Posted on Authorea 12 Dec 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.160776187.78854537/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. Ewald Buntrock-Doepke Einhauser Laub Otto PMIS to of mild courses with moderate children identifies screening antibody Coronavirus ftemlira muesnrm n ASCV2ifcin ncide n youths. and children in infections SARS-CoV-2 and syndrome immune multiorgan the of Gerling rmIay h KadteUS, of the transmitters settings and important UK the be affected. Italy, mildly to from only thought be were to spreaders. adolescents believed major also and were children but pandemic, disease the COVID-19 the in Early antibody positive with children capacity. those Introduction effects. neutralizing and COVID-19 lower antibodies late and for for correlated assessment antibodies screened Symptoms stepwise neutralizing be a of should identified. undergo similar levels SARS-CoV-2 should were symptoms low responses to minor symptoms concomitantly and exposed neuropsychological mild and Children and some high non-neutralizing showed cardiac showed Conclusions: of 30% children children, screening, levels positive and three up antibody June high in follow of between with the and 60% (5.7%) in Approximately disease children participated Bavaria. Kawasaki eligible who of those to 2832 to regions In were of volunteered affected tests levels antibodies. children strongly 162 neutralization of part antibody and in SARS-CoV-2 levels in parents SARS-CoV-2 with and three, PMIS if children against in of or and antibodies 2020 symptoms (b), identified parallel July and We or in signs check-up for Results: performed health screened were were regular performed. tests test) a available pediatricians antibody for commercially care Two the primary appointment (in through an high study. recruited with had were the those they 1-17 in in aged if PMIS participate children of (a), design, symptoms study mild cross-sectional and a the early In for for searched Methods: risk and at antibodies. children SARS-CoV-2 identify of To against the levels youths, antibodies on. and for later children searched occurs in we (PMIS) predominantly syndrome on, but immune early COVID-19, multiorgan of pediatric phase threatening acute life and the severe by potentially mildly rather affected are Children Background: Abstract 2020 12, December 8 7 6 5 4 3 2 1 amezg rdrgmintieTae GmbH FAU Trager gemeinnutzige Bruder Barmherzige Horn Ewald Dr. Dr. Office & ediatric Heuschmann Dr. Office Pediatric Universit¨atsklinikum Regensburg Regensburg of University Leipold Dr. Office Pediatric Laub Office Pediatric 5 6 ihe Horn Michael , 3 n seset frgsr aafo ieetcutisfollowed, countries different from data registry of assessments and uan Brandstetter Susanne , 4 1 aacaBorchers Natascha , er Leipold Georg , 2,3,4 3 aa Laub Sarah , oee,rprso utognimn ydoei hlrnadyuh surfaced youths and children in syndrome immune multiorgan a of reports However, 6 ao Niggel Jakob , 5 2 nont Toncheva Antoaneta , curn ek omnh fe h ASCV2wv.Suisi clinical in Studies wave. SARS-CoV-2 the after months to weeks occurring 3 3 1 lsneaSantos-Valente Elisangela , afWagner Ralf , arcaSch¨oberl Patricia , 3 nra Ambrosch Andreas , 1 3 n ihe Kabesch Michael and , 3 3 1 ai Peterhoff David , nraSchweiger-Kabesch Andrea , ae,eiec nrae htcide r not are children that increased evidence Later, 7 3 Klaus , aatoKheiroddin Parastoo , 7 n ugse h association the suggested and Uberla ¨ 4 Sebastian , 3 8 Stephan , > 3 7hpercentile 97th Dominik , 3 Heike , Posted on Authorea 12 Dec 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.160776187.78854537/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. h eti ae narcmiatncecpi N nie n a uo au f10(/o.The (S/Co). as titer 1.0 neutralization of SARS-CoV-2 value the with cutoff has correlates and a reactivity IgG detected has total The and quantifies (S/Co). domain, antigen IgG. 1.0 receptor-binding and (N) of S-protein’s IgM, value nucleocapsid SARS-CoV-2 IgA, cutoff recombinant on detect a based can a is and on present ELISA based type(s) in-house antibody is the test commer- between ELISA. the discriminate The in-house not Switzerland; kits: published does Rotkreuz, test assay and different Diagnostics, CoV-2 validated two (Roche of a Anti-SARS-CoV-2 use and Elecsys the https://diagnostics.roche.com) qualitative by evaluated licensed was available, SARS-CoV-2 cially to was response pediatrician antibody Specific attending the the on for therapy data tests antibody individual of SARS-CoV-2 anonymization while way, persisted That center study for purpose. possible. permission and that gave still dataset for participants the when code of