Brain imaging abnormalities in children with dysphagia with aspiration: A retrospective study.

OBJECTIVE: Head imaging is often performed in children with persistent dysphagia with aspiration to evaluate for Chiari malformations that may be associated with dysphagia. Unfortunately, the frequency of Chiari malformations or other head imaging abnormalities in children who aspirate is unknown. The goal of this study is to determine the frequency of head imaging abnormalities in children with evidence of aspiration or penetration on video fluoroscopic swallow study (VFSS). SETTING: Tertiary Children's Hospital. METHODS: We performed retrospective analysis of children with a diagnosis of aspiration evaluated at our center from January 2010 through April 2021. In this study, we included children with VFSS confirmed aspiration or penetration, brain magnetic resonance imaging (MRI) performed at our center, and without known genetic, congenital craniofacial, or neurologic abnormalities. RESULTS: Of the 977 patients evaluated in our system during that time with a diagnosis of aspiration, 185 children met the inclusion criteria. Eight children were diagnosed with Chiari malformations (4.3%) and 94 head MRIs were abnormal (51.4%). There was no difference in VFSS findings (frequency of aspiration, penetration, penetration-aspiration score, or recommended thickness of liquid) in children with a Chiari malformation versus other abnormalities or normal brain imaging. The majority of other non-Chiari brain imaging abnormalities were nonspecific. There was no difference in VFSS findings in children with abnormal MRI findings versus normal MRI. CONCLUSIONS: Brain imaging abnormalities are common in children who aspirate. Intervenable lesions are rare. Further studies are required to determine patients that will most likely benefit from brain imaging.

COVID-19: Data-Driven optimal allocation of ventilator supply under uncertainty and risk.

This study presents a new risk-averse multi-stage stochastic epidemics-ventilator-logistics compartmental model to address the resource allocation challenges of mitigating COVID-19. This epidemiological logistics model involves the uncertainty of untested asymptomatic infections and incorporates short-term human migration. Disease transmission is also forecasted through a new formulation of transmission rates that evolve over space and time with respect to various non-pharmaceutical interventions, such as wearing masks, social distancing, and lockdown. The proposed multi-stage stochastic model overviews different scenarios on the number of asymptomatic individuals while optimizing the distribution of resources, such as ventilators, to minimize the total expected number of newly infected and deceased people. The Conditional Value at Risk (CVaR) is also incorporated into the multi-stage mean-risk model to allow for a trade-off between the weighted expected loss due to the outbreak and the expected risks associated with experiencing disastrous pandemic scenarios. We apply our multi-stage mean-risk epidemics-ventilator-logistics model to the case of controlling COVID-19 in highly-impacted counties of New York and New Jersey. We calibrate, validate, and test our model using actual infection, population, and migration data. We also define a new region-based sub-problem and bounds on the problem and then show their computational benefits in terms of the optimality and relaxation gaps. The computational results indicate that short-term migration influences the transmission of the disease significantly. The optimal number of ventilators allocated to each region depends on various factors, including the number of initial infections, disease transmission rates, initial ICU capacity, the population of a geographical location, and the availability of ventilator supply. Our data-driven modeling framework can be adapted to study the disease transmission dynamics and logistics of other similar epidemics and pandemics.

Probiotics Modulate a Novel Amphibian Skin Defense Peptide That Is Antifungal and Facilitates Growth of Antifungal Bacteria.

Probiotics can ameliorate diseases of humans and wildlife, but the mechanisms remain unclear. Host responses to interventions that change their microbiota are largely uncharacterized. We applied a consortium of four natural antifungal bacteria to the skin of endangered Sierra Nevada yellow-legged frogs, Rana sierrae, before experimental exposure to the pathogenic fungus Batrachochytrium dendrobatidis (Bd). The probiotic microbes did not persist, nor did they protect hosts, and skin peptide sampling indicated immune modulation. We characterized a novel skin defense peptide brevinin-1Ma (FLPILAGLAANLVPKLICSITKKC) that was downregulated by the probiotic treatment. Brevinin-1Ma was tested against a range of amphibian skin cultures and found to inhibit growth of fungal pathogens Bd and B. salamandrivorans, but enhanced the growth of probiotic bacteria including Janthinobacterium lividum, Chryseobacterium ureilyticum, Serratia grimesii, and Pseudomonas sp. While commonly thought of as antimicrobial peptides, here brevinin-1Ma showed promicrobial function, facilitating microbial growth. Thus, skin exposure to probiotic bacterial cultures induced a shift in skin defense peptide profiles that appeared to act as an immune response functioning to regulate the microbiome. In addition to direct microbial antagonism, probiotic-host interactions may be a critical mechanism affecting disease resistance.

