Healthcare e-Compendium
A joint initiative of DPSRU & DRSC
Healthcare e-Compendium
A joint initiative of DPSRU & DRSC
Author: Dr. Arvind Kr Pandey
MBBS, MS (General Surgery), Mch. CTVS, Assistant Professor, Department of CTVS, IMS, BHU
download ArticleAbstract
A novel coronavirus named ‘SARS-CoV-2’ or ‘COVID-19’ by the World Health Organization has come into origin at the beginning of December 2019 near Wuhan City, Hubei Province, China, and become one of the foremost dangerous pandemics in recent history. SARS-CoV-2 is a zoonotic pathogenic virus and like many other viruses, coronavirus is also prone to changes in its genetic structure and acquired mutations enabling it to infect humans. Due to the regular mutation, the novel coronavirus, SARS-CoV-2 that is continuing to spread around the world may not be the same as the virus that emerged in China in late 2019 and quickly became the cause of global pandemic in 2020.
Keywords: SARS-CoV-2, COVID-19, Coronavirus, 2019-nCoV, Mutation, Strains
Introduction
Coronaviruses and its Different Strains
Coronaviruses are single-stranded RNA viruses. They are prone to mutation and are therefore highly diverse. There are about 40 different varieties and that they mainly infect human and non-human mammals and birds.
There are seven different strains of the corona virus that cause disease in humans (Figure 1) [1]:
The virus that causes COVID-19 is assumed to originate in bats then spread to snakes and pangolins and hence to humans, perhaps by contamination of meat from wild animals, as sold in China’s meat markets.
Figure 1: Alpha- and beta- coronaviruses in humans
SARS-CoV-2 Virus
SARS-CoV-2 virus is the novel coronavirus that causes COVID-19 disease and identified as the cause of an outbreak of upper and lower respiratory tract infections in Wuhan, a city in the Hubei Province of China at the beginning of Dec 2019.
The virus has spread rapidly, resulting in an epidemic throughout China and then gradually spreading to other parts of the world in pandemic.
Epidemiology
Since the first case from Wuhan, China, at the end of 2019, cases have been reported in all continents except Antarctica and have spread to 193 countries in the world.
From the inception of the disease, up to now, more than 206million COVID-19 cases have been reported globally with 4.4million total deaths and over 11,19,63,561 recovered cases by WHO as on August 15th 2021. COVID-19 mortality increased by 40% in second wave in India.
Currently global case and death incidences continued to decrease with over 3 million new weekly cases and over 73,000 new deaths, 14% and 8% decrease respectively, compared to the previous week (Figure 2). The European and South-East Asia Regions reported noticeable declines in the number of new cases in the past week, whereas the African Region reported a hike compared to the previous week (Table 1).
Figure 2: COVID-19 cases reported weekly by WHO Region, and global deaths, as of August 15, 2021
Though global case and death incidences are in a downward trend for a sixth and fifth consecutive week respectively, many countries across all six regions have reported rises in the number of cases and deaths [2].
The highest number of new cases were reported from US of America (883 996 new cases; 9% Increase), Republic of Iran (26 9975 new cases, a 9% increase), and India (258 121 new cases; 7% decrease) [2].
Table 1: Newly reported and cumulative COVID-19 cases and deaths (WHO, as of 15 August 2021) [2]
The case fatality rate (CFR) of COVID-19 is estimated to be 2-7% depending on age and presence of co-morbid conditions [1, 3], especially in the elderly patients.
The WHO data has shown that the mortality occurring due to COVID-19 was between 2-8 weeks [1]. The disease has diverse presence with mild disease in 80-95% cases; severe disease is accompanying with increased viral loads (up to 60 times higher in severe versus mild cases) and prolonged viral shedding [4].
Mortality in critically ill patients requiring hospital admission may be as high as 60% [5].
Pathophysiology
At present, there are two known modes of COVID-19 transmission: the fecal-oral route and respiratory droplets [6-9]. Droplets can infect a healthy person within 3 to 6 feet (1 meter) distance. Droplets on the surfaces can survive for more than 24 hours, remaining infectious and the virus can remain airborne for about 3 hours which is long enough to permit transmission.
Once infected with SARS-CoV-2, the virus infects type II pneumocytes of the alveoli which are responsible for surfactant production. Surfactant is responsible for reducing the surface tension within alveoli and decreases the collapsing pressure.
