key: cord-0763258-a3qhcn4k authors: Martin, M. C.; Jimenez, A.; Page, I.; Parrado, A.; Ortega, N.; Gonzalez, M. I.; Blanco-Peris, L. title: Long term positivity of SARS-CoV-2 total immunoglobulins in convalescent plasma and blood donors date: 2021-06-25 journal: nan DOI: 10.1101/2021.06.24.21259079 sha: 7a2c61cc45cccb61e66e964c45ffccedfffde425 doc_id: 763258 cord_uid: a3qhcn4k Background: One of the most questioned issues about SARS-CoV2 immunity is how long does it last. Whether lasting differences exist between infection and vaccination boosted immunity is yet to be known. The answer to this question will determine key issues such as the reliability of individual and herd immunity or the need of sanitary restrictions or periodical revaccination. The aim of this study was to determine how long total anti SARS-CoV2 antibodies due to past infection persist in peripheral blood and whether sex, age or haematological features can influence their lasting. Material and Methods: A total of 2432 donations SARS-CoV-2 from 662 repeat donors from April 2020 to February 2021 were analysed. Donors were 69.7% males and their average age was 46. An automated chemilumiscence immunoassay for total antibodies recognizing N protein of SARS-CoV-2 in human serum and plasma was performed. Results and discussion: In 97.6% donors with follow-up, anti SARS-CoV-2 protein N total antibodies remained positive up to 46 weeks after first positive determination. Blood group was not related to antibody waning. Lower lymphocyte counts and higher neutrophils and as well higher seric IgA would help predict future negativization of antibodies. The vast majority of donors keep their total immunoglobulins anti SARS-CoV-2 positive for longer than 10 months. Ageing might have a protective effect against antibody waning but, given the small number of cases that become negative, more studies, or larger cohorts would be needed to confirm these facts. Antibody assays are not equivalent: they either detect antibodies against different 12 viral proteins (S1, S1/S2, RBD or NC) or different immunoglobulin classes: IgG, 13 IgM, IgA or their combinations. Many factors can influence test performance, 14 including cross-reactivity with other coronaviruses, that can occur in up to 28% CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 25, 2021. ; https://doi.org/10.1101/2021.06.24.21259079 doi: medRxiv preprint development or antibody waning. Blood donors constitute a representative 31 subset of population aged 18-65 and are reasonably free of biases that could 32 over represent symptomatic or exposed individuals. 33 Heterogeneity of susceptibility and transmission is hard to evaluate but does exist 34 [8]. A portion of the population may have pre-existing immunity via cross-35 reactivity or particular host factors such as mucosal immunity or trained innate 36 immunity protection (as it has been reported to be conferred by Diphtheria- Our starting hypothesis was that the vast majority of either recovered or 51 asymptomatic SARS-CoV-2 cases would develop and keep antibodies against 52 the novel coronavirus [1, 2, 9]. They will subsequently contribute to herd 53 immunity. Anyone holding antibodies due to prior infection, should be kept from 54 receiving the second dose of vaccines requiring booster, so far their cellular 55 response could even result impaired [12] . 56 The main aim of this study was to determine which percentage of the 57 seropositive population due to natural infection keeps total antibodies recognizing 58 SARS-CoV2 and how long can they last. A secondary goal was to establish 59 whether sex, age, blood group or haematological features might influence the 60 fact of keeping or loosing circulating antibodies. This knowledge would help 61 optimize immunization strategies, and would ease decisions about the need of 62 . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 25, 2021. ; https://doi.org/10.1101/2021.06.24.21259079 doi: medRxiv preprint periodical revaccination either overall or for determined population groups by 63 reliably knowing the lasting of specific humoral immunity. The aim of this study was to determine how long anti SARS-CoV2 antibodies CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 25, 2021. positive for IgG (Chemiluminiscence, N protein, Abbott Alinity S, Chicago USA) and IgA (ELISA, S protein, Euroimmunn, Lübeck, Germany) antiSARS-CoV-2. 96 Another set of ten prepandemic samples, therefore supposed to be negative, 97 were equally analysed. 405 donations were analysed both in serum and plasma 98 to verify interchangeability. A 100% concordance was yielded by all these 99 validation assays. The cut-off was that recommended by manufacturer (OD>1 to Donors whose second OD were under 90% of the first of that of their first positive 109 were recoded into decay group. Donors over 110% were recoded as rise and 110 those who were +/-10% of the first one were in the stay group. A total of 2432 donations (either whole blood, plasmapheresis or platelet 125 apheresis) were tested for total anti SARS-CoV2 antibodies recognizing N 126 . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 25, 2021. CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 25, 2021. . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 25, 2021. ; (Table 3) . When an age-stratified analysis was performed, some facts become noticeable . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 25, 2021. infection phase while those against the S protein would persist over time [13] . . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 25, 2021. . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 25, 2021. ; https://doi.org/10.1101/2021.06.24.21259079 doi: medRxiv preprint Brief clinical 334 evaluation of six high-throughput SARS-CoV-2 IgG antibody assays kinetics of anti-SARS-CoV-2 antibodies over time Results of 10 month follow up in over 300 seropositive Health Care Workers. Eur 339 Persistence of serum and saliva antibody 343 responses to SARS-CoV-2 spike antigens in COVID-19 patients COVID-19: age, Interleukin-6, C-346 reactive protein, and lymphocytes as key clues from a multicentre retrospective 347 study The 349 age again in the eye of the COVID-19 storm: evidence-based decision making Neutrophil/lymphocyte 353 ratio-A marker of COVID-19 pneumonia severity Infectious agents including COVID-19 and the involvement of 357 blood coagulation and fibrinolysis. A narrative review Distinct phenotypes of platelet, monocyte, and neutrophil 362 activation occur during the acute and convalescent phase of COVID-19 Changes in SARS-CoV-2 Spike LB and MCM conceived and designed the study. NO and AP acquired data, IP, AJ and MIG performed analysis and interpretation of laboratory data, MCM and LB drafted the article and revised it critically for important intellectual content, all authors provided final approval of the version to be submitted.The authors thank to all blood donors for making this work possible by allowing research use of their samples by the Biobanco del Centro de Hemoterapia y Hemodonación de Castilla y León. They also thank the staff in charge of blood donation, and lab technicians for their efforts and from Roche Diagnostics International Ltd. for its support.