In November 2002, when the first atypical pneumonia case was reported in Guangdong, China, WeChat, China’s enormously popular social messaging app, was a dream. Those three months before the WHO office in Beijing received information about a ‘strange contagious disease’ that had left 100 people dead. The three months gave the deadly SARS-Co-V virus enough time to get a foothold and set off an epidemic that, within months, infected at least 8,000 people, killing 774 before dying out in the summer of 2003.
Seventeen years later, on 30 December 2019, Li Wenliang, a young ophthalmologist, shared that "seven cases of SARS confirmed" to his WeChat group, called ‘Wuhan University Clinical 04’. Within days, the Public Security Bureau in Wuhan called him in and got him to sign a statement saying he was lying and disturbing public order. What made Li a hero was he published the statement on Weibo. In January, Li took to Weibo again, saying,
‘I started having cough symptoms on 10 January, fever on 11 January and hospitalisation on 12 January’.
On 23 January, Wuhan, the epicentre of the epidemic shut down. There were far less than 700 publicly reported, confirmed cases of COVID-19 in China at that point of time. The truth is, China or the world did not know truly how many cases there really were. The world had never seen a quarantine of that scale — Wuhan alone had a population of 11 million. There were sporadic images coming through on the internet: people dying in the corridors of hospital, hospitals being overwhelmed. Doctors dying.
In February, Li gave his final social media update,
‘Today the nucleic acid test result is positive, the dust has settled and the diagnosis has finally been confirmed.’
Within a week, he was dead, falling prey to the COVID-19 disease, that he had tried to warn the world about. It was clear that Chinese leadership, including Xi Jinping, knew about the outbreak well before the lockdown. In the transcript of a 3 February speech, Xi clearly states he had asked for the control of the pneumonia outbreak as early as 7 January. China swung into action as only China can – shutting down cities, factories, clearing land and building a 1,000-bed hospital from scratch in less than two weeks. These are measures that democracies could not, at that point, contemplate.
On 19 March, Wuhan, the initial epicentre of the COVID-19 Pandemic, declared no new case, about 3.5 months after they reported the first case. Clearly, the virus could be beat — at a price. Ironically, China has now instituted quarantines against visitors from overseas. The pandemic had almost come full circle.
Coronaviruses get their name from their spiked profile, which looks like a crown when viewed under a microscope. The SARS-CoV-2 virus, popularly called ‘The Corona Virus’, causes the COVID-19, a respiratory infection that can be lethal for older people with pre-existing health conditions like hypertension. Humanity has periodically dealt with coronavirus infections, that tend to be, for the most part, upper respiratory tract infections. Bats are considered the natural reservoir of coronaviruses, such as this one, and the one that caused the SARS outbreak about 17 years ago. The SARS-CoV-2 virus is 96 percent identical at a whole genome level to a bat coronavirus. It is also 79.6 percent similar to the coronavirus that caused SARS, which gives us a place to start for mechanism and cure. More on that later.
While virulent WhatsApp images of bats in a soup have fed the imagination, scientists believe there was an intermediate host, most likely the pangolin. That’s because the coronaviruses isolated from smuggled pangolins were between 85-92 percent genetically identical to the coronavirus currently causing havoc in humans. Pangolins are internationally banned, but are still smuggled into China, where they are prized for their scales in traditional Chinese Medicine and for their meat. Which is why they feature in the live animal markets like the one in Huanan Seafood Wholesale Market in Wuhan. These markets are called ‘wet’ because of the spillage from aquatic tanks and the blood from the slaughtered animals. In the spattering from the slaughter, viruses can jump from animal to man.
The SARS epidemic is suspected to have started in a wet market, with civets as the assumed intermediate host. Camels were considered to be the intermediate host in the MERS epidemic. The Huanan Seafood Wholesale Market in Wuhan, which had a section with wildlife, has been the prime suspect for this pandemic. At least, that’s the theory. A Lancet paper considering the history of 41 early patients showed a significant number did not visit the wet market, and importantly, the earliest case did not. Given this Bin Cao, one of the co-authors wrote, “Now it seems clear that [the] seafood market is not the only origin of the virus,” he wrote. “But to be honest, we still do not know where the virus came from.” To be safe, China shut down the market on 1 January 2020.