The spike protein of the virus binds to ACE-2 on the pneumocytes (Figure 3) allowing virion entry into the host cell [6]. The virus hijacks the host cell’s ribosomes to enable the translation of its genome into different protein molecules and can also produce additional copies of its genome (Figure 4). The translated polyproteins are further processed into different separate components within the host cell and produce multiple virions, which are then released upon pneumocyte damage.
Figure 3: Structure of SARS-COV-2 adapted from Encyclopedia Britannica [6]
Type II pneumocytes release specific inflammatory mediators in response to this process that instructs macrophages to secrete interleukins 1 and 6 (IL-1 and IL-6) and tumor necrosis factor-alpha. These cytokines cause the endothelial cells lining blood vessels to dilate, leading to increased capillary permeability. As a result, fluids accumulate in the alveoli leading to edema [6]. As surface tension increases, the collapsing pressure of the alveoli also increases and a decrease in gas exchange is observed. This leads to hypoxia and difficulty in breathing (dyspnea). This can turn into a critical condition such as acute respiratory distress syndrome (ARDS).
Figure 4: Pathophysiology of COVID-19
Inflammatory mediators damage the alveoli, leading to consolidation and alveolar collapse by stimulating neutrophils, which release reactive oxygen species and proteases. This process damages the alveoli, leading to consolidation and alveolar collapse. High levels of IL-1 and IL-6 travel through the blood to the CNS leading the hypothalamus to release prostaglandins and causes fever. Severe lung inflammation results in systemic inflammatory respiratory syndrome. This can progress into increased capillary permeability. There is a decrease in overall blood volume, and through a series of processes involving hypotension and decreased perfusion of multiple different organs, multiple system organ failure (MSOF) can occur. During MSOF, levels of blood urea, nitrogen, and creatinine are increased and accumulated in the kidney. The liver also releases specific inflammatory biomolecules like aspartate transaminase, alanine transaminase, bilirubin, C - reactive protein [CRP], fibrinogen, and IL-6 that can serve as biomarkers for patients with COVID-19.
Transmission of SARS-CoV-2 through the Eyes
It has been found that health care providers, including a Perking University Physician, may have contracted the virus while not wearing eye protection during patient’s treatment [10]. Researchers have stated that avoidance of touching the eyes, nose or mouth with unwashed or unsterilized hands can reduce COVID-19 transmission, as mucous membranes are the most susceptible to viral transmission [11]. SARS-CoV2 upper respiratory tract infections can result in ocular symptoms such as viral conjunctivitis [12]. Other research also found that 1 out of 30 patients hospitalized with COVID-19 were diagnosed with conjunctivitis [13]. Thus, eyes are an assumed route of exposure and transmission of SARS-CoV-2.
Diagnosis
Early symptoms of SARS-CoV-2 are fever, dry cough, and pneumonia, and the first step to diagnose it is a nasopharyngeal swab test. Polymerase chain reaction (PCR) / Reverse transcriptase-polymerase chain reaction (RT-PCR) are the diagnostic test of choice for SARS-CoV-2 using nasal swab, aspirate, sputum, or blood as samples. These methods have some limitations as they are time-consuming and have variable sensitivity (30%–80%) [14-16].
The main aim of SARS-CoV-2 diagnosis is to accurately detect the virus and to minimize further transmissions by timely isolation and treatment of infected patients. Other non-specific tests for SARS-CoV-2 which are used in combination with the above methods are based on clinical manifestations. This includes blood tests such as CBC, comprehensive and basic metabolic panels, and assessment of liver/kidney markers and procalcitonin levels. Inflammatory markers are also assessed including CRP, ESR, IL-6, D-dimer, ferritin, troponin and creatine kinase-MB. Imaging investigations include computed tomography scans: in COVID-19 patients, these often show glass opacities, areas of consolidation, and paving patterns in cases of severe and progressive disease. Chest X-ray can also be used to observed glass opacities. Ultrasound can be used for seeing B-lines, pleural line thickening, and lung consolidation. All these tests are non-specific but helpful in defining patients’ health status.
Prevention
The spread of COVID-19 could potentially increase if precautionary measures are not taken. It’s therefore very crucial and urgent to prevent the spread of COVID-19 globally. This can be done by detection and isolation of individuals with COVID-19.
Examples of measures to control spread include self-quarantine, isolation of infected individuals, social distancing, good personal hygiene which include frequent hand washing with soap and water/alcohol-based sanitizers and avoiding, touching the eyes, nose and the mouth, and use of personal protective equipment.
