By GELINDE NAREKINE
CORONAVIRUSES are not new to infecting human beings. Over the course of human history, they have long been known to present a high pandemic risk.
Till 2009, six different coronavirus species were known to infect humans. Of these, four species are known to cause common cold in immunopotent people (those with strong immunity). Of the two other species, SARS-CoV was responsible for severe acute respiratory syndrome that swept across Asia in 2002 and 2003, while MERS-CoV, caused the Middle East respiratory syndrome in 2012.
The coronavirus SARS-CoV-2 is the causative agent of the disease, Covid-19. It is the seventh identified in the last 20 years, and the ninth documented coronavirus that infects humans. This species of coronavirus originated in Wuhan City, China in December 2019 and evolved rapidly into a global threat just within a period of three to four months. In the course of its transmission, it created waves of panic across the globe, sending governments the world over into developing and implementing various stringent measures in an attempt to contain the spread of infection. By the month of March 2020, the World Health Organisation declared the infection a global pandemic. Within just a year, and at record time in the history of vaccine development, vaccines were produced and certified for public use.
Coronavirus disease emerged as a unique type of pneumonia and spread to all the provinces of China in a matter of days, and then to every continent of the world, except Antarctica, within just a couple of months. Unparalleled research and exhaustive studies of everything about the disease and its causative virus, SARS-CoV-2, were initiated since its emergence. The results of the genetic makeup and sequence of the virus were made available within a record short time by China, making possible immediate study of its structure and characteristics.
Its routes of transmission, signs and symptoms, the asymptomatic period, its process of infection, and how it affects the human body, have been extensively studied and presented in various scientific articles and review papers. The number of conﬁrmed cases and case of infection and death are being updated regularly.
The different diagnostic mechanisms have been characterised with testing, and management criteria and protocols adopted and implemented in every single country. With extensive efforts, teamwork, and collaboration between teams of scientists across the globe, vaccines for SARS-CoV-2 were developed. In addition, more and more ways of personal protection and prevention of the disease are being explored and shared all over the world.
While the outbreak has been declared as pandemic, the response of the scientific community was timely and enormous. Thousands of publications about various aspects and impact of the diseases and its causative virus have been freely available for access by all concerned parties. As a result, the global community was able to roll out preventative measures including vaccines, to contain and control further infection in a timely manner. Many more studies are still underway.
All in all, the high level of global response to this pandemic in its totality has been like none other. The international collaboration and teamwork with efforts to control infection and to establish evidence-based diagnosis, treatment, and infection prevention measures have been simply overwhelming, by any known standard. In other words, this pandemic is simply unique. This is not only in the sense of the infection itself, but also in the way in which it has awakened the global community to respond in a highly organised and coordinated manner like never before. And so, should there be any plague or epidemic situation of similar catastrophic magnitude in the future, we can be rest assured that we are now better prepared to respond in like manner, or even better.
Origin of SARS-CoV-2
Since SARS-COV-2 was first reported in Wuhan, China, there has been intense interest in understanding how this coronavirus emerged in the human population. Recent debate has centered around three competing ideas: (1) laboratory bioengineered theory, (2) laboratory escape scenario, and, (3) animal-origin (zoonotic) emergence proposition.
Though nothing could be stated with ultimate ﬁnality, most of the scientists are in the view that the virus is not laboratory-originated, meaning, it was never bioengineered, nor was it an accidental escape of a known coronavirus kept in a laboratory for research purposes. The argument now points more to animal-origin of the virus. It has been documented that all previous human coronaviruses have zoonotic origins, as have the vast majority of human viruses. The emergence of SARS-CoV-2 bears several signatures of these prior zoonotic events and thus, displays clear similarities to SARS-CoV.
Even with such compelling arguments, scientists have not arrived at a deﬁnite conclusion on the origin of SARS-CoV-2 being zoonotic. This now suggests that the true origin of SARS-CoV-2 has not been determined, and therefore, still a controversial area.
Routes of transmission
Covid-19 is transmitted through various respiratory and extra respiratory routes. Some of the known and more important ways of transmission are: (1) direct contact with the infected person, that is, human-to-human transmission (main mode), (2) respiratory droplets, (3) oral-fecal transfer, (4) infected blood and body fluids (5) touching contaminated surfaces (6) viral aerosols in a given conﬁned space, (7) sewage waste, air condition systems, and contaminated water/food, and, (8) transfer from asymptomatic and pre-symptomatic infected persons.
According to the World Health Organization, the time taken in the appearance of symptoms after infection (incubation period) is between one to fourteen days. Based on studies on conﬁrmed cases of COVID-19, some experts have concluded that the average incubation period was about five days, with the possibility that some may still develop the symptoms after fourteen days. Moreover, it was further suggested that the duration of incubation may also depend upon the age and immune status of the person infected – the older the person and weaker the immune system, the shorter will be the incubation period.
Entry of SARS-CoV-2 in the target receptor
The target receptor for SARS-CoV-2 on the host cell is the cellular protein angiotensin-converting enzyme 2 (ACE-2). Another cellular protein called type 2 transmembrane serine protease (TMPRSS2) binds to and cleaves the ACE-2 receptor. The expression of TMPRSS2 activates the Spike protein and thereby, increases entry of coronavirus into the host cell. Whichever cell that expresses this combination of cellular proteins serves as the target cell for attachment and entry of the virus.
