COVID-19 infection recurrence in ESRD

An end-stage renal disease (ESRD) patient on in-center hemodialysis contracted symptomatic coronavirus disease 2019 (COVID-19) within a rehab unit in March 2020.[1] The 79-year-old, obese male with multiple comorbidities developed a new non-productive cough and was positive on COVID-19 reverse transcription polymerase chain reaction (RT-PCR) testing.[1] Treatment included hydroxychloroquine and doxycycline. The RT-PCR test 22 days from the first test remained positive. He was discharged after 24 days to an isolation hemodialysis unit.[1] A third and fourth RT-PCR tests, 32 and 33 days, from the first test were negative, and he was returned to general in-center hemodialysis [Table 1].[1] Given renal clearance of COVID-19 RNA (ribonucleic acid), we hypothesized that COVID-19 RNA persistence was likely in ESRD.[1]

Two months later, after the above documentation and publication, he was subsequently readmitted to our hospital with headache and syncope. COVID-19 RT-PCR was negative. He was discharged and improved with no specific treatment. Two weeks later, he was readmitted with nausea, vomiting, shaking tremors, and diarrhea. Contact with a possible COVID-19 subject was reported. COVID-19 RT-PCR was again positive. COVID-19 control measures were reinstituted. Two of three daily RT-PCR tests and a SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) IgG (immunoglobulin G) antibody test returned positive [Table 1]. He was managed conservatively and was discharged after 5 days to isolation hemodialysis. RT-PCR test 4 days post-discharge remained positive. RT-PCR tests, 11 and 13 days post-discharge were negative, and he was again returned to regular in-center hemodialysis. In early August 2020, he was readmitted about 4 hours after an uneventful hemodialysis treatment with fever (103°F) and shaking tremors. No new COVID-19 exposure was reported. He was hypotensive (80/50 mm Hg) and improved with 250 cc bolus of normal saline. RT-PCR test returned positive, but this positive RT-PCR test was overruled by Infectious Disease consultation as “noninfectious” – only one of his genetic targets was positive with cycle threshold (Ct cycle) of 43 (cutoff for negative is 45). He was discharged after 3 days to general in-center hemodialysis. No further RT-PCR testing was envisaged.

Our knowledge of COVID-19 is evolving. The time course of PCR positivity and seroconversion remains speculative.[234] An Italian case report demonstrated COVID-19 recurrence one month after initial recovery despite the demonstration of IgM (immunoglobulin M) and IgG antibodies against the COVID-19 virus.[5] Our patient, we posit, is most unique in many respects with multiple comorbidities, on hemodialysis for ESRD, and had repeated re-exposures to COVID-19 in two of four of these hospitalizations. Indeed, we would argue that our patient is the most COVID-19-tested patient ever reported. Did he experience a truly recurrent COVID-19 infection? The jury remains out on these questions. The impact of the possible implications of COVID-19 recurrence in patients vis-a-vis the inherent protection derived from the several new COVID-19 vaccines, then at the time, in development, is even more perplexing.

Finally, we surmise that the persistence of COVID-19 RNA in our patient may represent the syndrome of prolonged viral non-clearance that may be peculiar to especially anuric ESRD patients on maintenance hemodialysis.[1] Furthermore, there is also the confounding observation that nonviable COVID-19 viral RNA may persist in some patients and therefore continue to give false-positive RT-PCR test results.[6] Such phenomenon had been described decades ago with HIV patients on highly retroactive antiviral therapy.[7] This persistence of nonviable COVID-19 RNA particles would also explain the simultaneous presence of positive IgG antibodies to COVID-19 from the initial infection together with the falsely positive COVID-19 RT-PCR RNA tests. COVID-19 viral cultures, arguably, would distinguish between nonviable viral RNA particles versus live viable COVID-19 viruses. Another management paradigm that we did not pursue with the patient's recurring positive RT-PCR RNA tests was to complete next-generation sequencing of nasopharyngeal specimens taken from the patient at different times.[8] Genomic analysis for significant genetic discordance from different nasopharyngeal specimens could assist in the diagnosis of relapse, recurrence, or reinfection with a new different COVID-19 archetype.[8]