Why do origins matter?
The Centre for Disease Control (CDC) in America says that three of four new infectious diseases come from animals. Knowing how and controlling for this is important to prevent future pandemics – this is something our bodies have not faced and have no immunity for. At the very least, given the global economic and human carnage, there need to be very strict slaughtering rules. China shut down wildlife trade, which many conservationists hailed as a positive step. However, there are loopholes. The ban does not cover animal use for medicinal uses or fur, leaving open the door for future animal-human jumps.
How does the virus work?
The virus particle consists of a fatty sheath in which spike proteins are embedded, and which
surrounds a strand of RNA. There are other proteins provided structural integrity, but let us focus on the sheath, the spike and the RNA, because these hold the key, quite literally.
Let us start with the sheath: Washing one’s hands with soap breaks open the sheath. Washing
thoroughly and long ensures every virus particle (hidden in crevices or under nails) is
The spike is what enables the virus to enter our cells. The virus needs to enter our cells to reproduce — it cannot do so on its own. If the spike protein is the key, what is the lock? The lock, researchers have found, is the ACE2, a protein found on the surface of many cells in the human body, especially and significantly for this pandemic, the lungs. ACE2 functions in a complex of proteins that modulate vascular functioning. Importantly, ACE2 appears to have a significant role to play in organ protection and blood pressure control, which is why persons with blood pressure, or hypertension, seem to have a rougher time during COVID-19 infections.
A key ingredient of the SARS-CoV-2 virus is the the replication-transcription complex, which is what makes more RNA copies of the virus. This is important. Human cells make RNA from DNA — they have no machinery to make RNA from RNA. This act is foreign, and as such makes a great target for anti-viral drugs.
Remdesivir is an antiviral drug developed by Gilead Biosciences, to work against Ebola, another RNA virus. In trials, this was shown to mess up viral RNA replication. The hope is this should work here too, which very limited trials show promise. However, the question also is will Remdesivir be available quickly and cheaply enough? And in the quantities required?
Other early (very small) trials showing promise include treating COVID-19 patients with a combination of anti-HIV drugs. However, there have been other trials that show that this combination of lopinavir and ritonavir, don’t really do the trick, lessening death rate by only 5.8 percent over the control group. Others say that this trial is not reflective of the efficacy, because patients had already been symptomatic for two weeks before starting treatment, and that 13 patients on the combo were stopped given the combo in the middle of the trial because of adverse events.
In this kind of a battle, every arrow in the arsenal is important, and doctors in Kasturba Hospital have been treating COVID-19 patients with the lopinavir-ritonavir combo.
Another approach is to trick the virus. This is the thinking behind APN01, a floating ACE2 if you will, made by Apieron Biologics. The hope is that APN01 will act as a honey trap for the virus, preventing from latching onto human cells. Data from a trial in China to check the effectiveness of APN01, the synthetic ACE2, is awaited.
In addition, the virus, like RNA viruses are wont to do, is mutating. One paper, summarized that there are two known strains of SARS-CoV-2, the deadlier, “L” strain, and the older, “S” Stain. China’s initial cases were primarily from the L strain, which gave way to the more docile S strain. Others point out that one mutation does not a strain make. The important point is that these mutations pose challenges to vaccine development and building immunity, depending on where they occur within the virus.
Comparisons with other large scale infections show that SARS-CoV-2 is more infectious than the seasonal flu and the 1918 Spanish Flu and about as infectious as tuberculosis.
On average, COVID-19 is far less deadly than tuberculosis. But not if one is above 65, and
especially not if one suffers from diabetes, hypertension, asthma, smoking-history or heart-disease. Then, the virus can be deadly. Children and young people, the least likely to be hospitalised, can be silent carriers of the disease, or face a mild version of COVID-19.
