Coronavirus disease 2019 (COVID-19) and human pregnancy: a scoping review

Co ona i us disease 2019 (COVID-19) and human p egnancy: a scoping e iew In oduc ion Co ona i us disease 2019 (COVID-19) is caused by an RNA i us, se e e acu e espi a o y synd ome co ona i us 2 (SARS-CoV-2), which has gene ic simila i ies wi h o he co ona i uses such as he ba co ona i us (Ba -CoV), SARS- CoV-1, and he Middle Eas espi a o y synd ome co ona i us (MERS-CoV) [1]. The la e wo ha e he abili y o in ec hu- mans. Cases o SARS-CoV-1 we e ini ially diagnosed be ween 2002 and 2004 and his is cu en ly conside ed an e adica ed i us, whe eas MERS-CoV-1 was ini ially iden i ied in 2012, and some cases a e s ill epo ed in Saudi A abia [2]. Nei he o hese i uses eached pandemic s a us, bu in 2013 he WHO decla ed MERS-CoV a global h ea [3]. Al hough he new i us is mo e con agious han he p e ious ones, he a e age mo - ali y is lowe o SARS-CoV-2 (3-4%) han o SARS-CoV-1 (10%) and MERS-CoV (37%) [4-6]. A he ime o w i ing, we a e acing a e y apid sp ead and a con inuous inc ease in he numbe o COVID-19 cases wo ldwide, al hough some coun- ies, such as China, Sou h Ko ea and Japan, a e con olling new cases and beginning o li es ic ions. Con a y o his, o he a eas, such as he USA, Cen al and Sou h Ame ica and he Ca ibbean, a e jus s a ing o epo inc eases in hei num- be s o cases. Howe e , he numbe o cases does no seem o be he mos eliable pa ame e o measu ing he magni ude o i al sp ead, since up o 86% o ca ie s o he i us a e asymp- oma ic and we e p obably no epo ed as a clinical p oblem [7]. Fu he mo e, he lack o eliable es s, he low capaci y o each coun y o pe o m es s, and he a e o alse nega i es due o low quali y es eagen s, do no allow a p ecise es ima ion o he e olu ion o he pandemic [8,9]. Gene al aspec s o COVID-19 COVID-19 pneumonia has simila clinical cha ac e is ics o pneumonia p oduced by bac e ia o o he i uses. The as e Rica do Sa i ón-Co nudella1, I án E. Al ami ano-Ba cia2,3, Pe e Ched aui2,3, Me cedes Andey o-Ga cía1, Mau icio C. Tajada-Duaso4, Faus ino R. Pé ez-López5 1 Depa men o Obs e ics and Gynecology, Villalba Gene al Hospi al, Collado Villalba, Mad id 28400, Spain; 2 Ins i u o de In es igación e Inno ación en Salud In eg al, Facul ad de Ciencias Médicas, Uni e sidad Ca ólica de San iago de Guayaquil, Guayaquil, Ecuado ; 3 Hospi al de la Muje Al edo G. Paulson, Guayaquil, Ecuado ; 4 Depa men o Obs e ics and Gynecology, Miguel Se e Uni e si y Hospi al, Za agoza 50009, Spain; 5 Ins i u o de In es igación Sani a ia de A agón and Uni e si y o Za agoza Facul y o Medicine, Za agoza 50009, Spain ABSTRACT Co ona i us disease 2019 (COVID-19) is caused by in ec ion wi h a co ona i us (SARS-CoV-2). P egnan women show mild o mode a e symp oms, wi h 5% p esen ing as se e e pneumonia. The p e alence and e olu ion o COVID-19 in p egnancy, including he isk o ma e nal dea h, a e simila o wha is obse ed in he gene al popula ion. Radiog aphy, compu ed omog aphy o ul asound imaging examina ions a e pi o al o he diagnosis and pe o med when he e is clinical suspicion o COVID-19 pneumonia. Lab indings include lymphocy openia, h ombocy openia, leukopenia, and ele a ion o D-dime and e i in. To da e, he e is no speci ic ea men o accina ion o COVID-19. Clinical manage- men o p egnan woman is