Lt Col (Dr) Inam Danish Khan, Dr Shashi Sudhan
India is facing a public health emergency with massive morbidity and mortality due to nationwide second wave of Covid-19 which has dwarfed the first wave in daily incidenceand daily deaths. The healthcare infrastructure is inundated with massive surge of Covid-19 patients, including entire families with apparently healthy people in younger age groups and children, compared to first wave when majority of deaths occurred in senior citizens and people with comorbidities.A full blown commotion and crisis looms large. People are queuing up in front of testing labs and hospitals, with long waiting time for sample collection, Covid-19 RTPCR and reports, unavailability of hospital beds leading to bed sharing by patients, inadequate supply of oxygen, unavailability of general beds, ICU beds and ventilators, shortage of vaccines and shortage of experimental Covid-19 drugs such as Remdesevir and Favipravir. A large number of Covid-19 cases and deaths are going unreported. Lage number of healthcare personnel including doctors, nurses and paramedics are getting infected and some have died. Mortuaries, crematoriums and graveyards have prolonged waiting times for the deceased.Heart-wrenching news is piercing peace as Covid-19 second wave wreaks havoc. Clouds of doubt overshadow reason, logic and all that has been. Did we take everything for granted? Fear and desperation amplified multifolds as there are many unknowns.
The second wave is steep with three-fold rise in daily infections, R-naught of 1.32and a pandemic doubling time reducing from 20 days to 10 days in certain regions. Overall deaths during Covid-19 second wave are likely to increase due to both complications of Covid-19 and inaccessibility for non-Covid-19 healthcare. Governmental machinery is working day and night to curb and curtail the pandemic, amidst hopelessness and despair of losing Indian citizens across the length and breadth of the nation. Fresh curfews, restrictions and lockdowns are being exercised as measures of last resort, in view of devastating socioeconomic waves of multiple dip economic recession, migrant crisis, and possibly stagflation. US has labelled Indian second wave as level 4, and many countries have advised to avoid traveling to India. Indians are also not being allowed to enter other countries.
In the middle of a grave situation for India, the crisis is not seeming to end Pandemics come in multiple waves. While India is facing the second wave, the national capital Delhi has already witnessed four waves. Internationally, Hong Kong is witnessing the fifth wave and Vietnam is facing a sixth wave. Multiple consecutive waves are expected worldwide with emergence of multiple variants of concern armed with immune escape mutations and increased infectivity. Such mutations can increase chances of re-infections, post vaccine infections and morbidity, hopefully and wishfully without increasing mortality. Globally, second waves of Covid-19 were more intense and devastating than first wave.
The dynamics of second wave are possibly driven by novel mutations which not only have a tendency to escape immunity but also increase transmission multifolds, leading to multiple generations of transmission from asymptomatic superspreaders. Coronaviruses mutate faster than other viruses as their genome has RNA instead of DNA. After the emergence of Wuhan strain, 50000 mutationswith 4000 mutations in the spike-protein, and hundreds of variants have been documented worldwide. All mutations may not alter viral fitness (ability to survive and reproduce) or be dangerous to humanity, though some can change the fate of Covid-19. Noteworthy are UK variants (lineages B.1.1.7 and B.1.525), US variants (B.1.526/5 and B.1.429/7), recombinant UK and California variant (B.1.1.7 + B.1.429), South Africa variant (B.1.351), Brazil variants (P.1 and B.1.1.28.2 or P.2), Philippines and Japan variant B.1.1.28.3 or P.3, France variant B.1, Angola-Tanzania super variant A.VOI.V2 with 34 mutations and many more variants in Spain, Nigeriaand India. India is the fifth country worldwide to sequence Covid-19 genome. So far, more than 24000 mutations have been detected in 7000 variants in India. The INSACOG genomics surveillance consortium headed by National Centre for Disease Control, New Delhi, has found 771 Variants of concern (VoCs) amongst 10,787 samples, including UK (736), South African (34), Brazilian (1) and Indian variant in 18 states with E484Q and L452R mutations (20% samples). The Indian variant has been detected in many other countries.
