Luc Montagnier, who received the Nobel Prize for Physiology or Medicine in 2008 for the discovery of HIV, shocked the world recently with his announcement that the novel coronavirus genome has elements of the HIV-1 retrovirus, suggesting that it could well be man-made, possibly as part of an effort to develop an AIDS vaccine.
Montagnier’s theory has since been rejected by the scientific world. Yet, rumours that the virus might have escaped from a lab experiment are rife because the origin and behaviour of the SARS-CoV-2 are getting more and more mysterious as the days go by.
Viral RNA sequencing has established that the pathogen has all the footprints of coronaviruses, a family of viruses that cause respiratory infections in humans. The new virus also shows similarities with the SARS virus.
Virus genomes sourced from patients in Wuhan showed a 96% similarity with those from a coronavirus found in bats.
Nevertheless, the identity of the intermediate host, probably an animal, which would have been involved in the transmission of the virus from bats to humans is yet to be determined.
WHO maintains that, notwithstanding the data on the identity of the intermediate animal host, all available evidence indicates the novel coronavirus has a natural zoonotic source.
If SARS-CoV-2 were a manipulation or a construct, its genomic sequence would show a mix of known elements, it argues.
The full genetic sequence of the novel coronavirus and the sequences of several other viruses show that the novel coronavirus has an ecological origin in bat populations, says the global public health watchdog.
It is not just the origin of the virus that is shrouded in mystery; healthcare professionals across the world are still struggling to estimate the virus’ rate of transmission, the total number of active cases and recoveries, and the percentage of mortality.
Even as the pandemic continues to spread relentlessly, infecting, sickening and killing people the world over, scientists and political leaders are currently left with more questions than answers.
Unlike SARS-CoV-1, the speed at which novel coronavirus spreads is breath-taking. Within just 2 months, the number of laboratory-confirmed COVID-19 cases worldwide has already exceeded the total number of SARS cases by nearly ten times.
Even as health experts call for frequent handwashing and maintaining a distance of at least one metre between people as precautions against contracting the infection, the question of how the virus spreads is still an active topic of discussion among researchers around the world.
In a study led by the US National Institutes of Health (NIH), SARS-CoV-2 was found to remain stable and detectable for up to three hours in aerosols, up to four hours on copper, up to 24 hours on cardboard and up to two to three days on plastic and stainless steel.
The virus shows some degree of resemblance to SARS-CoV-1 in terms of its stability. But, when it comes to spreading and infectivity, SARS-CoV-2 surpasses its cousin with a rate that is far higher. This is something researchers are still trying to get their heads around.
However, what is clear is that aerosol transmission of the virus is considered a significant route of infection in indoor environments. This mode of transmission refers to infection via small droplets exhaled by an infected person. These droplets can travel for several meters in the air, carrying the viral content.
At the same time, experts are yet to reach a conclusion on whether the virus can transmit by air, without the aid of aerosols.
WHO, for its part, says airborne transmission is possible in specific circumstances and settings in which procedures or support treatments that generate aerosols are performed; such as endotracheal intubation, bronchoscopy, cardiopulmonary resuscitation etc.
At the same time, the agency asserts that the evidence of the existence of viral RNA “is not indicative of viable virus that could be transmissible”.
However, even as the mechanisms and risk factors for airborne transmission remain largely unconfirmed, evidence suggestive of airborne spread is growing.
The iceberg of undetected infections
Another challenge is determining the extent of active infections.
Studies highlight that people infected with SARS-CoV-2 could be infecting others without recognising their symptoms, or even before symptoms appear. This asymptomatic spread of the infection by unwitting individuals poses one of the biggest challenges to the control of the contagion.
Reports also show that secondary infections by the new virus appear to be occurring mostly in community settings rather than healthcare settings, a characteristic that sets it apart from SARS.
At the same time, there is enough evidence to prove that healthcare settings are also vulnerable to the introduction and spread of the virus. The observed stability of the virus on various surfaces could contribute to its transmission in these settings, scientists say.
Complicating matters further is the fact that about 80% of people with the infection show only mild or moderate symptoms.
Therefore, epidemiologists assume that a large number of people may have encountered and fought off the virus already.
While cotton swab-based molecular tests rapidly identify active infections, only an individual’s blood sample analysis can tell if that person has encountered SARS-CoV-2 previously.
In a first of its kind attempt to gauge the extent to which novel coronavirus has spread undetected in the US, the Centers for Disease Control and Prevention (CDC) has launched a study recently. The preliminary serosurvey aims to analyse two types of antibodies, anti-SARS-CoV-2 S protein IgG and IgM, in as many as 10,000 volunteers using an ELISA developed by CDC researchers.
“A serological surveillance will help determine herd immunity in the population,’’ says a Clinical Professor in Microbiology from a leading super-specialty quaternary care medical centre in India.
The IgM antibodies would identify infected individuals who may be confirmed by RT-PCR and isolated, while the IgG antibodies would determine who all are immune, are no longer at risk of getting infected and can get back to normal economic activities, he adds.
Without estimating the actual number of people infected with the virus, it is impossible to reach an accurate number pertinent to the infectivity or the fatality of the novel virus.
However, many countries including India are yet to initiate a massive serological evaluation of the population to assess the extent of undetected infection. India’s health ministry continues to maintain that it has not come across any evidence suggestive of community infection in the country.
Experts say that it is not practical to deny community infection in any population without serological survey data.
