Intensifying Covid-19 Genomic Surveillance
Mutations of SARS-CoV2 causing Covid-19 are now a major topic of discussion, especially regarding their impact on infection, disease severity and vaccine effectiveness.
Mutations of SARS-CoV2 causing Covid-19 are now a major topic of discussion, especially regarding their impact on infection, disease severity and vaccine effectiveness.
The World Health Organization (WHO) leadership on 11 January 2021 stated that virus mutations would be highly problematic for global Covid-19 control. On 2 March 2021, Director of the US Centers for Disease Control and Prevention said the progress made in dealing with Covid-19 in the US lately could be wiped out with the expanding mutations.
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Mutations are indeed known to cause the disease to be more infectious, some even claim that the increase in infection can reach 30-70 percent. As for their impact on vaccines, experts agree that if mutations are protracted, vaccine producers will be able to modify their vaccines to maintain their effectiveness.
Furthermore, it has been reported that people can be infected with two mutations at the same time.
The mutation identified since February 2020 is in the D614G strain, which has not affected the epidemiologic situation too much. However, the mutation in Britain in the form of B 1.1.7 and that in South Africa, E484K, have turned out to bear a greater impact. Furthermore, it has been reported that people can be infected with two mutations at the same time.
On 1 February 2021, Britain identified 11 samples with B.1.1.7 and E484K mutations at the same time, after analyzing 214,159 sequence samples. Simultaneous B.1.1.7 and E484K mutations will concretely increase the number of antibodies needed to counter the infection so that it is more difficult to overcome.
The other thing requiring attention is that the South African variant (especially if it comes along with B.1.17) can make reinfection easier to affect people who have previously been infected with Covid-19 by the virus not yet mutating. New York has also reported that a mutation of the B.1526 type whose quantity increased by 12.3 percent in two weeks until end-February 2021.
What is more worrying is the report about the double mutation of B.1.1.7 from Britain and B.1.429 from California in the middle of February 2021. This is called recombination, which later form a heavily mutated hybrid version.
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It is reported that the recombination may cause a surge in cases in Los Angeles and also invulnerability to antibodies so that it is harder to defeat. It’s no exaggeration to say that we can be entering a new phase of the present pandemic. In order to anticipate this situation, properly structured genomic sequence surveillance should certainly be conducted in a country with a good organizational system. Surveillance in this case means that observation should be done continuously rather than intermittently. Genomic sequencing means a more detailed examination of the virus, not only its positive or negative condition, but also whether certain changes have occurred in the virus in the form of mutations.
We are aware that on 2 March 2021 Indonesia reported the discovery of a B 1.1.7 mutation and it is necessary to anticipate the possibility of its wider transmission and also other types of mutation. Therefore, increased genomic surveillance activity is actually needed and the following study may be worthy of consideration.
National and local scales
The state can surely conduct genomic surveillance on a national scale like that intensively carried out by Britain through the Covid-19 Genomics Consortium (COG-UK), which has found the N501Y mutation now known as B.1.1.7. The COG-UK activity launched in Britain in March 2020 aims at sequencing SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) in 230,000 patients.
With this information, the pattern of transmission of SARS-CoV-2 in Britain will be traced to detect the presence of mutations and integrate it with health data, so as to obtain complete information about how virus genomes interact with Covid-19 cases in that country. The information gathered will serve as important material for pandemic control decision making there.
To make it clear, in spite of the small scale, it may in fact be useful and for this purpose it should be executed in a structured and consistent fashion.
Surveillance can also be conducted in a certain region rather than on a national scale. In June 2020, for instance, South Africa launched the Network for Genomic Surveillance, which in its realization only obtained 50-100 samples in a week. Although the number was limited, its result turned out to be quite important with the discovery of the new 501Y.V2 variant now widely discussed. To make it clear, in spite of the small scale, it may in fact be useful and for this purpose it should be executed in a structured and consistent fashion.
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Some data are later sent to GISAID, a nonprofit organization managing the database of virus genomes. This is necessary to enable experts to utilize the information in order to find out the spread of mutations epidemiologically and also make anticipation of therapy and Covid-19 vaccines as may be needed.
WHO guidelines
Based on WHO guidelines of the February 2021 edition, in general all specimens of PCR (+) with a cycle-threshold (Ct) value of 30 constitute the right material for genomic sequencing.
If an examination is to be conducted in a certain region by the sentinel system, at least four things should be considered. First, it is necessary to cover several age groups, such as infants to under two years, two to under five years, five to under 15 years, 15 to under 50 years, 50 to under 65 years, and 65. This is needed because there may be mutation variations in certain age groups.
Second, the activity should be undertaken in several regions in a country so that it can more or less represent the situation of the country as a whole. Third, it is necessary to carry out the activity in several periods/months, not just in one period, so as to notice the possible emergence of a mutation pattern in a certain period of one year.
Fourth, targets of those prioritized for genomic sequence examinations should be set. They can be patients with specific clinical conditions and or certain groups like those already vaccinated, cases of death, those with immunity system disorders, patients receiving plasma or monoclonal antibody therapy and Covid-19 relapse or reinfection cases.
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For SARS-CoV-2 sentinel surveillance, the WHO has recommended that ideally 150 specimens should be examined in a week. It is also suggested that countries should execute genomic sequencing of all Covid-19 cases with positive PCR and a Ct value of 30. At least the WHO suggests that countries should carry out a minimum of 15 sample examinations per week of the current national sentinel surveillance system and deliver their results to the existing international database so that the world can monitor them.
The Covid-19 pandemic is still with us and the various possibilities of its developments should be profoundly anticipated. The preparedness to face contingencies should be part of the national pandemic control program of a country. The necessity for applying the genomic sequence surveillance system becomes a very vital part, especially because we realize that SARS CoV-2 will keep mutating and such mutations will likely affect state policies in the future, which should be prepared at an early stage.
Tjandra Yoga Aditama, Postgraduate Director, Yarsi University; Professor, School of Medicine, University of Indonesia; Former Director of WHO SEARO; Former Director-General of Disease Prevention and Control and Head of Health R&D Agency
(This article was translated by Aris Prawira)