also simila o ha o he gene al popula ion, wi h p ophylac ic an ibio ic ea men o bac e- ial pneumonia and oxygen suppo . Th ombop ophylaxis should be indica ed in se e e cases, gi en ha p egnancy is a hype coagulable s a e ha may be exace ba ed by COVID-19. Hospi al managemen should ocus on ea ing he mo h- e and p o ec ing he newbo n and he heal hca e pe sonnel. As ega ds COVID-19 and pe ina al ou comes, p ema u e deli e ies a e mainly associa ed wi h ia ogenic p egnancy e mina ion h ough cesa ean sec ion aimed a conse ing ma e nal well-being. To da e, e ical ansmission o he e us has no been demons a ed, ei he in au e ine o h ough he bi h canal. The i us has no been de ec ed in aginal luids, o in b eas milk. B eas eeding may be allowed de- pending on ma e nal and neona al heal h s a us. Al hough he e a e s ill many open issues, scien i ic in o ma ion ela ed o p egnancy and COVID-19 is being upda ed con inuously. KEYWORDS Co ona i us, COVID-19, p egnancy, SARS-CoV-2, se e e acu e espi a o y synd ome co ona i us 2. A icle his o y Recei ed 12 May 2020 – Accep ed 18 May 2020 Con ac Faus ino R. Pé ez-López; aus ino.pe ez@uniza .es Depa men o Obs e ics and Gynecology, Uni e si y o Za agoza Facul y o Medicine, Domingo Mi al s/n, Za agoza 50009; Spain. Tel: +34 976 761734; Fax: +34 976 76 1735 70 Gynecological and Rep oduc i e Endoc inology and Me abolism 2020; 1(2):70-75Licens e ms 71Gynecological and Rep oduc i e Endoc inology and Me abolism 2020; 1(2):70-75 COVID-19 and Human P egnancy sp ead o SARS-CoV-2, as compa ed o o he co ona i uses such as SARS-CoV-1, appea s o be ela ed o he ac ha i is housands o imes mo e con agious, wi h a basic ep oduc ion a io o 2.5 [10,11]. In e es ingly, unlike SARS-CoV-1, i no only mul iplies in he lungs, bu also eplica es ac i ely in he h oa du ing he i s week when symp oms appea [12]. SARS-CoV-2 has an incuba ion pe iod o 5-6 days [13], a - e which a ious complain s may occu : anosmia, headache, myalgia, gas o-in es inal symp oms, cough, e e , dyspnea and pneumonia being some o he mos impo an [14]. Se e e disease occu s mo e equen ly in pa ien s wi h associa ed como bidi ies (obesi y, hype ension, ch onic obs uc i e pul- mona y disease, diabe es melli us) and highe mo ali y a es (up o 15%) ha e been obse ed in men aged 80 yea s o o e [15-17]. Mo ali y a es will also depend on a ailable local heal h esou ces a a gi en momen , which in u n will depend on he speed o ac ion ega ding disease p e en ion o con ol [18]. The clinical pic u e is associa ed wi h a cy okine s o m wi h o e - p oduc ion o umo nec osis ac o , in e leukin (IL) 6, and IL- 1β. The massi e in lamma o y esponse is associa ed wi h mul- io gan lesions (hea , li e , kidneys among o he s) ha , a he same ime, po en ia es he in lamma o y eac ion and impai s an icoagulan mechanisms. Cases wi h se e e pneumonia show mic o h ombosis, dissemina ed in a ascula coagula ion, and mul io gan ailu e wi h aised D-dime concen a ions (a poo p ognos ic ea u e). Dissemina ed in a ascula coagula ion is common in non-su i o s [19]. Al hough he mos p e alen gene al COVID-19 symp- oms include espi a o y di icul y, cough, myalgia, and loss o appe i e, some mild o mode a e cases may equen ly epo ol ac o y and gus a o y dys unc ion. A mul ina ional Eu ope- an s udy analyzed hese symp