Increased Doubling Time with Significant Recovery and Low Mortality from COVID-19 following Extended Lockdown: Implication for Development of Protective Immunity against SARS-CoV-2 In a Population

COVID-19 is fast spreading around the globe in a highly contagious manner. The results from our study showed that after intervention with successive Lockdowns, there was marked decrease in the rate of COVID-19 cases, though there was sporadic volatility in number of COVID-19 cases due to some extrinsic factors. Concomitant with reduction in rate of COVID-19 there was gradual increase in doubling time of COVID-19, steady increase in number of discharged/recovered patients from COVID-19 reaching to ≥58% taking the entire Indian population into consideration. Another important aspect was consistent low mortality rate was accompanied by gradual increase in recovery rate of COVID-19 in the population. The possible implication of these results in the development of protective immunity in the population has been discussed.


INTRODUCTION
The novel coronavirus (SARS-COV-2) originated in Wuhan in Hubei province of China during December 2019, and has now spread across the world making it a pandemic. Until date there are no therapeutic agents/vaccines developed which could be of promise to control this highly 5 25 th March 2020, there was marked decrease in the rate of COVID-19 cases in the population, which was stably maintained until 31 March 2020.
However, on the 1 st of April, 2020 a spurt was noted in the COVID-19 cases and there was 2.5 folds increase in COVID-19 cases compared to 31 March, 2020. This abrupt change in number of COVID-19 cases was due to contribution of cases from a 'single source' (2). Later contribution from a 'second source' representing migrant labourers caused abrupt increase in number of COVID-19 cases. All such spurts appeared as small peaks in the percent graph. As reflected in the graph, around 14 th May, 2020, the rate of COVID-19 cases stabilised at ≤ 4% which was maintained until the end of Lock-down 4. However, the trend line suggests that by the end of Lockdown-4, the rate of COVID-19 case should have been much lower than the actual value recorded in the graph ( R 2 = 0.320). The trend line also confirmed that the 'spurts' had a negative impact in the rate of spread of COVID-19 cases among the population. The Figure-3 gives a comparative rate of COVID-19 during Lockdown-3 and Lockdown-4 respectively. The comparative study shows that the volatility in rate of COVID-19 cases had decreased during the period of Lockdown-4 with R 2 value being = 0.674, and the value of R 2 being = 0.266 during Lockdown-3. It is also clear from the graph that the actual rate of growth of COVID-19 came down from 5% to ≤ 4.5 % by the end of Lockdown-4 on 31 May, 2020. Interestingly, with noticeable stability achieved in rate of COVID-19 cases by the end of Lockdown-4, the number of patients recovering from COVID-19 also increased steadily. The Figure: 4 shows that the percent of recovered patients were consistently high compared to reported cases, at the end of Lockdown-4 and subsequently the percentage gradually increased which is demonstrated in Doughnut chart ( Figure 5). A Doughnut chart meant to express a "part-to-whole" relationship, where all pieces together represent 100%, shows the recovery rate on 01 June, 2020 (immediately after lockdown-4) and later on 15 June 2020. It is clear from the chart that the recovery rate was 48% on 01 June, 2020 and 54% on 15 June, 2020 as compared to total confirmed cases.
Interestingly, the number of recovered individuals was approximately equal to the number of active cases of COVID-19 after lockdown-4. Due to significant recovery from COVID-19 cases, it was of interest to see if any correlation existed between rate of recovery and rate of COVID-19 cases. The Figure-6 reflects that there was a weak negative correlation between the two variables with R 2 = 0.296. Another noteworthy aspect of the study was that with gradual increase in recovery rate, the mortality rate was consistently very low as shown in Figure-7. The mortality rate has been consistently maintained at ~2.8% from the beginning, whereas the recovery rate continues to rise and presently it is ~60%. When a correlation was drawn between the mortality rate and the rate of COVID-19 cases a weak negative correlation between the two variables with R 2 = 0.21 was observed as shown in Figure-8. With gradual decrease in the rate of COVID-19 cases to below ~4% at the end of lockdown-4, the doubling time of the COVID-19 cases also increased to 15 days as on 5 June 2020. When the two variables were plotted on correlation coefficient graph, a weak negative correlation was noted with R 2 = .082, as shown in Figure-9. The results discussed so far, suggests that gradual increase in the number of Recovered/disease free individuals with time to above 50% along with a negative correlation between the doubling time and the rate of reported COVID-19 cases implies that the Indian population could be steadily moving towards developing protective immunity against COVID-19. The Figure-10 shows the distribution of COVID-19 cases in some states of India with high number of COVID-19 cases compared to rest of India. The figure emphasizes that a few states have the bulk of COVID-19 cases compared to rest of the country.

III. DISCUSSION:
The disaster caused all over the world by COVID-19 pandemic has prompted a massive global effort to control spread of this disease in their respective population. At present due to lack of any specific treatment regimen for COVID-19, the importance of implementing Lockdown/social distancing at the appropriate time cannot be ignored at all. Delaying implementation of intervention/social distancing in the USA even by few weeks resulted in heavy loss of human lives as depicted in the model shown in Figure-  graph reflects that the volatility seen during earlier Lockdowns was reduced and stabilised during lockdown-4 and the rate of reported cases of COVID-19 was ≤ 4.6%.

FIGURE 4:
The graph shows that the number of recovered cases of COVID-19 compared to reported cases during lockdown-4. The number of recovered individuals gradually increased to more than 30% in the graph. Later, as of 29 June 2020, nearly 60% patients suffering from COVID-19 recovered.