dataset individual the level their in on providing entered code detail. by were individual in an pediatricians data-linking using described their participant by previously the acquired data as to acquired symptoms level (www.qnome.eu) All individual platform an questionnaires. Qnome at parental accessible self-administered the only using study and survey anonymized The online fully an was study. in the collected were into 20-1865-101). data included All (file-number: were Regensburg years of management 14 University and than the collection group to older of voluntarilyData age invited Committee siblings participate that were Ethics to also of wanted the pediatrician cases, children themselves by respective those children All approved the the In was (1) with and tested. 2020 approaches: parents county; two whose also in and children were on visit all city based program (2) prevention was Regensburg and a years participate (Tirschenreuth; for 14 scheduled areas to were willful 1 study who of age collections. three number children 22 sample the the for May supported participate where in from team areas region study place In a and Robert alpine took the pediatricians, Oberbayern/ moderate 1). to collection to local high, (figure volunteered according of sample very prevention inhabitants capacity who The with disease 100,000 the Bavaria pediatricians for per exceeded within center participants tests of areas/counties study PCR German network three positive the a by on Institute, indicated established focused Koch as We and rates study infection design. average the in cross-sectional part a take has study This population and protocol. work-up Design three-stage Study a a using screen elevated PMIS to significantly of we with still signs Thus, Children Methods is for PMIS. wave. and clinically disease severe pandemic neutralizing evaluated the develop first for were while Germany) the to responses (Southern in or risk Bavaria antibody SARS-CoV-2 manifests of at against areas PMIS children levels affected those before severely antibody rather detect present overall in could to be children which used of should infection, number be they large SARS-CoV-2 could PMIS, after thus, of children and onset in mild the occur for responses causal antibody strong be syndrome. if symptoms. the that severe of speculated for occurrence We hospitalized the been that to had suggested contribute and authors fact PMIS some on in acquired and based may SARS-CoV-2 were SARS-CoV-2 observations to against these antibodies However, antibodies of presence of 5 the levels of to high age PMIS linked the studies before Recent frequent presents more pandemic. usually are COVID-19 symptoms disease the neurologic Kawasaki before and gastrointestinal even while peculiar as years some well showed PMIS. 17 as also shock in to it and 3 dysfunction but Cardiac disease from in Kawasaki years. syndrome ranges the immune multi- PMIS of multiorgan characteristics inflammatory or many differences. pediatric (PIMS-TS) features (PMIS), SARS-CoV-2 It syndrome (MIS-C). with children immune associated multiorgan temporally syndrome pediatric system named was syndrome The 8 neetnl,a soito fKwsk ies ihcrnvrsifcin a endiscussed been has infections coronavirus with disease Kawasaki of association an Interestingly, 9 nd othoc post oJl 22 July to esrmnso nioisi hlrnwohdalready had who children in antibodies of measurements 2 nd 00i ldn idwapoc.Ivtto to Invitation approach. window sliding a in 2020 11 lnclflo-pdt nPMIS on data follow-up Clinical 12 h lcy Anti-SARS- Elecsys The 10 Posted on Authorea 12 Dec 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.160776187.78854537/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. nTrceruh .%i eesugad78 nOebyr/Apn ein gi aigol n child one only taking again positive region, found Alpine were Oberbayern/ 15.9% in been in 2), 1.8% have account. 7.8% (approach may into and patient and that family Regensburg COVID-19 Regensburg symptoms per a in in to to 3.1% due 2.3% contact e.g. Tirschenreuth, Tirschenreuth, included suspected testing, in in were or for family positive volunteered COVID-19 When per who where to regions. (youngest) those related children test child In other tested one region. two of Alpine only the Oberbayern/ 7.2% and in tests/100.000 analysis, 1) than PCR (figure (approach the often positive selected children more in 1638 randomly in times (with children 3-4 Tirschenreuth antibodies those of response SARS-CoV-2 only county antibody of affected positive prevalence heavily had Elecsys the the inhabitants) the in tested in in children successfully observed only Overall, of one were 1). 