In the history of mankind, there have been several pandemics from the Justinian Plague in the 6th century to the Spanish Flu (HINI influenza) in 1918. The 21st century remarkably has already seen three coronavirus-related outbreaks — the Severe Acute Respiratory Syndrome (Sars) in 2002 which claimed 800 lives, the Middle East Respiratory Syndrome (Mers) in 2012 (862 deaths), and now the coronavirus disease (Covid-19). Despite advancements in medical sciences, it is impossible to predict when the next infectious disease outbreak will take place. So, we need to be on full alert.
With India surpassing China in the overall number of infections, a comparison between the two in terms of infection trajectories is interesting. Compared to the more gradual increase of infections in India since mid-March, China witnessed a steep rise in January and February, forcing the administration to impose a strict lockdown in Wuhan on January 23 — two months earlier than India — lasting for over 70 days by which time the curve was flattened and has remained, by and large, static till date. The United States (US) and Europe have shown a trajectory similar to that of China, which makes India something of an outlier.
Noticeably, India recorded nearly 45% fewer fatalities than China, although active cases remain over 60% of the total number of persons infected, as against nearly zero in China. India’s over 38% recoveries are higher than those of many nations at the same level of infection, although still lower than hotspot European nations such as Germany, Spain and Italy. Further, while the disease remained primarily confined in China to the Hubei province in general, and Wuhan in particular, India witnessed a more widespread infection with the four states of Maharashtra, Tamil Nadu, Gujarat and Delhi accounting for two-thirds of India’s total cases.
Higher recovery rates are indicative of effective adaptive immunity developing against the pathogen. On the other hand, the largely inherent immunity of the Indian population might explain the comparative lower fatality/severity rates so far observed. At this point of time, the important question is whether people who clear a SARS-CoV-2 infection can ward off the virus in the future? An answer to this will have implications for creating better vaccines.
Epidemiological and nutritional factors have been discussed to explain the population-specific differential susceptibility, progression and severity/mortality of Covid-19 across the globe. Nevertheless, deciphering genetic polymorphism of the immunologically-relevant genes that influence host immunity could reveal population-specific correlates of protection and/or vulnerability to the Covid-19 challenge.
The two most important of these are those encompassing the human leucocyte antigen (HLA) system and the Killer-cell Immunoglobulin-like Receptor (KIR) genes, both of which have evolved in humans to maintain a robust immune challenge to invading microbes. Substantial data exists on the genetic propensity of HLA and KIR systems in autoimmune and infectious diseases including HIV/AIDS.
The highly polymorphic nature of the two genetic systems signifies their functional importance acquired during the course of evolution. They functionally regulate the body’s immune warriors, namely, the cytotoxic T-cells on one hand, and the natural killer cells on the other, both of which directly target the virus and help to eliminate it. A deep understanding of these in Covid-19 will be vital in developing effective screening tools for predicting prognosis and response to therapy, including designing individualised therapeutic strategies.
In the Indian context, scientists must find answers to two critical observations. First, the observed predominantly asymptomatic clinical course of the disease, and second, the rather limited number of severe and critical cases in India so far. All efforts must be made to discover measurable immunological biomarkers that are predictive of severe disease and favourable treatment outcomes. Despite limitations in understanding the mechanistic aspects of Covid-19 pathology, the challenge is to develop strategies for recruiting innate and adaptive arms of the immune system against the virus. A recent study found that some people who have never been infected with SARS-CoV-2 harbour T-cells that target this virus, indicating that they might have previously been infected with other coronaviruses sharing sequence similarities. Again, this is encouraging data for designing therapies.
The question is how long does it take to develop reasonably effective treatments for contagious diseases? Historically, while smallpox and polio took thousands of years to get an effective vaccine, HIV/AIDS took a mere 15 years before antiviral drug therapy was developed although an effective vaccine has still not been found. For Covid-19, the rapidity with which the world scientific community has got together, sharing knowledge and information in the singular task of defeating the novel coronavirus, is indeed unprecedented.
Currently, all eyes are on the World Health Organization-sponsored solidarity trial that tests, in addition to the standard care, four different lines of treatment regimens to save lives in the short-term. The trial involving thousands of patients worldwide from genetically disparate population groups will test the efficacy of remdesivir, hydroxychloroquine, lopanavir/ritonavir combination with or without interferon-beta. Analysing the population-specific influence of genetic systems could provide valuable information on possible differential response to treatment and long-term protection. Identifying HLA variants in infected people can help predict the severity of infection and determine who would eventually benefit from a vaccine.
Science alone can motivate tomorrow’s health care providers to rise to their fullest potential and deliver life-saving devices to prevent and treat this and future viral pandemics. In this context, innovative technologies to tackle global emergencies are urgent necessities
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