ID. ANTAGE [rsGsapal, 202091] Ierratina Journal of Antimicrobial Agents Ge) 200 ELSEVIER Contents lists available at ScioncaDiract International Journal of Antimicrobial Agents Journal homepage: www.clsevier com/ocataiiantimicag SARS-CoV-2: fear versus data Yanis Roussel®’, Audrey Giraud-Gatineau““*, Marie-Thérése Jimeno, Jean-Marc Rolain*», Christine Zandotti*”, Philippe Colson*, Didier Raoult®* “inti Hosp amivestie Méierande infection, Marl, Fence °c Mere UnerstéIstt de Recherche pour fe evlopementAstoce Publique Hiptux de Mase, Mcrabes Evolution Mhyogni et Infetons Mandi France hi Marile Unerat Istiat de Recherche pore Développement, AsitancePublign-Hiptaut de Masi, Service de Som dex Armes, Vcteurs = Infections rps et deranente, Masel Fence ere pinged sant Pabge des ren, Manele, Pace ARTICLE INFO ABSTRACT ‘ele sy De Posen Hsueh SARS-CoV.2, the novel coronavirus ffom China. is spreading around the world. causing a huge reattion despite its curtent low incidence ousice China and the Far East. Four commen corenavirses are in cur reot circulation and cause miions of cases worldwide. This article compares the incidence and mortality rates of these four common coronaviruses with those of SARS-CoV-2 in Organisation for Economic Co- Rovers operation snd Development courte, is concluded that the problem of SARS-COV. ob being So overestimated as 26 lion people dio espatory infections each year compared wi es than 4000 Sees Sst fr SARSCoV-2 at he tine of wing {© 2020 ever BV and Iteratonal Sct of Cemabeapy. Al ight reseed. 1. Introduction 90 000 people worldwide [2.1920], at the time of waiting, 3 Coronaviridae represent avery important family of animal and human viruses [1,2) that are in permanent circulation. Four ‘common human cofonaviruses (HKUI, NLS3, OC43 and £229) ‘cause 10-20% of respiratory infections worldvride and are present in all continents (314) (Table 1). Mortality is poorly assessed, but it is clear that there are chronic carviers as well as asymptomatic carriers. Studies have shown that there are as many asymptomatic ‘artiers as symptomatic patients [3,9]. Three epidemic episodes of ‘emerging coronaviruses have been reported. The first, severe acute respiratory syndrome (SARS) coronavirus, had very little impact on global morbidity and mortality, with mote than 8000 recognized ‘eases and 74 deaths (15.16). The second, Middle East respira- tory syndrome (MERS)-coronavirus, remained localized in Saudi ‘Arabia, with a small epidemic of mainly nosocomial infections in South Korea [17], MERS-coronavirus, like SARS-coronavirus, high- lighted the major danger of nosocomial transmission to healthcare personnel, the health of whom is essential in these epidemics [16 Finally, SARS-CoV-2, the novel coronavirus that appeared in December 2019, has expanded and has now affected more than Conesponding. autor, Aléress: THU Mediteranée Inecon, Face de Médecine. AicNarsile Université, 27 Roulevard Jen. Modlin, 13385 Masel (CEDEX 5. ance Te: +33 (O81 324375: fe + 35 (09 81 3877 72 ma dr: erasers (. Rael. psd rg)01016 antimieg 207010597 Significant number of cases had occurred in the Far East. It is incontestably contagious, as a quasi-experimental study on the Diamond Princess cruise ship showed that confinement of infected patients with uninfected patlents resulted in rapid infection of the ‘uninfected patients, leading to 700 additional cases on board [21 However, coronaviruses in common circulation remain predomi- nant because of their global distribution and their non-negligible mortality (14,22), The aim of this study was to share the experi- fence of a reference laboratory representing approximately 1% of serious and diagnosed respiratory infections, particularly seasonal, in France. This will allow the evaluation of the relative mortality of| lifferent human coronaviruses presented in hospitals in Marseille ‘compared with that of SARS-CoV-2. 