5.7% tests, 2). differences Overall, both (figure case. regional ELISA in positive Strong in-house positive a the were defined by 138 tests 23 two antibodies: 2). and the SARS-CoV-2 (figure test of exceptions for one some positive least with were at responses children antibody in tool. with test-centers result children of online positive same locations the A the and in identified 1 consistently data of table tests 1. in study one Both given figure least necessary are in entered at study depicted with also the are successfully in had counties participating tested (96.5%) across children were 2832 the 2906 and of whom data tests Demographic of antibody study applied the two in the participated children 2934 Overall, SPSS.23. using by performed were stratified using analyses presented Results All analyzed are respectively. (in- were symptoms groups, median groups independent and and between for characteristics t-test data Differences Participants’ categorical response. data. for metric antibody (percentages) for frequencies range) using online terquartile calculated accessible were cardiac statistics is and Descriptive evaluation coagulopathies this blood for for used analyses screening Statistical protocol stage, The third the performed. At were (www.cokiba.we-care.de). erythrocytes echocardiography) and blood. (by second leukocytes in skin protein, effects The for markers enanthema, hypotension. examination clinical inflammatory exanthema, study urine arterial as lymphadenopathy, included approach and and such evaluation problems, to investigations conjunctivitis, gastrointestinal laboratory of possible, more, responses comprised extremities, stage not stage or of antibody first was erythema days strong The this oedema/ three with when pealing, experts. for cases Children Kawasaki at fever in and PMIS syndrome. or, cardiologists parameters: on Kawasaki’s pediatrician available pediatric caring from information being their deduced on doctors contact and based to developed 2020 asked was May were that of protocol end in evaluation analyzed the three-stage further a and used We response’ normalized neu- protocol HEK293T-ACE2 USA). was vs. Diego, of evaluation ffu (inhibitor) San infection PMIS 25,000 Software, ‘log post of (GraphPad h software algorithm: inoculum 20 8 fixed the determined Prism was a GraphPad using activity samples, fitted luciferase all were and For values h microscopy. 1 fluorescence for tralized and previously. dilution described limited VSV- as by on neutralization based SARS-CoV-2 is with Stom- test Vesicular correlates pseudotyped The SARS-CoV-2 (VSV). against sera Virus of atitis titration by evaluated were antibodies clinical Neutralizing for considered were Test test Neutralization Anti-SARS-CoV-2 SARS-CoV-2 Elecsys the in PMIS. [?]100 for S/Co follow-up of responses antibody strong previously. described 12 l ape ihS/Co with samples All Δ < *Lcpedtpdwt SARS-CoV-2-Spike- with pseudotyped G*FLuc . eecniee eaie nti xeietlsetting, experimental this In negative. considered were 1.0 3 13,14 χ ² suoia ieswr determined were titers Pseudoviral et o aeoia aibe and variables categorical for tests + Δ cls IC50 -cells. Rwhich ER Posted on Authorea 12 Dec 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.160776187.78854537/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. nioismyhl odtc hs ticesdrs o MS ept h lsn fshos kindergartens schools, of closing the Despite PMIS. for risk increased at those infections detect SARS-CoV-2 to of help wave, rates may first prevalence antibodies the representative in investigate N-protein Germany children to in high aimed children of without PMIS in primarily children with sera of not from children was subgroup, forms sera study this those This to moderate Within Of compared to as symptoms. mild SARS-CoV-2. capacity virus. PMIS-like with for neutralizing or the lower infection suggestive PMIS significantly of suspected symptoms showed antibodies in proteins the symptoms and SARS-CoV-2 adults S with after for signs in months and positive showed COVID-19 to N tested 18 of weeks children the incidence levels, of high against antibody 6% relatively directed specific approximately a tests pandemic, with two the Germany in of of phase regions first in the performed study, our In PMIS. this for sum, suggestive to In symptoms compared and (figure sera. as signs patients groups Discussion tested observation develop symptomatic the the defined not in confirming of did more ELISA, titers capacity who into based neutralization neutralizing (p=0.034), S-protein lower split children with the significantly were for correlate revealed values degree) titers table analysis lesser IC50 