key: cord-0826001-5unh2a3f authors: Murillo-Zamora, E.; HERNANDEZ-SUAREZ, C. M. title: Performance of suspected influenza case definitionbefore and during the COVID-19 pandemic date: 2020-06-02 journal: nan DOI: 10.1101/2020.06.01.20119446 sha: 5512afdb48d03f4782659e29ab8fb025ac7cea00 doc_id: 826001 cord_uid: 5unh2a3f Background: The influenza-related burden remains high and the COVID-19 pandemic may difficult its accurate surveillance. This study aimed to evaluate the performance, before and during the COVID-19 pandemic, of the case definition of suspected influenza used in community surveillance in Mexico. Methods: A cross-sectional analysis of a cohort study took place and cases fulfilling the suspected case criteria (n = 20,511), and with laboratory-conclusive evidence (quantitative real-time polymerase chain reaction) to confirm or discard influenza virus infection were analyzed. Results: A high sensitivity and modest specificity were documented, and this later decreased during the COVID-19 outbreak, as well as its diagnostic accuracy. However, no significant differences were observed in the Area Under the Receiver Operating Characteristics among the analyzed periods. Conclusions: The evaluated case definition remains to be a cost-effective alternative to identify patients who may benefit from influenza-specific antiviral drugs, even during the COVID-19 global outbreak. The influenza-related burden remains high globally despite vaccination efforts [1] . In the northern hemisphere, seasonal cases start in October and tail off by May [2] . The case definitions of suspected influenza used in national and regional surveillance programs commonly differ from those recommended 5 by WHO. In Mexico and according to normative standards [3], the case definition in patients aged 5 years or above includes the presence of fever (38°C or higher), headache and cough accompanied by (at least 2): rhinorrhea, coryza, arthritis, arthralgia, myalgia, prostration, odynophagia, thoracic pain, abdominal pain, nasal congestion or diarrhea. Fever is not a cardinal symptom among The first registered cases of locally acquired coronavirus disease 2019 in Mexico occurred in late February 2020 [6] . About three months later, over 75 thousand cases and 8 thousand deaths had been registered at national level [7] . Given that suspected cases of COVID-19 and influenza share clinical 20 similarities [8] , timely identification of these later, and which may benefit the start of neuraminidase inhibitors (NAIs) [9] , may be challenging in source limited healthcare settings. We aimed to evaluate the performance of the influenza case definition before and during the COVID-19 pandemic in Mexico. We analyzed two consecutive flu seasons (2018-2020) for the benefit of a wider time 25 framework. We conducted a cross-sectional analysis of a nationwide retrospective cohort study. Suspected cases of influenza among individuals aged 5 years or older, and 2 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 2, 2020. Data from 20,511 cases were analyzed. The overall prevalence of laboratoryconfirmed influenza in the study sample was 38.8% (n = 7, 955). Table 1 The overall specificity computed during the pandemic period was 12.2%(95% CI 10.5-14.0) and it was higher than the estimate from Period 3 (p = 0.001) but lower than the estimate from March-April 2019 (p < 0.001). The diagnostic 3 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 2, 2020. . https://doi.org/10.1101/2020.06.01.20119446 doi: medRxiv preprint accuracy went from 48.7% to 38.0% (22% decrease; p < 0.001) in Period 3 and 4, respectively; it was the similar to the accuracy from Period 1 (p = 0.459). The AUROCs are presented in Figure 1 and ranged from 0.544 (95% CI 0.533-0.556) to 0.607 (95% CI 0.586-0.628). No significant differences were documented between the pre-and during-pandemic periods (p = 0.855). This study evaluated the performance of influenza case definition based on 65 a national and normative influenza cohort. Our results suggest no significant changes in the evaluated parameters before and during the COVID-19 pandemic. The analyzed cohort study has several strengths and include: (i) influenza virus infection was confirmed by qRT-PCR analysis, which is the gold standard; (ii) the database included cases from all age groups and (iii) data of influenza A 70 and B viruses was available. Timely identification of influenza virus infection can assist healthcare providers in determining optimal strategies for preventing or treating influenza, including the use of antiviral drugs. These interventions also reduce the spread of influenza [11] . 75 Multiple suspected influenza case definitions are currently being used worldwide and include, among others, the proposed by CDC [11], WHO [12] , and the GROG [13]. All of them have a similar performance in detecting laboratorypositive cases and their sensitivity and specificity ranges from 90 to 96%, and from 7 to 21%, respectively [5]. The computed AUROCs by using any of these 80 classifications are similar to those that were estimated in our study (≈ 0.550). No differences in the performance of the case definition or symptoms in influenza cases according to virus type were found in a recently published study [14] . The identified influenza virus sub-types were as following (n = 7, 955): A/H1N1, 57%; B/Victoria, 17%; A/H3, 16%; B/Yamagata, 9% and B uniden-85 tified, 1%. Seasonal influenza vaccination has been proven to be cost-effective in the 4 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 2, 2020. Our findings suggest that the suspected case definition employed in community surveillance of influenza has a good performance, even during the COVID-19 pandemic. Therefore, this definition may be used in identifying patients who 95 may benefit from early access to neuraminidase inhibitors. Timely use of antiviral drugs, together with immunization promoting, may reduce the social and economic burden of influenza. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 2, 2020. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 2, 2020. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 2, 2020. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 2, 2020. . https://doi.org/10.1101/2020.06.01.20119446 doi: medRxiv preprint Tables and Figures 9 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 2, 2020. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 2, 2020. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 2, 2020. . https://doi.org/10.1101/2020.06.01.20119446 doi: medRxiv preprint . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 2, 2020. . https://doi.org/10.1101/2020.06.01.20119446 doi: medRxiv preprint World Health Organization and others, Q&a: Similarities and differencescovid-19 and influenza Neuraminidase inhibitors for influenza: a systematic review and meta-analysis of regulatory and mortality data Analysis of influenza data generated by four epidemiological surveillance laboratories in mexico Manual for the surveillance of vaccine-preventable diseases World Health Organization and others, Who surveillance case definitions for ili and sari Heterogeneous case definitions used for the surveillance of influenza in europe