“The government’s claim of no community transmission, in the absence of community-based testing, is like claiming that the absence of evidence is the evidence of absence,” remarks the professor, preferring to be anonymous.
‘Silent hypoxia’, dialysis crisis…
As new cases and deaths continue to surge day after day, clinicians and pathologists are struggling to figure out the havoc the novel coronavirus wreaks on the body of its victims.
Inevitably, the respiratory tract is ground zero for the new coronavirus. Though it remains confined to the upper respiratory tract for most of the patients, the virus goes deep down in some, causing severe inflammation in the lungs and leading to ARDS or acute respiratory distress syndrome, characterised by low oxygen levels, shortness of breath, chest pain and a rapid heart rate.
Critical care specialists manning corona wards say SARS-CoV-2 patients are reporting a strange phenomenon which they have never seen before: Patients present with extremely low oxygen levels, but without showing any symptoms of ARDS like breathlessness. At the same time, their chest X-rays show extensive white opacities.
Clinicians believe that this “silent hypoxia” constitutes the initial stage of COVID-19 pneumonia. By the time these patients reach the hospital, they will already be in a critical condition. Silent hypoxia rapidly progresses to respiratory failure and death.
Even patients without respiratory complaints report COVID-19 pneumonia.
Secondly, experts say that SARS-CoV-2 behaves like no pathogen humanity has ever seen. It can attack almost every organ and tissue in the body with devastating consequences.
According to European Society of cardiology, almost one fifth of COVID-19 patients may develop a cardiac injury in the context of COVID-19, leading to an increased risk of in-hospital mortality. Apart from arterial and venous thrombotic complications presenting as acute coronary syndromes and venous thromboembolism, myocarditis plays an important role in patients with acute heart failure.
Treating physicians are recommended to watch out for myocarditis symptoms in cases with high GRACE scores and dynamic ECG changes. They need to follow the usual guidelines to exclude the possibility of an acute myocardial infarction, including measuring troponin and doing an angiogram within 24 hours.
Similarly, healthcare professionals in New York City dealing with COVID-19 patients have recently reported that they were faced with a crisis that too was unexpected: a surge in kidney failure.
The system, which was already grappling with an overwhelming demand for ventilators, was suddenly running short of dialysis machines as the number of patients requiring the procedure rose threefold.
It is estimated that 20 to 40 percent of ICU patients with coronavirus had kidney failure, requiring emergency dialysis.
Nephrologists, however, are not yet sure whether the kidney failure is a result of the virus injuring the organ or just one more organ failing as a secondary effect of a critical COVID-19 illness.
Researchers from China had reported cases with direct kidney injury from the new coronavirus infection, even though such incidences were considerably low.
Neurologists are also on the job, collecting data from select centres to assess the damage the virus can cause to the brain, as symptoms like a temporary loss of consciousness, seizures, inflammatory encephalitis and strokes are being recorded in COVID-19 patients.
US physicians have reported a surge in the incidence of stroke in the young and middle-aged in populations hit hard by the virus.
Like in the case of the coronavirus that causes SARS, novel coronavirus also infects the inner intestinal lining of the lower abdomen, evidence shows. However, there is no proof for faecal transmission of the virus.
Cytokine release syndrome, a virally driven hyper inflammation, has been associated with a subgroup of patients with severe COVID-19 infection. Some researchers say that deaths caused by this disease are probably due to an immune overdrive in response to the virus, while others warn that efforts to rein in a hyperactive immune system through immunosuppressive agents can actually result in weakening the body’s innate defences to the pathogen.
Resurgence: No evidence for acquired immunity
Another important aspect of the fight against SARS-CoV-2 is the question of whether, and to what extent, people once infected develop an immunity to this disease.
South Korea’s Centers for Disease Control and Prevention recently reported that 91 SARS-CoV-2 patients who had tested negative for the virus on discharge returned positive again.
Japan and China too have reported cases of second time coronavirus infection. Virologists, however, still hold that reinfection is common with certain coronaviruses that cause common flu, but is unlikely with SARS-CoV-2. The new coronavirus resembles the SARS virus closely and, to a lesser extent, the MERS virus, and in neither of these cases have reinfections been reported.
At the same time, virologists do not deny the probability of reinfections either. Their stand is not that reinfection will never occur, but that it is unlikely in such a short time.
People who have recovered from even the mildest of infections will at least get short-term immunity, they say, despite the reports of the reactivation of the virus for the second time in some patients. These patients may have been harbouring low levels of the virus when they were discharged from the hospital or these may be cases of failed testing, they point out. Yet another alarming possibility is regarding the virus’s ability to linger long in people even after they became asymptomatic.
Generally, the level of acquired immunity depends upon the severity of the infection. Immunity after any infection can range from lifelong and complete to nearly non-existent. A few studies that measured antibodies in the blood of people who have survived such infections found that such immunity may persist for two years in case of SARS, and nearly three years for MERS. We are not yet sure how long such immunity can last in case of SARS-CoV-2.
According to a recent WHO statement, there is no evidence that an individual acquires immunity against the virus as soon as the infection is cured.
“There is currently no evidence that people who have recovered from COVID-19 and have antibodies are protected from a second infection,” a WHO statement.
So far, no study has established whether the presence of antibodies to SARS-CoV-2 confers immunity to subsequent infections. However, such data is absolutely essential for countries as they figure out ways to reopen their societies after the lockdown.
Without getting a clear answer to this question, it is impossible to say that the survivors can go back to life as usual without becoming infected again or spreading the virus to others.