SARS-CoV-2 outbreak investigation in a German meat processing plant.

Accep ed A icle This a icle has been accep ed o publica ion and unde gone ull pee e iew bu has no been h ough he copyedi ing, ypese ing, pagina ion and p oo eading p ocess, which may lead o di e ences be ween his e sion and he Ve sion o Reco d. Please ci e his a icle as doi: 10.15252/emmm.202013296 This a icle is p o ec ed by copy igh . All igh s ese ed SARS-CoV-2 ou b eak in es iga ion in a Ge man mea p ocessing plan Thomas Gün he 1§, Manja Czech-Sioli2, Daniela Indenbi ken1, Alexis Robi aille1, Pe e Tenhaken3, Ma in Exne 4, Ma hias O inge 5, Nicole Fische 2*, Adam G undho 1§*, Melanie M. B inkmann6,7* 1Hein ich Pe e Ins i u e, Leibniz Ins i u e o Expe imen al Vi ology, Hambu g, Ge many; 2Ins i u e o Medical Mic obiology, Vi ology and Hygiene, Uni e si y Medical Cen e Hambu g-Eppendo , Hambu g, Ge many; 3Heal h O ice, Osnab ück, Ge many; 4Ins i u e o Hygiene and Public Heal h, Uni e si y o Bonn, Bonn, Ge many; 5Omik on Sys ems GmbH, B aunschweig, Ge many; 6Vi al Immune Modula ion Resea ch G oup, Helmhol z Cen e o In ec ion Resea ch, B aunschweig, Ge many; 7Ins i u e o Gene ics, Technische Uni e si ä B aunschweig, B aunschweig, Ge many §equal con ibu ion * Co esponding au ho s: Melanie M. B inkmann, m.b inkm[email p o ec ed], phone: +49-531-6181-3069; Nicole Fische , [email p o ec ed], phone: +49-40-7410- 55171; Fax: +49-40-7410-53250; Adam G undho , adam.g undho @leibniz-hpi.de; phone: +49-40-48051-275; Fax: +49-40-48051-277 Cha ac e coun o he manusc ip : 25,613 cha ac e s/4,732 wo ds Accep ed A icle This a icle is p o ec ed by copy igh . All igh s ese ed Abs ac We desc ibe a mul i ac o ial in es iga ion o a SARS-CoV-2 ou b eak in a la ge mea p ocessing complex in Ge many. In ec ion e en iming, spa ial, clima e and en ila ion condi ions in he p ocessing plan , sha ing o li ing qua e s and anspo , and i al genome sequences we e analyzed. Ou esul s sugges ha a single index case ansmi ed SARS-CoV-2 o co-wo ke s o e dis ances o mo e han 8 me e s, wi hin a con ined wo k a ea in which ai is cons an ly eci cula ed and cooled. Vi al genome sequencing shows ha all cases sha e a se o mu a ions ep esen ing a no el sub-b anch in he SARS-CoV-2 C20 clade. We iden i ied he same se o mu a ions in samples collec ed in he ime pe iod be ween his ini ial in ec ion clus e and a subsequen ou b eak wi hin he same ac o y, wi h he la ges numbe o con i med SARS-CoV-2 cases in a Ge man mea p ocessing acili y epo ed so a . Ou esul s indica e clima e condi ions, esh ai exchange a es, and ai low as ac o s ha can p omo e e icien sp ead o SARS-CoV-2 ia long dis ances and p o ide insigh s in o possible equi emen s o pandemic mi iga ion s a egies in indus ial wo kplace se ings. Keywo ds Ae osol ansmission/mea p ocessing plan ou b eak/SARS-CoV-2 supe sp eading e en / i al genome sequencing Accep ed A icle This a icle is p o ec ed by copy igh . All igh s ese ed In oduc ion The i s wa e o SARS-CoV-2 in ec ions peaked in Eu ope om Ma ch o mid o May 2020. Implemen a ion o social and physical dis ancing measu es esul ed in declining in ec ion numbe s in mos Eu opean coun ies. Cu en ly, coun ies seek o implemen al e na i e measu es, o example in ec ion managemen ocused on ho spo s, con ac acing and sen inel es ing. Gi en his, i is impo an o immedia ely ollow up on local in ec ion clus e s o p e en e-eme gence