Detection of High Level of Co-Infection and the Emergence of Novel SARS CoV-2 Delta-Omicron and Omicron-Omicron Recombinants in the Epidemiological Surveillance of Andalusia

Abstract

Recombination is an evolutionary strategy to quickly acquire new viral properties inherited from the parental lineages. The systematic survey of the SARS-CoV-2 genome sequences of the Andalusian genomic surveillance strategy has allowed the detection of an unexpectedly high number of co-infections, which constitute the ideal scenario for the emergence of new recombinants. Whole genome sequence of SARS-CoV-2 has been carried out as part of the genomic surveillance programme. Sample sources included the main hospitals in the Andalusia region. In addition to the increase of co-infections and known recombinants, three novel SARS-CoV-2 delta-omicron and omicron-omicron recombinant variants with two break points have been detected. Our observations document an epidemiological scenario in which co-infection and recombination are detected more frequently. Finally, we describe a family case in which co-infection is followed by the detection of a recombinant made from the two co-infecting variants. This increased number of recombinants raises the risk of emergence of recombinant variants with increased transmissibility and pathogenicity.

Keywords: SARS-CoV-2; co-infection; epidemiology; recombination; surveillance.

Figure 1

(A) Prevalence of main lineages in Andalusia in the period January to May 2022. (B) Epidemiologic map with the distribution of SARS-CoV-2 lineages in Andalusia in the same period.

Figure 2

Mutation frequency plots of: (upper panel) delta-omicron (sample AND17799), co-infection, and (lower panel) omicron-omicron (sample AND20157) BA.1-BA.2 co-infection.

Figure 3

Percentage of co-infection events and recombinants observed in the samples sequenced along the period January-May 2022 (scale in the left Y axis). Bars indicate the total number of samples sequences per month (scale in the right Y axis).

Figure 4

Novel Delta-omicron recombinant. Samples AND21237 and AND23187 (Illumina, San Diego, CA, USA, sequencing) and AND23055 (Oxford nanopore sequencing) correspond to the same patient (see Tables S1 and S3). 3seq outputs AY.98 and BA.1.17 lineages and their corresponding breakpoints. sc2rf outputs for Delta-BA.1 lineage with similar breakpoints to 3seq ones. A breakpoint interval (grey bar) spans between the lowest and the greatest position value of breakpoints provided by the two recombinant detection tools. Plots of distribution of mutations is also shown for AND21237 sample.

Figure 5

Novel omicron-omicron recombinants corresponding to two different, unrelated samples: AND21266 and AND22043 (see Tables S1 and S3). 3seq outputs for BA.2 and BA1.1 lineages and their corresponding breakpoints, sc2rf outputs BA.2 and BA.1 lineages with similar breakpoints to 3seq ones. A breakpoint interval (grey bar) spans between the lowest and the greatest position value of breakpoints provided by the two recombinant detection tools. Plots of distribution of mutations is also shown for AND21266 sample.

Figure 6

Representation in time scale of the distinct infections and co-infections by AY.98 and B.1.17 in the family in which the emergence of a recombinant was detected. The son, from which the first sequence of AY.98 was isolated is represented by an oval. The wife is represented by a rectangle with rounded corners and the rest of rectangles correspond to the patient. AY.98 is represented in red and B.1.17 in yellow. The last step between samples corresponds to the recombinant virus (arrow red and yellow). On the right part of the figure the plots of distribution of mutations corresponding to any of the samples sequenced can be found (Figure S5 has a version of the plots in a larger format).

Figure 7

Histogram of the occurrence of breakpoints along the SARS-CoV-2 genome. The Y axis represents the number of samples in which the breakpoint was observed. The lower part represents the different SARS-CoV-2 proteins.