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Correspondence| Volume 52, ISSUE 8, P816-818, August 2020

Lights and shadows of SARS-CoV-2 infection risk assessment in endoscopy

      Dear Editor
      The literature related to endoscopy during the SARS-CoV-2 pandemic makes for interesting reading. The current advice and guidelines proposed by Scientific Societies are unfortunately based on low-grade evidence (expert opinions/observational studies) [
      • Gralnek I.M.
      • Hassan C.
      • Beilenhoff U.
      • et al.
      ESGE and ESGENA position statement on gastrointestinal endoscopy and the COVID-19 pandemic.
      ]. Moreover, no studies provide a true estimate of the infection risk in the Endoscopy Unit (EU), but the limited evidence available concludes that SARS-CoV-2 transmission in EUs is low risk, if all the preventive measures are adopted [
      • Repici A.
      • Pace F.
      • Gabbiadini R.
      • et al.
      Endoscopy units and the COVID-19 outbreak: a multi-center experience from Italy.
      ,
      • Repici A.
      • Aragona G.
      • Cengia G.
      • et al.
      Low risk of covid-19 transmission in GI endoscopy.
      ]. However, this assumption is based on surveys conducted in centers not homogeneously involved in the SARS-CoV-2 pandemic [
      • Repici A.
      • Pace F.
      • Gabbiadini R.
      • et al.
      Endoscopy units and the COVID-19 outbreak: a multi-center experience from Italy.
      ,
      • Repici A.
      • Aragona G.
      • Cengia G.
      • et al.
      Low risk of covid-19 transmission in GI endoscopy.
      ]. Furthermore, regarding the methodology of the administered questionnaires, some of the information was collected using only the personal impression of the physicians about both the risk of infection and the possible transmission route [
      • Repici A.
      • Pace F.
      • Gabbiadini R.
      • et al.
      Endoscopy units and the COVID-19 outbreak: a multi-center experience from Italy.
      ]. During the pandemic, routine endoscopic procedures have been mostly cancelled or postponed and restricted to urgent cases [
      • Maida M.
      • Sferrazza S.
      • Savarino E.
      • et al.
      Impact of the COVID-19 pandemic on gastroenterology divisions in Italy: a national survey.
      ]. Hence, after the first “pandemic wave”, the topic of re-opening the EU to outpatients and to routine procedures is a matter of debate. Therefore, we believe that the limitations of both available studies and guidelines should be accurately examined. This is mandatory in order to properly assess the SARS-CoV-2 infection risk in EUs and accurately plan their re-opening to outpatients. To date, the only papers that focused on this topic, although very interesting, are mainly descriptive [
      • Elli L.
      • Raimondi A.
      • Scaramella L.
      • et al.
      Endoscopy during the COVID-19 outbreak: experience and recommendations from a single center in a high-incidence scenario.
      ] and base their observation solely on the aforementioned low-grade evidence [
      • Cennamo V.
      • Bassi M.
      • Landi S.
      • et al.
      Redesign of a GI endoscopy unit during the COVID-19 emergency: a Practical Model.
      ].
      Firstly, little is known about the biology of the virus and its infection routes (e.g. fecal-oral route). The risk estimation is difficult considering that the diagnosis of SARS-CoV-2 infection is currently based on throat swab testing, with overall sensitivity ranging from 56 to 83%: 66.7% in the first week of the infection and lower in the following weeks [
      • Zou L.
      • Ruan F.
      • Huang M.
      • et al.
      SARS-CoV-2 viral load in upper respiratory specimens of infected patients.
      ]. Moreover, the test represents only a “single frame” over a long period, as undetectable viral load could be present in the different stages of the infection. The low accuracy of throat swab testing could be related to improper collection or contamination of samples, inappropriate sites of the throat, inexperienced staff, improper laboratory equipment or storage [
      • Mungroo M.R.
      • Khan N.A.
      • Siddiqui R.
      • et al.
      Novel Coronavirus: current understanding of clinical features, diagnosis, pathogenesis, and treatment options.
      ].
