Diabetes IN hospital - Glucose and Outcomes in the COVID-19 pandemic (DINGO COVID-19): the 2020 Melbourne hospital experience prior to novel variants and vaccinations.

BACKGROUND AND AIMS: A relationship between diabetes, glucose and COVID-19 outcomes has been reported in international cohorts. This study aimed to assess the relationship between diabetes, hyperglycaemia and patient outcomes in those hospitalised with COVID-19 during the first year of the Victorian pandemic prior to novel variants and vaccinations. DESIGN, SETTING: Retrospective cohort study from March to November 2020 across five public health services in Melbourne, Australia. PARTICIPANTS: All consecutive adult patients admitted to acute wards of participating institutions during the study period with a diagnosis of COVID-19, comprising a large proportion of patients from residential care facilities and following dexamethasone becoming standard-of-care. Admissions in patients without known diabetes and without inpatient glucose testing were excluded. RESULTS: The DINGO COVID-19 cohort comprised 840 admissions. In 438 admissions (52%), there was no known diabetes or in-hospital hyperglycaemia, in 298 (35%) patients had known diabetes, and in 104 (12%) patients had hyperglycaemia without known diabetes. ICU admission was more common in those with diabetes (20%) and hyperglycaemia without diabetes (49%) than those with neither (11%, P < 0.001 for all comparisons). Mortality was higher in those with diabetes (24%) than those without diabetes or hyperglycaemia (16%, P = 0.02) but no difference between those with in-hospital hyperglycaemia and either of the other groups. On multivariable analysis, hyperglycaemia was associated with increased ICU admission (adjusted odds ratio (aOR) 6.7, 95% confidence interval (95% CI) 4.0-12, P < 0.001) and longer length of stay (aOR 173, 95% CI 11-2793, P < 0.001), while diabetes was associated with reduced ICU admission (aOR 0.55, 95% CI 0.33-0.94, P = 0.03). Neither diabetes nor hyperglycaemia was independently associated with in-hospital mortality. CONCLUSIONS: During the first year of the COVID-19 pandemic, in-hospital hyperglycaemia and known diabetes were not associated with in-hospital mortality, contrasting with published international experiences. This likely mainly relates to hyperglycaemia indicating receipt of mortality-reducing dexamethasone therapy. These differences in published experiences underscore the importance of understanding population and clinical treatment factors affecting glycaemia and COVID-19 morbidity within both local and global contexts.

A 1-Pot Synthesis of the SARS-CoV-2 Mpro Inhibitor Nirmatrelvir, the Key Ingredient in Paxlovid.

A newly devised route to the Pfizer drug nirmatrelvir is reported that reduces the overall sequence to a 1-pot process and relies on a commercially available, green coupling reagent, T3P. The overall yield of the targeted material, isolated as its MTBE solvate, is 64%.

A sustainable synthesis of the SARS-CoV-2 Mpro inhibitor nirmatrelvir, the active ingredient in Paxlovid.

Pfizer's drug for the treatment of patients infected with COVID-19, Paxlovid, contains most notably nirmatrelvir, along with ritonavir. Worldwide demand is projected to be in the hundreds of metric tons per year, to be produced by several generic drug manufacturers. Here we show a 7-step, 3-pot synthesis of the antiviral nirmatrelvir, arriving at the targeted drug in 70% overall yield. Critical amide bond-forming steps utilize new green technology that completely avoids traditional peptide coupling reagents, as well as epimerization of stereocenters. Likewise, dehydration of a primary amide to the corresponding nitrile is performed and avoids use of the Burgess reagent and chlorinated solvents. DFT calculations for various conformers of nirmatrelvir predict that two rotamers about the tertiary amide would be present with an unusually high rotational barrier. Direct comparisons with the original literature procedures highlight both the anticipated decrease in cost and environmental footprint associated with this route, potentially expanding the availability of this important drug worldwide.

Cardiopulmonary resuscitation and defibrillation for cardiac arrest when patients are in the prone position: A systematic review.

