Evaluation of Strategies to Fight COVID-19: The French Paradigm
Authors: Hervé Chaudet
Didier Raoult
Audrey Giraud-Gatineau
Philippe Colson
Philippe Gautret
Journal: Journal of Clinical Medicine (2021)
Discipline: CLINICAL MEDICINE
Keywords: COVID-19; France; Marseille; Paris; SARS-CoV-2
Affiliations: IHU Méditerranée Infection, 13005 Marseille, France., Institut de Recherche pour le Développement (IRD), Assistance Publique-Hôpitaux de Marseille (AP-HM), Service de Santé des Armées (SSA), Vecteurs-Infections Tropicales et Méditerranéennes (VITROME), Aix Marseille University, 13005 Marseille, France., French Armed Forces Center for Epidemiology and Public Health (CESPA), Service de Santé des Armées (SSA), 13014 Marseille, France., Assistance Publique-Hôpitaux de Marseille (AP-HM), 13005 Marseille, France., Institut de Recherche pour le Développement (IRD), Assistance Publique-Hôpitaux de Marseille (AP-HM), Microbes Evolution Phylogeny and Infections (MEPHI), Aix Marseille University, 13005 Marseille, France.

Abstract:  (1) Background: We collected COVID-19 mortality data and the age distribution of the deceased in France and other European countries, as well as specifically in the cities of Paris and Marseille, and compared them. (2) Methods: Data on mortality related to COVID-19 and the associated age distribution were collected from government institutions in various European countries. In France, data were obtained from INSEE and Santé Publique France. All-cause mortality was also examined in order to study potential excess mortality using EuroMOMO. The Marseille data came from the epidemiological surveillance system. (3) Results: France is one of the European countries most impacted by COVID-19. Its proportion of deaths in people under 60 years of age is higher (6.5%) than that of Italy (4.6%) or Spain (4.7%). Excess mortality (5% more deaths) was also observed. Ile-de-France and the Grand-Est are the two French regions with the highest mortality. The proportion of deaths in the under-60 age group was considerable in Ile-de-France (9.9% vs. 4.5% in the Southern region). There are significantly higher numbers of patients hospitalized, in intensive care and deceased in Paris than in Marseille. (4) Conclusions: No patient management, i.e., from screening to diagnosis, including biological assessment and clinical examination, likely explains the high mortality associated with COVID-19. 

Retracted: No

PubPeer comments:
 In the introduction, the authors explain that u201c*no mass screening was then carried out systematically on a national scale in the early stage of this pandemic, which would have made it possible to quickly obtain information on the incidence of the disease*u201d. They should have discussed whether **this strategy was possible or whether testing capacities were sufficient**. This is not discussed. When they later claim that u201cupsurge in the number of cases was observed in early July 2020 when borders were reopenedu201d citations supporting the link between the upsurge and borders reopening are required. They define their strategy, stating that in their institute a therapy, made of hydroxychloroquine and azithromycin was available, relying on reference 8 . It should be noted that this study has u201c*major methodological shortcomings*u201d and is u201c*fully irresponsible*u201d according to Frits Rosendaal https: retractionwatch.com 2020 07 19 french-hydroxychloroquine-study-has-major-methodological-shortcomings-and-is-fully-irresponsible-says-review-but-is-not-being-retracted Thus one can think no therapy was available by July 2020 against Covid-19, neither in Marseille nor anywhere else and understand easily with this suggested unproved treatment was not recommended by authorities as the authors seem to regret. As one can only agree with the statement that u201c*the case fatality due to COVID-19 is a key point of the epidemic situation and provides insights into the management and outcome of COVID-19 according to the health policies*u201d, one should not forget many confounding factors in the correlation between CFR and health policies. One could cite incidence, local particularism, health care coverage and many more. The authors later explain that they collected u201c*mortality in France and at the regional level according to the decedentsu2019 place of residence between 1 January and 31 August for 3 years*u201d. The **place were people were infected** would have been more relevant to compare local policies since we know that, especially in Paris, **many people have travelled** before the first lockdown: https: www.lemonde.fr pixels article 2020 03 26 confinement-plus-d-un-million-de-franciliens-ont-quitte-la-region-parisienne-en-une-semaine_6034568_4408996.html It should also be noted that if u201c*Adjusted estimates of