2. Materials and methods ‘Assistance Publique-Hpitaux de Marseille (AP-tM) covers all public hospitals in Marseille, including four university hospitals: La Timone Hospital, Conception Hospital, North Hospital and South Hospital; this corresponds to 3400 beds and 125 000 admissions each year [23]. The IHU Méditerranée Infection diagnostic Iabo- ratory tests all samples ftom AP-HM in which respiratory viruses are suspected. Molecular biology is used for diagnosis. The re- sults are monitored by a weekly automated surveillance system In the diagnostic laboratory, coupled with a laboratory informa- (324857916 2020 Eleier BV. ad ntermaonlSaciety of Chemotherapy Al rit reserved. Please cite this article as: ¥. Roussel, A. Giraud-Gatineau and M-T. Jimeno et al, SARS-CoV-2: fear versus data, International Journal of| ‘Antimicrobial Agents, hps:/(do.org10-1016)jijantimicag-2020.105947,BD ANTACE 2 Studies tat ested for coronavius in patents with ever i various counties [rsciApe 5 220950) Rouse A Goud Cainews ond MT nen e/ieratona ore of AntnirobialAgns xx x) SARS-CoV-2 Intemational epidemloiea! stuation (Organisation fr Fzonomie Co-operation and Developrent counties, 3 Match 2020, Fie author cuniy Tested cases (@) agnosis af [etrence number coranaes Countries Confined ses (e) Deaths (w)__ Movaly rate) ‘mbes [7] eal 75 7a Germany 157 ° ry ‘hang (10) Coane, china 15 048 24 2258) stala 30 1 33 2eng 11] {Guangzou, Chine 11.399, 499 438) Asta is ° oo Kilesby 14) USA 18805 22 Pelgium s ° bo iyuka 13] rena 3513 sors canada ey ° oo Ow (9), hana 505 cases wr South Korea 4535 cn os Dube (30) South Alta 620 controls 108% Deana 4 ° oo 214 (uberculass) 5 spas iv ° oo Sipuva [i2] ena ar bas ton t ° ry Subramoney (31) South Aiea 860 ro tsa 10 5 60 Nunes [32 South Aiea D5 1s Finland 7 ° oo tei 3) Vieam a8 (1.05%) France 191 3 16 Gree 7 ° oo irl 1 ° bo ‘able? lela 3 ° oo sults ftom Assance PublgueHopitaux de Musee (APM) dignostc ach, 0 ° oo bratry aly 2036 32 25 aso Location Confirmed Deaths Mortality ee ve 3 a eases) tees) tet ° ee Coronavins MMA3 Mare 78 2 0270 Norway Fa ° oo Coronavins HKU sell, 1 00158 New Zealand ° oo Corenavnis £229 France 92 1 ‘0109 Netherands 18 ° oo Cownavnis AP Portugal 2 ° oo Corenavinis 0683 HM, 77 1 00190 sweden is ° ry Coronavinis lex Mars 48 0 ° Switzerland 38 ° bo coronavirus HKU elle, 277 1 0036 ris 0 ° bo Corenavins £229 France 48, o ° Tea maT 96 3 * From {January 2013 fe 31 December 2018. From 1 Janary 2020 02 March 2020 tion system (Nexlabs) [23]. SARS-CoV-2 epidemiological data were fobiained through an online platform gathering data from public agencies |24). Statistical analyses were performed using BiostatGV software 3. Results In 2016, there were 594 000 deaths in France; 59.2% of these deaths occurred In a cate establishment [25]. In the same year, ‘AD-HM reported 2854 deaths. As such, it can be estimated that approximately 0.8% of deaths in care establishments in France oc- cuted in AP-HM hospitals. This estimate provides an approxima- tion of the number of people affected by a pathogen in France ac- cording to the number of people who died each year at AP-HM hospitals. From 1 January 2013 to 31 December 2019, 21 662 samples, were tested by the IHU Méditerranée Infection diagnostic labora- tory. Among these, 770 samples were positive for coronavirus, with eight deaths (mortality rate 1%). Among identified coronaviruses, 63 were identified as HKU1 (one death, mortality rate 16%), 74 were identified as NLO3 (two deaths, mortality rate 2.7%), 92 were Identified as £229 (one death, mortality rate 11%) and 160 were identified as 0C43 (four deaths, mortality rate 2.5%). Three hun- red and eighty-one coronaviruses, diagnosed before 2017, were ot assigned to any of these four strains (Table 2). ‘Systematic testing (molecular biology) for SARS-CoV-2 was per- formed from 1 January 2020 to 2 March 2020. In total, 7059 samples from patients presenting with infectious symptoms were tested by the IHU Méditerranée Infection diagnostic laboratory, ‘Among them, 543 samples were positive for coronaviruses, with two deaths (mortality rate 0.36%): 277 samples were HKUI, 146 samples were NL63, 77 samples were OC43 and 43 samples were 2296. No cases of SARS-CoV-2 were identified among these sam- ples. Of the two deaths, one patient had OC43 (mortality rate 138) land one patient had HKUI (mortality rate 0.36%). There were no Geaths from NL63 or £229 during this period. ‘Over the same period, IHU Méditerranée Infection was the re sional centre for detection of the novel coronavirus SARS-CoV-2 [At the time of writing. 596 analyses have been performed on sus- pected cases since the emergence of the novel pathogen, from Which four cases of SARS-CoV-2 have been identified. In addition, 337 French nationals returning from Hubei Province have been tested twice, and all were negative for SARS-CoV-2 By 2 March 2020, a total of 90 307 patients have tested posi- tive for SARS-CoV-2 worldwide, with 3086 deaths (mortality rate 3.4x). Among the Organisation for Economic Co-operation and De- velopment (OECD) countries, 7476 patients have tested positive for SARS-CoV-2, with 96 deaths (mortality rate 13%) (Table 3). In France, 191 people have tested positive for SARS-CoV-2, with three deaths (mortality rate 1.6%) ‘his study compared the mortality rate of SARS-CoV-2 in OECD countries (13%) with the mortality rate of common coronaviruses identified in AP-HM patients (0.8%) from 1 January 2013 to 2 “March 2020. Chi-squared test was performed, and the P-value was 041 (not significant). 