Beyond Neutralizing Antibody Levels: The Epitope Specificity of Antibodies Induced by National Institutes of Health Monovalent Dengue Virus Vaccines.

BACKGROUND: Dengue virus is an emerging mosquito-borne flavivirus responsible for considerable morbidity and mortality worldwide. The Division of Intramural Research, National Institute of Allergy and Infectious Diseases of the US National Institutes of Health (NIH) has developed live attenuated vaccines to each of the 4 serotypes of dengue virus (DENV1-4). While overall levels of DENV neutralizing antibodies (nAbs) in humans have been correlated with protection, these correlations vary depending on DENV serotype, prevaccination immunostatus, age, and study site. By combining both the level and molecular specificity of nAbs to each serotype, it may be possible to develop more robust correlates that predict long-term outcome. METHODS: Using depletions and recombinant chimeric epitope transplant DENVs, we evaluate the molecular specificity and mapped specific epitopes and antigenic regions targeted by vaccine-induced nAbs in volunteers who received the NIH monovalent vaccines against each DENV serotype. RESULTS: After monovalent vaccination, subjects developed high levels of nAbs that mainly targeted epitopes that are unique (type-specific) to each DENV serotype. The DENV1, 2, and 4 monovalent vaccines induced type-specific nAbs directed to quaternary structure envelope epitopes known to be targets of strongly neutralizing antibodies induced by wild-type DENV infections. CONCLUSIONS: Our results reported here on the molecular specificity of NIH vaccine-induced antibodies enable new strategies, beyond the absolute levels of nAbs, for determining correlates and mechanisms of protective immunity.

L. donovani XPRT: Molecular characterization and evaluation of inhibitors.

Among all PRT enzymes of purine salvage pathway in Leishmania, XPRT (Xanthine phosphoribosyl transferase) is unique in its substrate specificity and their non-existence in human. It is an interesting protein not only for drug designing but also to understand the molecular determinants of its substrate specificity. Analysis of the 3D model of L. donovani XPRT (Ld-XPRT) revealed that Ile 209, Glu 215 and Tyr 208 may be responsible for the altered substrate specificity of Ld-XPRT. Comparisons with it's nearest homologue in humans, revealed significant differences between the two. A 28 residue long unique motif was identified in Ld-XPRT, which showed highest fluctuation upon substrate binding during MD simulations. In kinetic analysis, Ld-XPRT could phosphoribosylate xanthine, hypoxanthine and guanine with Km values of 7.27, 8.13, 8.48µM and kcat values of 2.24, 1.82, 1.19min-1 respectively. Out of 159 compounds from docking studies, six compounds were characterized further by fluorescence spectroscopy, CD spectroscopy and enzyme inhibition studies. Fluorescence quenching experiment was performed to study the binding of inhibitors with Ld-XPRT and dissociation constants were calculated. Four compounds are bi-substrate analogues and show competitive inhibition with both the substrates (Xanthine and PRPP) of Ld-XPRT. The CD spectral analysis revealed that the binding of inhibitors to Ld-XPRT induce change in its tertiary structure, where as its secondary structure pattern remains unchanged. Two Ld-XPRT inhibitors (dGDP and cGMP), which also have ability to inhibit Leishmanial HGPRT, are predicted as potential drug candidates as it can inhibit both the important enzymes of the purine salvage pathway.

Temporal trends of splenectomy in pediatric hospitalizations with immune thrombocytopenia.