subgroup (supplementary antibody a when symptoms specific (to pronounced seen showed S-protein also activity more that titers symptomatic, was neutralizing even effect be antibody This high was to neutralizing out with 4d). effect of turned children This mean distribution of below the with capacity (n=3) 2). Analysing titers neutralization found 15% with neutralizing be only b). children the could of while 4a, While correlation (n=15) (figure 48% no available. test 4c), R=0.495) data (figure Elecsys p=0.0002, up based follow (Spearman’s N-protein selected with ELISA children, the signal S-protein in-house 52 a of the antibody In our subgroup with N-specific with this neutralization. correlated within high correlate with titers their correlate not antibody on nicely neutralizing did of to based (Elecsys) levels earlier the titers demonstrated determined antibody we been analysis, specific has N-protein which child ELISA, 2, One S-protein figure fatigue. two chronic in least signs. while excessive highlighted clinical at (LDH)) with As showed dehydrogenase more one the lactate or test) and of (elevated two Elecsys findings (34.6% showed parameters cardiac the 18 (15.4%/8.2%) laboratory with in 8 these, the presented measurements in while Of elevated changes PMIS; approach. signs highly additional to for three-stage showed with related screened a those symptom be in could all clinical 53.6%) disease one of 97, Kawasaki 18.6% of team to out study and similar (52 their the responders by PMIS with responded directly follow-up who of approached children clinical As symptoms be those a results and not only cases. in test could and positive participate link children pediatrician the to could positive their app of participants highly or study 69.8% parents/ and the in positive the results through Thus, and only invited of tested which pediatrician. were interpretation children (in children way qualitative all proband), anonymous of a a the an have 3.4% to for of in to follow-up in licensed point observed considered performed is clinical time were were was test the kind Anti-SARS-CoV-2 testing a at the that Elecsys selection in of though the Values for even in participate criteria only. 100 response, better to antibody [?] any overall S/Co responses of with strong absence antibody children the study, in positive the study, highly designing this allow For with would 3). 1). that (figure table children a examination features (supplementary invited children specific in in we few lived infections very Next, children association viral found related prominent common 238 but potentially from most symptoms population found. assessed COVID-19 single study We be discriminate SARS- the our population. to against could study in is our antibodies infections member tests in developed SARS-CoV-2 family children two 32.4% responses with in positive the these infection antibody SARS-CoV-2 SARS-CoV-2 of of elevated a a and any showed with with member individuals in living without family 15 Thus, response those tested test these, CoV-2. no positively than PCR Of a 344) SARS-CoV-2 subjects result. with 0-6 a of 6 test household received the (4.3% in positive already (n=684). positive in while had a year-olds often children positive had (71.4%) 11-17 263 less 4.9% 21 the population, slightly in and with study be positive previously found, the 7.3% to Within were and tended diseases. tests (n=849) diseases chronic year-olds SARS-CoV-2 chronic 7-10 with positive the Children more in 5.7% the (n=1299), children, year-olds the older The 15 u oase h usini cenn fcide o SARS-CoV-2 for children of screening if question the answer to but 4 othoc post Posted on Authorea 12 Dec 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.160776187.78854537/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. soitdee ihml MSsmtm ugssta hsmya es otiuei o as the cause antibodies not N-specific if high contribute of value least predictive at the may confirm this to that need suggests studies found Further symptoms also were PMIS. PMIS titers of mild neutralization development Lower COVID-19. with active antibodies. even to N-specific within associated compared of titers neutralization titers PMIS low high severe and with of symptoms in children PMIS-like effects of / neuropsychological PMIS subgroup for between a correlation infection significant COVID-19 a a found in We after reported children As up course effects. follow the COVID-19 to in long-term COVID-19. necessary clear from seems became suffer it it children Thus Furthermore, affected mildly symptoms. SARS-CoV- , initially PMIS for to adults positive that referred cardiac (tested be study with participants