oms in he gene al popula ion using ol ac o y and gus a o y ques ionnai es based on he smell and as e componen o he Ques ionnai e o Ol ac o y Diso - de s-Nega i e S a emen s [20]. Facial pain and nasal obs uc ion we e he mos equen disease- ela ed o o hinola yngological symp oms. Ol ac o y and gus a o y dys unc ions we e epo - ed by 85.6% and 88.0% o pa ien s, espec i ely. A signi ican associa ion was ound be ween he wo diso de s. Ol ac o y dys unc ion appea ed be o e he o he symp oms in 11.8% o cases. Among he 18.2% o pa ien s who did no p esen na- sal obs uc ion o hino hea, 79.7% we e hyposmic o anos- mic. The ea ly ol ac o y eco e y a e was 44.0%, and sudden anosmia o ageusia may be sugges i e o COVID-19. Howe - e , he e is no in o ma ion abou hese symp oms in p egnan women. Cu aneous mani es a ions o COVID-19 ha e also been e- po ed [21]. Vesicula e up ions appea ea ly in he disease, in some cases e en de eloping be o e o he symp oms. O he pa - e ns appea la e in he disease e olu ion, such as ac al a eas o e y hema-edema, usually asymme ical, wi h some esicles o pus ules wi h small ed o pu ple spo s caused by bleeding un- de he skin. O he lesions include small mac opapules, some- imes a ound hai ollicles o simila o pi y iasis osea. I ching was e y common o u ica i o m (92%) and o maculopapu- la (57%) lesions [21]. SARS-CoV-2 du ing p egnancy The espi a o y sys em is mo e ulne able in p egnan women han in he gene al popula ion [22]. Like he es o he popula ion, p egnan women can become in ec ed wi h bo h SARS-CoV-1 and 2, and wi h MERS-CoV [23-24]. Howe e , no inc eased suscep ibili y o co ona i us in ec ion has been demons a ed du ing p egnancy [25] and he clinical e olu ion is simila o ha seen in non-p egnan women o simila age [26]. Du ing p egnancy, ma e nal dominan T-helpe 2 (Th2) p o- ec s he e us, whe eas he Th1 esponse (inc ease o in e leu- kin 1) is associa ed wi h highe mo ali y isk among hose wi h COVID-19 [27]. Respi a o y ailu e p og esses apidly among p egnan women wi h in ol emen o he ca dio espi a o y sys em [22]. Despi e he ac ha da a on hese aspec s a e accu- mula ing, he e is no speci ic in o ma ion on he eal incidence o COVID-19 du ing p egnancy. Clinical cha ac e is ics du ing p egnancy and pe ina al ou comes A high a e o ma e nal a ali ies has been desc ibed in p eg- nan women in ec ed wi h SARS-CoV-1 and MERS-CoV (up o 25% and 35% espec i ely) [28,29]. This igu e seems o be much highe han wha is cu en ly desc ibed o SARS-CoV-2. The clinical cou se o p egnan women wi h COVID-19 has been epo ed o be gene ally mild o mode a e, e e and cough being he wo mos equen symp oms [23,30]. Only 5% o cases we e se e e [31-33]. The e o e, p egnan women do no seem mo e suscep ible o COVID-19 o mo e likely o de elop se e e pneumonia [34]. In gene al, he pe ina al p ognosis will depend on p ema u i y, o en due o ia ogenesis, and on ma e - nal well-being a he end o he p egnancy. Qiancheng e al. [26] epo ed a e ospec i e s udy o he se e i y o COVID-19 in p egnan (n=28) and non-p egnan (n=54) women o simila ep oduc i e age hospi alized a he Cen al Hospi al o Wuhan du ing a wo-mon h pe iod in 2020. They de e mined ha he e was no isk o i al e ical ansmission du ing he hi d imes e o p egnancy including du ing aginal deli e y. Como bidi ies we e no equen