Systematic Genomic and Clinical Analysis of Severe Acute Respiratory Syndrome Coronavirus 2 Reinfections and Recurrences Involving the Same Strain

Abstract

Estimates of the burden of severe acute respiratory syndrome coronavirus 2 reinfections are limited by the scarcity of population-level studies incorporating genomic support. We conducted a systematic study of reinfections in Madrid, Spain, supported by genomic viral analysis and host genetic analysis, to cleanse laboratory errors and to discriminate between reinfections and recurrences involving the same strain. Among the 41,195 cases diagnosed (March 2020–March 2021), 93 (0.23%) had 2 positive reverse transcription PCR tests (55–346 days apart). After eliminating cases with specimens not stored, of suboptimal sequence quality, or belonging to different persons, we obtained valid data from 22 cases. Of those, 4 (0.01%) cases were recurrences involving the same strain; case-patients were 39–93 years of age, and 3 were immunosuppressed. Eighteen (0.04%) cases were reinfections; patients were 19–84 years of age, and most had no relevant clinical history. The second episode was more severe in 8 cases.

Risk of reinfection and disease afterSARS‐CoV‐2 primary infection: Meta‐analysis

“…Of the 3282 papers initially retrieved, we included 91 cohort studies evaluating the onset of reinfection, severe and very severe/lethal COVID‐19 among 15,034,624 previously infected subjects (Figure 1), either among health care workers (27 publications; n = 37,598 2,8,9,15,17,24,36,38,42–59 ) or in the general population (67 publications; n = 14,997,026 3–7,10,12,16–23,25–27,43,49,60–106 ).…”

“…As shown in Table S1, most of the included studies ( n = 43) were carried out in Europe, 2,4–10,12,15,17,18,21,24,26,36,38,44,46–51,58,66,69,71,72,75,81,85–88,91–93,95,99,102 24 in the USA, 20,22,23,25,42,43,57,59,63,67,77,79,82–84,89,90,97,98,103,105–107 18 in Asia 3,16,19,27,45,52–54,56,60,62,64,65,70,73,74,100,101 and the remaining six in South America or South Africa 61,68,80,94,96,104 . The mean age of the participants ranged from 15 to 87 years, and the average follow‐up ranged from 29 to 371 days.…”

“…In the 59 available datasets, 2,3,5,6,10,16–22,25–27,36,44,46–59,63–67,69,71–74,79,82,84–87,90,93–95,99–104 a total of 1380 severe COVID‐19 diseases were diagnosed among 5,006,604 subjects with a previous infection, corresponding to a pooled rate of 0.02% (95% CI: 0.00%–0.04%—Table 1). This rate did not substantially vary when only the studies with longer time lag were considered, while it increased—still, however, remaining below 0.1%—when only the studies that used CDC criteria to define reinfections were included (summary rate 0.07%; 0.04%–0.10%).…”

“…The mean age of the participants ranged from 15 to 87 years, and the average follow‐up ranged from 29 to 371 days. Overall, 38 publications strictly followed the CDC criteria to identify the reinfections and were classified at low risk of misclassification bias 10,16,19,20,22–24,26,36,44,45,48–50,54,56,58,59,68,71,72,75,84,86,89–91,94,99,100,102 . All but five studies ( n = 3,854,961) 66,71,88,91,96 were completed before the emergence of BA.1/B.1.1.529 (Omicron) variant.…”

“…Overall, a total of 158,478 reinfections were recorded among the 15,034,624 subjects with a previous infection, 2–10,12,13,15–27,36,38,42–107 corresponding to a pooled rate of 0.97% (95% CI: 0.71%–1.27%—Table 1; Figure 2). The summary rate of reinfection rose to 1.07% (95% CI: 0.73%–1.46%) when only the 69 datasets with a more conservative time lag of ≥90 days between the two episodes were considered 3–6,8–10,12,18–23,25,26,36,42–44,46–50,52–56,59,61–65,67–69,72–84,86,87,89,91–96,98,101,103,105–107 and it slightly varied by reinfection definition criteria (0.93% vs 1.01% when considering studies with high vs low risk of misclassification).…”