblains, shingles, and herpes simplex flares explained in Table 1 [70]. However, inadequate access to vaccines in low-income countries has limited the impact in these settings, reinforcing the need for global vaccine equity and coverage [65].

5.1 Impact of COVID-19 on the global healthcare management

The COVID-19 pandemic has presented unprecedented challenges to the healthcare field, affecting global medical institutions, healthcare professionals, patients, hospitals, healthcare researchers, and the prevention and treatment of COVID-19 (Figure 5). We have critically analyzed the multifaceted impact of the pandemic, exploring the implications on healthcare systems, the challenges faced by various players, and the strategies implemented for prevention and treatment. Understanding these dynamics is crucial for enhancing future pandemic preparedness and improving healthcare response strategies [90].

5.2 Economic impact

Since the 2008–2009 financial tragedies, World Trade Organization and Organization for Economic Co-operation and Development have indicated COVID-19 as the next emerging global economic crisis and the era of the worst recession in history since the 1930s. The United States and the United Kingdom, two of the world's largest economies, are shrinking every day; worldwide trade fell by 13%–32% in 2020 due to COVID-19 and is still falling [137]. It is true that some industries thrived during the lockdown era, like online entertainment and broadcasting, the telecommunications industry, and the pharmaceuticals and diagnostics sector. However, others, such as banking, automobiles, textiles, tourism and aviation, IT, electronics, shipping, and solar power, will have a much harder time making it [138]. Yet, several countries' economies have already begun to slow. The Indian economy also suffered the same fate, its severity determined by the pandemic's intensity, spread, and persistence [139]. The growth rate of the Indian economy, for instance, slowed to 5% this year from 7% in 2018, the slowest pace in a decade. Rural consumer growth at zero, employment at a 40-year high, and no progress in the manufacturing sector all contribute to a stagnant economy. Hence, a shutdown would have halted industrial production, leading to an economic collapse [140]. The government of India and the Reserve Bank of India's combined efforts will help in changing the current economic scenario and boosting market growth [139]. The world's stock exchanges have experienced a sharp decline in value. Governments throughout the world have enacted a variety of economic, fiscal, and monetary policies to mitigate the fallout from the economic crisis brought on by COVID-19 [141].

5.3 Health and sociopsychological impacts

The worsened global pandemic situation has left a negative impact on human health. India is severely affected due to strict nationwide disease intervention policies, such as lockdown and burden of restriction; people are scared and mentally traumatized. Daily wage labors, farmers, low-income families, and migrated citizens are stressed and filled with anxiety due to the unavailability of income sources, unemployment, scarcity of two-time meals, facilities to stay, and primary healthcare issues [142]. Healthcare professionals were engaged in the service of treating COVID-19, and staff and patients were experiencing community negligence due to social stigma or fear. To prevent such circumstances, the WHO issued a report addressing mental health considerations to manage the psychosocial well-being of all citizens [143]. To circumvent such behavioral health issues, ICMR and MoHFW mutually address the people to manage stress and anxiety [144] and awareness regarding the social stigma related to COVID-19 [145]. Social restrictions are enforced at malls, schools, companies, workplaces, and entertainment areas, limiting the public movement space. COVID-19 can also spread when people travel long distances to visit family during religious holidays, especially if they take public transportation between cities [146]. Based on variables including the number of COVID-19 cases and the rate at which COVID-19 cases doubled, the red, orange, and green zone classification was determined. The economic costs of violence against women range from 1% to 4% of the world's gross domestic product. Nonetheless, rape and sexual assault complaints fall in areas with the strictest lockdowns, which was in line with a reduction in the mobility of women in public areas, on public transportation, and at work, where they may be more vulnerable to rape and sexual assault [147].

5.4 Impact on education

The widespread pandemic has led to a temporary shutdown of many schools, academic institutions, universities, and research institutions across the globe [148]. Indian schools, colleges, and universities were closed but many healthcare R&D institutions working on COVID-19-related research. The Ministry of Human Resource Development has endorsed digital learning programs (online education) so as to reduce educational loss and streamline the process amid the lockdown. Almost 200 million school employees and 1.6 billion students were unable to attend school during the COVID-19 health crisis because many schools had to remain closed while educational procedures had to be changed. Around 60 million instructors will be forced to participate in online learning to maintain some semblance of education if academic institutions that still exist are not drastically reorganized. Obviously, the rapid adoption of remote instructional techniques and altered school management procedures posed a challenge to the pedagogic foundation of education, requiring both teachers and students to quickly modify their pedagogies and teaching methodologies [149]. A major drawback of the online mode of attending classes is that economically stable parents can afford the requirements of the students but lower-income parents are still a question mark for this question. Along with this, online modes of teaching and attending classes have an impact on students who are physically and mentally disabled [150].

5.5 Impact on food chain, agriculture, and transport

The disruptions caused by the COVID-19 pandemic have had a significant impact on the food supply chains of many countries, according to food consumption patterns and other political, economic, and social considerations [151]. Nearly, 820 million people in the world were experiencing chronic hunger, whereas 113 million are dealing with critical severe hunger insecurity. There are drastic consequences of COVID-19 on food insecurity in around 44 countries and they need external assistance for food supplies [152]. Due to the perishability of the majority of agricultural products in Iran, particularly summer crops, greenhouse goods, flowers, and ornamental plants, as well as the drop in demand brought on by the financial crisis, many of these goods go unused and are lost. In Liberia, 47% of farmers said they were unable to cultivate their fields due to the prevalence of corona illness. Moreover, regulations that were in place made it difficult to harvest goods for the fall. The likely effects of this pandemic on food production, particularly in key importing and exporting nations like the United States, China, and the European Union, may have serious repercussions for global food prices and access. Global food security and nutrition faced enormous challenges as a result of this predicament [153]. The food supply cycle is complex inclusive of producer, consumer, distributor, dairy and fisheries, meat market, grains, and vegetables [154]. Their warehousing, transport, and marketing-related sectors will be affected immensely. The nations with the highest diffusion of COVID-19 will receive the worst impact on food supply, agriculture, FMCG products, and essential services like transportation and marketing. The majority of transportation services have not been subject to controlled closures despite being acknowledged as being crucial to food supply networks. To safeguard both their workers and their clients, they have nevertheless implemented a number of social distance protocols.

Thankfully, spatially dispersed labor deployment in current transportation systems often requires little to no face-to-face interaction. The variable cost of trucking has decreased as a result of the 15%–20% decline in diesel prices [155].