Blood Transcriptomes of Covid-19 Infected Kidney Recipients Demonstrate Frequent and Persistent SARS-CoV-2 Virome Gene Expression

ABSTRACT

Purpose: Kidney transplant recipients (KTRs) have poor outcomes vs non-KTRs with acute COVID-19. To provide insight into management of immunosuppression during acute COVID-19, we studied peripheral blood transcriptomes during and after COVID-19 from a multicenter KTR cohort. Method(s) Clinical data were collected by chart review. Paxgene blood RNA was polyA-selected and sequenced at enrollment. Result(s) A total of 64 KTRs with COVID-19 were enrolled (31 Early cases (<4weeks from a positive SARS-CoV-2 PCR test) and 33 late cases). Out of the 64 patients, eight died and three encountered graft losses during follow-up. Due to presence of mRNA reads in the blood transcriptome unmapped to the human genome, we aligned the mRNA short reads to the SARS-CoV-2 genome. Surprisingly, our strategy detected the SARS-Cov2 mRNA, especially Spike mRNA in 27 (87%) early cases, and 18 (54%) of late cases (Fig 1A and B). We then analyzed the raw reads from a public dataset of non-KTRs with Paxgene RNA (GSE172114). The SARS-CoV-2 Spike mRNA was detected in 2/47 (4.2%) critically ill COVID-19 cases and 0/25 noncritically ill cases in this non-KTR dataset (compared to KTRs, Chi-square P<0.001;Fig 1B). Among our KTRs, the amount of Spike mRNA was associated positively with the COVID-19 severity score (scale of 1 to 7 of increasing severity;Fig 1C) and inversely with time from initial positive PCR (Fig 1D). More interestingly, 7/64 patients had detectable Spike RNA-emia beyond 60 days after COVID-19 diagnosis. Of the 3 graft losses in our cohort, 2 occurred among these 7 patients. Conclusion(s) Blood transcriptome of KTRs with COVID-19 demonstrated a risk for persistent viremia with implications for pathogenesis of COVID-19 disease. This finding also supports using passive immune strategies in COVID-KTRs. (Figure Presented).