ly epo ed in ei he o he wo g oups. The majo i y o women we e classi ied as ha ing mode a e pneumonia: 85.7% o he p egnan women, and 98% o he non-p egnan ones. Only 2 p egnan women and 1 non-p egnan woman had se e e pneu- monia. The au ho s acknowledged among he limi a ions o he s udy ha (i) mo e se e e pa ien s migh ha e been admi ed o o he hospi als, o he han he s udy cen e , and (ii) he p egnan women s udied we e in ec ed wi h SARS-CoV-2 in he la e s age o p egnancy, and he p obabili y o e ical ansmission du ing he i s hal o p egnancy could no be assessed. A e ospec i e s udy analyzed he clinical eco ds o p eg- nan women wi h COVID-19 pneumonia ea ed a 25 hospi als in China be ween Janua y 20 and Ma ch 24, 2020. Possible e ical ansmission o he i us was s udied by es ing o SARS-CoV-2 in amnio ic luid, co d blood, and neona al pha - yngeal swab samples [35]. All es s we e nega i e and he e we e no cases o e al dea h. In addi ion, aginal sec e ion samples we e collec ed om he lowe hi d o he agina upon admis- sion and we e nega i e. 72 Zaigham and Ande sson [30] pe o med a sys ema ic e iew o pee - e iewed publica ions bo h in English and Chinese o summa ize he clinical mani es a ions o 108 p egnancies wi h COVID-19, as well as ma e nal and pe ina al ou comes. Cases o SARS-CoV-2 in ec ion we e con i med by a labo a o y es ( epo ed in 18 a icles). Women s a ed o ha e symp oms in he hi d imes e o ges a ion, e e (68%) and coughing (34%) be- ing he mos equen . Women p esen ed lymphocy openia (59%) and ele a ed C- eac i e p o ein (CRP) (70%). Deli e y by ce- sa ean sec ion was pe o med in 91% o g a idas. Th ee ma e - nal in ensi e ca e uni admissions we e no ed bu he e we e no ma e nal dea hs. One neona al dea h and one in au e ine dea h we e epo ed. The au ho s concluded ha al hough he majo i y o mo he s we e discha ged wi hou majo complica ions, se e e ma e nal mo bidi y and pe ina al dea hs as a esul o COVID-19 we e also epo ed. Ve ical ansmission o COVID-19 could no be uled ou . Ca e ul moni o ing o p egnancies wi h COVID-19 and measu es o p e en neona al in ec ion a e equi ed. Di Mascio e al. [23] pe o med ano he sys ema ic e iew o p egnancy and pe ina al ou comes o 79 co ona i us spec- um in ec ions, pa icula ly SARS-COV-2. Pneumonia was diagnosed in 91.8% o cases, he mos common symp oms be- ing e e (82.6%), cough (57.1%) and dyspnea (27.0%). Fo all co ona i us in ec ions, he a e o misca iage was 39.1%; he a e o p e e m bi h < 37 weeks was 24.3%), while p e- ma u e p elabo up u e o memb anes was epo ed in 20.7%, p eeclampsia in 16.2%, and e al g ow h es ic ion in 11.7%. Deli e y was by cesa ean sec ion in 84% o women; pe ina al dea h occu ed in 11.1%, and 57.2% o newbo ns we e admi - ed o he neona al in ensi e ca e uni (NICU). When ocusing on COVID-19 in ec ions, he mos common ad e se p egnancy ou come was p e e m bi h < 37 weeks, occu ing in 41.1% (95% CI 25.6-57.6) o cases, while he a e o pe ina al dea h was 7.0% (95% CI 1.4-16.3). None o he 41 assessed new- bo ns showed clinical signs o e ical ansmission. Elsha eey e al. [36] epo ed a sys ema ic e iew and me- a-analysis o COVID-19 du ing p egnancy and childbi h. They summa ized he clinical p esen a ion and obs e ic ou comes o 33 s udies including da a om 385 cases o which 14 (3.6%) we e se e e