Among countries with a death rate of more than 4,000, India has recorded the fastest increase in confirmed cases and the biggest jump in the death count over the last week
Given the precarious combination of population density, poverty and poor sanitation, India’s urban areas have long been susceptible to infectious diseases. The world’s first cholera outbreak began in Kolkata in 1817 and India saw an excess mortality of 4.5 per cent during the 1918 flu pandemic. This is almost twice as high as any other developing country for which data is available. Now, more than 100 years later, the country is standing in the middle of a contagion, facing a storm of virus waves infecting more than 9,000 people every day. With the easing of the lockdown, the country is ascending the global list of worst-hit countries fast. But in spite of the numbers, India is now reopening its economy even as the hospitals are getting inundated with covid-19 patients.
Among countries with a death rate of more than 4,000, India has recorded the fastest increase in confirmed cases and the biggest jump in the death count over the last week. The number of deaths has nearly doubled in the last 17 days and the number of infections is twice what it was 15 days ago. It took about 111 days to reach the first one lakh cases but it only took 14 days to hit the two lakh mark. Though socio-economic and administrative factors are the major contributors to this surge, there are other factors as well that may have been impacting the disease curve.
Over 60 per cent of the total cases are in just five cities — Mumbai, Delhi, Chennai, Ahmedabad and Thane — and more than half the total number of cases across the country are traceable to these cities. Delhi ranks the first in terms of the highest spike in cases in the last seven days. Mumbai holds the first position in the number of deaths and total infections.
India’s response to the current pandemic has arguably been swifter and more decisive than that of other developing countries. But in spite of all efforts, with the phase-wise easing of the lockdown over the last couple of weeks, the number of cases started soaring exponentially, raising the Corona curve. Though the lowest in the world at 2.8 per cent, the death rate is also on the rise. The country was adding on an average 15 deaths per day in the first week of April, it has now increased to 225 deaths per day as on June 2.
Policy makers crafting the lockdown exit plan partially attribute the worsening status to migrant labourers bringing the virus into suburban and rural India. Besides these migrants, vegetable vendors and vegetable/fruit and flower markets are known to be a major source of spread of the contagion. Resumption of cross-country transportation and industry has led to previously green States confronting imported cases. Test results for thousands of migrant workers who travelled from Maharashtra and New Delhi to Bihar last month found that one in every fourth person had contracted Covid-19. Bihar now has one of the steepest infection curves in India (next to Delhi) and infection clusters have also been tracked to labourers travelling to their homes in Uttar Pradesh (UP).
The disease trajectory of the contagion in India has emerged differently from other countries. In contrast to China, US or European countries that saw a steep initial rise of cases followed by a lockdown and then flattening of the curve, there has been a gradual increase of infections in India since mid-March and then a steep rise of the curve from mid-May when the lockdown was eased off. There are two other critical observations that are unique to our country: First, most of the cases are asymptomatic/of limited clinical severity and second there are higher recovery rates which are indicative of the effective adaptive immunity fighting the pathogen as well as inherent innate immunity. A major area of concern/suspicion of the disease worsening is viral mutations. The covid-19 is a single-stranded RNA virus with a protein shell. When the virus enters the human body, it starts making new copies of itself within a cell in order to infect other cells. In the process, the virus makes mistakes in its genomes leading to permanent mutations.
Mutations are part of a virus’ life cycle and in general, RNA viruses tend to have high mutation rates than DNA viruses. Most mutations do not cause any advantages or disadvantages either to the virus or the host. As of now, the Covid-19 virus is said to be mutating slowly. COVID-19 originated from mutations within the Coronavirus family which leads to the thoughts that as it spreads around the world, it might/will have mutated into various forms in various geographies leading to a more transmissible, more virulent form or both. This apparently poses a threat of worsening the global health crisis.
Scientists have explored this by analysing about 13,000 samples in Britain since mid-March and found that new mutations appear roughly twice a month. The rate of mutations is important because the faster a virus mutates, the more unpredictable it is. Though most mutations have little effect, some of them — single or multiple mutations — can build up over time making the virus more successful in thriving in people of varied ethnic origins and genetic variations.
So far SARS-Cov2 is known to be a stable virus in terms of the rate of mutation. According to experts, the Coronavirus has differentiated into about 10 clades as it spread globally.
Scientists at Hyderabad’s Centre for Cellular and Molecular Biology have discovered that a clade (I/A3i) is found in about 41 per cent of genomes sequenced in India and is a milder form than strains found in other parts of the world. This clade (I/A3i) has four variants out of which one variant, C13730T, is a more virulent strain, which may be causing the surge in deaths and the rate of infections recently.
This strain is likely to have emerged through a mutation in India in different genetic material. The study is currently under peer review by BioRxiv journal and clade (I/A3i) is not known to be seen in any other country.
As we dive deeper into the causes of the steep rise of the positive cases with gradual easing of the lockdown, the relation of air quality index of our highly-polluted cities to disease vulnerability needs to be considered, too. In a paper published in Elsevier’s journal of Environmental Pollution on April 4, scientists pointed out that mortality was 12 per cent in northern Italy, as compared to 4.5 per cent in the rest of the country. Northern Italy is one of Europe’s most polluted regions based on data from NASA’s Aura satellite.
Another recent study explains how air pollutants cause hyper-activation of the innate immune system. A small cohort of mice was exposed for months to air pollutants. The fine particulate matter (PM 2.5) are seen to impact the immune response, causing significant increase in inflammatory cytokines in both serum and as well as lung parenchyma. This leads to high systemic inflammation, impairing heart function as well. In the current context, Indian scientists should now focus on developing strategies against the virus recruiting innate and adaptive arms of the immune system. A recent study found that some people who have never been infected with Covid-19 harbour T-cells (part of our innate immune system) that fight this virus, indicating that they might have previously been infected with other Corona viruses sharing similar characteristics.
Researchers should work on making a skin test akin to the Mantoux test for tuberculosis available to test T cell response (type-IV cellular response). The serological antibody tests may be weak and wane off over time but a T cell response measured by a skin test will remain with a longer memory.
Scientists around the world observe that India may be seeing a lesser virulent disease due to a non-specifically strengthened T cell response from the routine use of BCG vaccination at birth.
Lastly and most importantly, in spite of better recovery rates in our country, there is still a concern for people who have recovered or had a sub-clinical disease. Viral infection sequelae are quite common and can be worse than the initial disease which may be mild. Sequelae observed in SARS outbreak were pulmonary damage (at times permanent) and osteonecrosis (from high dose steroid treatment).
Given the panoply of symptoms seen in sick patients and one prominent disease sequela MISC (multisystem inflammatory syndrome in children) seen in the western world, I hope that healthy, young people will restrain the urge to “go out and have fun” as there is every reason to worry that there might be an Act-II in this contagion drama waiting to unfurl.
(The writer is an author and doctor by profession)