      The general transmission risk of an infectious disease is strictly related to its prevalence in the population. While the rate of spread was especially high in northern Italian regions, each province showed a very different official disease prevalence (Table 1). At the time of the conducted surveys, the risk both inside and outside the enrolled centers was very different, thus 3 out of 41 centers accounted for almost 55% of all Health Care Worker (HCW) infections [
      • Repici A.
      • Pace F.
      • Gabbiadini R.
      • et al.
      Endoscopy units and the COVID-19 outbreak: a multi-center experience from Italy.
      ]. The authors attributed these differences to suboptimal preventive measures, and did not consider the different rates of disease prevalence. It would have been interesting to extend the survey period, in order to make the evaluation more reliable, as the illness prevalence became more homogeneous after the first weeks, and COVID-19 patients were more equally distributed within the different centers after saturation of first line hospitals.
      Table 1Prevalence of SARS-CoV-2 infected subjects in the northern Italian provinces at the end of the periods considered in the surveys (1,2] (data from Italian National Health Institute).
      ProvincesPopulationInfected (N.) on 13 th MarchInfected (%)Infected (N.) on 23 th MarchInfected (%)
      Milano3,197,00013070,04053260,166
      Cremona359,00013440,37429250,814
      Monza876,0001430,01611300,128
      Pavia546,0004820,08814440,264
      Bergamo1,116,00023690,21264710,579
      Brescia1,266,00017840,14059050,466
      Como599,0001180,0195810,096
      Lecco337,0002370,0709340,277
      Varese891,0001250,0144210,047
      Lodi230,00011330,49018170,790
      Piacenza287,0007100,24718850,656
      Bologna1,003,0001550,0158330,083
      Rimini339,0003630,10710350,305
      Forlì-Cesena395,000490,0123800,096
      Ravenna389,000550,0143420,087
      Ancona471,0001580,0337020,149
      Pesaro359,0004960,13813120,365
      Novara368,000480,0134200,114
      Verona929,0002100,02210990,118
      Moreover, the re-organization of hospitals and activities during the pandemic strongly influenced the infection risk assessment among operators and patients. At the beginning of the pandemic, many public hospitals were almost completely converted into COVID-19 facilities, whereas other Institutes were only partially dedicated to it. Furthermore, EU personnel in northern Italy was redeployed to COVID-19 direct assistance roles. Hence, there is no possible way to definitively understand where HCW infections happened: in EUs, in COVID-19 dedicated Units or outside the hospitals, since the surveys were conducted temporally close to the Italian lockdown date.
      Lastly, the studies stating a low risk of infection in EUs evaluated only the development of clinically relevant COVID-19 [
      • Repici A.
      • Pace F.
      • Gabbiadini R.
      • et al.
      Endoscopy units and the COVID-19 outbreak: a multi-center experience from Italy.
      ,
      • Repici A.
      • Aragona G.
      • Cengia G.
      • et al.
      Low risk of covid-19 transmission in GI endoscopy.
      ]. However, no definitive data is available to predict who could develop a severe disease versus who could remain asymptomatic but infectious. Moreover, recent evidence from Wuhan highlighted that more than 59% of infections were not confirmed by tests, thus asserting the presence of potentially contagious asymptomatic subjects [
      • Ozma M.A.
      • Maroufi P.
      • Khodadadi E.
      • et al.
      Clinical manifestation, diagnosis, prevention and control of SARS-CoV-2 (COVID-19) during the outbreak period.
      ]. The viral load in asymptomatic patients was also found to be similar to that of symptomatic ones. On this basis, coupling more diagnostic tests (e.g. serology) could be useful.
      Accounting for these factors and for the lack of real prevalence data, the estimation of the general risk of acquiring SARS-CoV-2 in the population and consequently in the hospital and EUs is challenging. Our province of Cremona has, up to now, the highest Italian prevalence of SARS-CoV-2 infections (1/65 people) and our Institute admitted almost 3000 COVID-19 inpatients during the first two months of the European pandemic. After three months, in our hospital, we reported overall 355 infected HCWs out of 1650 (21.5%). In our EU 6 out of 25 (24%) HCWs were infected, despite the adoption of recommended preventive measures; whereas in the Internal Medicine division (where 120 beds were entirely dedicated to COVID-19 assistance) 11 out of 51 HCWs were infected (21.5%). These limited figures did not show any statistically significant difference between the prevalence of infection within EUs, COVID-19 s department and overall hospital settings in an high risk area (p = 0.99). To our knowledge, no study has methodologically calculated the infection risk in EUs, while taking into consideration the disease prevalence inside and outside the hospital.