o la ge-scale communi y ansmission as seen du ing he i s wa e o SARS-CoV-2 in ec ions. T ansmission o SARS-CoV-2 is hough o mainly occu ia espi a o y up ake o d ople s ( an Do emalen, Bushmake e al., 2020) o ae osols. Ae osols a e belie ed o be pa icula ly impo an in cases whe e a single sou ce ansmi s he i us o a la ge numbe o indi iduals, so-called supe sp eading e en s (Dyal, G an e al., 2020, On Kwok, Hin Chan e al., 2020, Schwie zeck, Konig e al., 2020, Xu, Liu e al., 2020, Yuse , Hayajneh e al., 2020, Zhang, Diao e al., 2020, Zhang, Li e al., 2020). Whe eas d ople s ypically a el no a he han 2 m, ae osols can s ay in he ai o p olonged pe iods o ime and may deli e in ec ious i al pa icles subs an ially beyond 2m dis ances, especially in indoo se ings wi h low esh ai exchange a es (Asadi, Wexle e al., 2019, Asadi, Wexle e al., 2020, Liu, Li e al., 2017). Fac o s such as empe a u e, humidi y and ai ci cula ion a e hough o signi ican ly in luence s abili y and anspo o d ople s and ae osols and consequen ly ansmission e iciency ( an Do emalen e al., 2020). Mea p ocessing plan s ha e ecen ly eme ged as ho spo s o SARS-CoV-2 a ound he wo ld. This is hough o esul no only om ope a ional p ac ices (e.g. close p oximi y o wo ke s in he p oduc ion line combined wi h physically demanding wo k ha p omo es Accep ed A icle This a icle is p o ec ed by copy igh . All igh s ese ed hea y b ea hing), bu also om sha ing o housing and anspo a ion ha may acili a e i al ansmission (Dyal e al., 2020). The equi emen o ope a e a low empe a u e in an en i onmen wi h low ai exchange a es is ano he ac o ha may p omo e sp ead o he i us among wo ke s. Howe e , di ec scien i ic e idence o he na u e o ansmission e en s in a mea p ocessing plan o he ole o sha ed housing and anspo a ion has no been epo ed ye . He e, we epo a ansmission clus e in a Ge man mea p ocessing plan in May 2020 and p o ide da a sugges ing ha en i onmen al condi ions p omo ed i al ansmission om a single index case o mo e han 60% o co-wo ke s wi hin a dis ance o 8 me e s. Vi al sequence analyses e ealed a p e iously un epo ed SARS-CoV-2 geno ype ha is no only sha ed by all indi iduals o he ini ial clus e , bu also by samples collec ed sho ly be o e a subsequen ou b eak in mid-June, which ep esen s he la ges ou b eak in a mea p ocessing plan seen in Ge many hus a . Ou indings indica e ha a physical dis ance o 2 me e s does no su ice o p e en ansmission in en i onmen al condi ions such as hose s udied he e; addi ional measu es such as imp o ed en ila ion and ai low, ins alla ion o il e ing de ices o use o high-quali y ace masks a e equi ed o educe he in ec ion isk in hese en i onmen s. Resul s We s udied an ou b eak in he la ges mea p ocessing plan in Ge many, loca ed in Rheda- Wiedenb ück, coun y o Gü e sloh, s a e o No h Rhine Wes alia ( e e ed o as MPP-R in he ollowing). MPP-R pe o ms slaugh e and ine p ocessing as well as packaging o Accep ed A icle This a icle is p o ec ed by copy igh . All igh s ese ed bee and po k. A second, independen ly ope a ed p ocessing plan specialized on sow deboning (MPP-D in he ollowing) is loca ed in Dissen (coun y o Osnab ück, s a e o Lowe Saxony), app oxima ely 30 km away om MPP-R. Due o occasional SARS-CoV- 2 posi i e cases in he Ge man mea indus y, se e al s a e go e nmen s in Ge many a anged SARS-CoV-2 PCR-based se ies es ing o he en i e s a o mea p ocessing plan s in May 2020, including MPP-D and MPP-R. Se ies o e en s p eceding he ou b eak in mea p ocessing plan R (MPP-R) As shown in Fig. 1A, go e nmen manda ed se ies es ing in MPP-D and MPP-R ook place in he week o May 11. Tes esul s we e epo ed on Sunday May 17. 