BACKGROUND: Splenectomy is considered an effective treatment for immune thrombocytopenia (ITP) with 70-80% response rate. However, its current use is limited in children with ITP. It is unclear if the rates of splenectomy have changed over time. Using a large nationally representative database, we aimed to study the trends of splenectomy in pediatric hospitalizations with ITP, and the factors associated with splenectomy during these encounters. METHODS: Using National (Nationwide) Inpatient Sample (NIS), and international classification of diseases (9th revision), clinical modification (ICD-9-CM) codes, we studied pediatric ITP hospitalizations with occurrence of total splenectomy between 2005 and 2014. RESULTS: Out of 37,844 weighted ITP hospitalizations from 2005 to 2014; total splenectomy was performed in 954 encounters. Splenectomy rate declined over time (3.4% [2005-2006] to 1.6% [2013-2014], P < 0.001) with the younger age (≤5 years) having the most notable decline (0.91% [2005-2006] to 0.14% [2013-2014], P < 0.001). Splenectomy had higher odds of being performed electively than non-electively (odds ratio [OR]: 19.34, 95% confidence interval [CI]: 12.06-31.02, P < 0.001). Encounters with intracranial bleed were associated with the occurrence of splenectomy (OR: 17.87, 95% CI: 5.07-62.97, P < 0.001). Intracranial bleed (P < 0.001), gastrointestinal bleed (P < 0.01), sepsis (P < 0.001), and thrombosis (P < 0.001) were associated with longer length of stay and higher cost of hospitalization. CONCLUSIONS: Overall, splenectomy rates consistently declined over time. Intracranial hemorrhage during hospitalizations with ITP was associated with occurrence of splenectomy. Future studies should continue to reevaluate the rates of splenectomy in pediatric ITP in the presence of various second-line pharmacologic agents.

The Significance of Arachnoid Granulation in Patients With Idiopathic Intracranial Hypertension.

PURPOSE: The aim of this article was to study the significance of arachnoid granulations (AGs) in patients with idiopathic intracranial hypertension (IIH). METHODS: In an institutional review board-approved retrospective chart review study, 79 patients with clinical diagnosis of idiopathic increased intracranial pressure were compared with 63 patients with a diagnosis of multiple sclerosis. Inclusion criteria also included available magnetic resonance imaging (MRI) of the brain, older than 18 years, and female sex. Patients with elevated intracranial pressure due to other causes were excluded. The electronic medical records were mined for presence of the following: body mass index, age, headache, vision changes, tinnitus, and vertigo. The MRI of the brain was reviewed for the presence of the following features: empty sella, prominent cerebrospinal fluid space in the optic sheaths, tortuosity of the optic nerves and enlarged Meckel cave. In addition, the number, size, and location of AGs associated with major venous drainage sinuses were documented in all patients. Using statistical analysis, association between various imaging and clinical signs were evaluated. RESULTS: The association between AG and various imaging and clinical signs were evaluated. The percentage of patients with AG were significantly higher in patients with IIH. Patients with IIH tended to have 0 to 3 AG. The most common imaging findings observed in MRI of the brain of patients with IIH were empty sella and prominent cerebrospinal fluid space in the optic sheaths. The prevalence of these MRI findings in patients with IIH was inversely proportional to the number of AG. A similar inverse trend was also noted with the opening pressure of patients with IIH and number of AG. CONCLUSIONS: The study establishes that there is a relationship between presence of AG and IIH. Arachnoid granulation seems to act in a compensatory mechanism in patients with IIH.

Dengue viruses are enhanced by distinct populations of serotype cross-reactive antibodies in human immune sera.

Dengue viruses (DENV) are mosquito-borne flaviviruses of global importance. DENV exist as four serotypes, DENV1-DENV4. Following a primary infection, individuals produce DENV-specific antibodies that bind only to the serotype of infection and other antibodies that cross-react with two or more serotypes. People exposed to a secondary DENV infection with another serotype are at greater risk of developing more severe forms of dengue disease. The increased risk of severe dengue in people experiencing repeat DENV infections appear to be due, at least in part, to the ability of pre-existing serotype cross-reactive antibodies to form virus-antibody complexes that can productively infect Fcγ receptor-bearing target cells. While the theory of antibody-dependent enhancement (ADE) is supported by several human and small animal model studies, the specific viral antigens and epitopes recognized by enhancing human antibodies after natural infections have not been fully defined. We used antibody-depletion techniques to remove DENV-specific antibody sub-populations from primary DENV-immune human sera. The effects of removing specific antibody populations on ADE were tested both in vitro using K562 cells and in vivo using the AG129 mouse model. Removal of serotype cross-reactive antibodies ablated enhancement of heterotypic virus infection in vitro and antibody-enhanced mortality in vivo. Further depletion studies using recombinant viral antigens showed that although the removal of DENV E-specific antibodies using recombinant E (rE) protein resulted in a partial reduction in DENV enhancement, there was a significant residual enhancement remaining. Competition ADE studies using prM-specific Fab fragments in human immune sera showed that both rE-specific and prM-specific antibodies in primary DENV-immune sera significantly contribute to enhancement of heterotypic DENV infection in vitro. Identification of the targets of DENV-enhancing antibodies should contribute to the development of safe, non-enhancing vaccines against dengue.

