Development and external validation of a diagnostic multivariable prediction model for a prompt identification of cases at high risk for SARS-COV-2 infection among patients admitted to the emergency department (preprint)

BackgroundAn urgent need exists for an early detection of cases with a high-risk of SARS-CoV-2 infection, particularly in high-flow and -risk settings, such as emergency departments (EDs). The aim of this work is to develop and validate a predictive model for the evaluation of SARS-CoV-2 infection risk, with the rationale of using this tool to manage ED patients. MethodsA retrospective study was performed by cross-sectionally reviewing the electronical case records of patients admitted to Niguarda Hospital or referred to its ED in the period 15 March to 24 April 2020. Derivation sample was composed of non-random inpatients hospitalized on 24 April and admitted before 22 April 2020. Validation sample was composed of consecutive patients who visited the ED between 15 and 25 March 2020. The association between the dichotomic outcome and each predictor was explored by univariate analysis with logistic regression models. ResultsA total of 113 patients in the derivation sample and 419 in the validation sample were analyzed. History of fever, elder age and low oxygen saturation showed to be significant predictors of SARS-CoV-2 infection. The neutrophil count improves the discriminative ability of the model, even if its calibration and usefulness in terms of diagnosis is unclear. ConclusionThe discriminatory ability of the identified models makes the overall performance suboptimal; their implementation to calculate the individual risk of infection should not be used without additional investigations. However, they could be useful to evaluate the spatial allocation of patients while awaiting the result of the nasopharyngeal swab. Key Messages boxO_ST_ABSWhat is already known on this topicC_ST_ABS1 year after the onset of the coronavirus disease 2019 (COVID-19) pandemic, the trend of its spread has not shown a substantial global reduction. An urgent need exists for efficient early detection of cases with a high risk of SARS-CoV-2 infection and a number of diagnostic prediction models have been developed, but a few models were externally validated in high-flow and -risk settings, such as emergency departments (EDs). What this study addsThis study develops and validate predictive models for the evaluation of SARS-CoV-2 infection risk, with the rationale of using these tools to promptly manage patients who are afferent to the ED, allocating them accordingly to the risk of infection while awaiting swab result. History of fever, older age and low oxygen saturation showed to be significant predictors of the presence of SARS-CoV-2 infection. The use of laboratory findings, such as neutrophil count, showed to improve the discriminative ability of the model, even if its calibration and usefulness in terms of diagnosis is unclear.

Sex differences in electrolyte imbalances caused by SARS-CoV-2: a case-control study (preprint)

Background: - Since SARS-CoV-2 spread, evidences regarding sex differences in progression and prognosis of COVID-19 have emerged. Besides this, studies on patients’ clinical characteristics have described electrolyte imbalances as one of the recurrent features of COVID-19. Methods - We performed a case-control study on all patients admitted to the emergency department (ED) from 1st March to 31st May 2020 who had undergone a blood gas analysis and a nasopharyngeal swab test for SARS-CoV-2 by rtPCR. We defined positive patients as cases and negatives as controls. The study was approved by the local ethics committee Area 3 Milan. Data were automatically extracted from the hospital laboratory SQL-based repository in anonymized form. We considered as outcomes potassium (K+), sodium (Na+), chlorine (Cl-) and calcium (Ca++) as continuous and as categorical variables, in their relation with age, sex and SARS-CoV-2 infection status. Results - We observed a higher prevalence of hypokalemia among patients positive for SARS-CoV-2 (13.7% vs 6% of negative subjects). Positive patients had a higher probability to be admitted to the ED with hypokalemia (OR 2.75, 95% CI 1.8-4.1 p<0.0001) and women were twice as likely to be affected than men (OR 2.43, 95% CI 1.67-3.54 p<0.001). Odds ratios for positive patients to manifest with an alteration in serum Na+ was (OR 1.6, 95% CI 1.17-2.35 p<0.001) and serum chlorine (OR 1.6, 95% CI 1.03-2.69 p<0.001). Notably, OR for positive patients to be hypocalcemic was 7.2 (95% IC 4.8-10.6 p<0.0001) with a low probability for women to be hypocalcemic (OR 0.63, 95% IC 0.4-0.8 p=0.005). Conclusions - SARS-CoV-2 infection is associated with a higher prevalence of hypokalemia, hypocalcemia, hypochloremia and sodium alterations. Hypokalemia is more frequent among women and hypocalcemia among men.

Neurological Manifestations in Patients Hospitalized with COVID-19: A Retrospective Analysis from a Large Cohort in Northern Italy (preprint)

Background: SARS-CoV2 infection is a systemic disease that may involve multiple organs, including the nervous system. Aims of our study are to describe prevalence and clinical features of neurological manifestations, mortality and hospital discharge in subjects hospitalized with COVID-19.Methods: All individuals admitted for COVID-19 were retrospectively included. Patients were classified according to the symptoms at hospital entry in 1) isolated respiratory, 2) combined respiratory and neurologic, 3) isolated neurologic and 4) stroke manifestations. Descriptive statistics and non-parametric tests to compare the groups were applied. Kaplan Meier probability curves and multivariable Cox regression models for survival and hospital discharge were applied.Results: The analysis included 901 patients, 42.6% showed a severe or critical disease with an overall mortality of 21.2%. At least one neurological symptom or disease was observed in 30.2% of subjects ranging from dysgeusia/anosmia (9.1%) to post-infective diseases (0.8%). Patients with respiratory symptoms experienced a more severe disease and a higher in-hospital mortality compared to those who showed only neurologic symptoms. Kaplan Meier estimates displayed a statistically significant different survival among groups (p=0.003): subjects with stroke had the worst. After adjusting for risk factors such as age, sex and comorbidity, individuals with isolated neurologic manifestations exhibited a better survival (aHR 0.398, 95% CI 0.206-0.769, p=0.006).Discussion: Neurologic manifestations in COVID-19 are common but heterogeneous. Subjects with isolated neurologic manifestations, experienced a lower mortality than those with respiratory symptoms, suggesting that neurologic disease may have a different course than when the virus involves respiratory system.Funding Statement: None.Declaration of Interests: The authors declare that they have no conflicts of interest for this work.Ethics Approval Statement: The local Ethics Committee approved the protocol under the special conditions indicated by the Italian 648/96 law. All subjects provided written informed consent.