AIM: To perform a systematic review of cardiopulmonary resuscitation (CPR) and/or defibrillation in the prone position compared to turning the patient supine prior to starting CPR and/or defibrillation. METHODS: The search included PubMed, Embase, Web of Science, Cochrane, CINAHL Plus, and medRxiv on December 9, 2020. The population included adults and children in any setting with cardiac arrest while in the prone position. The outcomes included arterial blood pressure and end-tidal capnography during CPR, time to start CPR and defibrillation, return of spontaneous circulation, survival and survival with favorable neurologic outcome to discharge, 30 days or longer. ROBINS-I was performed to assess risk of bias for observational studies. RESULTS: The systematic review identified 29 case reports (32 individual cases), two prospective observational studies, and two simulation studies. The observational studies enrolled 17 patients who were declared dead in the supine position and reported higher mean systolic blood pressure from CPR in prone position (72 mmHg vs 48 mmHg, p < 0.005; 79 ± 20 mmHg vs 55 ± 20 mmHg, p = 0.028). One simulation study reported a faster time to defibrillation in the prone position. Return of spontaneous circulation, survival to discharge or 30 days were reported in adult and paediatric case reports. Critical risk of bias limited our ability to perform pooled analyses. CONCLUSIONS: We identified a limited number of observational studies and case reports comparing prone versus supine CPR and/or defibrillation. Prone CPR may be a reasonable option if immediate supination is difficult or poses unacceptable risks to the patient.

Repurposing food molecules as a potential BACE1 inhibitor for Alzheimer's disease.

Alzheimer's disease (AD) is a severe neurodegenerative disorder of the brain that manifests as dementia, disorientation, difficulty in speech, and progressive cognitive and behavioral impairment. The emerging therapeutic approach to AD management is the inhibition of ß-site APP cleaving enzyme-1 (BACE1), known to be one of the two aspartyl proteases that cleave ß-amyloid precursor protein (APP). Studies confirmed the association of high BACE1 activity with the proficiency in the formation of ß-amyloid-containing neurotic plaques, the characteristics of AD. Only a few FDA-approved BACE1 inhibitors are available in the market, but their adverse off-target effects limit their usage. In this paper, we have used both ligand-based and target-based approaches for drug design. The QSAR study entails creating a multivariate GA-MLR (Genetic Algorithm-Multilinear Regression) model using 552 molecules with acceptable statistical performance (R 2 = 0.82, Q 2 loo = 0.81). According to the QSAR study, the activity has a strong link with various atoms such as aromatic carbons and ring Sulfur, acceptor atoms, sp2-hybridized oxygen, etc. Following that, a database of 26,467 food compounds was primarily used for QSAR-based virtual screening accompanied by the application of the Lipinski rule of five; the elimination of duplicates, salts, and metal derivatives resulted in a truncated dataset of 8,453 molecules. The molecular descriptor was calculated and a well-validated 6-parametric version of the QSAR model was used to predict the bioactivity of the 8,453 food compounds. Following this, the food compounds whose predicted activity (pKi) was observed above 7.0 M were further docked into the BACE1 receptor which gave rise to the Identification of 4-(3,4-Dihydroxyphenyl)-2-hydroxy-1H-phenalen-1-one (PubChem I.D: 4468; Food I.D: FDB017657) as a hit molecule (Binding Affinity = -8.9 kcal/mol, pKi = 7.97 nM, Ki = 10.715 M). Furthermore, molecular dynamics simulation for 150 ns and molecular mechanics generalized born and surface area (MMGBSA) study aided in identifying structural motifs involved in interactions with the BACE1 enzyme. Molecular docking and QSAR yielded complementary and congruent results. The validated analyses can be used to improve a drug/lead candidate's inhibitory efficacy against the BACE1. Thus, our approach is expected to widen the field of study of repurposing nutraceuticals into neuroprotective as well as anti-cancer and anti-viral therapeutic interventions.

Challenges and measures during management of mounting biomedical waste in COVID-19 pandemic: an Indian approach.