It has been shown that this virus has a very high level of attraction to attach to its target cells. It has been further proposed that once SARS-CoV-2 gets access to the host’s upper respiratory tract through the mouth or nose, it can stay and replicate there for a while before going to the lungs. Although the expression of ACE-2 is quite small in the mouth and the larynx than that in the lungs, because of the very high affinity for its receptor, SARS-CoV-2 can still bind and enter the ACE-2 and multiply there before going to the lungs. After the primary replication, the virus goes to the lungs where it enters its target cells and rapidly multiply.
Scientists have noticed that upon infection with SARS-CoV-2, the body’s immune system responds immediately and rapidly. With excessive production of a multitude of various immune cells, the immune response eventually goes uncontrolled. A chain of uncontrolled immunological events occur, resulting in massive cell death and destruction of lung cells and tissues. Such events can cause more harm than good to the health of the infected person. More likely, those patients with good inborn immune responses can cope with the infection by decreasing or clearing the viral load, and subsequently, recover from the infection. Unfortunately, those that are not able to withstand the impact of such aggressive infection process, give in to Covid-19 and pass-on.
A lot of studies and trials were carried out within a very short period of time in order to develop viable vaccine candidates for SARS-CoV-2. Fortunately, it was not a from-ground-up kind of approach. Using data accumulated from studies done on previous species of coronaviruses, scientists were already collaborating in the right direction. It was no surprise that the first vaccine phase 1 safety trial started in March 2020, that was just four months since SARS-CoV-2 emerged in China.
As of November 2020, fifty-five vaccines were in clinical trials on humans, out of which thirteen reached phase three safety trials. The efforts and speed with which the scientific community raced to develop viable vaccine candidates to date, is unprecedented. Dozens of vaccines have been approved and now in use the world over.
In the journey to developing vaccines for SARS-CoV-2, no stone was left unturned. Every scientific effort was made to ensure an effective vaccine against COVID-19 should not induce undesired effects or enhance infection, but protect the people who are at more risk, especially, the older citizens, young children, those with underlying medical conditions, and the frontline health care workers. After numerous high level laboratory tests, stringent quality assessments, and widespread clinical trials, all vaccines for SARS-CoV-2 now in use have been certified, and therefore, beyond any reasonable doubt, are safe and effective, when appropriately managed and used under carefully control environment.
Immunity to SARS-CoV-2
During the course of the pandemic, there have been case scenarios all over the world that are strongly indicative of immunity and resistance to SARS-CoV-2. There are individuals, and especially, frontline health care workers, who have been repeatedly exposed but are still negative to all COVID-19 tests. As a matter of facts, these are interesting scenarios that most likely suggest some degree of immunity and resistance, and therefore, should not be disregarded as mere chances, but attract further scientific investigation.
It is quite evident here in Papua New Guinea, where our life style and daily conduct is already a very fertile soil for the virus to take a foothold and spread aggressively. Despite our outright ignorance and carelessness to prescribed safety measures, majority of our people in and around our urban settlements and villages are untouched by COVID-19.
In response to such observed scenarios, there is now a huge international collaboration involving more than sixty universities and laboratories, carrying out studies on people who are exposed but not infected. This is a massive global effort to determine the human genetic basis of resistance to SARS-CoV-2 infection.
The Coronavirus disease 2019 has spread globally in no time. Like SARS and MERS, the disease is suspected to be of animal-origin, because the genetic material of SARS-CoV-2 has similarities to the genome of coronaviruses found in bats and other similar animals. On the other end, scientists are of the view that the virus is not genetically manipulated, nor an accidental laboratory spill-out escape event. However, the origin of SARS-CoV-2 is still a controversial issue with no definite conclusion.
The infection is transferred via respiratory droplets from the infected person, contaminated surfaces, feces, and other contaminated sources. COVID-19 is a highly contagious infection. It has been estimated that a single infected individual can infect about three to four people, and that may vary depending on associated viral, host, and environmental factors. Despite the fact that it has quite low mortality rate and case fatality rate (the ability to cause death) than SARS and MERS, COVID-19 has caused a greater number of deaths across the globe. From a number of variants that have arisen during the course of the pandemic, the Delta variant and more recently, the Omicron variant are considered highly contiguous.
People from the older age group, having underlying health conditions, and those with poor immunity, are more at risk of being infected, and can progress to develop severe symptoms. The gold standard for diagnosis of the disease is by Polymerase Chain Reaction (PCR) which is a molecular-based test that directly detects the presence of SARS-CoV-2.
The target receptor of the virus is Ace-2 that is expressed in mucous membrane of mouth, pharynx, lungs, the gastrointestinal tract, the cardiovascular system, liver, and kidneys. The virus enters the receptor through its spike protein S which is activated by TMPRSS2. Following that, replication starts using host cell machinery, and if not cleared in time, it can trigger a vigorous immune response.
The so-called ‘immune cells storm’ is the main cause of acute respiratory distress, septic shock, and multi-organ failure seen in people severely affected by COVID-19. Speciﬁc safe and effective vaccines are freely available, and already saving millions of lives globally.
Sources of Information:
Naz, S, Zahoor, M, Sahibzada, MUK, Ullah, R, Alqahtani, AS 2021, COVID-19 and SARS-CoV-2: Everything we know so far – A comprehensive review, Open Chemistry, viewed 14 December 2021, https://doi.org/10.1515/chem-2021-0049
Rabi, FA, Zoubi, MSA, Kasasbeh, GA, Salameh, DM, Al-Nasser, AD 2020, SARS-CoV-2 and Coronavirus Disease 2019: What We Know So Far, Pathogens, 9, pp2-16, viewed 15 April 2020, http://www.mdpi.com/journal/pathogens
- Gelinde Narekine is a technical officer at the School of Medicine and Health Sciences, UPNG.