and 3 (0.8%) we e c i ical. These 17 women we e admi ed o he in ensi e ca e uni ; 6 o he 17 we e mechani- cally en ila ed and one case died. A o al o 252 women ga e bi h, 175 (69.4%) by cesa ean sec ion and 77 (30.6%) h ough aginal deli e y. Ou comes o 256 newbo ns included ou e- e se- ansc ip ion polyme ase-chain- eac ion (PCR) posi i e cases, wo s illbi hs, and one neona al dea h. The au ho s con- cluded ha he clinical cha ac e is ics and se e i y o he disease we e simila o wha is obse ed in non-p egnan women o men. In addi ion, he e iew o 256 newbo ns showed ha 8 we e ad- mi ed o he NICU (3.1%), 3 needed neona al mechanical en- ila ion (1.2%), 12 had espi a o y dis ess synd ome (4.7%), 3 had pneumonia (1.2%), and 3 dissemina ed in a ascula coagu- la ion (1.2%). Mo ali y occu ed in 3 cases and he e we e wo s illbi hs in ol ing wo c i ical women (one case o ma e nal mo ali y and one woman on ex aco po eal memb ane oxygen- a ion). In addi ion, he e was one ea ly neona al dea h, which occu ed due o complica ions o p ema u i y ollowing cesa ean deli e y a 34 weeks a e an epa um hemo hage. Respi a o y assessmen Ches adiog aphy, compu ed omog aphy (CT) and/o ches ul asound o pa ien s wi h COVID-19 pneumonia a e e y impo an o ea ly diagnosis and ollow-up. Radiog aphic im- ages o hese pa ien s show inc eased opaci ies wi h bila e al lowe lobe p edominan dis ibu ion, whe eas lung ul asound shows hickened pleu al lines and pa chy consolida ions, and CT shows consolida ions [14,37-39]. These indings we e consis - en wi h he expe ience epo ed by Peng e al. [40] and Poggiali e al. [41], con i ming he impo an ole o lung ul asound in he managemen o pa ien s wi h SARS-CoV-2, gi en ha i al- lows apid diagnosis and moni o ing o COVID-19 pneumonia and i s e olu ion owa d acu e espi a o y dis ess synd ome (ARDS) in c i ically ill pa ien s. Ul asound ches exam may be p e e ed in p egnan women. As men ioned abo e, his shows hickened pleu al lines and pa chy consolida ions. These ypes o image ha e epea edly been epo ed by adiologis s as a undamen al pa o he ea ly diagnosis and moni o ing o he e ec s o ea men in COVID-19 pneumonia [37,38]. Labo a o y indings and diagnos ic es du ing p egnancy Labo a o y es indings include lymphocy openia, h ombocy- openia, leukopenia, and ele a ion o D-dime and e i in [14]. Lymphocy openia (59%) and ele a ion o CRP (70%) a e among he mos equen labo a o y abno mali ies obse ed in g a idas [30]. In p egnancy, D-dime canno be conside ed a ma ke o se- e i y due o i s physiological ele a ion du ing ges a ion [42]. Xu e al. [17] epo ed e ospec i e esul s o i e p egnan women a > 34 weeks’ ges a ion wi h a posi i e PCR es o SARS-CoV-2. These women displayed lymphopenia (<1.1 × 109/L) and eosinopenia (<0.02 × 109/L) a he onse o e e . The iming o eosinopenia la gely ma ched ha o lymphope- nia. Lymphopenia and eosinopenia pe sis ed un il he pa ien s’ illness clinically and adiog aphically imp o ed a e an i i al/ an ibac e ial ea men . In con as , leukopenia was obse ed in only one pa ien , while all he women had anemia, dec eased albumin, and inc eased CRP and D-dime le els. Diagnos ic es s pe o med o SARS-CoV-2, an ibodies and/o PCR, whe he an epa um, in apa um o pos pa um, will depend on he possibili ies o each cen e o heal hca e sys- em. Howe e , gi en he possibili y o alse nega i es i is im- po an also o ake in o accoun he symp oms o he pa ien [43]. This app oach would allow us o classi y hem as con i med, possible, imp obable, o unin ec ed, and ac acco dingly. Based on da a om se e al publica ions, Se hu aman e al. [44] ha e desc ibed how o in e p e diagnos ic es s used o SARS- CoV-2 and sugges mo e es o be done. Despi e his, hey speci y ha he epo ed ime in e als should be conside ed app oxima ions and may in ac a y o e ime. Thus, hei sug- ges ion is only applicable i pa ien s a e p oac i ely ollowed since he ime o exposu e, which is no easy in clinical p ac- ice, and expensi e when aking in o accoun all he echniques equi ed and all he se ings in ol ed. The mos commonly used and eliable es o diagnosis o COVID-19 has been he e e se- ansc ip ion polyme ase PCR es , pe o med om na- sopha yngeal swabs o o he uppe espi a o y ac specimens, including h oa swabs o , mo e ecen ly, sali a samples. The Pe ez-Lopez FR e al Gynecological and Rep oduc i e Endoc inology and Me abolism 2020; 1(2):70-75 73 COVID-19 and Human P egnancy Gynecological and Rep oduc i e Endoc inology and Me abolism 2020; 1(2):70-75 i us can be de ec ed a day 1 o symp oms and peaks wi hin he i s week o symp om onse ; he posi i i y declines by 3 weeks and om hen on i becomes unde ec able. A “posi i e” PCR esul e lec s only he de ec ion o i al RNA and does no necessa ily indica e he p esence o iable i us. Managemen o COVID-19 and p egnancy The ini ial managemen o COVID-19 p egnan cases was no associa ed wi h se e e ma e nal mo bidi y o mo ali y. Howe - e , mo e ecen epo s sugges ha a subse o p egnan wom- en may su e o gan ailu e o e en die. P egnan women ha e a s a e o inc eased h ombin and p o h ombin sec e ion ha enhances he h ombosis isk when hey a e a ec ed by COV- ID-19. Hospi al managemen should be ocused on ea ing he mo he and p o ec ing he newbo n and heal h pe sonnel. In gen- e al, managemen is also ex apola ed om ha used o he gen- e al popula ion, and consis s o moni o ing i al signs, oxygen he apy, moni o ing e al well-being and p ophylac ic an ibio ic use o bac e ial pneumonia. Some cen e s ha e used an i i al he apies (i.e. lopina i , i ona i and hyd oxychlo oquine) bu , o da e, he e is no clea e idence o hei e ec i eness. A p ophylac ic dose o a low molecula weigh hepa in (LMWH) is ecommended o hospi alized pa ien s wi h COV- ID-19 o p e en enous h omboembolism, and a ea men dose o LMWH is con empla ed o hose wi h signi ican ly aised D-dime concen a ions due o conce ns o h ombin in he pulmona y ci cula ion; LMWH also has an i-in lamma o y p ope ies ha migh be bene icial in COVID-19 pa ien s. The In e na ional Socie y o Th ombosis and Hemos asis has gen- e a ed a simple algo i hm o he managemen o COVID-19 coagulopa hy [45]. The use o LMWH has been ecommended in all such pa ien s [46]. This body o e idence should be con- side ed by obs e icians ca ing o p egnan women a ec ed by COVID-19. A coagula ion p o ile o de ec he p esence o sub- clinical dissemina ed in a ascula coagula ion and he use o LMWH o he p e en ion o h omboembolic diso de s should be conside ed and discussed be ween clinicians and pa ien s [46]. Misca iage and p e e m bi h isk Al hough misca iage and second imes e losses ha e been desc ibed in SARS-CoV-1 