94 ou o 279 es ed MPP-D employees we e ound o be SARS-CoV-2 posi i e, sugges ing an ongoing ou b eak among MPP-D wo ke s. In MPP-R, only ou ou o a o al o 6,289 employees we e ound o be posi i e. None o he ou cases in MPP-R was in ol ed in mea p ocessing and he cases we e judged o likely be independen . On Tuesday May 19 (Fig. 1B), wo MPP-R wo ke s om he ea ly shi ( e e ed o as cases B1 and B2 in he ollowing) epo ed o he managemen o ha ing had a b ie con ac wi h employees om MPP-D (D1 and D2 in he ollowing) on Sunday May 17, bo h o whom had ecei ed posi i e es esul s la e ha day (Fig. 1A). Cases B1 and B2 epo ed o ha e no symp oms. SARS-CoV-2 ou b eaks in MPP-R du ing May and June 2020 B1 and B2 we e es ed in he company’s es cen e on May 20 (Fig. 1B). Because he con ac wi h MPP-D wo ke s was no classi ied as high isk, bo h con inued o wo k. On Accep ed A icle This a icle is p o ec ed by copy igh . All igh s ese ed May 21, he ea ly shi did no wo k due o a holiday. Upon ecei ing posi i e es esul s on May 21, B1 and B2 and i e wo ke s wi h whom hey had sha ed an apa men we e qua an ined. B1 and B2 we e mo ed o a sepa a e apa men , whe eas hei la ma es emained in hei o iginal qua e s. On Monday May 25, all emaining wo ke s om he ea ly shi (n=140) we e es ed. Tes esul s om May 27 ound 18 ea ly shi wo ke s o be posi i e. All ea ly shi wo ke s we e immedia ely qua an ined he ea e . Follow-up Accep ed A icle This a icle is p o ec ed by copy igh . All igh s ese ed es ing pe o med be ween May 27 and June 3 iden i ied ano he 11 posi i e cases among he al eady qua an ined wo ke s. Following his ou b eak in May, isk- and e idence-based sc eening pe o med by heal h au ho i ies, gene al p ac i ione s and he in e nal MPP-R es cen e iden i ied inc easing numbe s (>110) o posi i e cases ac oss di e en pa s o he plan in June, sugges ing an ongoing and mo e wide-sp ead second ou b eak e en . Indeed, subsequen se ies es ing by heal h au ho i ies be ween June 17 and 23 iden i ied mo e han 1,400 posi i e cases, cons i u ing he la ges ou b eak in a Ge man mea p ocessing acili y seen hus a (Fig. 1C). Vi al geno ypes in he May 2020 ou b eak The iming o e en s sugges ed employees B1 and B2 as he mos likely sou ce(s) o he ea ly MPP-R in ec ion clus e . To u he subs an ia e his hypo hesis, we pe o med ull i al genome sequencing o he 20 cases es ed posi i e by May 27. In Fig. 2A, we p esen a hea map showing posi ions and colo -coded equency alues o nucleo ide de ia ions om he Wuhan SARS-CoV-2 e e ence s ain. A o al o eigh exchanges we e ound wi h nea 100% equency ac oss all samples. A sea ch agains 56,366 ull leng h sequences a ailable h ough GISAID iden i ied six o hese mu a ions o be commonly p esen in he 20C clade o SARS-CoV-2, a b anch which accoun s o app oxima ely 17% o all SARS-CoV-2 sequences deposi ed in GISAID a he ime o his w i ing. In e es ingly, howe e , we did no ind GISAID en ies sha ing he wo emaining mu a ions (ma ked wi h as e isks in Fig. 2A; see Appendix Table S1 and Figu e S3 o u he de ails). Combined, he eigh mu a ions he e o e ep esen a no el Accep ed A icle This a icle is p o ec ed by copy