MAP2K1 and MAP3K1 mutations in Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is now understood to be a neoplastic disease in which over 50% of cases have somatic activating mutations of BRAF. However, the extracellular signal-related (ERK) pathway is activated in all cases including those with wild type BRAF alleles. Here, we applied a targeted massively parallel sequencing panel to 30 LCH samples to test for the presence of additional genetic alterations that might cause ERK pathway activation. In 20 BRAF wild type samples, we found 3 somatic mutations in MAP2K1 (MEK1) including C121S and C121S/G128D in the kinase domain, and 56_61QKQKVG>R, an in-frame deletion in the N-terminal regulatory domain. All three variant proteins constitutively phosphorylated ERK in in vitro kinase assays. The C121S/G128D and 56_61QKQKVG>R variants were resistant to the mitogen-activated protein kinase kinase (MEK) inhibitor trametinib in vitro. Within the entire sample set, we found 3 specimens with mutations in MAP3K1 (MEKK1), including two truncation mutants, T779fs and T1481fs; T1481fs encoded an unstable and nonfunctional protein when expressed in vitro. T779fs was present in a specimen carrying BRAF V600E. The third variant was a single nucleotide substitution, E1286V, which was fully functional and is likely a germline polymorphism. These results indicate that LCH cells can harbor additional genetic alterations in the RAS-RAF-MEK pathway which, in the case of MAP2K1, may be responsible for ERK activation in a wild type BRAF setting. The resistance of some of these variants to trametinib may also have clinical implications for the combined use of RAF and MEK inhibitors in LCH.

Clinical Pathways and Outcomes of Andexanet Alfa Administration for the Reversal of Critical Bleeding in Patients on Oral Direct Factor Xa Inhibitors.

Background Andexanet is U.S. Food and Drug Administration (FDA) approved for the reversal of critical bleeding from factor Xa inhibitors and off-label for surgical reversal. Data are lacking on andexanet administration processes. Methods We retrospectively studied patients at a 23-hospital system who received andexanet from November 2019 to March 2023. Abstractors coded demographics, comorbidities, anticoagulant use, andexanet indication, and process times. The primary outcome was presentation-to-andexanet time; diagnosis, ordering, and administration times were calculated. Secondary outcomes included in-hospital postandexanet major thromboembolism/bleeding and mortality. Results In total, 141 patients were analyzed. Andexanet indications were predominantly neurologic bleeding (85.8%). Twenty-four patients (17.0%) were transferred from nontertiary/academic centers to tertiary/academic centers. The median presentation-to-administration time was 192.5 minutes (interquartile range [IQR]: 108.0-337.0 minutes). Components were as follows: 72.5 minutes (IQR: 39.0-137.5 minutes) for bleeding diagnosis; 35.5 minutes (IQR: 0-96.5 minutes) for andexanet ordering; and 53.0 minutes (IQR: 38.5-78.5 minutes) for administration, which was longer at tertiary/academic hospitals (ratio 1.5, 95% confidence interval [CI]: 1.2-2.0, p = 0.002). Gastrointestinal or other critical bleeding (ratio 2.59, 95% CI: 1.67-4.02, p < 0.001), and tertiary/academic center treatment (ratio 1.58, 95% CI: 1.15-2.18, p = 0.005), were associated with increased time. Major thromboembolism, bleeding, and mortality occurred in 10.6, 12.0, and 22.9% of patients, respectively. Conclusions In our cohort, the median presentation-to-administration time was over 3 hours. Cumulative times were longer at tertiary/academic hospitals and for gastrointestinal/other bleeding. Postandexanet major thromboembolism/bleeding occurred more at tertiary/academic hospitals, possibly related to transfers. Prospective studies may elucidate clinical decision-making bottlenecks.

Clinical applications of arterial spin labeling of the intracranial compartment in vascular anomalies-A case-based review.

Arterial spin labeling (ASL) is a magnetic resonance perfusion technique that allows for quantification of cerebral blood flow (CBF) without the use of contrast or radiation. Several applications of ASL have been described in diagnosis of strokes and stroke mimics, intracranial tumors, and other conditions. Various vascular anomalies exhibit specific CBF patterns that correlate with different signal intensities on ASL. In this case-based review, we demonstrate the utility of ASL in diagnosis and surveillance of vascular anomalies in the intracranial compartment.

Highlighting COVID-19 racial disparities can reduce support for safety precautions among White U.S. residents.