to study the study) enough of thoracic sick of siblings the I; be 2 outside identified to grade also recognized block antibodies study not (A-V 2 our were affection note, children cardiac Of the with though hospital. PMIS even the showed deviation), children axis 2 left symptoms least and absent case, pain at or index population, mild study the our of in In despite diagnosis infections the SARS-CoV-2 after weeks childhood 4 potential children. system- on in e.g. should developed out household responses, had missing the antibody members not in SARS-CoV-2 thereby COVID-19 family for with when screened confronted SARS-CoV-2 children be against that atically for suggest antibodies screening we useful. of acquired Thus, Therefore, be loss children children. COVID-19. to indicate of in to seem number identify weeks able not large hand, could were the does we A other age symptoms in COVID-19 of the by for symptoms years children symptom On of 6 in specific free as infections only children. young were the SARS-CoV-2 as in antibodies - children taste COVID-19 SARS-CoV-2 even and Interestingly, detectable for smell with test. specific children antibody are all the 162 evaluate symptoms before the to few of point very 23% this that only symptoms. at PMIS PMIS indicates strategy predict for study good could SARS-CoV-2 we Our a which to study, seems responses, responses our it antibody antibody of However, Therefore, show in who points values. design sensitivity. children antibody cutoff anonymous and/or lower possible specificity with the investigate those greater positively to to to with the follow-up Due needed follow-up, the of our PMIS. be extend half in and would developed participants than responses this that for study more antibody to made children in N-specific back was some go observed strong observation cannot were missed with similar values children have a only high may and included also we test, we where Elecsys As test, the individuals. in-house in in tested based COVID-19 100 of protein beyond courses S S/Co severe of the values In in show children. outcome be children in the also Many observed worsen can as to It infection seem initial basis. the antibodies regular of S-specific adults. a course of acute on levels studies. milder adults high only to previous than contrast, contribute to our SARS-CoV-2 may children compared of this to values it seropositive one that such responses a of applied in speculated had antibody 70% we of disease infection, stronger almost mild pandemic, absence SARS-CoV-2 Surprisingly, mount with initial the the children approach. the adults in in screening of seropositive point nevertheless, course first this of early asymptomatic this but 21% as to the in test responses, mild study at qualitative a antibody a responses with a strong of antibody is context for strong the assay proxy determine in a the to as that measure test aware better Elecsys are We the in 97 communication). 100 the of approximately further was is S/Co overwhelming. which value was beyond tested, study children values the their used get in We to participation limited. parents were that showed of capacities observation need children test in the unmet when participated community. of by an pandemic the addressed the who supported number in have of parents outbreaks may beginning high many or study the symptoms that the in surprisingly to tested Thus, be due not a children could explicitly their Bavaria, were that in children for in infection Indeed, coronavirus explanation pandemic a possible suspected the study One the in study. our on in early antibodies very nurseries and 17 18 hshptei hudb ute netgtdi ogtdnlstudies. longitudinal in investigated l further be should hypothesis This eietfidacs fcrncftgesnrm ieyascae ihSR-o- infection. SARS-CoV-2 with associated timely syndrome fatigue chronic of case a identified we th ecnieo l rvosaalbets aus(rvddb oh,personal Roche, by (provided values test available previous all of percentile 19 u bevto htlwrnurlzto aaiisare capacities neutralization lower that observation Our 5 16 hs aamysgetthat suggest may data These Posted on Authorea 12 Dec 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.160776187.78854537/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. ihe on adarcoc;D.Hr;Shea mCime;Germany Chiemsee; am Schoenau Horn; Dr. office; paediatric Horn; Germany Michael Germany Mitterteich; Regensburg/Regenstauf; Hofmann; Ewald; office; paediatric Dr. Hofmann; & Meike Heuschmann Dr. the office; of Germany paediatric Heuschmann; Edling; Hedwig Daniela Herbst; St. Dr. Germany office; Regensburg, Hospital paediatric , the Herbst; Regensburg at Christoph of