seroprevalences in Ile-de-France, in the Grand-Est, and in New Aquitaine were collected in an article preprinted on MedRxiv in September 2020*u201d this pre-print **still hasnu2019t been published by July 2021**. In the results paragraph, the author starts by a comparison of the number of tests in Iceland Sweden and Denmark while noticing that these countries u201c*did not have strict lockdown measures*u201d. No argument is explained that could give **relevance to this comparison**, furthermore when intending to discuss French data. It should be noted that **Iceland is an island**, thus being difficult to compare to a continental country, and two of these three countries have among the **lowest population density in Europe** ( Iceland 3.6, Denmark 160.6, Sweden 24.3 and France 119.1 https: fr.wikipedia.org wiki Liste_des_pays_par_densit%C3%A9_de_population). Later, the authors are comparing the CFR within European countries. Since it is well established that the CFR is age-dependant, discussing age structure in these countries would have been relevant for the meaning of this comparison. https: royalsocietypublishing.org doi 10.1098 rsif.2020.0982 Discussing incidence of diseases known to be associated with more severe diseases would also have been relevant and is done only by mentioning the lack of data in the conclusion. https: link.springer.com article 10.1007 s15010-020-01502-8 Then, the authors are making comparisons of CFR between French regions relying on figure 2: ![file] It should be noted that other parameters were different, like local incidences differences which are not discussed. ![file] https: geodes.santepubliquefrance.fr #c=indicator i=covid_hospit_incid.incid_hosp s=2020-07-01 t=a01 view=map2 Indeed, we can see a correlation between a high incidence and a high CFR. Since a high load of the hospitals is known to be associated with higher fatality rate, its influence on the observed differences should have been discussed. https: www.nature.com articles s41467-021-22214-z Furthermore, since the authors explain that u201c*Significant differences, particularly in screening and treatment strategies, were observed between Paris, where outpatients were not tested, and Marseille, where outpatients and asymptomatic people were tested*u201d the influence of this factor on the total number of cases, thus on the CFR should also be discussed. This comparison is later graphed: ![file] It should be noted that IHU-Mi does not have Intensive Care Unit and one can reasonably think that the worst cases, those who need ICU will not be sent to IHU, thus decreasing mathematically the CFR for its outpatients, thus this comparison does not seem relevant. https: actu.orange.fr france marseille-l-ihu-de-didier-raoult-ne-dispose-pas-de-lits-de-reanimation-pour-les-patients-atteints-d-une-forme-grave-du-covid-19-magic-CNT000001tUzB0.html One can then be surprised that the authors claim that u201c*The global lockdown or restricted confinement of meeting places has not been able to prove its effectiveness*u201d while the literature has plenty of articles showing the opposite opinion. This assertion should, at least, have been discussed further. https: doi.org 10.3390 ijerph17155574 Furthermore, they assert that u201cseroprevalence surveys and showed that locked-down people tended to have more antibodies against SARS-CoV-2 than othersu201d in Spain, Italy and France, relying on three references. Thee first one (http: doi.org 10.1101 2020.09.16.20195693) is a pre-print simply estimating seroprevalence in u00cele de France, Grand Est and Nouvelle Aquitaine, only 3 french regions. In the second one 31483-5), the authors are much more cautious when writing that u201cWhile mass quarantine during the lockdown would reduce the number of potentially infective contacts, it would also increase the transmission of the virus in a confined space, as a recent simulation study has suggestedu201d. The last one does not even talk about lockdown. Thus, using these three references to support the authorsu2019 assumption can not be endorsed without further explanation or discussion. Their conclusion is simple: u201cthe lockdown does not appear to be essentialu201d. They give 2 references. The first one has important concerns on Pubpeer **regarding methodology** The second one arises several critics for **suggested biases and concerns**: https: pubpeer.com publications 3D81CAC483C2021C00E27C8826DF71 When at last evocating a role of the incidence, the authors write that u201c*The lack of beds cannot therefore explain this high mortality, although France is a country where the number of hospital beds is higher than the average for OECD countries*u201d. Since comparing different French regions, this comparison within Europe is irrelevant. A **comparison between French region** would have been more