igh . All igh s ese ed sub-b anch wi hin he 20C clade ha de ines he p o o ypical i al genome signa u e o he in ec ion clus e (submi ed o GISAID, accession numbe 476705, s ain id NRW-MPP- 1). Whe eas he B1 sequence is an exac p o o ype ep esen a i e, we ind an addi ional nucleo ide exchange a 100% equency (C7735T) in B2. The ac ha his mu a ion is absen om he o he samples ules ou B2 as a possible sou ce o he clus e wi h nea ce ain y. Ano he six cases also exhibi a single addi ional nucleo ide exchange ha is no sha ed wi h any o he sample. Taken oge he , hese obse a ions sugges p o o ype i us ansmission by B1 as he common sou ce o in ec ion in he clus e . Gi en he o e all sca ci y o non-p o o ypical nucleo ide a ian s, he p esence o addi ional exchanges mos likely esul ed om ongoing i al mu agenesis in a subse o newly in ec ed indi iduals. Howe e , he sequencing da a alone canno ule ou he o mal possibili y ha a leas some o hese a ian s ep esen independen in ec ion e en s. Po en ial ansmission ou es in he May 2020 ou b eak Gi en he abo e, we in es iga ed po en ial ansmission ou es be ween he suspec ed index case B1 and he o he employees wi hin he clus e . The uni e sal poin o po en ial con ac among all cases was wo k in he ea ly shi o he bee p ocessing plan . The shi comp ises 147 indi iduals, mos o whom wo k a ixed posi ions in a con eyo -bel p ocessing line. The p ocessing line occupies an elonga ed a ea app oxima ely 32 me e s (m) long and 8.5 m wide (see loo plan in Appendix Fig. S1A). Qua e s o bee en e a one end o he line ( e e ed o as p oximal in he ollowing) and a e p ocessed as hey mo e in longi udinal di ec ion ac oss he oom, un il cu s a e inally packaged nea he a Accep ed A icle This a icle is p o ec ed by copy igh . All igh s ese ed end o he line ( e e ed o as dis al in he ollowing). Eigh ai condi ioning uni s placed nea he ceiling in he p oximal hal o he oom cons an ly cool he ai . Fans p ojec he ai in a la e al di ec ion, ei he di ec ly om on al openings in he uni o ia pe o a ed Accep ed A icle This a icle is p o ec ed by copy igh . All igh s ese ed commi ee issued a s a emen o no objec ion o publish he s udy unde e e ence numbe 337/20. SARS-CoV-2 amplicon sequencing and bioin o ma ic analysis Sample p epa a ion o SARS-CoV-2 amplicon sequencing was pe o med as desc ibed (J., 2020) wi h modi ica ions (P e e le, Guen he e al., 2020). P ime sequences a e p o ided in he Appendix Table S4. Samples we e sequenced on an Illumina MiSeq using 500cycle MiSeq 2 eagen ki s (Illumina). All samples we e sequenced wice (including independen cDNA syn hesis and lib a y p epa a ion eac ions) o exclude he possibili y o a ian equencies esul ing om andom ampli ica ion a i ac s. Excep o sample B14 (in which one sequencing eac ion was excluded due o insu icien quali y), epo ed a ian equencies e lec he a e age alues om independen eplica es. Bioin o ma ic analysis was pe o med as desc ibed (P e e le e al., 2020), (see Appendix Table S5 o de ails on he amplicon-Seq s a is ics), wi h he ollowing modi ica ions: Inpu h esholds we e se o a leas 10 a ian suppo ing eads wi h a minimum base quali y o 30 (-C10 - q30). Only high con idence a ian s p esen in > 20% o eads in a leas one indi idual sample we e included and anno a ed using ANNOVAR 16. Mino equency a ian s esul ing in ame shi , s opgain o s a loss we e excluded. Compa ison o i al geno ypes wi h GISAID