**5. Suggested measures for controlling an epidemic of COVID 19**

One needs to understand about how an imported epidemic starts and progresses its course as time passes by. Based on our understanding it may be categorised as:


It may be noted that incubation period of COVID 19 infection ranges between 2 to 14 days with an average incubation period of 5–7 days. Maximum colonisation of virus occurs in oropharynx and naso-pharynx on second or third day from the onset of symptoms of an infected person. Hence maximum chance of transmission of virus from an infected person in his/her early days following development of symptoms. As a result, chance of transmission is relatively higher following detection by RT-PCR (considering the fact that patient usually comes on second day following onset of symptoms), when there is an opportunity of intervention. If that opportunity is missed, infection will keep on spreading in nearby population. On the other hand, it is easily understood that an epidemic is easy to control if it is detected early when very few people are affected. In the event of any delay in detection and/or lack of required intervention at the beginning due to any reason, the community/ country needs to pay a heavy price for that. COVID 19 epidemic is the best example of it in recent time. Apart from direct consequences of high morbidity and mortality, indirect consequences are havoc such as downfall of country's economy, loss of jobs, loss of wages, poverty, starvation leading to malnutrition, increase of mental diseases etc. It may be kept in mind that because of high global population movement, any infectious disease with pandemic or high epidemic potential, it may spread to people of other parts of the world with the passage to time unless strict vigilance and control activities are undertaken rigidly.

COVID-19 test detects genetic material of the virus using a laboratory technique called real time RT-PCR reaction (Real-Time Reverse Transcription – Polymerase Chain Reaction). RT-PCR testing can tell us whether there is a detectable virus present in an individual. Still, it does not accurately tell us whether that individual is infectious or is capable of spreading the disease. Cell culture is the standard technique for determining whether a patient is contagious or not. In the absence of

#### *Control of an Epidemic of SARS-CoV-2 by Assessing Transmissibility of Its Infected Cases... DOI: http://dx.doi.org/10.5772/intechopen.96201*

viral culture data, one can use viral load or cycle threshold (Ct) values derived from RT-PCR as a proxy for the likelihood of transmission. RT-PCR is a sensitive technique for mRNA detection and quantification currently available. It is a laboratory technique facilitating reverse transcription of RNA into DNA and amplification of specific DNA targets using polymerase chain reaction (PCR). It primarily wants to measure the quantity of a selected RNA. This is achieved by the amplification reaction using fluorescence, a way called real-time PCR or quantitative PCR (qPCR). Combined RT-PCR and qPCR are routinely used for analysis of organic phenomenon and quantification of viral RNA in research and clinical settings. Compared to the two other commonly used techniques for quantifying mRNA levels, Northern blot analysis and RNase protection assay, RT-PCR wants to quantify mRNA levels from much smaller samples. In fact, this system is sensitive enough to enable quantitation of RNA even from one cell. In a real time PCR assay a positive reaction is detected by accumulation of a fluorescent signal. The Ct (cycle threshold) is defined as the number of amplification cycles required for the fluorescent signal to cross the limit (i.e. exceeds set detection level). In other words, The Ct is the number of replication cycles required for a signal of RT-PCR product to cross a determined threshold. Ct values are inversely proportional to the quantity of target nucleic acid within the sample (i.e. the lower the Ct level the greater the quantity of targeted nucleic acid within the sample).

Considering above, it appears with reasonable certainty that viral load during early infection is an important determinant for transmission in the community by various routes including fomites based transmission. If viral load is high, chance of transmission is higher among nearby susceptible population with lack of proper precaution. Medical fraternity caring COVID 19 patients must take it seriously as many of the patients attended by them are with higher viral load with increased transmission potential and any lapse of precautionary measures on their part would make many of them infected as was observed in several countries. It is understood that virus multiplication occurs within first few days inside the body of an infected person. Antiviral agents such as Remdesevir may be beneficial not only for the patients but also for the attending health care personnel as it helps in reducing transmission to them by reducing viral load if given early in the disease. It is understood that there is hardly any benefit if anti-viral agents are given in late phase of the disease.

It is now evident that magnitude of viral load may be obtained easily from RT-PCR test of a COVID 19 positive case without any extra cost. More the cycle threshold (Ct) value, lower is the viral load (inversely related). Similarly, lower is the Ct value, higher is the viral load. Any Ct value of 35 and higher is considered as non-infectious although infected. Similarly, Ct value of 20 or below may be considered as highly infectious with higher transmission potential. Recently a number of qualitative COVID 19 detection kits are available in the market (such as rapid antigen detection kit) that does not indicate Ct value based viral load. Further studies are required to add viral load assessing facility in those rapid antigen detection kits for assessing infectivity of an infected case. Apart from viral load, it is now obvious that transmission will occur if favourable conditions are available such lack of protection measures, population density, population mobility, lack of awareness about the disease etc. So, mass awareness is an essential component of any public health control measures.

