key: cord-0960136-2mea0kn1 authors: La Milia, Vincenzo; Tonolo, Silvia; Luzzaro, Francesco; Bonato, Claudio; Cavalli, Andrea; Foglieni, Barbara; Debiase, Consuelo; Limardo, Monica; Longhi, Selena; Ravasi, Chiara; Viganò, Sara title: The humoral immune response to SARS-CoV-2 mounts and is durable in symptomatic hemodialysis patients date: 2021-02-19 journal: Nephrol Dial Transplant DOI: 10.1093/ndt/gfab047 sha: 77c8490506ff76b925d3d19c6dfa23dc5c2110e5 doc_id: 960136 cord_uid: 2mea0kn1 nan After March 2020, in our HD center, NPS swabbing and blood sampling for serology were part of the normal clinical assessment of all HD patients. All patients and health care staff members signed informed consent. The data were expressed as mean values ± s.d. or as median values and interquartile ranges. The HSD test of Tukey-Kramer, repeated measures analysis of variance and paired t-test and Wilcoxon's signed-rank test were used. Between March 9 th to April 6 th 2020, 210 HD patients were studied. Fifty-six (27%) of them were positive to SARS-CoV-2 NPS while 154 (73%) did not (3). Among those with positive NPS, 29 patients (52%) were CoV-sympt and 27 (48%) remained CoVasympt. Twenty-six CoV-sympt patients were treated as inpatients because of severe symptoms (fever and interstitial pneumonia), while 3 with mild symptoms were treated as outpatients. Within the inpatients CoV-sympt group, 13 (50%) died and 13 (50%) recovered (one of them refused to continue HD and was lost to follow-up) while all 3 CoV-sympt outpatients recovered. Eleven members (26%) of the HD health care staff had positive NPS and symptomatic for SARS-CoV-2 infection in the same period; they were all treated as outpatients ( Figure S1 in Supplementary Material). All 15 CoV-sympt survivors patients developed anti-SARS-CoV-2 spikes IgG (one patient was transplanted at 5 th month). Mean CoV-sympt survivors patients anti-SARS-CoV-2 spikes IgG titers were 98 ± 46 AU/mL, 150 ± 111 AU/mL, 107 ± 65 AU/mL, 110 ± 67 AU/ml, 80 ± 48 AU/mL, respectively at 2, 3, 4, 5 and 6 months ( Figure 1 ). The anti-SARS-CoV-2 spikes IgG titers had a peak at the 3 rd month of follow-up and then a slow reduction until 6 th month, reaching almost the threshold of statistical significance (p=0.05), but always well above the cut-off threshold of positivity (>15 AU/mL). One CoV-sympt survivors patient lost anti-SARS-CoV-2 spikes IgG at 3 rd month of follow-up. Only two CoV-asympt patients (7%) were seropositive 2 months from the first NPS: at 3 months follow-up one of them became seronegative and the other died with persistent seropositivity (21.4 AU/mL). All other CoV-asympt patients had anti-SARS-CoV-2 spikes IgG titer below the limit of positivity in all assays performed (at 2 nd month after NPS positivity for SARS-CoV-2 and then every month until the 6 th month). Only two negative NPS patients (1%) developed anti-SARS-CoV-2 spikes IgG which remained positive until the 6 th month. Mean anti-SARS-CoV-2 spikes IgG of the 11 HD health care staff members who suffered from SARS-CoV-2 infection was 68±51 AU/mL at six months. Only two (18%) nurses resulted seronegative. Anti-SARS-Cov2 spikes IgG titer of Cov-sympt survivors patients were not lower than Cov-sympt health care staff members (80 ± 48 AU/mL vs 68±51 AU/mL, respectively, p=0.5). To date it is not known whether HD patients infected with SARS-CoV-2 develop a long lasting HIR and if the Abs response is different between Cov-sympt, CoV-asympt patients and general population (7, 10) . Data from studies published until now showed that HD patients are able to mount an Abs response against SARS-CoV-2 (9) and is more frequent in symptomatic patients. Our data confirmed these results, in fact 100% of our Cov-sympt survivors patients developed an Abs response and a subsequent titer decline with persistent seropositivity at 6 months. Of course, a protective role of anti-SARS-CoV-2 spikes IgG, must be still demonstrated especially against reinfection. Studies regarding general population showed that asymptomatic SARS-CoV-2 infected patients tend to lose their HIR against the virus over time (10) (11) . In our case, CoV-asympt patients tended to not produce a HIR. However, in individuals with asymptomatic or mild COVID-19, the SARS-CoV-2 seems to induce a stronger memory T cell than HIR, therefore seroprevalence might be a bad indicator of protection against the virus (12). Our study is monocentric and involves a small HD population. However, the main advantage of our study is that the whole HD population of patient was tested by NPS and serology. In addition, we were able to assess, not only the HIR of HD patients but also the persistence over time of this Abs response. To the best of our knowledge, this is the first study to assess Abs response persistence in a (relative) long period of time (6 months). The results of a recent study are comparable to our results, but in a smaller HD patient population and with a short follow-up of about 3 months (13). The epidemiological trend of the SARS-CoV-2 pandemic will provide us with important information on the ability of anti-SARS-CoV-2 spikes IgG to protect against a virus re-infection. This information would be of high value, seen that it would allow HD patient to access to a vaccination campaign as, as we demonstrated, they seem responsive to viral immune stimulation. In conclusion, in survivor HD patients, symptomatic Covid-19 disease confers higher and durable anti-SARS-CoV-2 spikes IgG titers then asymptomatic one in chronic HD patients and these Abs titers were not lower than Cov-sympt health care staff members. In CoV-asympt and CoV-sympt survivors, anti-SARS-CoV-2 spikes IgG titer was dosed at 2 months and then monthly from symptoms onset/NPS positivity. In NPS swab negative patients, anti-SARS-CoV-2 spikes IgG titer was dosed about 2 months and 6 months from the first NPS for SARS-CoV-2. In CoV-sympt health care staff members, anti-SARS-CoV-2 spikes IgG titer was dosed only once, approximately 6 months after the onset of symptoms. In the Figure are showed the outlier box plot; the horizontal line within the box represents the median sample value; the ends of the box represent the 75 th and 25 th quantiles, respectively; the distance or the difference between the 75 th and 25 th , also expressed as 3 rd and 1 st quartile, is the interquartile range; each box has lines, called whiskers, that extend from each end; the whiskers extend from ends of the box to outermost data point that falls within the distances computed as follows: 3 rd quartile + 1. High Prevalence of Asymptomatic COVID-19 Infection in Hemodialysis Patients Detected Using Serologic Screening Epidemiology of COVID-19 in an Urban Dialysis Center COVID-19 Outbreak in a Large Hemodialysis Center Results from the ERA-EDTA Registry indicate a high mortality due to COVID-19 in dialysis patients and kidney transplant recipients across Europe Targeting Immunity in End-Stage Renal Disease Serology assays to manage COVID-19 Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections Detection of antibodies against SARS-CoV-2 in patients with COVID-19 IgG Antibody Response to SARS-CoV-2 Infection and Viral RNA Persistence in Patients on Maintenance Hemodialysis Humoral Immune Response to SARS-CoV-2 in Iceland Rapid Decay of Anti-SARS-CoV-2 Antibodies in Persons with Mild Covid-19 Robust T Cell Immunity in Convalescent Individuals with Asymptomatic or Mild COVID-19 A Longitudinal, 3-Month Serologic Assessment of SARS-CoV-2 Infections in a Belgian Hemodialysis Facility All Authors have no conflicts of interest and have not received any funding for this study. Supplementary data are available at ndt online.