The Indian variants may be contributory to the current health emergency as they have been found to cause 20% to 70% infections in second wave, though not yet labelled as Variants of Concern. First one is single source double mutant triple helix-variant lineage B.1.617 with E484Q, L452R, P681R immune escape mutations in the spike glycoprotein, declared on 07 Dec 2020. E484Q mutation increases viral entry and transmissibility, while L452R mutation increases infectivity possibly by evading neutralizing antibodies. This variant can case re-infections and post vaccine breakthrough infections. Govt of India has released the prevalence of 0.04% breakthrough Covid-19 after Covaxin and 0.03% after Covishield. Clinically, patients with this variant present with high fever with watery diarrhoea, cramps, conjunctival redness or pink eye, loss of hearing and palmar rashes. Sometimes, there is no fever initially and fever can come after a week. Even after symptoms subside, there is a rebound phenomenon where symptoms come back after 7-12 days. Patients who are relatively stable are deteriorating rapidly. This variant is also affecting people in 18-45 year age group as well as children which can act as superspreaders. Multiple outbreaks and clusters are formed due to superspreader events which can increase morbidity and mortality.There are reports that RTPCR is coming negative with this variant as the virus is not found in throat and nasopharyngeal swabs. Patients are sometimes reporting with severe Covid-19 pneumonia detectable by HRCT Chest with CORADS V and CT score >13/25.
The second one is Indian triple mutant-variant lineage B.1.618 with E484K, D614G, immune escape mutations with increased infectivity plus two immune escape spike amino acid deletions H146del and Y145del, declared recently in Apr 2021. B.1.618 is likely to be prevalent in Maharashtra, Delhi, Chattisgarh and West Bengal.
Is there light at the end of the tunnel?Covid-19 waves are likely to stop if a sizeable population develops immunity to Covid-19 which is possible by either Covid-19 infection or vaccination. This phenomenon of herd immunity or social/community/populationimmunitydisrupts the chain of transmission and can either stop or slow the progress of disease. Unfortunately, immunity developed against Covid-19 is neither very strong nor long lasting, which can lead to re-infections and breakthrough infections. This happens because a significant portion of antibodies produced are non-neutralizing. Fortunately, there is hope on development of cell mediated immunity towards Covid-19 which can possibly cover deficiencies of antibody mediated immunity.
Achievement of herd immunity is based on herd immunity threshold which is estimated to be 70-90% population becoming immune to Covid-19. Three systematic nationwide seroprevalence surveys have revealed a seroprevalence of 0.73% in May-Jun 2020 which increased to 7% in Aug-Sep 2020 and further to 25% in Jan 2021. India is still far away from the critical threshold of 70-90%, which reflects the possibility of multiple waves of Covid-19 in times to come.
Government of India has taken various prudent steps towards management, control and mitigation of pandemic waves. Firstly,first wave strategy of test-treat-trace has been augmented to test-treat-trace-vaccinate with more than 15 crore population already vaccinated. Vaccination drive has been boosted with expanded eligibility of all citizens above 18 years which is a step towards speedy attainment of herd immunity. Secondly, all social, cultural (not necessarily political), religious, familial, economical, entertainment and other gatherings have been restricted as there are higher chances of transmission in closed spaces due to droplet and aerosol mediated transmission.Thirdly, ICMR- National Institute of Virology has successfully cultured many variants. Both Covishield and Covaxin have been demonstrated to neutralize UK, Brazil and Indian double-mutant variants. Fourthly, the INSACOGgenomics surveillance consortium is entrusted for genomic surveillance of Covid-19 intends to test 5-10% of all Covid-19 positive samples to keep a track of new mutations and emergence of newer variants.
Post second wave public health interventions such as seroepidemiology to ascertain Covid-19 prevalence, protective immunity in infected and vaccinated individuals, boosting of healthcare infrastructure and mass education of Covid-19 appropriate behaviour is mandated to build adroit preparedness and community resilience. Reiteratively, complacency and procrastination is bound to boomerang another pandemic wave. And yet, somewhere deep in the dark corners of the heart, there is hope!Hope for humanity! Hope for an economically progressive world! Hope for re-globalization! Hope for freedom of movement! Hope for life!
(The authors are Associate Professor Microbiology, Command Hospital NC Udhampur and Principal, GMC Jammu, Principal, Govt Ayurvedic Medical College and Professor & HoD Microbiology)
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