University (KUNO) John Regensburg St. Hospital of Germany Childrens‘ Order Cham; University Habash; Harner, Germany Dres. Susanne Regensburg; office; Segerer; paediatric Habash; Dr. Sonja Gutdeutsch, Habash, Dr. Thomas office; paediatric Segerer; Florian Germany Gutdeutsch, Neuoetting; Peter Grombach; Dr. office; paediatric Germany Grombach; Freilassing; Germany Jens Geuder; Regensburg; Heihoff; Dr. office; Dr. paediatric Fleck, Geuder; Dr. Jurgen Germany office; Regensburg/Regenstauf; paediatric Ewald; Heihoff; Alfred Dr. Fleck, & Gudrun Heuschmann Dr. office; paediatric Germany Ewald; Regensburg; Dominik Eichhorn; Dr. office; paediatric Germany Eichhorn; Rosenheim; Renate Dieckerhoff; Dr. office; Germany paediatric Dieckerhoff; Regensburg; Jost Castrop; Dr. office; paediatric Castrop; Germany Mona Trostberg; Blueml; Germany office; Inn; paediatric am Blueml; Wasserburg Germany Andreas Birkinger; Marktredwitz; Schirmer; Dr. Dr. office; Germany Beer, paediatric Aibling; Birkinger; Dr. Bad Georg office; Becker; paediatric Koskul, Schirmer; von Hubert Dr. Beer, office; Elisabeth paediatric Becker; Christian Koskull, Germany von Traunstein; Stephan Antos; Mair, Dr. Dr. office; Aichholzer, paediatric Antos; Dr. David office; Germany paediatric Endorf; Reischl; Bad Imke Reischl; Wruk, Wruk, Michaela Dr. in Mair, order): Hedwig Georg alphabetical Aichholzer, St. (in Bettina hospital are KUNO group the Study lab at CoKiBa graphic all providing campus The work; support. for development routine logistical Kulawik and their generous Birgit of research the and top WECARE for hours; on weekend the helped Regensburg job and thank who tremendous extra We assistants students a for the did the design. laboratories areas; who involved study Schedel; clinics the the outpatient across support, in Mr. pediatric samples great personal especially and all their sets for in and parents transporting helpers Tirschenreuth sets, their and in study and packing support blood study, giving for the in organizing cross bravery their red for Bavarian participants the all to Kawasaki grateful are with We experience the on Based regular any or PMIS. a protein if Acknowledgment for S on COVID-19, follow-up if clinical of matter cases no prevalence a COVID-19 antibodies, offered high have with be with to disease, found should households areas are directed, from that from protein Those children children N as occur. screen COVID-19 well for to as suggestive symptoms antibodies propose independent SARS-CoV-2 we are for capacity results basis neutralization our symptoms. low PMIS-like on and and Based titers PMIS antibody of development N-specific the high for not predictors or whether clarify and 20 al nevninsest aeteptnilt vi ogtr rcrncilesas nPMIS. in also illness chronic or long-term avoid to potential the have to seems intervention early 6 Posted on Authorea 12 Dec 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.160776187.78854537/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. .MnoAS as N hlrnaentCVD1 ue pedr:tm og akt school. to back go to time spreaders: super COVID-19 Population. not Icelandic are the Children in SN. Child SARS-CoV-2 Faust of APS, Munro Spread systematic 4. al. A et - H, 2020 pandemic Med Jonsson COVID-19 J A, the Helgason Engl of DF, drivers Gudbjartsson main 3. the be age. patient to by unlikely load are viral Children review. SARS-CoV-2 JF. of Ludvigsson analysis An 2. al. Sciences et Health T, for Veith Server B, Preprint Muhlemann T, Jones 1. Germany Regensburg; References Volz-Fleckenstein; Germany Dr. Roding; office; Arnim; paediatric Volz-Fleckenstein; von Marlene Dr. Germany office; Waldnaab; paediatric der Arnim; an von Germany Altenstadt Victor Traunstein; Tretter; Steidle; Dr. Dr. office; Theurer, paediatric Tretter; Dr. German office; paediatric Steidle; Guenter Germany Theuerer, Ampfing; Guenter Sperlich; Dr. office; paediatric Germany Sperlich; Wasserburg; Michael Senjor; Dr. office; paediatric Germany Miesbach; Senjor; Germany Marko Schoetzau; Bruckmuehl; Strobelt; Dr. office; Dr. paediatric Schmid, Schoetzau; Germany Dr. Nina Muehldorf; office; Kaesbauer; paediatric Strobelt; Dr. Michael Scheffel, Schmid, Dr. Roland office; Germany paediatric Kolbermoor; Kaesbauer; Rehe; Ludwig Scheffel, Dres. Matthias office; paediatric Germany Rehe; Miesbach; Klaus Razeghi; Rehe, Dres. Christine office; paediatric Razeghi; Stefan Germany Razeghi, Regensburg; Germany Christiane Puchner; Rosenheim; Dr. Reitz; office; Dr. paediatric Pawlak, Puchner; Dr. Georg Germany office; Regensburg; paediatric Schmid-Seibold; Reitz; Leipold Michaela Pawlak, Dr. Johannes office; paediatric Schmid-Seibold; Petra Leipold, Germany