U.S. media has extensively covered racial disparities in COVID-19 infections and deaths, which may ironically reduce public concern about COVID-19. In two preregistered studies (conducted in the fall of 2020), we examined whether perceptions of COVID-19 racial disparities predict White U.S. residents' attitudes toward COVID-19. Utilizing a correlational design (N = 498), we found that those who perceived COVID-19 racial disparities to be greater reported reduced fear of COVID-19, which predicted reduced support for COVID-19 safety precautions. In Study 2, we manipulated exposure to information about COVID-19 racial disparities (N = 1,505). Reading about the persistent inequalities that produced COVID-19 racial disparities reduced fear of COVID-19, empathy for those vulnerable to COVID-19, and support for safety precautions. These findings suggest that publicizing racial health disparities has the potential to create a vicious cycle wherein raising awareness reduces support for the very policies that could protect public health and reduce disparities.

Structural differences in 3C-like protease (Mpro) from SARS-CoV and SARS-CoV-2: molecular insights revealed by Molecular Dynamics Simulations.

Novel coronavirus SARS-CoV-2 has infected millions of people with thousands of mortalities globally. The main protease (Mpro) is vital in processing replicase polyproteins. Both the CoV's Mpro shares 97% identity, with 12 mutations, but none are present in the active site. Although many therapeutics and vaccines are available to combat SARS-CoV-2, these treatments may not be practical due to their high mutational rate. On the other hand, Mpro has a high degree of conservation throughout variants, making Mpro a stout drug target. Here, we report a detailed comparison of both the monomeric Mpro and the biologically active dimeric Mpro using MD simulation to understand the impact of the 12 divergent residues (T35V, A46S, S65N, L86V, R88K, S94A, H134F, K180N, L202V, A267S, T285A and I286L) on the molecular microenvironment and the interaction between crucial residues. The present study concluded that the change in the microenvironment of residues at the entrance (T25, T26, M49 and Q189), near the catalytic site (F140, H163, H164, M165 and H172) and in the substrate-binding site (V35, N65, K88 and N180) is due to 12 mutations in the SARS-CoV-2 Mpro. Furthermore, the involvement of F140, E166 and H172 residues in dimerization stabilizes the Mpro dimer, which should be considered. We anticipate that networks and microenvironment changes identified here might guide repurposing attempts and optimization of new Mpro inhibitors. Supplementary Information: The online version contains supplementary material available at 10.1007/s11224-022-02089-6.

Corrigendum: Insights Into Co-Morbidity and Other Risk Factors Related to COVID-19 Within Ontario, Canada.

[This corrects the article DOI: 10.3389/frai.2021.684609.].

Ile209 of Leishmania donovani xanthine phosphoribosyltransferase plays a key role in determining its purine base specificity.

Xanthine phosphoribosyltransferase (XPRT) and hypoxanthine-guanine phosphoribosyltransferase (HGPRT) are purine salvaging enzymes of Leishmania donovani with distinct 6-oxopurine specificities. LdXPRT phosphoribosylates xanthine, hypoxanthine, and guanine, with preference toward xanthine, whereas LdHGPRT phosphoribosylates only hypoxanthine and guanine. In our study, LdXPRT was used as a model to understand these purine base specificities. Mutating I209 to V, the conserved residue found in HGPRTs, reduced the affinity of LdXPRT for xanthine, converting it to an HGXPRT-like enzyme. The Y208F mutation in the active site indicated that aromatic residue interactions with the purine ring are limited to pi-pi binding forces and do not impart purine base specificity. Deleting the unique motif (L55-Y82) of LdXPRT affected enzyme activity. Our studies established I209 as a key residue determining the 6-oxopurine specificity of LdXPRT.

Insights Into Co-Morbidity and Other Risk Factors Related to COVID-19 Within Ontario, Canada.

The worldwide rapid spread of the severe acute respiratory syndrome coronavirus 2 has affected millions of individuals and caused unprecedented medical challenges by putting healthcare services under high pressure. Given the global increase in number of cases and mortalities due to the current COVID-19 pandemic, it is critical to identify predictive features that assist identification of individuals most at-risk of COVID-19 mortality and thus, enable planning for effective usage of medical resources. The impact of individual variables in an XGBoost artificial intelligence model, applied to a dataset containing 57,390 individual COVID-19 cases and 2,822 patient deaths in Ontario, is explored with the use of SHapley Additive exPlanations values. The most important variables were found to be: age, date of the positive test, sex, income, dementia plus many more that were considered. The utility of SHapley Additive exPlanations dependency graphs is used to provide greater interpretation of the black-box XGBoost mortality prediction model, allowing focus on the non-linear relationships to improve insights. A "Test-date Dependency" plot indicates mortality risk dropped substantially over time, as likely a result of the improved treatment being developed within the medical system. As well, the findings indicate that people of lower income and people from more ethnically diverse communities, face an increased mortality risk due to COVID-19 within Ontario. These findings will help guide clinical decision-making for patients with COVID-19.