Background: During coronavirus pandemic, an unpredictable pile of biomedical waste (BMW) gathers at the top. India produces 710 tonnes of biomedical waste daily. The contribution of COVID-19 related biomedical waste was 126 tonnes per day in first wave of the pandemic. BMW's rapid growth is putting a strain on current waste management facilities, especially in developing countries. A sudden boost in biomedical waste needs rapid and proper segregation and disposal methods to avoid future consequences. Main body of the abstract: From literatures and statistical data available on Central Pollution Control Board (CPCB) it shows that India lags behind in large-scale sorting, collection, careful storage, transfer and disposal of bio waste. India has its own guidelines set by the CPCB to ensure the safe disposal of biomedical waste during diagnosis, treatment and quarantine of COVID-19 patients. Although there are strict guidelines for bio-waste management, many hospitals in the process of implementing them often dispose of waste in inappropriate, chaotic and indiscriminate ways due to negligence or laziness. Often, due to poor separation practices, hospital waste is mixed with general waste, resulting in harmful overall waste flow. Waste disposal handlers are not safe due to their exposure to various health risks and inadequate training in waste management. The present review sheds light on guidelines, measures, and challenges related to biomedical waste management. Short conclusion: Improper waste separation leads to improper waste disposal. Waste generation and management issues are causing daily problems as they have a profound impact on the dramatically changing global environment, including air, water and soil pollution. In addition, BMW's daily production and its processing are inversely proportional. This situation suggests that India will soon be drowning in its own garbage. The focus of this review is on the generation and disposal of biomedical waste. Based on a review of the literature, this evaluation provides a comparative picture of the current status of waste generation, national waste management strategies, and some measures to contribute to waste management and avoid future disasters.

In-hospital hyperglycemia but not diabetes mellitus alone is associated with increased in-hospital mortality in community-acquired pneumonia (CAP): a systematic review and meta-analysis of observational studies prior to COVID-19.

The objective of this review was to quantify the association between diabetes, hyperglycemia, and outcomes in patients hospitalized for community-acquired pneumonia (CAP) prior to the COVID-19 pandemic by conducting a systematic review and meta-analysis. Two investigators independently screened records identified in the PubMed (MEDLINE), EMBASE, CINAHL, and Web of Science databases. Cohort and case-control studies quantitatively evaluating associations between diabetes and in-hospital hyperglycemia with outcomes in adults admitted to hospital with CAP were included. Quality was assessed using the Newcastle-Ottawa Quality Assessment Scale, effect size using random-effects models, and heterogeneity using I2 statistics. Thirty-eight studies met the inclusion criteria. Hyperglycemia was associated with in-hospital mortality (adjusted OR 1.28, 95% CI 1.09 to 1.50) and intensive care unit (ICU) admission (crude OR 1.82, 95% CI 1.17 to 2.84). There was no association between diabetes status and in-hospital mortality (adjusted OR 1.04, 95% CI 0.72 to 1.51), 30-day mortality (adjusted OR 1.13, 95% CI 0.77 to 1.67), or ICU admission (crude OR 1.91, 95% CI 0.74 to 4.95). Diabetes was associated with increased mortality in all studies reporting >90-day postdischarge mortality and with longer length of stay only for studies reporting crude (OR 1.50, 95% CI 1.11 to 2.01) results. In adults hospitalized with CAP, in-hospital hyperglycemia but not diabetes alone is associated with increased in-hospital mortality and ICU admission. Diabetes status is associated with increased >90-day postdischarge mortality. Implications for management are that in-hospital hyperglycemia carries a greater risk for in-hospital morbidity and mortality than diabetes alone in patients admitted with non-COVID-19 CAP. Evaluation of strategies enabling timely and effective management of in-hospital hyperglycemia in CAP is warranted.

Apitherapy and Periodontal Disease: Insights into In Vitro, In Vivo, and Clinical Studies

Periodontal diseases are caused mainly by inflammation of the gums and bones surrounding the teeth or by dysbiosis of the oral microbiome, and the Global Burden of Disease study (2019) reported that periodontal disease affects 20–50% of the global population. In recent years, more preference has been given to natural therapies compared to synthetic drugs in the treatment of periodontal disease, and several oral care products, such as toothpaste, mouthwash, and dentifrices, have been developed comprising honeybee products, such as propolis, honey, royal jelly, and purified bee venom. In this study, we systematically reviewed the literature on the treatment of periodontitis using honeybee products. A literature search was performed using various databases, including PubMed, Web of Science, ScienceDirect, Scopus, clinicaltrials.gov, and Google Scholar. A total of 31 studies were reviewed using eligibility criteria published between January 2016 and December 2021. In vitro, in vivo, and clinical studies (randomized clinical trials) were included. Based on the results of these studies, honeybee products, such as propolis and purified bee venom, were concluded to be effective and safe for use in the treatment of periodontitis mainly due to their antimicrobial and anti-inflammatory activities. However, to obtain reliable results from randomized clinical trials assessing the effectiveness of honeybee products in periodontal treatment with long-term follow-up, a broader sample size and assessment of various clinical parameters are needed.