and MERS-CoV in ec ed p egnancy [28,47], no di ec associa ion could be demons a ed [48]. To da e, he ela ionship wi h SARS-CoV-2 has no been demons a ed ei he [32], al hough he i s case o pe ina al mo ali y in a p ema u e newbo n has al eady been desc ibed [30]. A ecen sys ema ic e iew by Di Mascio e al. [23] epo ed ha co ona i us in ec ed p egnan women (including SARS- CoV-1, SARS-CoV-2 and MERS-CoV) p esen misca iages, p ema u i y, p obably due o ia ogenesis, and pe ina al dea h among he > 90% who also had pneumonia. As ega ds he e- la ionship be ween SARS-CoV-2 and p e e m bi h, his e en has been mainly associa ed wi h ia ogenesis, being due o he e mina ion o p egnancy o main ain ma e nal well-being [23,49]. The isk o e al hypoxia is p obably seconda y o ma e nal hy- poxia due o COVID-19 pneumonia, a he han o di ec i al in ol emen which has no been demons a ed. New in o ma ion has come om a single p egnan woman wi h symp oma ic COVID-19 associa ed wi h se e e p eec- lampsia and placen al ab up ion, in whom i al p esence was demons a ed by molecula and immunohis ochemical assay and elec on mic oscopy [50]. SARS-CoV-2 was localized in he ma e nal in e phase o syncy io ophoblas ic cells, sugges ing ha in some g a idas he i us can a ec he placen a. Deli e y Du ing he pandemic, i is impo an pe o m a PCR sc een- ing a deli e y in o de o know who is i ally ac i e o he SARS-CoV-2. This is necessa y o imp o e he clinical ca e o p egnan women and newbo ns, and o p o ec heal hca e pe sonnel, who mus also be equipped wi h pe sonal p o ec i e equipmen (PPE). I sc eening is no possible, he decision o ake hese p o ec i e measu es would ha e o be based on he p esence o symp oms compa ible wi h he disease. Cau ion should also be exe cised wi h asymp oma ic cases who had symp oms in he pas wo weeks, who ecen ly had a isky con- ac , o who a e unde i al sc eening. A he ime o deli e y, p egnan women wi h COVID-19 may ha e e iden clinical symp oms o he espi a o y synd ome and PPE mus be wo n o assis hem. Howe e , he e a e also cases wi hou clinical symp oms o signs o he disease who may subsequen ly be diagnosed wi h COVID-19. Managing e e y ype o pa ien as a high- isk case may gene a e huge heal hca e cos s. Vin zileos e al. [51] sc eened, o COVID-19 immune s a- us, 161 p egnan women admi ed o he labo and deli e y a ea. They ound ha 19.9% we e COVID-19 posi i e (32/161 pa ien s). O hese, 34% (n=11) we e asymp oma ic and 66% (n=21) we e symp oma ic. The au ho s epo ed se e al ind- ings ela ed o ou ine COVID-19 es ing: (i) ou ine es ing would ha e shown he need o PPE use in an addi ional 21 (asymp oma ic) pa ien s; (ii) he e we e 5 pa ien s wi h clinical symp oms who had a nega i e es ; (iii) es ing would inc ease by 10% he iden i ica ion o in ec ed g a idas (16/161); and (i ) all 32 COVID-19-posi i e mo he s had nega i e COV- ID-19 es ed neona es. Ma e nal es ing du ing labo makes i possible o iden i y g a idas needing o be ca ed o using PPE, and o be e alloca e clinical esou ces such as ches imaging, oxygen use, and ans e s o nega i e-p essu e ooms. In addi- ion, es ing may o e come he p oblem o mo he s ending o “downplay”/deny hei symp oms in o de no o be sepa a ed om hei newbo ns. This ype o s udy should be con i med in di e en clinical scena ios and coun ies. All