key: cord-0719625-j6ycfc6y
authors: Marina, Valente; Matteo, Ricco; Francesco, Tartamella; Luciano, Petracca Gabriele; Giorgio, Dalmonte; Diletta, Fabbi; Federico, Marchesi
title: Clinical case definition of COVID-19 and morbid obesity: Is it time to move on?
date: 2021-02-05
journal: Infect Dis Now
DOI: 10.1016/j.idnow.2021.02.002
sha: 1a2554d78e5464999ed45834a80d84bb9409f7b9
doc_id: 719625
cord_uid: j6ycfc6y

nan

Morbid obesity (i.e., body mass index ≥ 30 kg/m 2 ) is a well-known risk factor for severe outcomes of infectious respiratory diseases (1) (2) . Interestingly, some reports on COVID-19 have suggested that morbidly obese patients may be characterized by a distinctive symptomatology, being more likely to report cough, headache and myalgia (3) . The underlying mechanisms remain unclear. In fact, obesity is associated with low-grade chronic inflammation, which impairs both innate and adaptive responses of the immune system (4). Moreover, Angiotensin-Converting Enzyme 2 receptor (ACE2), the functional receptor for SARS-CoV-2, is upregulated in obese patients (3) (4) . As a result, the World Health Organization's (WHO) clinical criteria defining "probable cases" of COVID-19 may be somewhat inappropriate in morbidly obese patients (5) . A clinical definition was introduced by WHO to address settings characterized by limited diagnostic resources, and includes all patients with a previous contact with another probable or confirmed case, or linked to a COVID-19 cluster, who had experienced since February 24, 2020 at least one episode of anosmia/dysgeusia or had chest imaging suggestive of COVID-19, or an association of rapid onset fever (self-measured temperature ≥ 37.5°C) and cough, or an association of any three or more of the following signs and symptoms: fever, cough, general weakness, headache, myalgia, sore throat, nose discharge/swelling, nausea/vomiting or diarrhoea (5) .

Recently, as part of a multicentric study in Emilia Romagna, Northern Italy (June to August 2020) [6] , we assessed the diagnostic performances of clinical criteria regarding 90 morbidly obese patients who had undergone a diagnostic test for SARS-CoV-2 infection with RT-qPCR on nasopharyngeal specimens ( Table 1) . In this group, 21.1% were males with mean age 46.4  10.6 and BMI of 35.3 kg/m 2  4.6. All in all, 14 (15.6%) patients had SARS-CoV-2 infection confirmed by RT-qPCR. All subjects were specifically interviewed about any symptoms included in the WHO case definition about which they had complained since February 2020. Association between SARS-CoV-2 infection and reported symptoms was calculated by means of chi squared test with Yates correction. All symptoms that in univariate analysis were associated with a positive RT-qPCR test were included in a binary logistic regression model as explanatory variables. Sensitivity, specificity, predicted positive/negative values, and test agreement (i.e. Cohen's kappa) were calculated by means of 2x2 tables.

Interestingly, 48 out of 90 morbidly obese patients were "probable cases" (53.3%) according to the WHO case definition, but only fever (T > 37.5°C or having a sudden onset), cough, anosmia/ageusia, myalgia, and asthenia were associated with positive RT-qPCR status. As anosmia and ageusia were highly correlated (r = 0.865, p < 0.001), a dummy variable "anosmia OR ageusia" was included in logistic regression analysis. Finally, only cases reporting either anosmia or ageusia (aOR 51.002 95%CI 3.359 to 774.441) were significantly associated with the positive RT-qPCR assay outcome variable.

Clinical case definition exhibited exceedingly high sensitivity (100%), but low specificity (55.3%) and minimal agreement (0.278) with laboratory diagnostics (see Table 2 ). While reporting of either anosmia or ageusia was characterized by exceedingly high sensitivity (92.9%), and moderate specificity (73.7%) with weak agreement (0.428), myalgia and asthenia were characterized by moderate sensitivity (71.4% in both cases) and specificity (79.0% for myalgia, 73.7% for asthenia), with no agreement (0.373 for myalgia, 0.323 for asthenia). Assuming as probable that all cases presenting at least one symptom among fever, cough, anosmia, ageusia, myalgia, asthenia were reported, sensitivity of 100% was found, along with specificity of 60.5% and minimal agreement Despite the limits of our study, particularly convenience sampling without preventive power analysis, self-reporting of symptoms, and the reduced number of participants with a potential oversampling of SARS-CoV-2 positive cases, our estimates confirm that the clinical case definition of "probable" COVID-19 cases may potentially be useful, but is not totally reliable in morbidly obese patients. Although exceedingly high sensitivity substantially rules out the risk of misdiagnosing actual COVID-19 cases, with subsequent delays in treatment and confinement procedures, unsatisfactory specificity means that a high proportion of assessed patients will be at risk of receiving unnecessary and costly treatment, with a possible waste of valuable resources. On the other hand, our estimates suggest that, when dealing with morbidly obese patients in a setting with high SARS-CoV-2 endemicity, as was Emilia Romagna Region at the time of our survey (6), reporting at least one among a group of six symptoms (i.e. fever > 37.5°C, cough, anosmia, ageusia, myalgia, asthenia) should suffice to raise clinical suspicion. This is particularly true for patients with anosmia or ageusia, while the clinician should be cognizant of the fact that symptoms such as productive sore throat, running nose, productive cough, shivering, nausea, diarrhea, headache and conjunctivitis are apparently of lesser reliability in obese patients (5) (6) . However, as neither the WHO case definition nor a revised assessment of clinical symptoms radically improved diagnostic performances per se, confirmatory diagnosis by means of RT-qPCR on nasal swabs still remains unavoidable (7) (8) .

Each author declares that he or she has no commercial associations (e.g. consultancies, stock ownership, equity interest, patent/licensing arrangement etc.) that might pose a conflict of interest in connection with the submitted article. The facts, conclusions, and opinions stated in the article represent the authors' research, conclusions, and opinions, and are believed to be substantiated, accurate, valid, and reliable. However, as this article includes the results of personal research of the authors, presenting correspondent, personal conclusions, and opinions, parent employers are not forced in any way to endorse or share its content and its potential implications.

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