da abase en ies We pe o med a blas sea ch o he p o o ypical NRW-MPP-1 geno ype iden i ied in his s udy agains all 56,366 sequences deposi ed in GISAID as o July 6, 2020. None o he en ies con ained he combina ion o he wo nucleo ide a ian s C6406T and G18972A ha Accep ed A icle This a icle is p o ec ed by copy igh . All igh s ese ed a e sha ed ac oss all samples in es iga ed in ou s udy. As shown in Appendix Table S6, a e y limi ed numbe (23 ou o 56,366 sequences) con ain one o he wo mu a ions. Two samples om he US (collec ed on he same da e as B1 and B2) also ca y he a ian C6406T, bu addi ionally exhibi ano he 7 and 8 mu a ions. These samples clea ly belong o a di e en sub-b anch o clade 20C de ined by a p e iously in oduced mu a ion a posi ion 27964. 21 samples om he UK also con ain one o he wo mu a ions bu belong o he sepa a e clade 20B. The occu ence o hese a ian s in di e en clade iden i ies hem as homoplasies and sugges s ha hese isola es a e no closely ela ed o he NRW- MPP-1 geno ype. S a is ical analysis P- alues in Fig. 3B and Appendix Table S2 indica e he cumula i e p obabili y o in ec ion a es among wo ke s wi h ixed s a ions in he indica ed dis ance anges being equal o highe han obse ed, unde he null hypo hesis ha he p obabili y o any gi en indi idual being posi i e is independen o spa ial loca ion and e lec s o e all posi i e a es among wo ke s wi h ixed s a ions a ound he index case (20 ou o 78 = 25.6%; see Appendix Table S2). Simila ly, o each sha ed uni in Fig. 3C and Appendix Table S3 we calcula ed p- alues o in ec ion equencies being equal o highe han obse ed among all indi iduals who sha e one o mo e uni (22 ou o 65 = 33.8%; please no e ha due o da a p o ec ion egula ions we canno e eal which wo ke IDs belong o a sha ed uni ). Cumula i e p obabili y mass alues we e calcula ed using he BINOM.DIST.RANGE unc ion om Mic oso Excel o Mic oso 365 MSO ( 16.0.12827.20328) wi h he ollowing inpu alues: p obabili y p: a e age in ec ion a e among wo ke s wi h ixed Accep ed A icle This a icle is p o ec ed by copy igh . All igh s ese ed s a ions (0.256) o wo ke s sha ing one o mo e uni (0.338), minimum numbe o successes s: obse ed numbe o posi i e wo ke s in dis ance ange o sha ed uni , ials and maximum numbe o successes s2: : o al numbe o wo ke s in dis ance ange o sha ed uni . Desc ip ion o housing condi ions, wo k a ea condi ions, and wo king condi ions Housing condi ions: Many o he wo ke s sha e apa men s and hose usually commu e oge he o hei wo kplace in ans o ganized by he company. The company p o ided us wi h anonymized in o ma ion abou he housing si ua ion o he wo ke s ega ding in o ma ion on sha ed apa men s, bed ooms and ca pools. The la ges housing uni encompassed se en wo ke s o he ini ial ou b eak in May in he bee p ocessing plan (see Appendix Table S3; no e ha due o da a p o ec ion egula ions we canno e eal which wo ke s belong o indi idual sha ed uni s). In addi ion, we collec ed in o ma ion abou he wo k a ea and he wo king condi ions du ing ou on-si e isi on June 2 2020. Du ing ha isi , we isi ed he bee p ocessing plan du ing ope a ing hou s accompanied by echnical s a om MPP-R. Wo k a ea condi ions: The plan comp ises sepa a e a eas in which slaugh e ing and mea p ocessing is pe o med. While slaugh e ing akes place a ambien empe a u es wi h highe ai exchange a es, bee and po k p ocessing a e pe o med in ooms cooled o app