heal hca e pe sonnel a ending women in ac i e labo should wea ull PPE. Ashokka e al. [45] ha e gi en some gen- e al/s anda d ecommenda ions abou ma e nal ca e du ing de- li e y o educe he isk o in ec ion. Due o he possibili y o i al dissemina ion du ing in ense exhaling ela ed o he pain o ac i e labo , ea ly epidu al analgesia o pain con ol should be conside ed. Ad anced en ila o y and ci cula o y suppo , in an in ensi e ca e uni , should be p o ided, by specialis s, o cases p esen ing wi h se e e complica ions such as pneumonia, ARDS, and mul i-o gan dys unc ion synd ome.. Up o 93% o desc ibed COVID-19 p egnancy cases ha e 74 been deli e ed by cesa ean sec ion, he majo i y due o he e - ec s o COVID-19 du ing ges a ion and he isk o impai ed e al well-being [30,52]. In o he cases cesa ean sec ion has been indica ed o main enance o ma e nal well-being, which can lead o ia ogenic p ema u i y [23,24,49]. In some elec i e cases i s jus i ica ion should be ques ioned [53]. Pue pe ium and e ical ansmission The i s se ies o p egnan SARS-CoV-2 cases ailed o demons a e e ical ansmission o he e us, ei he in au e - ine o h ough he bi h canal. Fu he mo e, he i us has no been de ec ed in aginal luid o in ma e nal milk [24,54-58], al- hough i appea s o ha e been de ec ed in s ool [9]. Six newbo ns wi h ele a ed IgG an ibodies in he blood and some cases wi h ele a ed IgM ha e been desc ibed, al hough none o hese cases yielded a posi i e PCR es [59,60]. The e is a need o mo e co ela ional s udies. The e is one case in which SARS-CoV-2 was diagnosed by PCR in a newbo n a 36 hou s o li e, bu he au ho s hemsel es indica ed ha al hough his could be a case o e ical ansmission, con i ma ion was no possible and his possibili y s ill needs o be con i med [61]. Rod igues e al. [62] ca ied ou a sys ema ic e iew o 30 o ig- inal s udies wi hou language es ic ion, and i espec i e o s udy quali y. These s udies epo ed 182 deli e ies esul ing in one s illbi h and 185 li e bi hs. In all cases amnio ic luid, placen a and/o co d blood we e analyzed and ound o be neg- a i e o COVID-19. In addi ion, b eas milk samples om 13 mo he s showed no e idence o p esence o he i us. B eas eeding may be allowed depending on ma e nal and neona al heal h s a us, and i s p ohibi ion should be decided on an indi idual case basis, a e discussion wi h a physician (in ec ious disease specialis ) and neona ologis [63]. Fu u e di ec ions COVID-19 has changed he way medical p ac ice should be add essed in he nea u u e. The e is no speci ic ea men o COVID-19 and cu en managemen is ocused on main- aining en ila o y and ca dio ascula unc ions and p e en ing h omboembolism. Fo he momen , he e is no clea e idence o any speci ic co ona i us an i i al he apy. Fu u e p og ess may be ela ed o he de elopmen o a speci ic accine o p e- en he in ec ion. Re e ences 1. Kim JM, Chung YS, Jo HJ, e al. Iden i ica ion o Co ona i us Isola ed om a Pa ien in Ko ea wi h COVID-19. 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Con lic o In e es : None ORCID Iden i ica ions RSC, h ps://o cid.o g/0000-0001-9585-0187 IAB, h ps://o cid.o g/0000-0001-6381-5758 PC, h ps://o cid.o g/0000-0002-1556-3979 MAG, h ps://o cid.o g/0000-0003-3500-8822 MCTD, h ps://o cid.o g/0000-0003-4720-8231 FRPL, h ps://o cid.o g/0000-0002-2801-416X