Evidence for SARS-CoV-2 Spike Protein in the Urine of COVID-19 Patients

Abstract

Background: SARS-CoV-2 infection has so far affected over 133 million people worldwide, causing over 2.5 million deaths. With the large majority of SARS-CoV-2 infected individuals being asymptomatic, major concerns have been raised about possible long-term consequences of the infection. Methods: We developed an antigen capture assay to detect SARS-CoV-2 spike protein in urine samples from COVID-19 patients whose diagnosis was confirmed by PCR from nasopharyngeal swabs (NP-PCR+). The study used a collection of 233 urine samples from 132 participants from Yale New Haven Hospital and the Children's Hospital of Philadelphia obtained during the pandemic (106 NP-PCR+ and 26 NP-PCR-) as well as a collection of 20 urine samples from 20 individuals collected before the pandemic. Results: Our analysis identified 23 out of 91 (25%) NP-PCR+ adult participants with SARS-CoV-2 spike S1 protein in urine (Ur-S+). Interestingly, although all NP-PCR+ children were Ur- S-, 1 NP-PCR- child was found to be positive for spike protein in urine. Of the 23 Ur-S+ adults, only 1 individual showed detectable viral RNA in urine. Our analysis further showed that 24% and 21% of NP-PCR+ adults have high levels of albumin and cystatin C in urine, respectively. Among individuals with albuminuria (>0.3 mg/mg of creatinine) statistical correlation could be found between albumin and spike protein in urine. Conclusions: Together, our data showed that 1 of 4 of SARS-CoV-2 infected individuals develop renal abnormalities such as albuminuria. Awareness about the long-term impact of these findings is warranted.

The SARS-CoV-2 Spike protein disrupts human cardiac pericytes function through CD147 receptor-mediated signalling: a potential non-infective mechanism of COVID-19 microvascular disease

“…Establishing the kinetics of S protein in vivo may provide valuable diagnostic and therapeutic insights. The presence of S protein in patients’ blood was previously reported by another group [ 52 ]. In our study, low amounts of the S protein could be detected in pre-pandemic control sera.…”

The spike protein of SARS-CoV-2 induces heme oxygenase-1: Pathophysiologic implications

“…The importance of ACE2 expression in syncytia formation is underscored by the fact that syncytia formation also occurred in Vero E6 cells (which express ACE2), when Vero E6 cells are transfected with spike plasmid; in contrast, HEK293 cells, which do not express ACE2 protein, do not form syncytia when transfected with spike plasmid. The clinical relevance of the current approach in investigating spike protein-dependent kidney disease in COVID-19 is thus validated because of the following salient findings in the recent literature: first, cell spike protein expression per se causes cell adherence to neighboring ACE2-expressing cells [24] ; second, SARS-CoV-2 is present in the urine of patients with COVID-19, and the viral titer correlates with AKI and mortality [17] ; third, the spike protein is present in urine in patients with COVID-19 and AKI [18] .…”

“…Remarkably, the SARS-CoV-2 virus is detected in the urine in patients with COVID-19; the virus co-localizes with the ACE2 receptor in tubular epithelial cells as demonstrable on renal biopsy; and higher viral titers in the urine correlate with AKI and increased mortality [17] . Moreover, in over 25% of humans with COVID-19 and AKI, the spike protein is present in urine [17] , [18] . How the spike protein reaches the urinary space is uncertain, but on a priori grounds, this may reflect filtration of the SARS-CoV-2 virus/its spike protein from plasma across the glomerular filtration barrier; the sloughing of spike protein into the urinary space from the plasma membrane of kidney cells infected with SARS-CoV-2; or the sloughing of kidney cells infected with the virus into the urinary space and the subsequent detachment of the spike protein from cell membranes.…”

“…How the spike protein reaches the urinary space is uncertain, but on a priori grounds, this may reflect filtration of the SARS-CoV-2 virus/its spike protein from plasma across the glomerular filtration barrier; the sloughing of spike protein into the urinary space from the plasma membrane of kidney cells infected with SARS-CoV-2; or the sloughing of kidney cells infected with the virus into the urinary space and the subsequent detachment of the spike protein from cell membranes. Whatever the basis for such urinary appearance of the spike protein, these seminal clinical observation attest to the fact that the spike protein is in contact with kidney cells that line the urinary space in patients with COVID-19 and AKI [17] , [18] .…”

Detection of SARS-CoV-2 RNA in Urine by RT-LAMP: A Very Rare Finding

“…A recent study has shown that the spike protein of SARS-CoV-2, particularly subunit S1, can be detected in the urine of patients with a nasopharyngeal RT-qPCR-positive result using an antigen-capture assay. However, sensitivity of this methodology is highly reduced compared to nasopharyngeal RT-qPCR (only 25% of SARS-CoV-2 infected individuals are detected) [ 20 ].…”