COVID-19: Diagnosis and Management-Part I

Pandemic is the term coined for the widespread of a disease or infection on a very large scale and across borders. COVID-19, an outcome of the spread of coronavirus, reportedly started from China and spread to almost all the countries of the world. Though it is not for the first time that there was an outbreak of a disease at such a high magnitude but the duration for which it has continued to grapple the world with its virulence and contagious nature, it has become important to take a peek into the history of other pandemics of the world too. Before COVID -19, about 20 major outbreaks of infectious diseases took place and claimed millions of lives in a sweep. The awareness of government bodies, WHO, and non-government organizations grew better with every pandemic. Understanding the role of basic hygiene, self-immunity, social distancing, living in coherence with other living and non-living components of the planet are some positive outcomes of these pandemics. These pandemics also necessitated the need for discovering new drugs and vaccines.

In the mid 20th century, virologists identified a new category of the virus, which has a fringe of projections on its surface that appears like a crown and named coronavirus. Coronavirus belongs to the family of pleomorphic spherical viruses recognized by bulbous surface projection and ssRNA. As the virus belongs to the family of RNA-virus, the chances of mutation are very high, which further increases its pathogenicity. The coronavirus mainly attacks the respiratory tract and ultimately leads to respiratory failure. Recent outbreaks of coronaviruses are severe acute respiratory syndrome and the Middle East respiratory syndrome, which cause a great threat to human health with a high mortality rate. Later on, in late 2019, a new form of coronavirus appears in Wuhan, China where numbers of people are recognized with pneumonia-like symptoms. The condition was entitled with COVID-19 by WHO on Feb 2020, which was declared to be pandemic by the same agency in Mar 2020. The COVID-19 is considered to be originated from bats, which then transmit to humans due to the consumption of contaminated animal raw. The virus is highly contagious and spread at a very high rate, which produces global health risks. Further various existing treatment is used for treating the infection but still the precise and accurate treatment yet to be investigated.

In the history, the year 2019 will be remembered as the year that has witnessed the beginning of a pandemic, primarily affecting the respiratory tract and then, spreading from human to human. A total of 25.18 million reported cases and 0.84 million deaths, as of 30th August 2020, and still counting, were caused by a novel coronavirus named COVID-19 that originated in Wuhan, China. By the beginning of the year 2020, this virus spread to several countries like Singapore, South Korea, Japan, Italy, Spain, Germany, the United Kingdom, and the United States of America. Between January 2020 and March 2020, the disease took a paradigm shift and started to affect the majority of European countries like Italy, Spain, France, Germany and UK. In the majority of the patients with a competent immune system, this disease goes unnoticed or without symptoms, thus making them highly susceptible to spread this disease to whoever comes in their contact. Aged patients (>60 years) or patients with chronic health issues like heart diseases, cancer, diabetes, and weak immunity are at greater risk of developing the symptoms. In severe conditions, patients need hospitalization and respiratory support (respirators/ventilators), thus causing an overload on the health system of the world. This initiated the movement of “flattening the curve” by social distancing and isolation to decrease the burden on the health system and to decrease the spread of the disease.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causal pathogen of the novel coronavirus disease 2019. This novel Covid-19 has created a serious public health crisis throughout the world. The primary symptoms of coronavirus infection are common cold and influenza-like illness and with time it causes pneumonia. Although various studies are going on throughout the world, its actual pathophysiology is not very well clear to date. The Coronavirus is a positively charged single-stranded RNA virus. This virus gets easily transmitted from human to human. Numerous investigations have been found that the virus enters into the human body via its spike (S) proteins. The S-protein binds to ACE2 receptors and silently comes in contact with alveoli via blood. This entry hypersensitizes various receptors, epithelial cells, macrophages, T-cells, dendritic cells and thus implants proinflammatory cytokines and chemokines, resulting in stressful conditions. Studies found that Hemagglutinin-Esterase protein, Spike protein, Nucleocapsid protein, small envelope protein, internal proteins, group-specific proteins take part in viral pathogenesis, whereas, replication proteins (eIF4A, Cyclophilin, 3CLpro, RdRp) participates in Coronaviruses (CoVs) replication and translation phases, influencing both pathogenesis and pathophysiological conditions. In this chapter, we elaborate on viral pathogenesis, the various functions of proteins, structural, enzymatic, and accessory that are linked with the pathological conditions and will also highlight the correlation causing physiological alteration associated with this infection.

Presently, the whole world is going through a historic yet a troublesome situation following COVID-19 outbreak. The clinicians have observed a wide variety of respiratory and non-respiratory clinical manifestations in COVID-19 patients. Accumulating reports revealed that the clinical features of COVID-19 may include asymptomatic/mild symptoms, neurological, cardiovascular complications, severe pneumonia and mortality. The most common features noticed are fever, dry cough, sore throat, shortness of breath, sputum production, fatigue, and myalgia. Recently, US health protection agency has also reported repeated shaking along with chills, loss of taste and smell in new case studies as additional symptoms. In addition to this, COVID-19 patients may show clinical signs like persistent pressure and pain in the chest, blue lips or face, confusion and GIT disturbances (diarrhea, nausea, vomiting and abdominal discomfort). The current ongoing pandemic has remarkably affected almost every age group of humans, starting from infants less than 3 months, adults, elder and older patients. Furthermore, the clinical presentations in these groups of COVID-19 infected patients were found to show considerable inter-individual variations. The findings also suggested that the comorbid conditions (heart injury, hyperglycemia, hypertension, neurodegenerative diseases) in elder/older patients further complicate the health of COVID-19 patients.

Diagnosis of COVID-19 is supremely valuable in unraveling the complex dynamics involved in SARS-CoV-2 infection and in vaccine development. With an extremely high transmission rate, and initial symptoms similar to other human respiratory viruses, there has been a tremendous urge to develop and supply accurate and rapid procedures for testing the presence of SARS-CoV-2 in a plethora of patient specimens. Scientific and healthcare communities globally have been racing to develop critically needed test kits and ensure ample supply worldwide. Containing the spread of COVID-19 poses multiple challenges, including being able to correctly identify asymptomatic viral carriers that result in the silent spread of the virus, and diagnosing the infection at early stages. Current strategies employ molecular and serological testing techniques in lower and upper respiratory tract samples. The first type detects the presence of viral genetic material and can diagnose an active COVID-19 infection, whereas serological immunoassays detect viral antibodies, which can help identify individuals who have developed an adaptive immune response to the virus, as part of an active or prior infection. The newly authorized antigen tests are designed for the rapid detection of viral antigenic proteins. More elaborative diagnostic testing based on viral genomic sequencing can determine the rate and degree of mutational variability associated with SARS-CoV-2 and identifying newly emerging viral strains for more effective vaccine development. The chapter also highlights the role of rapid, easy-to use point-of-care diagnostic tests in alleviating the challenge posed by the strain on the healthcare system and mitigating the cost of care for both individuals and the government.