Mutation in SARS-CoV-2 Virus
Like other viruses, SARS-CoV-2 also mutates. From the starting of this global pandemic, SARS-CoV-2 has been mutating at a rate of about 1–2 mutations per month [17]. Some recent emerging variants, however, have added significantly more mutations in short periods, causing concern for the whole world [18].
Emerging SARS-CoV-2 Variants
B.1.1.7 lineage (UK variant, Alpha)
The variant was initially detected in the UK in late 2020 and has since spread to multiple other countries. While B.1.1.7 shows increased transmissibility, preliminary evidence suggested there was no indication it was associated with increased disease severity [18, 19]. However, more recent studies do indicate that there is a realistic possibility of increased risk of death in patients infected with B.1.1.7 [20].
B.1.617.2 lineage (India, Delta)
It was first identified in India in December 2020 and has become one of the prevalent variants there and in several other countries. Data suggest that B.1.617.2 is more transmissible than B.1.1.7; the ratio of SARS-CoV-2 infections caused by B.1.617.2 rose, as that caused by B.1.1.7 declined, and the secondary household infection rate associated with B.1.617.2 infection was 13.6 % compared with 9.0 % for B.1.1.7 [21]. The report also suggests that B.1.617.2 is linked with a higher risk of hospitalization than B.1.1.7.
B.1.351 lineage (South African variant, Beta)
The variant was first reported in the US at the end of January 2021, however, was initially detected in South Africa in December 2020. B.1.1.7 and B.1.351 mutant are phylogenetically different and emerged independently [19]. While B.1.351 is associated with higher viral load and increased transmission, there is currently no evidence that B.1.351 is associated with increased severity of disease [19].
P.1 lineage (Brazilian variant, Gamma)
The first case of P.1 was reported from Japan in January 2021 when the variant was detected in travelers from Brazil. The variant was first detected in Manaus, Brazil, where sequencing results from December 2020 identified P.1 in 42% of samples tested. A recent study indicates P.1 is linked to increased transmissibility and potential for re-infection [22, 23].
B.1.427 and B.1.429 lineages (California variants, Epsilon)
The two variants were first recognized in California in February 2021 and were categorized as variants of concerns in March 2021. They carry similar, though slightly different, genetic mutations. Early studies indicated that one mutation, L452R, may be linked to increased infectivity, and new research suggests that B.1.429 and B.1.427 may be more transmissible [24].
Potential Consequences of Emerging Variants
Some of the potential consequences of emerging variants are the following:
Impact of Emerging SARS-CoV-2 Variants on Next Wave of Pandemic
It is conceivable that the new second wave of COVID-19 infections might represent several reinfection cases (figure 5). The principle for that may be that several younger people were infected throughout the primary wave of the illness being misdiagnosed since the primary infection was oligo symptomatic. As specific immunity decreased or the virus evolved resulting in matter drift, these exposed younger people would possibly act as a brand new inclined population to reload the epidemic, being the second infection a lot more symptomatic or severe.
Figure 5: Total number of deaths worldwide due to COVID-19
The reaction to SARS-COV-2, as well as protein production or cellular response, is heterogeneous, making it more difficult to use medical science tests for sero-prevalence studies. During infection period, shedding may be higher among healthy people. Normal immune serum globulin or neutralising antibodies erode quickly in both symptomatic and healthy people. It is possible that some infected people will not develop protective immunity or will require multiple infections to develop immunity [26].
Efficacy of Vaccines and Treatment that are being Administered Globally
Vaccines are made up of antigens, which are dead or weakened viral molecules that cause the immune system to produce antibodies that bind to the virus and kill it.
There are Four Main Varieties of Standard Vaccines:
World's Top-Rated COVID-19 Vaccines:
Difference between COVID-19 treatment of First Wave and Second Wave Patients
Second wave patients were treated most often for non-invasive machine ventilation and corticoids, as well as for conventional oxygen and blood therapy, which were less often treated with invasive mechanical ventilation. For other treatments, Lopinavir, Ritonavir, and Hydroxychloroquine were received during the first wave, while Remdesivir and Tocilizumab were received in the second wave [27].
Antiviral Therapies
Immunomodulatory Agents
Interferon-β-1a (IFN- β-1a)
Effect on Incidence Rate and Mortality
Global COVID-19 deaths in 2021 have crossed last year’s entire patient end, and the mortality rate has reached its limits.