relevant. Relying on Our World In Data to state that u201c*The earliness and magnitude of PCR testing campaigns seemed to be a determining factor both in Europe and in countries in the Far East such as Korea, Taiwan or China*u201d seems like a correlation whose causality is not discussed therefore being an abusive statement. When discussing about treatments, the authors wonder why u201c*The use of corticosteroid therapy in seriously ill patients considered as basic care by most encyclopedias but which has been strangely re-tested in the u201crecoveryu201d trial*u201d when later writing that u201c*corticosteroid therapy in patients with moderate to medium clinical presentations is not effective and probably leads to an increase in mortality, as was suspected and recently confirmed by the u201crecoveryu201d study*u201d, one can consider that **they have an answer to their question**. The authors writes that u201c*Hydroxychloroquine has shown in a study in 39 public hospitals on 4642 patients in Ile de-France a shortening of the duration of hospitalization*u201d relying on a **pre-print** while this the conclusion of this citation is that its authors u201c*found no evidence for efficacy of HCQ or HCQ combined with AZI on 28-day mortality. Our results suggested a possible excess risk of mortality associated with HCQ combined with AZI, but not with HCQ alone*u201d. Anyway, the authors later state that u201c*the strategy proposed in Marseille with the prescription of hydroxychloroquine and azithromycin may have played a role in the very low mortality observed in a series of 3700 cases*u201d. It should be noted that they do not discuss any of the cofounding factors described above, like incidence. They support this assertion on a self-citation (http: dx.doi.org 10.1016 j.tmaid.2020.101791) tagged on PubPeer for immortality bias and biased inclusion factors . The relevance of the following statement is not clear u201c*In France, during the first wave of the new virus, only one treatment was officially recommended to reduce fever in COVID-19 cases: paracetamol*u201d used as a symptomatic treatment.u201d The authors should explain this. When the authors state that u201c*the natural mortality, observable from three ships with outbreaks of CoV-2-SARS on board, was extremely low, suggesting that in other contexts, mortality should be extremely low in healthy people under 50 years of age*u201d, they rely on data including Diamond Princess whose passengers were mostly older than 50: ![file] https: cmmid.github.io topics covid19 diamond_cruise_cfr_estimates.html Since only concerning outpatients, the statement from the author that u201c*was extremely low in patients seen at Marseille IHU and significantly lower still in those who received hydroxychloroquine and azithromycin treatment in all age groups*u201d is irrelevant since **no link has been established between CFR and the suggested treatment**, furthermore without discussing important confounding factors like the absence of ICU at the IHU. When the authors write that u201c*the model very clearly shows excess mortality in the Ile-de-France and Grand-Est regions compared to the Bouches-du-Rhu00f4ne Department*u201d they explain that this is u201c*despite similar epidemic levels*u201d which is, as seen above, **untrue**. ![file] https: geodes.santepubliquefrance.fr #c=indicator i=covid_hospit_incid.incid_hosp s=2020-07-01 t=a01 view=map2 Simply acknowledging some of the biases evocated above u201c*disparities in the populations of each country but also within the same country, notably in terms of co-morbidities, risk factors or epidemiological situation*u201d is not enough. **The influence of these and other factors should have been discussed**. Later suggesting that u201c*the correlation of all these parameters suggests that this is not due to chance*u201d is also abusive. First, this **correlation as too many biases** to be able to analyse it from the data from the authors. Second, suggesting that **this can not be a chance can not be a scientific rigorous argument**. https: en.wikipedia.org wiki Correlation_does_not_imply_causation The authors conclude that u201c*Regarding France, the strategy was to give no treatment until its effectiveness had been proven by randomized trials. This difference in strategies between the rich Western world and the rest of the world is probably relevant to the very high mortality rate observed in France*u201d **can not be supported**. Neither the authors have been able to show a valid correlation between these two phenomena in France, nor have they discussed the rest of the world. This is clearly an abusive generalization of a biased correlation. The attempt to correlate the usage of their suggested treatment with local CFR has too many biases and approximations to be supported. ,