      Importantly, the number of potentially asymptomatic infections could be even higher than recognised. In our Institute HCWs were tested for high specific and early anti-SARS-COV2 neutralizing antibodies IgG3, a subclass usually associated with viral infections (the same antibodies used as treatment in COVID-19 patients) [
      • Chen L.
      • Xiong J.
      • Bao L.
      • Shi Y.
      Convalescent plasma as a potential therapy for COVID-19.
      ]. This test was offered to identify potentially asymptomatic but infected HCWs. Throat swab testing was then performed and assessed, if the serology resulted positive. From this, we observed that 1 out of 25 HCWs in EU and 2 out of 51 HCWs in the Internal Medicine COVID-19 Unit, with no clinical history, had positive antibodies and subsequently a negative swab test result (4 vs 3.9%, respectively p = 0.99). From this data we could hypothesize that several HCWs could have increased the infection risk as asymptomatic carriers and have since recovered.
      Hence, we think that considering EUs as low-risk areas for SARS-CoV-2 infection could be a premature assumption. Further studies are needed to investigate the real risk, above all in light of the re-opening of endoscopic activity to outpatients.
      CreSCoV Working Group (Gruppo Cremonese di studio clinico su COVID-19)
      Collaborators:
      Abruzzi Luciano†, UO Neurologia ASST di Cremona
      Bosio Giancarlo, UO Pneumologia ASST di Cremona
      Buffoli Federico UO Gastroenterologia e Endoscopia digestiva ASST di Cremona
      Buselli Paolo, UO Riabilitazione specialistica ASST di Cremona
      Barletta Giovanna, UO Anestesia e Rianimazione ASST Cremona
      Cammelli Lorenzo Direzione Medica ASST di Cremona
      Canino Rosario Direzione Sanitaria ASST di Cremona
      Caresana Gioacchino, UO Dermatologia ASST di Cremona
      Cavalli Claudio, UO Pediatria ASST di Cremona
      Coluccello Antonio, UO Anestesia e Rianimazione ASST di Cremona
      Coppeta Giovanni Paolo, UO Pronto Soccorso ASST di Cremona
      Crotti Massimo, UO Immunoematologia e Medicina Trasfusionale ASST di Cremona
      D'Anna Mauro, UO Medicina del Lavoro ASST di Cremona
      Danzi Gian Battista, UO Cardiologia ASST di Cremona
      De Gennaro Fabio; UO Medicina Interna ASST di Cremona
      Faliva Alessio, UO Terapia del dolore ASST di Cremona
      Fioravanti Antonio, UO Neurochirurgia ASST di Cremona
      Foramitti Marina, UO Nefrologia ASST di Cremona
      Fornabaio Chiara, UO Malattie Infettive ASST di Cremona
      Fornaciari Margherita, UO Medicina Legale e Rischio Clinico
      Generali Daniele, UO Patologia Mammaria e ricerca traslazionale ASST di Cremona
      Giannotti Guglielmo, UO Chirurgia Generale ASST di Cremona
      Giorgi Pierfranceschi Matteo, UO Medicina Generale ASST di Cremona
      Giossi Alessia, UO Neurologia ASST di Cremona
      Machiavelli Andrea Marco, UO Farmacia ASST di Cremona
      Malberti Fabio, UO Nefrologia ASST di Cremona
      Molteni Alfredo, UO Ematologia ASST di Cremona
      Nardecchia Anna Laura, UO Medicina Generale ASST di Cremona
      Paoletti Oriana, UO Centro Emostasi e Trombosi ASST di Cremona
      Pan Angelo UO Malattie Infettive ASST di Cremona, Cremona, Italy
      Pasin Federico, UO Medicina Generale ASST di Cremona
      Pasquali Nicola, UO Chirurgia Generale ASST di Cremona
      Passalacqua Rodolfo, UO Oncologia ASST di Cremona
      Pezzarossa Enrico, UO Dermatologia ASST di Cremona
      Pezzetti Federica, Direzione Medica ASST di Cremona
      Pianta Luca, UO Otorinolaringoiatria ASST di Cremona
      Romanini Laura, UO Radiologia ASST di Cremona
      Ruggeri Patrizia, Centro Diabetologico ASST di Cremona
      Silla Alberto, UO Gestione Operativa ASST di Cremona
      Soro Sara, UO Gastroenterologia ed Endoscopia Digestiva ASST di Cremona
      Tonoli Sandro, UO Radioterapia e Medicina Nucleare ASST di Cremona
      Ungari Marco, UO Anatomia Patologica ASST di Cremona
      Viola Erika Maria, UO Ortopedia ASST di Cremona
      Zoncada Alessia, UO Malattie Infettive ASST di Cremona

      Declaration of Competing Interest

      The authors declare they do not have any conflict of interest

      Acknowledgement

      None

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