Clinical Course of SARS-CoV-2 Infection in Adults with ESKD Receiving Outpatient Hemodialysis

Abstract

Background: Patients with ESKD on maintenance dialysis receive dialysis in common spaces with other patients and have a higher risk of severe SARS-CoV-2 infections. They may have persistently or intermittently positive SARS-CoV-2 RT-PCR tests after infection. We describe the clinical course of SARS-CoV-2 infection and the serologic response in a convenience sample of patients with ESKD to understand the duration of infectivity.

Methods: From August to November 2020, we enrolled patients on maintenance dialysis with SARS-CoV-2 infections from outpatient dialysis facilities in Atlanta, Georgia. We followed participants for approximately 42 days. We assessed COVID-19 symptoms and collected specimens. Oropharyngeal (OP), anterior nasal (AN), and saliva (SA) specimens were tested for the presence of SARS-CoV-2 RNA, using RT-PCR, and sent for viral culture. Serology, including neutralizing antibodies, was measured in blood specimens.

Results: Fifteen participants, with a median age of 58 (range, 37‒77) years, were enrolled. Median duration of RT-PCR positivity from diagnosis was 18 days (interquartile range [IQR], 8‒24 days). Ten participants had at least one, for a total of 41, positive RT-PCR specimens ≥10 days after symptoms onset. Of these 41 specimens, 21 underwent viral culture; one (5%) was positive 14 days after symptom onset. Thirteen participants developed SARS-CoV-2-specific antibodies, 11 of which included neutralizing antibodies. RT-PCRs remained positive after seroconversion in eight participants and after detection of neutralizing antibodies in four participants; however, all of these samples were culture negative.

Conclusions: Patients with ESKD on maintenance dialysis remained persistently and intermittently SARS-CoV-2-RT-PCR positive. However, of the 15 participants, only one had infectious virus, on day 14 after symptom onset. Most participants mounted an antibody response, including neutralizing antibodies. Participants continued having RT-PCR-positive results in the presence of SARS-CoV-2-specific antibodies, but without replication-competent virus detected.

Keywords: COVID-19; ESRD; SARS-CoV-2; chronic kidney failure; dialysis; end-stage renal disease; infectiousness; infectivity; outpatients.

Graphical abstract

Figure 1.

Longitudinal results from end-stage renal disease (ESRD) participants on maintenance dialysis. (A) Longitudinal results including RT-PCR, viral culture, symptom onset, SARS-CoV-2–specific antibodies, and positive neutralizing antibodies from participants with ESKD on maintenance dialysis with SARS-CoV-2 infection (N=15). (B) Longitudinal results including RT-PCR, viral cultures, symptom onset, and positive and negative symptoms from participants with ESKD on maintenance dialysis with SARS-CoV-2 infection (N=15). Thirteen participants completed the assessment. Participants D and K withdrew before the end of the assessment. Day of diagnosis is displayed as day 0 on the x axis and represents the day of diagnosis recorded in the facility’s medical record (either RT-PCR or antigen test). For each visit, a composite RT-PCR result was determined on the basis of available RT-PCR results from all specimens collected at each visit (oropharyngeal, anterior nasal, and saliva). We defined RT-PCR positivity as having any of the three specimens RT-PCR positive, inconclusive if there was no positive RT-PCR but at least one inconclusive test, and negative if all specimens were negative by RT-PCR. Antibody to the SARS-CoV-2 spike protein was positive if ≥100. Positive neutralization was defined as ≥70% of inhibition using a Genscript cPass Surrogate Neutralization Kit. Group 1: diagnosis of SARS-CoV-2 infection was ≤5 days before enrollment. Group 2: diagnosis of SARS-CoV-2 infection was 6–15 days before enrollment. Group 3: diagnosis of SARS-CoV-2 infection was >15 days before enrollment and evidence of recent RT-PCR positivity (i.e., positive RT-PCR ≤5 days of enrollment). Symptomatic was defined as reporting any symptoms from the coronavirus disease 2019 symptoms list (included in Table 1) during a particular visit. Participant A had rheumatoid arthritis and was taking 5 mg/d prednisone. Participants D and H had a history of kidney allograft failure and were taking immunosuppressive medications. Participant L received convalescent plasma and Ig in the first 2 days after diagnosis. The remaining patients had no immunosuppressive conditions. ID, identifier; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Figure 1.