4, Discussion ‘This study found that the mortality rate of common coronavirus Infections is 0.8% in France. In comparison, the mortality rate of SARS-CoV-2 in European or American developed countries of 2 comparable economic level is 1.3% (Table 3) If the extrapolation of deaths in AP-HM hospitals is correct, in metropolitan France, this Would represent 543/08 * 100 = 67 875 cases of patients hospi- talized with a respiratory infection with common coronaviruses In 2 months, which is almost as many cases as for SARS-CoV-2 worldwide. In fact, mortality from respiratory infections is ex- tremely dependent on the quality of care and access to care, and Please cite this article as: ¥. Roussel, A. Giraud-Gatineau and M7 Jimeno et al, SARS-CoV ‘Antimicrobial Agents, tips: /doiorg/10.10%6)jsjantimicag.2020.105947 Tear versus data, International Journal of|ies ¥. Rowse A. Gnu Gtinea and MT. ineo et aeration fara fAninicobial ens er) 3 severe forms have a better prognosis in countries with supetior ‘medical infrastructures. Under these conditions. there does not seem to be a significant difference between the mortality rate of SSARS-CoV-2 in OECD countries and that of common coronaviruses Ge test, P=0.1). OF course, the major flaw in this study is that the percentage of deaths attributable to the virus is not determined, ‘but this is the case forall studies reporting respiratory virus infec tions, including SARS-CoV-2. Indeed, viral infections are ecosystem infections where the outcome depends on the inoculums and the ‘surrounding microbiota [26]. Thus, certain bacteria seem to be associated with symptomatic manifestations, such as Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus, ‘which are known to cause an excess of mortality due to sec- ‘ondary infection, Finally, seasonality, geographic location, heat and humidity are co-actors, as are age, gender and underlying pathologies. Under these conditions, and all other things being ‘equal, SARS-CoV-2 infection cannot be described as being sta- tistically more severe than infection with other coronaviruses in ‘common circulation. Finally, in OECD countries, SARS-CoV-2 does not seem to be deadlier than other circulating viruses. In addition to coron- aviruses, there are 16 endemic viruses in common circulation jn developed countries (adenovirus, bocavirus, cytomegalovirus, ceoterovirus, influenza A HINT virus, influenza A H3N2 virus, influenza B virus, metapneumovirus, parainfluenzie virus 1, parainfluencae virus 2, patainfluencac vitus 3, parainfluenzac virus 4, parechovirus, picornavirus, rhinovirus, ‘syncytial respi- ratory virus), and 2.6' million deaths from respiratory infections (excluding tuberculosis) per year have been aoted in recent years ‘worldwide (27), There is little chance that the emergence of SARS- CoV-2 could change this statistic significantly. Fear could have a larger impact than the virus itself; a case of suicide motivated by the fear of SARS-COV-2 has been reported in India [28]. In addition, coronaviruses that have rarely been tested system= atically around the world may persist in the pharynx of asymp- tomatic people, representing 2 potential source of population immunity [29]. Furthermore, it should be noted that systematic studies of other coronaviruses (but not yet for SARS-CoV-2) have ound that the percentage of asymptomatic carriers is equal to or even higher than the percentage of symptomatic patients. The ‘same data for SARS-CoV-2 may soon be availabe, which will fur- ther reduce the relative risk associated with this specific pathology. Declarations Funding: This work was supported by the French Government un- dr the ‘Investments for the Future’ programme managed by the "National Agency for Research, Méditerrange-Infection 10-1AHU-D3. Competing interests: None declared. Ethical approval: Not applicable. Testing of repatriates was ap- proved by the ethical board of the Committee for the Protection of Persons (CPP lle de France VI, 6 February 2020) References 101 To KK Hung, Chan Yuen KY. 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