On June 27, 2021, the daily reported COVID-19 cases (seven-day rolling average) had fallen below 50,000, and have remained so for 15 consecutive weeks (Worldometer – Corona-India). That heralded the end of the second wave of India’s epidemic and marked its transition to ‘endemic’ state. It fell below 40,000 on September 9 , and below 30,000 on September 24 . The trend continues.
Population and infection
Endemic denotes steady weekly numbers without major fluctuations. Fifteen weeks of this trend spells consistency. Kerala, Sikkim, Mizoram and Meghalaya are outliers/exceptions to the national endemic state — they have not yet transitioned to endemic phase ( covid19india.org ) but their daily case-trends show they will soon catch up and become endemic. Country-level endemicity indicates that the vast majority of the population is already infected and immune, but how large is the majority?
The fourth ICMR sero-survey (June-July 2021) showed 67.6% had antibodies by end July — that is roughly 950 million. The reported cumulative COVID-19 cases by end-July were 30,410,577 (3.2 % of 950 million). So, actual infections were ~30 times the reported number. From August 1 to October 7 — 2,219,097 additional cases were reported, representing, by extrapolation, 70 million infections, taking the total to 1,020 million, the susceptible population therefore is 1,400 - 1,020 = 380 million. The Indian Council of Medical Research (ICMR) found, in the second sero-survey, that detected antibody prevalence underestimates true immunity prevalence, detecting only ~70% of those who were RT-PCR positive earlier, therefore the susceptible pool may be much smaller.
Endemic transmission will be sustained by new infections in previously uninfected remnants plus new additions to population by annual birth cohorts of 25 million (less mortality) and by re-infections in those previously infected.
The second wave of the pandemic was driven by the Delta variant, with a basic reproduction number (Ro) of 6-8. The epidemiology formula (1—1/Ro) is used to calculate the herd immunity threshold (HIT) necessary to end the epidemic, which is ~87.5%, in our estimations. Applying the principle of triangulation this observation corroborates the fact of epidemic-endemic transition.
On the jab
India rolled out its COVID-19 vaccines on January 16, 2021, but the pace of vaccination is slow, 20% having received two doses (2.2% per month). So, the major contributor to reaching HIT was natural infection in two waves. Two recent preprints, one from Christian Medical College Hospital Vellore and the other from Israel indicate that infection-induced immunity confers greater protection than vaccination. Thus, India’s immune population has good short-term protection against re-infection and disease. Indeed, the reinfection rate in India according to the ICMR was only 4.5%.
India’s COVID-19 control strategy, hitherto addressing epidemic COVID-19, has to be modified now for endemic COVID-19. Two important factors will dictate the modifications: Senior citizens, those with co-morbidity/cancer treatment/organ transplant, etc. and pregnant women, who had not been infected in the past or not yet vaccinated with two doses, would have risks of severe disease, need for hospitalisation, admission in an intensive care unit, and mortality. They have to be traced individually and vaccinated.
More by re-infections
Endemic transmission will be driven more by re-infections than by first infections. A paper in The Lancet Microbe , October 1, reported the durability of immunity against re-infection in coronavirus infections , the profiles of antibody decline and probabilities of re-infection over time, under endemic conditions. Re-infection is likely three months to 5·1 years after peak antibody response, median 16 months. Hence, all previously infected but unvaccinated persons require at least one dose of the vaccine.
Studies have shown that those who had natural infection may need only one dose of any approved vaccine to stimulate long-lasting immunity even against reinfection. A meticulous follow-up study of antibody levels in those who had infection is urgently needed to determine when such individuals will need a booster dose. Their immune response profile to one dose of different vaccines also needs to be documented.
Persons previously uninfected but vaccinated with two doses have to be given a booster dose of vaccine to offer protection against breakthrough re-infection. Immunology informs that the optimum time interval for a booster dose is six months to one year after the previous dose. We must monitor both the immune response levels and durability post-booster. Such data will then guide if and when any further booster(s) may be required.
Contact tracing, testing and quarantine requirements — very important during an epidemic spread — will now have to be confined to the elderly and vulnerable contacts so as to facilitate early recognition and treatment of COVID-19, rather than for everyone. Our two-dose vaccination coverage should be rapidly escalated — the current weekly rate of about 0.6% of the population given a second dose, is too slow and must be revved up — through intensive information-education-communication and by vaccination campaigns.
Vaccination should be targeted for the purposes of re-opening all schools and hubs of economic activities. The entire work force in India (organised, unorganised, self-employed, those in the travel and tourism industry) need to be targeted for vaccination; this is best done at the workplace with the help of the respective managements and State health authorities. Thereafter, all social, religious, cultural and recreational gatherings can be allowed.
Childhood infection
Childhood infection with the coronavirus is mostly mild and self-limiting as children have lower density of the ACE2 receptor (the portal of cell-entry of virus) in their respiratory passages. Multi-system-inflammatory syndrome, a severe complication encountered in children, is fortunately very rare and treatable. Under these circumstances, children are best protected by fully immunising all school personnel (teachers, non-teaching staff, transport) and all eligible subjects at home, thereby creating a protective mantle.
After any vaccine gets approved for use in children, (Covaxin and ZyCoV-D may be approved soon), they can be immunised – the easiest way forward would be school-based vaccination camps.
Continued endemic transmission is the opportunity to progressively relax restrictions of social contacts, but such return to normalcy must be under the umbrella of vaccination (as detailed above) and universal mask use. When endemicity is sustained over a longer time, seasonal outbreaks (minor waves) must be anticipated — but even they can be averted by vaccination. Vigilance cannot be let down until we ensure that no one remains at risk of severe COVID-19.
Dr. T. Jacob John is a retired professor of Clinical Virology, Christian Medical College, Vellore, Tamli Nadu and former President of the Indian Academy of Pediatrics. Dr. M.S. Seshadri is a retired Professor of Medicine and Clinical Endocrinology, Christian Medical College, Vellore, and currently Medical Director, Thirumalai Mission Hospital Ranipet, Tamil Nadu