Asymptomatic Cases, the Hidden Challenge in Predicting COVID-19 Caseload Increases.

The numbers of novel coronavirus cases continue to grow at an unprecedented rate across the world. Attempts to control the growth of the virus using masks and social-distancing, and, recently, double-masking as well, continue to be difficult to maintain, in part due to the extent of asymptomatic cases. Analyses of large datasets consisting of 219,075 individual cases in Ontario, indicated that asymptomatic and pre-symptomatic cases are substantial in number. Large numbers of cases in children aged 0-9 were asymptomatic or had only one symptom (35.0% and 31.4% of total cases, respectively) and resulted in fever as the most common symptom (30.6% of total cases). COVID-19 cases in children were more likely to be milder symptomatic with cough not seen as frequently as in adults aged over 40, and past research has shown children to be index cases in familial clusters. These findings highlight the importance of targeting asymptomatic and mild infections in the continuing effort to control the spread of COVID-19. The Pearson correlation coefficient between test positivity rates and asymptomatic rates of -0.729 indicates that estimates of the asymptomatic rates should be obtained when the test positivity rates are lowest as the best approach.

Corrigendum: Identification of Variable Importance for Predictions of Mortality From COVID-19 Using AI Models for Ontario, Canada.

[This corrects the article DOI: 10.3389/fpubh.2021.675766.].

Social Experience Interacts with Serotonin to Affect Functional Connectivity in the Social Behavior Network following Playback of Social Vocalizations in Mice.

Past social experience affects the circuitry responsible for producing and interpreting current behaviors. The social behavior network (SBN) is a candidate neural ensemble to investigate the consequences of early-life social isolation. The SBN interprets and produces social behaviors, such as vocalizations, through coordinated patterns of activity (functional connectivity) between its multiple nuclei. However, the SBN is relatively unexplored with respect to murine vocal processing. The serotonergic system is sensitive to past experience and innervates many nodes of the SBN; therefore, we tested whether serotonin signaling interacts with social experience to affect patterns of immediate early gene (IEG; cFos) induction in the male SBN following playback of social vocalizations. Male mice were separated into either social housing of three mice per cage or into isolated housing at 18-24 d postnatal. After 28-30 d in housing treatment, mice were parsed into one of three drug treatment groups: control, fenfluramine (FEN; increases available serotonin), or pCPA (depletes available serotonin) and exposed to a 60-min playback of female broadband vocalizations (BBVs). FEN generally increased the number of cFos-immunoreactive (-ir) neurons within the SBN, but effects were more pronounced in socially isolated mice. Despite a generalized increase in cFos immunoreactivity, isolated mice had reduced functional connectivity, clustering, and modularity compared with socially reared mice. These results are analogous to observations of functional dysconnectivity in persons with psychopathologies and suggests that early-life social isolation modulates serotonergic regulation of social networks.

Identification of Variable Importance for Predictions of Mortality From COVID-19 Using AI Models for Ontario, Canada.

The Severe Acute Respiratory Syndrome Coronavirus 2 pandemic has challenged medical systems to the brink of collapse around the globe. In this paper, logistic regression and three other artificial intelligence models (XGBoost, Artificial Neural Network and Random Forest) are described and used to predict mortality risk of individual patients. The database is based on census data for the designated area and co-morbidities obtained using data from the Ontario Health Data Platform. The dataset consisted of more than 280,000 COVID-19 cases in Ontario for a wide-range of age groups; 0-9, 10-19, 20-29, 30-39, 40-49, 50-59, 60-69, 70-79, 80-89, and 90+. Findings resulting from using logistic regression, XGBoost, Artificial Neural Network and Random Forest, all demonstrate excellent discrimination (area under the curve for all models exceeded 0.948 with the best performance being 0.956 for an XGBoost model). Based on SHapley Additive exPlanations values, the importance of 24 variables are identified, and the findings indicated the highest importance variables are, in order of importance, age, date of test, sex, and presence/absence of chronic dementia. The findings from this study allow the identification of out-patients who are likely to deteriorate into severe cases, allowing medical professionals to make decisions on timely treatments. Furthermore, the methodology and results may be extended to other public health regions.