**1. Introduction**

A baffling number of disparate symptoms have been ascribed to COVID-19 infection including respiratory, gastrointestinal, circulatory, urinary tract and nerve dysfunction that has resulted in multi-organ failure in some cases. An array of risk factors has also been identified ranging from age, sex, obesity, diabetes, and hypertension to cigarette smoking that can increase mortality rate dramatically [1]. So far, a surprising number of deaths have been recorded worldwide due to the coronavirus pandemic and the figure has surpassed the 5.5 million mark [2].

### **1.1 Symptoms**

In general, COVID-19 infection is associated with the increased production of pro-inflammatory cytokines, C-reactive protein, increased risk of pneumonia, sepsis, acute respiratory distress syndrome, and heart failure [3]. Early reports from China suggested the most common symptoms of COVID-19 infection were fever (88%) and dry cough (67.7%). Rhinorrhea (4.9%) and gastrointestinal symptoms (diarrhea 4–14%) were less common [4].

It has been concluded that COVID-19 may predispose to both venous and arterial thromboembolism due to excessive inflammation, hypoxia, immobilization, and diffuse intravascular coagulation [5]. In addition, the COVID-19 pandemic is associated with neurological symptoms and complications including anosmia, hypogeusia, seizures, and stroke [6]. COVID-19 complications in the brain can include delirium, inflammation, and encephalitis [7]. A temporary loss of smell (anosmia) can be a consistent indicator of COVID-19 infection [8]. COVID-19 is now recognized as a multi-organ disease with a broad range of effects. An unusually long recovery period also seems to be a common aftermath of COVID-19 (post-acute COVID-19 syndrome or, popularly, long-COVID) and may involve one or more of various clinical manifestations including fatigue/muscular weakness, joint pain, dyspnea, cough, sleep and cognitive disturbances, headaches, anxiety/depression, palpitations, chest pain, thromboembolism, chronic kidney disease, and hair loss [9].

Even though, initially, children were thought to be unaffected by the novel coronavirus, a cluster of children with hyperinflammatory shock and features similar to Kawasaki disease and toxic shock syndrome was first reported in England. Almost all these pediatric cases had positive SARS-CoV-2 test results. This hyperinflammatory condition can include serious inflammation of the blood vessels and coronary arteries. Consequently, this illness has been termed COVID-19-associated multisystem inflammatory syndrome [10].

#### **1.2 Internal risk factors**

Some scientists have opined that COVID-19 is highly contagious and highly lethal to a small subset of the population, while it produces milder symptoms in most people. Although, the SARS-CoV-2 virus infects people of all ages, the World Health Organization (WHO) has determined that the evidence to date suggests that older adults and adults with underlying medical conditions are at a higher risk of developing severe COVID-19 disease [11]. However, recent new mutations in variants of the virus may be shifting the age demographic to include younger populations under the age of 60 as reflected in the sudden rise in fatalities among young and middle-aged adults after identification of the Brazilian Gamma variant [12].

#### *COVID-19 Prevention through Vitamin C, D, and Zinc Supplementation: A Small Clinical… DOI: http://dx.doi.org/10.5772/intechopen.103963*

One large study seems to indicate that obesity, high blood pressure, and diabetes are strong risk factors for COVID-19 [13]. It has also been observed that cardiovascular disease and respiratory diseases could greatly affect the prognosis [14]. In fact, in an interesting study involving autopsies on 12 COVID-19 patients, the results revealed that coronary heart disease and asthma were common comorbid conditions in 50% of the deceased [15]. Other research suggests that certain cancer patients are more vulnerable to COVID-19 infection [16]. In addition, a surprising gender disparity appears to be present about SARS-CoV-2 infection. Statistics from Australia, Belgium, Germany, Italy, the Netherlands, South Korea, Spain, the UK and the US reveal that mortality rates from the virus are significantly higher in infected males than in infected females [17]. In the largest Chinese study to date assessing the severity of coronavirus infection in smokers, it was found that higher percentages of current and former smokers needed ICU support or mechanical ventilation. Higher percentages of smokers among the severe cases also died [18].

#### **1.3 External risk factors**

Italian researchers have proposed an association between higher mortality rates in Northern Italy and peaks of particulate matter concentrations in this region. The most polluted northern provinces of Italy were found to have more infection cases than the less polluted southern provinces and this correlated well with ambient particulate matter concentrations that often exceeded the legal limit in these areas [19].

This could have been a significant factor in the spread of the coronavirus in highly polluted and populated cities like Mumbai, India. Social conditions such as crowding in slums have also been considered contributory to the dispersal of the virus in developing countries like Brazil and India. Proximity to infected individuals increases the risk of person-to-person transmission since the SARS-CoV-2 virus is spread mainly by respiratory droplets, but can be aerosolized, as well [20].

No matter how healthy an individual may be, the more exposure they have to a particular virus, the greater risk they have of contracting the disease. The greater the number of particles of the virus one is exposed to, the greater the chance that they will overwhelm the body and immune responses. This is the reason that frontline healthcare workers have been getting serious cases of COVID-19 and, particularly, middle-aged male general practitioners have been dying at a higher frequency than the general population [21, 22].

#### **1.4 Rise of the coronavirus variants**

According to available information, during the first part of this study initiated in July 2020, the original strain of the novel coronavirus from Wuhan, China was the main agent of infection in India due to business travel, tourism, and trade between the two neighboring nations before lockdown and no vaccines were available [1]. In China, this would extend in the form of a ban on non-resident travelers from March 2020 and lifting it would not be contemplated until the February 2022 Winter Olympics.

Subsequently, the Alpha coronavirus variant, which had spread at least 50% faster than earlier lineages was linked to a rise in cases in southeast England by public health officials in November 2020. Approximately around the same time, the Beta variant was detected in South Africa and linked to the second wave of infections in the country. Not long after, the highly transmissible Gamma variant was localized to Amazonas state in Brazil. These three variants shared some common mutations,

particularly in key regions of the spike protein that is involved in recognizing the host-cell ACE2 receptors used by the virus for entering human cells [1, 23].

Thus, by the time the second part of this study was undertaken in January 2021, the Alpha, Beta, and Gamma variants were also present within the Indian population and the UK variant became the dominant strain in Punjab state mainly due to unimpeded travel abroad [24]. Simultaneously, the homegrown Delta variant with multiple mutations had become dominant in the Indian state of Maharashtra and several factors such as large public gatherings at celebrations like Holi, which were not tightly restricted, are likely to have contributed to the precipitous rise of Delta within the country. Moreover, people had started to mingle socially without restraint and to travel to adjoining states thereby distributing the virus and its variants, notably Delta [24]. This is probably what lead to nearly a doubling of cases in March [23]. Up to this point, vaccines had not been available, but became available to the clinic staff shortly after in April, 2021. Soon, the Delta variant had been exported all over India, back to China, and around the world, where it became the predominant strain in many places due to its high transmissibility [24, 25].