WHO declared a public health emergency of international concern in January 2020. New evidence accumulates; and our understanding of the transmission of the SARS-CoV-2 evolves. Some racial groups, comorbid and pregnant women are at higher risk of severe disease progression.
There is sharp rise in mortality cases in second wave of pandemic as compared to first wave of pandemic as stated by Ministry of Health and Family Welfare (figure 6). Rapid increase shows that the second wave has spreaded much faster across the country [29].
Figure 6: Rise in cases in Second Wave
Resistance to Action of Immune Responses Induced by Current Vaccines Mainly Targeting Spike Proteins
The history of vaccination begins with vaccines that are supported by a living, weakened bacterium that cannot cause illness. Because attenuated microorganisms retain the ability to replicate in vivo, causing a local state, they are useful in rousing the immune system and causing a robust and long-lasting immunological memory that prevents infection.
Vaccinations that aid in the killing of germs (inactivated vaccines) are part of an ancient technical platform that includes crystal rectifiers for a wide range of vaccines. The immunising agents were more stable than live attenuated vaccines in using this technology; however, their limit is linked to the short time of immunological memory.
There are many human vaccines supported proteins present on the surface of microbes. Initially, these proteins were refined from the microbes, whereas nowadays, in most cases, they are made in vitro, exploiting the recombinant DNA technology.
The DNA and mRNA-based platforms supply excellent flexibility in manipulating the coded substance and a nice potential for speed. Unfortunately, no DNA vaccines are registered for human use; but, DNA vaccines are usually employed in a medical specialty. These vaccines are stable and may be made in massive amounts in the bacterium.
While there is no recognised immunising agent based on informative RNA (mRNA), numerous immunising agents have come to use this technology to develop SARS-CoV-2 vaccines. Unlike DNA, the polymer should be transferred to the human cell in a variety of ways. The ribonucleic acid immunising agent briefly encourages the cell to provide the substance macromolecule coded by the ribonucleic acid immunising agent after it is injected.
Viral vectors can transmit the DNA coding for the Spike protein into the cells. The virus' high ability to infect and deliver the mRNA to human cells can be utilised by inserting the DNA in one of the viruses [30].
Difference between First and Second Wave Based on New Variants of Coronavirus
A very significant problem is human behavior. Like individuals, people, state and tribal governments differ about how the pandemic will be responded to. Some people take precautions of COVID-19, such as social distancing, manual washing and masking. Others do not seem to be strict enough to impose these regulations to limit the behavior of high risk.
Indeed, it is suggested that the second wave in India may be linked to the appearance of the variant B.1.617 of SARS-CoV-2, which resulted in surge of infection in India. Their prevalence has increased in most of Indian states compared to other variants suggesting enhanced infectivity over other variants. From International prospective the increase of mutant cases in India is of serious concern.
Its Impact on Patients and Healthcare Infrastructure
Slowly, but surely, the second wave of COVID-19 slipped out of hand. Sometimes people are left to fight for themselves, whereas sometimes people are totally carefree and pay little attention to the imminent danger. The pressure on medical personnel, on the other hand, is on the rise beyond limits (table 2) [31].
Table 2: Impact of Second Wave on Patients and Healthcare Infrastructure [31]
|
Category |
First Wave |
Second Wave |
|
Symptomatology |
More related to respiratory system |
Newer symptoms e.g. GIT disorder etc. |
|
Bed Capacity |
Limited |
Amplify |
|
Mortality rate |
Higher |
Lower |
|
Age group |
More Older people |
More Younger people |
|
Oxygen Cylinder/ Concentrator Requirement |
Less |
More as compared to first wave |
|
Mechanical Ventilation usage |
Less |
More as compared to first wave |
|
Ventilator Beds |
Less than 25000 |
Increased to more than 50000 |
|
Treatment affordability |
Increased test price, |
Reduced test price, |
|
Vaccine |
Not Available |
Vaccines availability and dosing started |
WHO advisory on variants of concern management
Conclusion
As a result of the COVID-19 pandemic, SARS-CoV-2 transmission models have arisen and are critical for the capture and management of infection and the promotion of public health efforts to mitigate and reduce the fatality rate of the COVID-19 pandemic. We have learned these things from second wave of coronavirus.
First, virus transmission may be reduced through the straightforward steps of systematically reinforcing applicable behaviours, and widespread testing for and chase of the virus.
Second, governments must be forced to prepare for many potential viruses by creating various transmission path conditions and identifying the most effective actions to stop the spread of those techniques while also controlling economic and societal implications.
References
