Emergence and Spread of a B.1.1.28-Derived P.6 Lineage with Q675H and Q677H Spike Mutations in Uruguay

Abstract

Uruguay controlled the viral dissemination during the first nine months of the SARS-CoV-2 pandemic. Unfortunately, towards the end of 2020, the number of daily new cases exponentially increased. Herein, we analyzed the country-wide genetic diversity of SARS-CoV-2 between November 2020 and April 2021. We identified that the most prevalent viral variant during the first epidemic wave in Uruguay (December 2020–February 2021) was a B.1.1.28 sublineage carrying Spike mutations Q675H + Q677H, now designated as P.6, followed by lineages P.2 and P.7. P.6 probably arose around November 2020, in Montevideo, Uruguay’s capital department, and rapidly spread to other departments, with evidence of further local transmission clusters; it also spread sporadically to the USA and Spain. The more efficient dissemination of lineage P.6 with respect to P.2 and P.7 and the presence of mutations (Q675H and Q677H) in the proximity of the key cleavage site at the S1/S2 boundary suggest that P.6 may be more transmissible than other lineages co-circulating in Uruguay. Although P.6 was replaced by the variant of concern (VOC) P.1 as the predominant lineage in Uruguay since April 2021, the monitoring of the concurrent emergence of Q675H + Q677H in VOCs should be of worldwide interest.

Epidemiological characterization of SARS-CoV-2 variants in children over the four COVID-19 waves and correlation with clinical presentation

“…No significant association was found between lineages and COVID-19 presentation, even if a lower number of moderate/severe cases were found during alpha-clade epidemic (Table 1). In line with this, patients involved in clusters of B.1.1.7 frequently reported only mild symptoms (moderate/sever infection was detected only in one in-cluster case), and no new amino acid mutation was detected in spike or nucleocapsid proteins, both implicated in SARS-CoV-2 virulence and pathogenicity 31,32,35,36 . B.1.1.7 variant was also found negatively associated with hospitalization in our multivariate model (Table 3).…”

“…While clusters of alpha clade involved 17.3% of total B.1.1.7 sequences and did not report evidences of genetic alterations able to increase transmission or pathogenicity, transmission chains of delta clade involved the 28.1% of delta sequences. Thirteen of them reported the Q677H mutation known to enhance viral infectivity and neutralizing antibodies resistance 35,36 . The rapid mechanism of delta clade adaptation, and its onward transmission in local paediatric population might explain its outcompeting and dominance respect pre-and co-existing lineages as P.1 and B.1.1.7, as previously observed in adult population 43 Differently by alpha and delta clade, a limited spread of gamma clade was observed.…”

“…The remaining individuals belonged to adolescent (n = 2, aged 15 and 18 years) and adult population (n = 11, age range: 20-85 years). Sequences were characterized by the RdRp:synC16111T, the NSP13:G17671A (V479I) and the S:G23593C(G677H), reported as recurrent arising independently in many SARS-CoV-2 lineages circulating worldwide by the end of 2020, and known to enhance viral infectivity and neutralizing antibodies resistance 35,36 .…”

High-depth sequencing characterization of viral dynamics across tissues in fatal COVID-19 reveals compartmentalized infection

“…We investigated whether these variants have been observed in other studies; GISAID data revealed that one mutation, Spike (S) Q675H, has previously been observed, present at as much as 3% frequency worldwide (January 2021). This mutation was not circulating at the time that this subject contracted SARS-CoV-2, but has since emerged in multiple SARS-CoV-2 lineages, indicating convergent evolution 32,33 . This mutation falls directly upstream of the furin-cleavage site and is predicted to enhance viral entry 32,33 .…”

“…This mutation was not circulating at the time that this subject contracted SARS-CoV-2, but has since emerged in multiple SARS-CoV-2 lineages, indicating convergent evolution 32,33 . This mutation falls directly upstream of the furin-cleavage site and is predicted to enhance viral entry 32,33 . This suggests that this was a functionally advantageous mutation for either infecting the heart specifically, or it may have been broadly advantageous, but did not spread to other tissues because the infection was compartmentalized.…”