COVID-19 Follows a Flattened Growth Curve Subsequent to Prolonged Intervention in A Population; Its Implication on Rate Of Doubling Time & Plausible Suppression of SARS-CoV-2 Infection

COVID-19 is fast spreading around the globe in a highly contagious manner. In this article we have described that after prolonged interventions the percentage growth curve for COVID-19 cases showed a flattened nature, after prolonged volatility in number of COVID-19 cases. The stability in the growth curve was continuously maintained from 18 April, 2020 to 29 April, 2020. The significance of this sustained stable curve on survival & doubling time has been discussed. One significant part of the study reflected that the doubling time of COVID-19 cases showed a negative correlation with the percent increase in COVID-19 cases (R=0.301). It is plausible that if such negative correlation is maintained with further flattening of the growth curve at a lower level, it may influence the infective ability of nCoV-19 & ultimately have a positive evolutionary implication on the spread of COVID-19 among the population.


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; the most affected being USA, Italy, Spain & now Germany. Until date there are no therapeutic agents which have shown any promise to control this highly infectious virus from spreading among human population.

SARS virus is an infectious agent belonging to the virus family
Coronaviridae, which causes severe respiratory illnesses in humans and animals. SARS (severe acute respiratory syndrome) coronavirus (CoV) is a novel member of this family that causes acute respiratory distress syndrome (ARDS), which is associated with high mortality rates. Its characteristic feature is long latency period before the typical flu-like fever, cough, and shortness of breath manifest. The people infected with this virus may not show any symptoms for up to two weeks, allowing them to pass it on to others in the meantime.
Due to alarming nature of this disaster world-wide and to contain its spread in Indian population, The Hon'ble Prime Minister of India declared one day of 'Janata Curfew' on 22 March 2020, from 7AM to 9 PM followed by 'National Lockdown-I' for 21 days starting from 23rd March, 2020 midnight to Midnight of 14 April, 2020. During this period the number of COVID-19 cases abruptly came down due to break in the chain of virus infection, and showed flattening of growth curve until 31 March, 2020. Following which the number of COVID-19 cases showed fluctuations on several occasions. Due to such variations the Lockdown was further extended for two weeks until 03 May, 2020 (Lockdown-II).
We have assessed the nature of spread of COVID-19 using a percentage graph which accurately reflects the changes in the spread of the disease (1).
In earlier studies we observed that (a) much of the success of Lockdown depends on 'early detection' of the intervention introduced in the population so that fine tuning of the intervention could be made possible; that was ascertained by percentage curve. (b) Any unprecedented changes taking place due to any unforeseen event was clearly detectable at an early stage from the plotted percent graph & (c) The percent graph elucidated that the long term down trend of COVID-19 cases remained intact in the population.
In this paper, we have endeavoured to further elucidate the role of prolonged Lockdown on the infectivity of this highly mutable Virus and its possible significance on disease control.

II.
METHOD AND RESULTS: The present study was carried out on the data collected from Indian & other countries, which were diagnosed as COVID-19 positive cases, starting from March 03, 2020 until 29 April, from the websites of Government of India and other national News agencies.
The March 2020 onwards, that is, after Lockdown-I was implemented, there was a significant decrease in COVID-19 cases and that was stably maintained until 31 March 2020. And on 1 st April, 2020 the percent graph reflected that there was 2.5 folds increase in COVID-19 cases. This change appeared as  Figure-7. The result showed a negative correlation suggesting that with the increase in one variable there will be a decrease in other variable, the R squared value being 0.301.

III. DISCUSSION:
The recent disaster caused all over the world by influx of nCoV-2 has prompted a massive global effort to hunt for a cure/vaccine for COVID-19.
Unfortunately, until date no drugs/vaccine is available which could help to fight the disease. In recent times much faith was put on the use of drug, Hydroxychloroquine sulphate, for the treatment of COVID-19 but results obtained so far has not been conclusive.
The  It was clear from this study that due to prolonged implementation of lockdown, there was stability in the growth curve of COVID-19 at the level of 10%. However, this also appears to be high and there is need to bring it down to 5%; though briefly there was a dip to 5% on two occasions as seen from Figure The SARS-CoV-2 is a highly mutating virus which is presently having ~10 strains, of which strain A-2a is most infectious by virtue of mutation, a change in a single amino acid from aspartic acid to glycine in the spike protein of the virus, which increases its ability to bind to the ACE-2 receptor on the pulmonary cells. At present strain A-2a is most prevalent in the world along with in India where ~45% of the cases were found to be infected by this strain.
Therefore, more efforts must be directed to implement social distancing and sustained Lockdown to bring the level of COVID-19 cases down to ≤ 5% that could further impact on the increase of doubling time of the virus infection, which could bring the correlation coefficient to a critical level. From the data available, it could be hypothesized that sustained waning in the ability of nCoV-2 to infect fresh targets may have a positive evolutionary significance; as the selective advantage obtained by A-2a to survive better in the population, due to non-use may be again eliminated by Natural selection leading to eventual suppression of this highly infectious virus.

V.
References:    FIGURE 7: The figure shows a weak negative correlation between doubling time and percent increase in COVID-19 cases. It demonstrates that when one variable increases other variable decreases. This has a direct bearing on the rate of increase of COVID-19 cases.