Longitudinal results from end-stage renal disease (ESRD) participants on maintenance dialysis. (A) Longitudinal results including RT-PCR, viral culture, symptom onset, SARS-CoV-2–specific antibodies, and positive neutralizing antibodies from participants with ESKD on maintenance dialysis with SARS-CoV-2 infection (N=15). (B) Longitudinal results including RT-PCR, viral cultures, symptom onset, and positive and negative symptoms from participants with ESKD on maintenance dialysis with SARS-CoV-2 infection (N=15). Thirteen participants completed the assessment. Participants D and K withdrew before the end of the assessment. Day of diagnosis is displayed as day 0 on the x axis and represents the day of diagnosis recorded in the facility’s medical record (either RT-PCR or antigen test). For each visit, a composite RT-PCR result was determined on the basis of available RT-PCR results from all specimens collected at each visit (oropharyngeal, anterior nasal, and saliva). We defined RT-PCR positivity as having any of the three specimens RT-PCR positive, inconclusive if there was no positive RT-PCR but at least one inconclusive test, and negative if all specimens were negative by RT-PCR. Antibody to the SARS-CoV-2 spike protein was positive if ≥100. Positive neutralization was defined as ≥70% of inhibition using a Genscript cPass Surrogate Neutralization Kit. Group 1: diagnosis of SARS-CoV-2 infection was ≤5 days before enrollment. Group 2: diagnosis of SARS-CoV-2 infection was 6–15 days before enrollment. Group 3: diagnosis of SARS-CoV-2 infection was >15 days before enrollment and evidence of recent RT-PCR positivity (i.e., positive RT-PCR ≤5 days of enrollment). Symptomatic was defined as reporting any symptoms from the coronavirus disease 2019 symptoms list (included in Table 1) during a particular visit. Participant A had rheumatoid arthritis and was taking 5 mg/d prednisone. Participants D and H had a history of kidney allograft failure and were taking immunosuppressive medications. Participant L received convalescent plasma and Ig in the first 2 days after diagnosis. The remaining patients had no immunosuppressive conditions. ID, identifier; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Figure 2.

SARS-CoV-2–specific IgA, IgG, and IgM titers over time from participants with ESKD on maintenance dialysis with SARS-CoV-2 infection (N=12). Day of diagnosis is displayed as day 0 in the x axis and represents the day of diagnosis recorded in the facility’s medical record (either RT-PCR or antigen test). The diamond in the middle of the box is the mean, the line in the box is the median, the box is the interquartile range, the lines above and below the box indicate the range, and trend lines connect the medians. Participant L, who received convalescent plasma and Ig in the first 2 days after diagnosis, was excluded. Participants D and E were excluded because they did not have documented seroconversion. 1E6, 1,000,000.

Figure 3.

Pan-Ig, IgA, IgG, and IgM antibody response to the SARS-CoV-2 spike protein per case-patient since diagnosis (N=13). Antibody to the SARS-CoV-2 spike protein was positive if ≥100 (1E2). All antibody results are displayed in this figure, including those that are not considered positive (i.e., <100). Day of diagnosis is displayed as day 0 in the x axis and represents the day of diagnosis recorded in the facility’s medical record (either RT-PCR or antigen test). Participant A had rheumatoid arthritis and was taking 5 mg/d prednisone. Participant H had a history of kidney allograft failure and was taking immunosuppressive medications. Participant L received convalescent plasma and Ig in the first 2 days after diagnosis. Participants K withdrew before the end of the assessment. Participants D and E were excluded because they did not have documented seroconversion.

Figure 4.

Detection of SARS-CoV-2 neutralizing antibodies among patients with ESKD on maintenance dialysis with SARS-CoV-2 infection (N=15) since diagnosis. Surrogate neutralization antibodies were measured using the Genscript cPass Surrogate Neutralization Kit. The results are presented as percentages and represent the percent that particular serum specimen blocked the interaction between the SARs-CoV-2 receptor binding domain and the angiotensin-converting enzyme 2 cellular receptor. The higher the number, the more surrogate neutralization activity; ≥70% (dashed line) was considered positive. Participant A had rheumatoid arthritis and was taking 5 mg/d prednisone. Participants D and H had a history of kidney allograft failure and were taking immunosuppressive medications. Participant L received convalescent plasma and Ig in the first 2 days after diagnosis. Participants D and K withdrew before the end of the assessment. Participants D and E did not have documented seroconversion. ID, identifier.