oxima ely 10°C wi h a high p opo ion o eci cula ed cooled ai . The bee p ocessing plan has a size o 2,800 m2 and is 6.1 m high (Appendix Figu e S1A-B). The en i e oom and he p oduc ion line a e cleaned and disin ec ed daily acco ding o ood hygiene egula ions in Ge many. On he day o he on-si e isi , he empe a u e in a ea 1 and 2 in Accep ed A icle This a icle is p o ec ed by copy igh . All igh s ese ed he bee p ocessing plan anged be ween 9.5-10.7°C and be ween 5.4-8.7°C in a ea 3. Rela i e humidi y was measu ed o be 34% igh below he cooling ans in a ea 1 and 68% in he emaining pa o a ea 1, and be ween 67-71% in a eas 2 and 3 (Appendix Figu e S1A). Cooling ans a e cooling eci cula ed ai wi hou il e s (C1-8). C3-8 a e connec ed o a pe o a ed hose di ec ed owa ds a ea 3 whe eas C1 and C2 lack a hose. C1 and C2 u n on only when empe a u es ise abo e 10°C. Cooled ai is expelled h ough he hall up o app oxima ely 12 me e s. Cooling ans 3-8 a e ope a ing pe manen ly and a e expelling cooled ai h ough a ached pe o a ed hoses. The ai exchange a e o he en i e bee p ocessing plan is <1. This means ha i akes mo e han one hou o ha e he ai eplaced by esh ai . Speci ica ion o he cooling ans is as ollows: Manu ac u e : Guen he AG & Co. KG, Fue s en eldb uck, Ge many, Model: S-GGHF 50Hz, Type 050.1E/17-AS, capaci y 18,6 kW, ai low 6440 m3/h, ai h ow 37 m, dimensions: Leng h 1363 mm, Heigh 747 mm, Dep h 713 mm. Wo king condi ions: The wo ke s in he bee p ocessing plan ha a e wo king on he pla o m (p oximal side) and he connec ed p ocessing line (s a ing in a ea 1 and ending in he middle o a ea 2) a e ained o speci ic cu s and he e o e ha e ixed wo kplaces (Appendix Figu e S1). Hence, wo ke s could be aced in de ail du ing hei wo king hou s. While 5-6 wo ke s handle he bee qua e s en e ing he plan on he pla o m and p epa e hem o cu ing, he qua e s a e hen ansloca ed on o h ee con eyo -bel p ocessing lines whe e 24-25 wo ke s sepa a e he mea om he bones. Nex , ine cu s a e pe o med (shea ing) by 26-27 wo ke s. Towa ds he dis al pa o he plan as well as in a ea 3, he bee is packed in o acuum packaging (Appendix Figu e S1B). While he p oduc ion line Accep ed A icle This a icle is p o ec ed by copy igh . All igh s ese ed wo ke s ha e ixed wo kplaces, he supe iso y s a has lexible wo kplaces and commu es wi hin he bee p ocessing plan . Shi s in he bee p ocessing plan change once pe day. The s a o ea ly and la e shi s a e p o ided by wo independen sub-con ac o s and hence no s a is exchanged be ween he shi s. A shi has wo 30 min b eaks and one b eak o one hou . Du ing b eaks, he wo ke s om a shi isi he can een. Wo ke s do no ha e ixed sea s in he can een. Supe iso y s a does no spend he b eak imes oge he wi h he p oduc ion line wo ke s. The supe iso s do no sha e housing o anspo acili ies wi h he p oduc ion line wo ke s. Measu es implemen ed by MPP-R du ing SARS-CoV-2 pandemic Wi h he onse o he SARS-CoV-2 pandemic, addi ional p e en i e measu es o he p oduc ion s a we e imposed by MPP-R. The company adhe ed o he ecommenda ions o he ele an occupa ional Heal h and sa e y guidelines (BGN “E gänzung de Ge äh dungsbeu eilung im Sinne des SARS-CoV-A bei sschu zs anda ds B anche Fleischwi scha ”). Addi ional measu es we e de eloped and implemen ed by he company. Hygiene egula ions like hand hygiene and one-way a ic in hallways we e ein o ced, and an in e nal mul i-lingual