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By: Col (Dr) MN Mishra
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease (COVID-19), has precipitated a global health crisis and this pandemic has impacted India significantly with over 40,000 cases, more than 10,000 recoveries and 1300 deaths (3.2%) as on 4 May, 2020.[i] With a surface area one-third of the USA and four times the population, we may have been sitting on the top of a potentially active volcano, if it was not for the 21 days lockdown from 25 March, which was later extended to 03 May 2020. In addition to well-publicised measures like regular hand washing and social distancing, the need of the hour is to study the immunological profile of both the individuals who have recovered from the disease and also of asymptomatic carriers to enable therapeutic use. The response of various governments has varied from complete lockdown as in China and India to selective lockdown as in Germany and the USA.
In this regard, one needs to examine the German model where despite very limited lockdown the mortality is 3.5% which is lower than that of other neighbouring EU nations having similar disease load: Italy 13%, UK 13.8%, France 13.9% and Spain 10% have a much higher mortality rate.[ii] Although the death rate in India is around 3%, with one eighth the number of cases as compared to EU nations, the challenge will be to maintain or reduce the death rate one month from now when the number of cases is likely to increase substantially. Germany is combating Covid 19 infection by performing half a million tests per week, identifying those with higher resistance and actively using convalescent plasma (personal communication). Use of convalescent plasma as a trial has yielded positive results in Delhi as per news reports on 24 April. National Institute of Health, USA is using convalescent sera for treatment and clinical trials, testing healthy volunteers for the presence of Covid 19 antibodies, patients who have recovered and are willing to donate plasma, patients and families willing to consider treatment with plasma. Convalescent sera have been used for similar virus respiratory tract infections earlier.[iii]
It is time to commence collection and maintain inventories of convalescent plasma to meet the growing demand for treatment of severe infections. “Convalescent” plasma refers to plasma that is collected from individuals, following resolution of infection and development of antibodies and is likely to result only in short term but immediate immunity as is also done for Class 3 dog bites to prevent rabies. However, this involves rising to the regulatory and logistical challenges spanning drawing up donor eligibility criteria, donor requirement and transfusion itself. This will also involve the inclusion of preferably RNA and at a minimum antibody testing regularly in blood banks as “healthy blood donors” be positive. In the past two decades Blood Banks in India realised that Nucleic acid testing (NAT) of blood donors for HIV, Hepatitis B and Hepatitis C virus is desirable, most blood banks have not been able to switch over. It is time to gradually introduce legislation to make it mandatory for the provision of safe blood and add Covid 19 NAT testing to the menu.[iv]
Although SARS-CoV-2 is novel, partial immunity to is some may be attributed to antibody cross-reactivity and partial immunity from previous infections with the common seasonal coronaviruses (OC43, 229E, NL63, HKU1) that have been circulating in human populations for decades. The case for SARS-CoV-2 can be this as well and might explain why some individuals (perhaps those who have recently recovered from a seasonal coronavirus infection) have milder or asymptomatic infections. Another concept for creating immunity in the population is “Herd Immunity” which occurs when a 60 per cent of the community is deemed immune to a disease (through vaccination and/or prior illness), making the spread of this disease from person to person unlikely. This can happen when many people contract the disease and in time build up an immune response to it (natural immunity). It may also occur when many people are vaccinated against the disease to achieve immunity. Now the strategy to protect residents of Stockholm by inducing herd immunity has got a stamp of approval from the country’s chief epidemiologist Anders Tegnell, who believes that the idea seems to be working and that “herd immunity” could be reached in Stockholm in few weeks. This very strategy did not work for the UK where a lockdown had to be imposed, albeit not complete which permitted 1-2 citizens to go out for exercise maintaining social distance during the process. India has done better as masks are widely available, but are in short supply for the denizens of London for personal use. In India, if we used Herd Immunity for protection the consequences could have been disastrous.
Methods of viral testing include point of care tests (POCT) for antigen and antibody detection and Real-Time Polymerase chain reaction (RT PCR). POCT has a sensitivity of 34 -80% and WHO does not recommend it for clinical decision making. While antigen detecting tests are specific, antibody detection kits are not and other shortcomings include both variability and delay in antibody response following infections. Most studies suggest that antibody response develops only in the second week after infection which implies that a diagnosis of COVID-19 infection based on antibody response will often only be possible in the recovery phase when many of the opportunities for clinical intervention or interruption of disease transmission have already passed. Secondly, antibody detection tests targeting COVID-19 may also cross-react with other pathogens, including other human coronaviruses causing false-positive results. Finally, there is no evidence to show RDTs detecting antibodies could predict whether an individual was immune to reinfection with the COVID-19 virus. WHO does not recommend the use of antibody-detecting rapid diagnostic tests for patient care but encourages the continuation of work to establish their usefulness in disease surveillance and epidemiologic research.[v]
It needs to be emphasised that cellular immunity imparted by lymphocytes, especially T cells and Natural Killer (NK) cells have a greater role in viral infections to which the viral peptides are presented by Human Leukocyte Antigen (HLA) molecules. A vaccine against the virus must be able to augment cellular immunity.
As on date, treatment for Coronavirus is purely supportive and no antivirals are very effective. ICMR advises the use of Hydroxychloroquine for health personnel who are at risk due to professional duties and don’t have any pre-existing heart disease. A recent study has also shown a definite reduction in viral load / its disappearance with the drug.[vi]Remedesivir is another antiviral drug which is being examined for its efficacy against Covid-19.
India needs to adapt to Coronavirus epidemic by augmenting testing facilities, commence nucleic acid testing in the majority of the blood banks to provide safe blood and license the storage as well as the use of convalescent sera. India also needs to do quality research to identify the more immune profile of immunological robust individuals against Covid 19 and fast track research directed towards the development of kits and vaccines against the virus. The usefulness of Hydroxychloroquine in an Indian setting also needs examination and documentation.
[i]https://www.worldmeter.info/coronavirus/ accessed 24 Apr 2020
[iii] Bloch EM et al. Deployment of convalescent plasma for the prevention and treatment of Covid 19. J Clin Invest. 2020. https://doi.org/10.1172/JCI138745
[iv] Chang L, Zhao L, Gong H, Wang Lunan, Wang L. Severe acute respiratory syndrome coronavirus 2 RNA detected in blood donations. Emerg Infect Dis. 2020 Jul [date cited]. https://doi.org/10.3201/eid2607.200839
[v]Advice on the point of care tests for Covid 19 Scientific Brief 08 Apr 2020 www. who. int.
[vi]Gautret P, Lagier JC, Parola P, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial [published online ahead of print, 2020 Mar 20]. Int J Antimicrob Agents. 2020;105949. doi:10.1016/j.ijantimicag. 2020. 105949