It is a fact that many countries in the world do not have an effective public health infrastructure such as required number of doctors, nurses, field workers, health technicians etc. as per WHO set guidelines, required number of various tiers of health establishments such as primary. Secondary and tertiary level of health establishments, diagnostics facilities, cold chain maintenance facilities and epidemic/infection control policy & strategies etc. Unless proper logistics supports

#### *Biotechnology to Combat COVID-19*

are available, vaccination is not possible even if it is made available. Hence, prevention of occurrence of cases much before it turns to an epidemic proportion should be a better choice. Appropriate infection control policy with an effective infection control strategy must be made available with experienced public health experts.

To summarise, COVID control strategies may include (based on already established evidence) the followings:


Home quarantine for cases with higher viral load is expected to facilitate intrafamilial transmission of COVID 19 cases in other family members, hence it is not suggested. On the other hand, same with low viral load may be quarantined at home with standard physical distancing, hand hygiene and face mask. Presently COVID 19 epidemic is largely concentrated on cities & urban areas that are gradually approaching towards semi-urban/rural areas through population movement. More number of rural population are expected to become infected in coming days since 60 to 70% of developing country's population reside in villages. Considering above, primary health care physicians must prepare themselves on Ct value-based segregation of COVID 19 infected cases with contact tracing of cases with high & moderate viral load of previous five days to reduce transmission of cases in the community. This will also reduce hospitalisation of cases & deaths and help improving bed availability, thereby better utilisation of public health infrastructure would be possible. Extensive community awareness about prevention & control of COVID 19 infection along with role of viral load. Ct value is essential for that. One needs to remember that success of Ct value based segregation will largely depend on dedication and motivation of grass root level field workers. If they work sincerely with supportive supervision by their immediate supervisors and higher leaders, cases are expected to decline soon, leading to control of epidemic. Proper training of various categories of health workers as well as logistic support must be in place. Moderate to severe symptomatic persons need to be referred to nearby hospital/health centre for management of COVID 19 infection. Asymptomatic and mild symptomatic may be sent to home or institutional quarantine as per their reported viral load as mentioned already.

#### *Control of an Epidemic of SARS-CoV-2 by Assessing Transmissibility of Its Infected Cases... DOI: http://dx.doi.org/10.5772/intechopen.96201*

We need to understand that to control an epidemic with high transmission potential such as COVID 19, multiple strategy based attacks are needed to break the all possible transmission chains. Vaccines whenever possible must be considered in addition to other public health measures. Safety & protective efficacy must be assured of a vaccine before going for mass vaccination in a community. Since the disease is new and vaccine(s) are also new, continuous monitoring & supervision of the recipients of vaccines are needed. Cases with vaccines failure must be identified early for their alternative protection against this disease. Detailed epidemiological information may be collected about possible factor/s that are associated with vaccine failure. Since, COVID 19 is originated from RNA virus, frequent genetic mutation is possible over a period with consequent changes of its virulence and also its epidemic transmission potential. Herd immunity may be another important factor that develops from earlier infection or due to vaccination to a section of population of the community. Monitoring of above issues from time to time will be helpful for taking a judicious decision about vaccination strategy for a particular community. It may also be noted that most epidemics undergo a natural decline as time passes by, irrespective of intervention measures undertaken or not. That does not mean that intervention is not important as delay in intervention measure increases morbidity and mortality. Last but not the least, there is no single strategy or a straight forward pathway to control the epidemic. Rather it is a diversified and complex mechanism which is based on various situations and interplay of agent, host and environmental factors. A judicious planning, timely intervention and efficient management with required logistic support services can reduce human sufferings to a great extent.

Lastly, it was observed that an overall 35% (21 out of 60) asymptomatic infected cases got detected while doing contact tracing in a community based study in western India (unpublished data). The magnitude of asymptomatic cases was higher with cases of low viral load (46.6%), whereas it was about 20% with cases of high viral load. Asymptomatic cases of higher viral load would spread the disease at higher rate, similar to that of symptomatic cases. Hence, precautionary measures such as hand hygiene, face mask, physical distancing etc. are extremely important and required to be practiced by all considering the fact that everyone around us is potentially infected and could transmit the disease. So, community people need to be educated about transmissibility of asymptomatic infection and about ways of its prevention. Similarly, awareness about safe disposal of their used items considering the possibility of transmission from them is equally important too.