ACE2 expression drops of with age, and women have higher ACE2 levels. ACE2 presence is thought to prevent lung damage, especially in people with high blood pressure. Which is why the virus appears to be particularly deadly for men, in general, and older men, in particular. This group, old men, comprising much of the world’s political and business leadership, is the most susceptible to SARS-CoV-2.
How does the disease progress?
According to the WHO, there are three stages of the disease: viral replication, immune response and pulmonary damage.
Soon after exposure, the SARS-CoV-2 starts to invade our cells and reproducing in the upper respiratory tract. This is called the prodrome period, and lasts for about five days. The exposed person, during this period, does not have any symptoms such as fever or a cough. Now comes the kicker – what makes COVID-19 a pandemic. The WHO says:
‘Infected individuals produce a large quantity of virus in the upper respiratory tract during a prodrome period, are mobile, and carry on usual activities, contributing to the spread of infection.’
Then comes infection. Almost everyone (97.5 percent) infected with the SARS-CoV-2, develop symptoms with 11.5 days, which is why quarantine periods have been set for 14 days. Fever, Fatigue and a dry cough, are the most common symptoms, but the disease has a wide range of manifestation, and not every person has every symptom. A significant proportion of people remain asymptomatic.
The immune response for most infected people likely involves a host of the body’s immune responses including antibodies and Helper T-cells, at a local level, which fights the infection and then recedes. The WHO estimates that 80 percent of people recover from COVID-19 without any specialist treatment.
What happens in severe cases? One hypothesis is that it takes a while for the immune to kick in, which could allow the infection to move deeper, from the airways to the air sacs. In other cases, the viral load is so high (medical care givers), that the disease moves quicker to the air sacs than the immune system can adapt. Air sacs look like bunches of grapes with very thin walls with tubes which allow oxygen from the air to enter our red blood cells. For them to do their job, the thin walls are a must. But in a serious infection, the coronavirus attacks and damages the wall of these air sacs and the tubes. The damaged material lines the walls, making them thicker, and block the easy transmission of oxygen to the blood cells. Which leaves you breathless and with very low oxygen levels in your blood, and needing hospitalization.
Runaway cases, where the immune responses is un-tempered, lead to lung damage and death. ACE2 levels appear to be lower in cases of acute lung injury, which may be why older men are at risk.
Studies show (it’s early days yet) that Chloroquine, and its less-toxic version, Hydroxychloroquine, show antiviral effect in vitro, and have been known to temper immune response. If this pans out, this is great news for India, because both these molecules are widely available and cheap. One team (with a small sample) showed that Hydroxychloroquine was tremendously effective against COVID-19 when used in conjunction with another cheap, widely available drug, Azithromycin.
Another way to boost immune response and prevent acute respiratory tract infections is to take Vitamin D. In a review paper published by the BMJ, of randomised control trials involving over 10,000 participants, showed that Vitamin D supplementation did protect against acute respiratory tract infections. Again, this is cheap to do at a mass scale.
A key need is for Indian teams to start trying and sharing results to what works in an Indian context. Thus far, we have looked at what happens should one get infected. How does one prevent infection?
How does the virus spread?
The SARS-CoV-2 virus is highly contagious. Studies indicate each infected person in turn infects about 2+ people.
As the WHO puts it:
‘The disease can spread from person to person through small droplets from the nose or mouth which are spread when a person with COVID-19 coughs or exhales. These droplets land on objects and surfaces around the person. Other people then catch COVID-19 by touching these objects or surfaces, then touching their eyes, nose or mouth. People can also catch COVID-19 if they breathe in droplets from a person with COVID-19 who coughs out or exhales droplets. This is why it is important to stay more than 1 meter (3 feet) away from a person who is sick.’
The chance of any person getting infected is a function of
1. Their own susceptibility,
a. Old > Young
b. Men > Women
c. Unhealthy (Diabetes/Hypertension/Lung impairment/Smokers) > Healthy
2. Viral load
At every step, the virus is fighting with the body’s immune system and the native flora (the normal viruses and bacteria) of our respiratory tract for getting a foothold. Usually, the more virus (called the virus load) gets into your body, the greater likelihood of getting the virus.