in o ma ion campaign was en olled o aise awa eness o p e en ion and sel -de ec ion o ea ly COVID-19 symp oms. A body empe a u e he mo scanne was se up o check all employees’ body empe a u e en e ing he building. Wo ke s ha e been made awa e o he company’s SARS-CoV-2 es cen e and we e mo i a ed o epo any e en s whe e hey see hemsel es being a isk. Speci ic wo kplace assessmen s we e pe o med o deciphe possibili ies o ex end dis ances Accep ed A icle This a icle is p o ec ed by copy igh . All igh s ese ed be ween wo ke s. Simple one-laye ace masks we e made compulso y. Regula ions we e in place o p ohibi o a ion be ween wo king places o he wo ke s. Measu es in he can een we e imposed o educe physical con ac and o en o ce ha wo ke s would spend hei b eak imes exclusi ely wi h wo ke s om hei own shi . Since he ou b eak o he pandemic, he company managed o p e en in a-company in ec ion chains un il he e en desc ibed in his pape . The implemen a ion o he measu es was audi ed on May 15 and May 29 by unannounced inspec ions o he Occupa ional Heal h and Sa e y Expe s o he compe en au ho i y and on May 20 by he Occupa ional Heal h and Sa e y expe s o he “Be u sgenossenscha Nah ungsmi el und Gas gewe be”. The company had se up hei own es cen e o PCR-based SARS-CoV-2 es ing in ea ly May 2020. In he SARS-CoV- 2 es cen e ained s a akes o opha yngeal swap samples om wo ke s and o he s a . The samples we e analysed by RT-qPCR in an acc edi ed labo a o y (Labo Kneißle GmbH & Co.KG, Bu glengen eld, Ge many). S a was es ed based on sel - epo ed symp oms, possible con ac s o o he in ec ed pe sons, e u ning o wo k a e mo e han 96 h absence om wo k, o based on isk-assessmen o possible wo kplace con ac s. Da a a ailabili y Vi us sequence da a ha e been deposi ed a Eu opean Nucleo ide A chi e, ENA, h ps://www.ebi.ac.uk/ena/; Accession numbe : PRJEB40387. Vi us sequences a e also a ailable a GISAID, www.gisaid.o g, see Appendix Table S1 o he indi idual accession link in o ma ion. Accep ed A icle This a icle is p o ec ed by copy igh . All igh s ese ed Acknowledgmen s We hank Ge eon Schulze Al ho , Di k Moo mann, Ca h in Becke , Uwe Golling, Holge Scholze and Dennis Junkmann om Tönnies Lebensmi el GmbH & Co. KG, Rheda- Wiedenb ück, Ge many, o sha ing in o ma ion necessa y o he ou b eak in es iga ion and he possibili y o isi he si e o he ou b eak. We hank Johannes Knobloch and Ma in Aep elbache , Ins i u e o Medical Mic obiology, Vi ology and Hygiene, UKE, and Thomas Schulz, Ins i u e o Vi ology, Hanno e Medical School, o help ul discussions on he manusc ip . We also g ea ly app ecia e he suppo o and aluable discussions wi h Anna Kebschull, Land ä in Osnab ück, Ge many. We hank he coun y’s heal h au ho i ies in ol ed in he ou b eak managemen o hei suppo . This wo k is suppo ed by he Helmhol z Associa ion, Ge many (W2/W3-090). MMB is suppo ed by he SMART BIOTECS alliance be ween he Technische Uni e si ä B aunschweig and he Leibniz Uni e si ä Hanno e , an ini ia i e suppo ed by he Minis y o Science and Cul u e (MWK) o Lowe Saxony, Ge many. AG is suppo ed by he Fede al Minis y o Heal h, Ge many (HPI-COVID-19). Au ho Con ibu ions TG, AG, MO, NF, and MMB designed he s udy. TG, AG, ME, MO, NF, and MMB pe o med li e a u e sea ch; AG, MO, NF, and MMB w o e he manusc ip ; TG, MCS, DI, AG, ME, MO, NF, PT, and MMB collec ed he da a. TG, AR, and AG pe o med bioin o ma ic da a