Dynamics of a dual SARS-CoV-2 strain co-infection on a prolonged viral shedding COVID-19 case: insights into clinical severity and disease duration

Abstract Objectives A few molecularly proven SARS-CoV-2 cases of symptomatic reinfection are currently known worldwide, with a resolved first infection followed by a second infection after a 48 to 142-day intervening period. We report a multiple-component study of a clinically severe and prolonged viral shedding COVID-19 case in a teenager Portuguese female. She had two hospitalisations, a total of 19 RT-PCR tests, mostly positive, and criteria for releasing from home isolation at the end of 97 days. Methods The viral genome was sequenced in seven serial samples and in the diagnostic sample from an infected close relative. A human genome-wide array (>900K) was screened on the seven samples, and in vitro culture was conducted on isolates from three late samples. Results The patient had co-infection by two SARS-CoV-2 strains, affiliated in distinct clades and diverging by six variants. The 20A lineage was absolute at the diagnosis (shared with a cohabitating relative), but nine days later the 20B lineage had 3% frequency, and two months later the 20B lineage had 100% frequency. The 900K profiles confirmed the identity of the patient in the serial samples, and allowed us to infer that she had polygenic risk scores for hospitalization and severe respiratory disease within the normal distributions for a Portuguese population cohort. Conclusions The early-on dynamic co-infection was the probable cause for the severity of COVID-19 in this otherwise healthy young patient, and for her prolonged SARS-CoV-2 shedding profile.