Georg Rosenheim; Laub; office; paediatric Laub; Germany Otto Rosenheim; Laub; Land- office; Dr. paediatric office; Laub; Marinus paediatric Schick-Niedermeier; Germany Traunreut; Gudrun Soehngen; Rasp, Dr. Karin vogt, Soehngen, Germany Claudia Landvogt, Altoetting; Koering; Niclas Dr. office; paediatric the Germany Koering; Oberaudorf; of Cosima Klein; Hedwig Dr. Germany office; St. Regensburg, paediatric Hospital , Klein; Regensburg the Annegret of at University (KUNO) John Regensburg St. Hospital of Order Childrens‘ Germany Corbacioglu, University Regensburg; Szulagyi-Kovacs; Dr. Kabesch, Bauer, Low, Baumgartner, Michael Alena Bauer, Dr. Meinel, Meinel, Judex, Bettina Dr. Dr. Lindner, Dr. Lindner, office; Dr. paediatric Sabrina Jork-Kaeferlein, Szulagyi-Kovacs; Corbacioglu, Annamaria Monika Low, Dr. Baumgartner, Hannes Bastian office; Judex, paediatric Guido Germany Hopfner; Prien; Reinhard Hopfner; Schwarz, Dr. Schwarz, Monika Jork-Kaeferlein, Birgit 2020; caPaediatr Acta 105 618-9. : ; 382 2020; 2302-15. : 109 1525-30. : 00 doi:10.1101/2020.06.08.20125484 2020: 7 medRxiV: rhDis Arch N Posted on Authorea 12 Dec 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.160776187.78854537/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. hrceitc fsuypriiat taie o nioy(B etresult test (AB) antibody for stratified participants study of Characteristics 1: Table Figures and Tables fKwsk ies:ASinicSaeetfrHat rfsinl rmteAeia er Associa- Heart American the From Professionals Health Management Long-Term for and Statement Treatment, Diagnosis, Scientific al. A Responses tion. et Antibody Disease: JW, Newburger and Kawasaki AH, Inflammation of Rowley Systemic BW, Mapping McCrindle (MIS-C). 20. al. Children et in R, - Syndrome Trachtman Inflammatory infections RS, Multisystem coronavirus Patel in of CN, manifestations Gruber Neurological 19. al. perturbations et immune A, of Tzortzakakis review. mapping T, systematic Comprehensive Granberg a care J, health al. Almqvist in et 18. SARS-CoV-2 W, to Meng COVID-19. response severe MB, with Immune Pampena associated L, al. Kuri-Cervantes higher et study. six-fold longitudinal S, 17. prospective a Roth A indicates S, outbreak: screening COVID-19 Brandstetter a antibody S, following health workers Malfertheiner Public Fill children. al. in activity 16. cases et antibody reported R, than neutralizing Assfalg rate L, SARS-CoV-2 exposure Holthaus Measuring SARS-CoV-2 and M, ACE2 Hippich al. on et 15. Depends F, viruses. Entry Muecksch chimeric Cell Y, and Weisblum SARS-CoV-2 pseudotyped using F, Inhibitor. al. Protease Schmidt Proven et Clinically 14. S, a by Schroeder Blocked H, Is Kleine-Weber and M, TMPRSS2 Hoffmann 13. SARS-CoV-2 detects assay neutralization. serological sensitive with and correlate specific staff that highly 020-01503-7. patients hospital A COVID-19 in al. in et development levels M, immunoglobulin Vogel antibody V, and Gluck D, Symptoms Peterhoff al. 12. children et outbreak. S, in SARS-CoV-2 Harner a syndrome S, to inflammatory Roth exposed multisystem S, of Brandstetter threat 11. disease. potential Kawasaki The with pandemic. SN. COVID-19 associated Byrareddy the infections during HA, Viral Rothan al. systematic 10. et A PL, children: Shao in CY, syndrome Lu Assoc inflammatory LY, PERFORM Multisystem Chang and al. 9. EUCLIDS et A, and Moreira Syndrome Group S, Multisystem Study Advani review. Inflammatory M, PIMS-TS Pediatric Ahmed a al. 8. with et Children SARS-CoV-2. J, 58 With Kenny of Associated Temporally Characteristics A, Clinical Bamford E, Consortia. Whittaker Associated Children from in 7. Study Syndrome Multi-institutional Inflammatory A (MIS-C): Multisystem Infection City. al. York 2 Coronavirus et New a Syndrome KR, Respiratory UK: Derespina Acute Severe SI, the with Aydin paediatric in S, with Kaushik (PIMS-TS) children of 6. SARS-CoV-2 admissions with care Intensive associated study. al. observational temporally et multicentre syndrome HK, Kanthimathinathan multisystem C, inflammatory Evans P, Davies 5. Circulation 2014; EClinicalMedicine 113 Pediatr J 2017; 148-54. : n lnTas Neurol Transl Clin Ann 135 2020; 2020; e927-e99. : 26 224 eit leg Immunol Allergy Pediatr actCidAoecHealth Adolesc Child Lancet c Immunol Sci 100527. : eit leg Immunol Allergy Pediatr 24-9. : x Med Exp J JAMA 2020; 2020; 7 00 21;324(3):259-269. 2020; . 2020; 2057-71. : 8 5 doi:10.1126/sciimmunol.abd7114. : 217 00 doi:10.1111/pai.13361. 2020: e NY) (N Med 2020; 00 doi:10.1111/pai.13278. 2020: doi:10.1084/jem.20201181. : Cell 4 2020; 669-77. : Cell 2020 Infection 183 2020; lnVirol Clin J : 8-5e14. 982-95 : c 9 o:10.1016/j.medj. doi: 29. Oct 181 00 doi:10.1007/s15010- 2020: 7-0e8. 