With over 2.7 million deaths reported so far, the novel coronavirus disease 2019 (COVID-19) pandemic has had an enormous impact on the world. Among the more than 117 million cases that have been documented so far, almost 80% are known to have occurred during the second wave of the epidemic, between September 2020 and March 2021, with only about 25 million associated with the first wave.
A new preprint, released on the medRxiv* server, examines a major consequence of the second wave of COVID-19 infection—namely, the rapid emergence of new viral lineages and variants.
Variants of concern
This includes the three variants of concern (VOCs), namely, B.1.1.7, B.1.351, and P.13. These are also called the UK, South African, and Brazil variants, respectively, due to where they were first detected.
The first was detected in the UK towards the end of September 2021, and has 17 genetic variants in different parts of the genome, including the spike gene. Some important alterations in the spike include the N501Y mutation and a deletion at positions 69 and 70.
The South African and Brazilian variants have the N501Y mutation, but they also contain the E484K mutation.
In all cases, these have shown greater transmissibility, replacing older lineages in their regions of origin and spreading rapidly across the continents. The possibility of relative resistance to antibodies elicited by the older lineages is also real, which may allow reinfection, pushing the end of the pandemic farther away.
This resistance may extend to vaccine-induced antibodies as well. These reasons make it mandatory to monitor the emergence of new SARS-CoV-2 lineages with great alertness.
Lockdown in Italy
The earliest cases of SARS-CoV-2 in Italy were reported in January 2020, and the outbreak rapidly progressed to a peak in late March, when more than 6,500 cases were being reported every day. In response, Italy led the way in Europe by implementing a national lockdown on March 9, 2020, which lasted for nine days.
The first wave was dwarfed by the second wave, which hit in September 2020. During this period, there were about 40,000 cases a day by mid-November 2020. By the end of the first week of March 2021, over 3 million cases and more than 100,000 deaths have been reported in Italy alone.
This is despite the introduction of color-coded restrictions on social mobility. With regions being assigned colors from yellow to red, travelers between such regions were subject to correspondingly tighter restrictions.
These barriers were further increased all over Italy in anticipation of the Christmas and New Year celebrations. Schools and restaurants were also closed down from December 21, 2020, to January 6, 2021. One day before these came into effect, flight travel between Italy and the UK was shut down, and this was extended to Brazil as well from January 16, 2020.
The current study aimed to explore the role played by travelers who imported the virus from abroad into the local community, followed by community spread. The study included over 6,500 viral sequences collected between January 29, 2020, and March 1, 2021.
The researchers observed over a hundred separate lineages, of which the UK variant made up over a third. Other lineages found at high frequencies included B.1.177 (24%), B.1 (11%), and B.1.1.74 (5%).
Since viral genome sequencing was begun relatively late, most of the lineages from North Italy come from the first wave of the pandemic in Italy in March to May 2020 and from January to March 2021, unlike those from Central and South Italy.
What were the results?
The findings show that both B.1 and B.1.1.74 emerged early in 2020 in Italy but were then replaced by B.1.177 towards the latter part of the year. B.1 appeared in North, Central and South Italy within a period of a week from February 20, 2020, and February 24, 2020, respectively.
Low levels of B.1.1.74 persisted in the latter two regions until the end of the study period, but not in North Italy after May 27, 2020.
Lineage B.1.1.74 appeared on August 13, 2020, in North Italy, followed rapidly by the other two regions.
Unusually, certain lineages were sampled at excessive levels in specific regions on particular days. Notably, over a hundred B.1.177 lineages were found in Campania, in South Italy, on one day in October, and 42 B.1.1.187 sequences in one day in June,
The latter has been found elsewhere only in 14 UK samples and one Japanese sample, other than the 81 Italian samples sequenced so far, of which over half were from the same day.
The UK VOC
Of the VOCs, the UK variant was by far the dominant at the date of the study, on March 8, 2021, with over 2,100 samples, followed by about 110 Brazil and only eight South African samples from all three regions.
The UK variant emerged within five days in all three areas. The researchers note that the UK variant appears to have been introduced independently into the country by multiple travelers, with corresponding transmission clades within the country – extended transmission chains.
About 80% of these clades were confined to specific areas. One such clade comprised over a hundred samples from infected individuals, all from South Italy.
Again, 80% of the remaining clades were spread over two regions, with only one being found in all three. In the latter scenario, 80% of the sampled clade came from a single area and only a few from the other two regions.
Six clades had more equal mixing between the regions, such as one chain of 35 infections, comprising 10, 12 and 13 from North, Central and South Italy, respectively. “Notably, this is the only example of prolonged transmission between macro areas for this time period.”
The Brazil VOC
The Brazil sequence was detected in Central Italy on January 7, 2021, in three Brazil-returned travelers. The next isolation occurred only after a gap of two weeks in North Italy and after another three weeks in South Italy.
The January 7 sequences were distinctive because of the presence of a single T->C synonymous mutation in the viral polypeptide ORF1ab. Almost all the P.1 sequences from Italy formed a single clade, in addition to ten from Germany.
Of these 104 sequences, 61 formed another clade with an additional synonymous spike mutation, while 43 had a non-synonymous spike mutation S813N. Unlike the E484K and N501Y mutations, the latter is not in the receptor-binding domain (RBD) of the spike, but is between the two fusion peptides.
The first time this mutation was detected was on January 13, 2021, in Central Italy, while the last so far was on the first of March. It has not yet been found in any sequenced sample from North Italy.
The South African VOC
Only eight sequences belonging to the B.1.351 lineage were found, with five being dispersed across the globally sequenced range of clades. This confirms multiple independent introductions by travelers. However, some were also found to be part of a local transmission chain.
What are the implications?
The researchers point out the obvious pattern of the rise to dominance of the lineage B.1.177 during the second wave, while recently, the UK variant is spreading rapidly, to become the most frequent sequence, obtained in over half of the samples obtained over January and February 2021.
The lockdown has limited transmission of the virus between the Central, South and North regions of Italy but not within them. Though the direction of spread is difficult to tell, different lineages have been introduced within a week in all three regions, indicating multiple independent introductions.
The South African VOC does not appear to have established itself in Italy so far, but the other two VOCs are showing community transmission. It is likely that the UK VOC will soon be the dominant strain at the current rate of spread. This agrees with its known enhanced transmissibility, which has led to its dominance in several countries in Europe already, as Denmark.
The Brazil VOC is curiously found at a relatively high frequency in Italy, second only to Brazil, in fact. Notably, it was first sequenced in Manaus, Brazil, in a region where three of four inhabitants had already been infected during the first wave. This suggests that it is resistant to existing antibodies and causes reinfection with SARS-CoV-2.
The findings in this study with respect to the Brazil VOC indicate a single introduction into Italy, with vigorous community spread thereafter, and even perhaps to Germany. The fact that both the UK and Brazil VOCs gained entry before the closure of international borders with these countries shows the essential need for rapid global vaccine rollout to contain the pandemic effectively.
The rapid emergence and replacement of new lineages in Italy despite imposed lockdown restriction [suggests] that the disease management policies employed were insufficient to halt the spread of emerging variants.”
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.