The viral load, in turn, depends on a number of factors.
Assume average guy, Joe, has COVID-19. How many people Joe infects depends on,
Closeness of contact: If Joe shakes hands with Jill, while Joe says namaste to Jack, then Jill is more likely to catch COVID-19 from Joe. Which is why kindergarten and primary classes, where children lick their fingers, dig their nose, hug other children, lick other children’s fingers etc., are great sources of spreading infection. These virus-bearing-children then come home and kiss and snuggle with their parents and vulnerable grandparents. That’s why many countries, even though children were not directly showing symptoms, shut down schools, especially primary schools.
Length of time of exposure: If people pass by Joe, without staying too long next to him, then there is less chance of them getting infected. If Susan travels on a flight with Joe for 4 hours, while Sara passes him by in the airport, Susan has a higher chance of getting infected from Joe than Sara does.
Length of virus survival outside the host: How long the virus survives on various surfaces, which itself is a function of —
1. Ambient temperature
Consider temperature (and humidity).
Joe coughs in a room and leaves. How long is the room ‘contagious’? At least three hours, it turns out. Of course, if there are more Joes and they cough more often, the infectiousness of the room would go up. These trials to show how long viruses were active were conducted at an ambient temperature of 21-23°C.
A new study by Jingyuan Wang and team shows the contagiousness of the SARS-CoV-2 virus is highly influenced by temperature. This relationship, where R indicates how contagious a virus is, is shown in the graph below, reproduced from their paper.
This helps explain why warmer countries such as India have been less impacted. They are not exempt, as the rising case incidence in India and other warm countries shows. Rising Indian infections could have something to do with more widespread testing, but rising cases in Singapore does speak to warm, humid weather not being an effective deterrent.
Now, let us consider surface.
Again, trials showed that the virus stays infectious on stainless steel and plastic for days, although progressively in smaller quantities. The virus does not like copper, but stays active on cardboard for up to 24 hours.
Putting all this together, how should Joe behave, if he does not want to infect others?
Joe minimises the spread of virus by covering his nose/mouth while coughing or sneezing.
When Joe goes out, Joe does not into crowded places.
Joe does not travel, especially on flights.
People around Joe wash their hands. This is not infallible. Joe touches his body, gets virus on hands. Joe then touches door knob. Virus moves to door knob. The door knob is not copper, which means anyone else touching the door knob within 24 hours can potentially get exposed.
Consider one scenario: You and Joe work in an office. Joe coughs, and a droplet containing the virus lands on your phone. You have your mask on, but you grab your phone and put it into your pocket. You then leave the room (Joe coughed!), and wash your hands meticulously for 20 seconds, and destroy the fatty sheath of every last virus on your hand. Feeling jittery, you grab your phone out of your pocket and type a WhatsApp message: ‘this jerk Joe coughed, but thank god, I had my mask on, and I washed my hands.’ You then rub your nose. Bingo, chances are you are exposed. Since you are younger than 65, chances are no serious harm done.
Italy, where the average high temperatures in February/March range between 10-15°C, with a large older population (a fifth are 65+) and a culture that cherishes intergenerational mixing (everyone loves Nonna/grandma), seems tailor-made for COVID-19.
India, where temperatures are warmer and the people are younger, is still at risk for two reasons:
- Our healthcare sector, including testing capabilities, treatment infrastructure and monitoring facilities are dwarfed by our large population.
- Large sections of our people live in close proximity, where spacing of 1 metre between families, is a pipe dream.
Given this, what can India do?
The writer is the founder of the Sundaram Climate Institute, cleantech angel investor and author of The Climate Solution — India's Climate Crisis and What We Can Do About It published by Hachette. Follow her work on her website; on Twitter; or write to her at email@example.com.
Find latest and upcoming tech gadgets online on Tech2 Gadgets. Get technology news, gadgets reviews & ratings. Popular gadgets including laptop, tablet and mobile specifications, features, prices, comparison.
Updated Date: Mar 23, 2020 19:53:11 IST