271-80 : 2020; omsMed Formos J 130 104575. : Posted on Authorea 12 Dec 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.160776187.78854537/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. n ypo,%()7. 17)7. 14 .080 Strong (N=2832). protein population S study the total and the Ig) in (total (IgG) assay IgG Anti-SARS-CoV-2 detecting Elecsys assay directed SARS-CoV-2 protein in-house directed N are the children between prevalence tested Comparison COVID-19 positively and and (124) negatively dots) 76.5 overall, 2: (red for Figure survey .138 Number chart the county). circle to by the contributing coded in centers given (color of 2020 location July until with Bavaria of Map 1: Figure (1871) *: 70.1 Notes: (17) 10.5 (N) % symptom, Any (N) % COVID-19, member Household (N) % COVID-19, to due Hospitalization (N) % test, (296) PCR 11.1 SARS-CoV-2 Positive (N) % testing, PCR (N) (8) SARS-CoV-2 % 4.9 them, of None (38) .792 (N) 23.5 % needs, special for School .070 (N) % school, Grammar (N) % (Realschule), school Secondary (163) (N) 6.1 % (Mittelschule), (733) (82) 27.5 school 50.6 Secondary (4.7-11.0) 8 (N) % school, Elementary (N) % Kindergarten, (N) % Nursery, . . attend. usually child your Does (1380) 51.7 (4.0-10.0) (N) % 7 disease, chronic Any IQR) (Md, (years) Age (N) % (male), Sex (N) % symptoms/contacts, COVID-19 . . . (N) % health check-up, regular . . . to due participation Study CHARACTERISTICS GENERAL p < 0;chi .05; ² et -etfridpnetgop Q neqatl ag,M median - Md range, interquartile - IQR groups independent for t-test test, . 6 . 2 .019* (77) 47.5 (2) 1.2 (15) 9.3 (29) 17.9 (161) 6.0 (2) 1.2 (6) 0.2 (16) (6) 9.9 0.2 (18) 11.1 (234) 8.8 (16) 9.9 .247 (17) 0.6 (47) 29.0 (295) 11.0 (227) 8.5 (130) 4.9 (15) 9.3 (809) 30.3 0-16) (range (110) 67.9 (329) 12.3 0-17) (range (52) 32.1 (N=162) test AB Positive (907) 34.0 (1763) 66.0 (N=2670) test AB Negative 9 < < < < p .001* .001* .001* .001* Posted on Authorea 12 Dec 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.160776187.78854537/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. ersnaino h etaiigatbd ieso l hlrneaie nteflo psuy visualizing study, up children. titer. follow asymptomatic antibody the shape. neutralizing in and examined to children colour according all dot titers. of by antibody titers children neutralizing antibody symptomatic with neutralizing (S/Co) the titers of antibody representation binding ELISA S-protein of N-specific Correlation with up follow from Legend: children of analysis titer antibody S/Co binding signal specific report S-protein could the and Individuals into Neutralizing ** dehydrogenase included possible. lactate be was is reminder could LDH 4: no antibody, pediatrician Figure study is their the AB of contacted symptom. design one actively anonymous than who the more to individuals Due 52 up. those follow only * PMIS for panel) Legend: children (lower seropositive study SARS-CoV-2 CoKiBa of follow-up the the in from findings symptoms and panel) (upper flowchart Study 3: Figure assays. both for given values, are cutoff ratios assay the represent lines dotted A. > orlto fNseicatbd inl(lcy,SC)wt etaiigatbd titers. antibody neutralizing with S/Co) (Elecsys, signal antibody N-specific of Correlation 100 E. oprsno h etaiaincpct fsmtmtcand symptomatic of capacity neutralization the of Comparison ± 0 odrieitras(ryaes.Sga-octff(S/Co) Signal-to-cutoff areas). (gray intervals borderline 10% D i hr itiuino ypoai hlrngrouped children symptomatic of distribution chart Pie . 10 C. Dotplot B. Posted on Authorea 12 Dec 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.160776187.78854537/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. 11 Posted on Authorea 12 Dec 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.160776187.78854537/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. A D

IC50 lowest 10% IC50 lowest neutralisation IC50 100 200 300 400 500 0 80 100 120 140 160 180 symptoms=3/5 60% N-signal vs neutralization N-signal Spearman's R = 0.1071; ns =0.1071; R Spearman's N-protein ELECSYS S/Co ELECSYS N-protein PMIS1 PMIS2 IC50 10%-mean symptoms=12/26 46% fatigue cardio IC50 mean -90% IC50 mean symptoms=3/15 neutralisation IC50 B 100 200 300 400 500 20% no symptoms no 0 0 2 4 6 8 10 S-protein-ELISA vs neutralization vs S-protein-ELISA Spearman's R = 0.4952; p = 0.0002 0.4952;p= R= Spearman's S-protein-ELISA S/Co S-protein-ELISA 12 IC50 highest10% symptoms=0/5 0% C E

neutralization IC50 neutralization IC50 100 200 300 400 500 100 200 300 400 500

s 0 0

ympto neutralization IC50 neutralization IC50 m ati a

symp c p=0.024

to ✱ ma t ic fatigue PMIS cardio & cardio 2 PMIS 1 PMIS PMIS no