analysis; TG, AG, MO, NF, and MMB gene a ed he igu es and ables, PT e iewed he manusc ip . Accep ed A icle This a icle is p o ec ed by copy igh . All igh s ese ed Con lic o In e es The au ho s decla e ha hey ha e no con lic o in e es . Fo Mo e In o ma ion GISAID Ini ia i e; h ps://www.gisaid.o g ENA B owse - Eu opean Nucleo ide A chi e; h ps://www.ebi.ac.uk/ena Accep ed A icle This a icle is p o ec ed by copy igh . All igh s ese ed The Pape Explained P oblem O igina ing om an index case ha had sel - epo ed p e ious con ac wi h po en ially SARS-CoV-2 in ec ed pe sons, we desc ibe he i s clus e o SARS-CoV-2 ansmission in a mea p ocessing plan in a con ined wo king a ea. This in ec ion clus e p eceded a la ge SARS-CoV-2 ou b eak in he same mea p ocessing plan sho ly he ea e in ol ing 1,413 SARS-CoV-2 posi i e es ed employees. Resul s By pe o ming a mul i ac o ial analysis o housing and commu ing pa ame e s along wi h spa ial and clima e condi ions in he wo k a ea and i al genome sequencing, his s udy p o ides e idence ha ansmission occu ed likely ia ai bo ne ansmission o SARS- CoV-2 o e long dis ances in a con ined a ea o he mea p ocessing plan . Physical wo k and ela i ely low esh ai exchange a es oge he wi h con inuous eci cula ion o cooled ai may ha e a o ed he ansmission o SARS-CoV-2 among employees. Impac Ou s udy implica es ha common ope a ional condi ions in indus ial mea p ocessing plan s p omo e he isk o SARS-CoV-2 supe sp eading e en s. Addi ional measu es such as imp o ed en ila ion, op imized ai low managemen , ins alla ion o il e ing de ices o he use o high-quali y ace masks a e equi ed o educe he in ec ion isk in hese en i onmen s. Re e ences Accep ed A icle This a icle is p o ec ed by copy igh . All igh s ese ed Asadi S, Wexle AS, Cappa CD, Ba eda S, Bou ie NM, Ris enpa WD (2019) Ae osol emission and supe emission du ing human speech inc ease wi h oice loudness. Sci Rep 9: 2348 Asadi S, Wexle AS, Cappa CD, Ba eda S, Bou ie NM, Ris enpa WD (2020) E ec o oicing and a icula ion manne on ae osol pa icle emission du ing human speech. PLoS One 15: e0227699 Co man VM, D os en C (2020) Au ho s' esponse: SARS-CoV-2 de ec ion by eal- ime RT-PCR. Eu o Su eill 25 Dyal JW, G an MP, B oadwa e K, Bjo k A, Wal enbu g MA, Gibbins JD, Hale C, Sil e M, Fische M, S einbe g J, Basle CA, Jacobs JR, Kennedy ED, Tomasi S, T ou D, Ho nsby-Mye s J, Oussaye NL, Delaney LJ, Pa el K, She y V e al. (2020) COVID-19 Among Wo ke s in Mea and Poul y P ocessing Facili ies - 19 S a es, Ap il 2020. MMWR Mo b Mo al Wkly Rep 69 J. Q (2020) nCoV-2019 sequencing p o ocol 2. a icne wo k/nco -2019, dxdoio g/1017504/p o ocolsiobbmuik6w Liu L, Li Y, Nielsen PV, Wei J, Jensen RL (2017) Sho - ange ai bo ne ansmission o expi a o y d ople s be ween wo people. Indoo Ai 27: 452-462 On Kwok K, Hin Chan HH, Huang Y, Cheong Hui DS, Anan ha ajah Tambyah P, In Wei W, Kwan Chau PY, Shan Wong SY, Tze Tang JW (2020) In e ing supe -sp eading om ansmission clus e s o COVID-19 in Hong Kong, Japan and Singapo e. J Hosp In ec P e e le S, Guen he T, Kobbe R, Czech-Sioli M, Noe z D, Sau e R, Oh J, Kluge S, Oes e eich L, Peldschus D, Indenbi ken D, Huang J, G undho A, Aep elbache M, Knobloch J, Lue gehe mann M, Fische N (2020) Low and high in ec ion dose Accep ed A icle This a icle is p o ec ed by copy igh . All igh s ese ed Accep ed A icle This a icle is p o ec ed by copy igh . All igh s ese ed