Multisystem inflammatory syndrome in Indian adolescents associated with SARS-CoV-2 infection: a case report.

BACKGROUND: Adolescents with coronavirus disease 2019 (COVID-19) associated multisystem inflammatory syndrome (MIS) can present with shock and myocardial injury and mimic Kawasaki disease. CASE PRESENTATION: We describe 4 previously well adolescents (age 13-14 years), presenting with clinical features of MIS in children (MIS-C). All patients had nearly similar clinical presentation. Hematological investigations revealed elevated inflammatory markers, anemia, thrombocytopenia, and decreased neutrophil:lymphocyte ratio. All patients were negative on real-time polymerase chain reaction against severe acute respiratory syndrome coronavirus 2, but had elevated immunoglobulin G titers. Two patients had atypical Kawasaki disease. Three patients had severe disease with hypotensive shock and required intensive care with fluids and inotropes. Two patients required non-invasive respiratory support for dyspnea and one patient had biventricular dysfunction. All received empiric antibiotics, low-molecular weight heparin, steroids, and intravenous immunoglobulin. One patient succumbed, while others recovered well. CONCLUSIONS: MIS-C may be a late presentation in adolescent with COVID-19. Individualized treatment with empiric antibiotics, immunomodulation, and thromboprophylaxis can result in significantly better outcome.

Target Specific Inhibition of Protein Tyrosine Kinase in Conjunction With Cancer and SARS-COV-2 by Olive Nutraceuticals.

The fact that viruses cause human cancer dates back to the early 1980s. By reprogramming cellular signaling pathways, viruses encoded protein that can regulate altered control of cell cycle events. Viruses can interact with a superfamily of membrane bound protein, receptor tyrosine kinase to modulate their activity in order to increase virus entrance into cells and promotion of viral replication within the host. Therefore, our study aimed at screening of inhibitors of tyrosine kinase using natural compounds from olive. Protein tyrosine kinase (PTK) is an important factor for cancer progression and can be linked to coronavirus. It is evident that over expression of Protein tyrosine kinase (PTK) enhance viral endocytosis and proliferation and the use of tyrosine kinase inhibitors reduced the period of infection period. Functional network studies were carried out using two major PTKs viz. Anaplastic lymphoma kinase (ALK) and B-lymphocytic kinase (BTK). They are associated with coronavirus in regulation of cell signaling proteins for cellular processes. We virtually screened for 161 library of natural compounds from olive found overexpressed in ALK and BTK in metastatic as well as virus host cells. We have employed both ligand and target-based approach for drug designing by high throughput screening using Multilinear regression model based QSAR and docking. The QSAR based virtual screening of 161 olive nutraceutical compounds has successfully identified certain new hit; Wedelosin, in which, the descriptor rsa (ratio of molecular surface area to the solvent accessible surface area) plays crucial role in deciding Wedelosin's inhibitory potency. The best-docked olive nutraceuticals further investigated for the stability and effectivity of the BTK and ALK during in 150 ns molecular dynamics and simulation. Post simulation analysis and binding energy estimation in MMGBSA further revealed the intensive potential of the olive nutraceuticals in PTK inhibition. This study is therefore expected to widen the use of nutraceuticals from olive in cancer as well as SARS-CoV2 alternative therapy.

Impact of the COVID-19 pandemic on urologic care delivery in the United States

Introduction & Objectives: The impact of the COVID-19 pandemic on health care access and delivery in the US has been reported for hospital admissions and in the outpatient setting for a few selected health conditions. However, the impact on specialty care has not been adequately characterized. We therefore aimed to determine trends in outpatient urologic care visit and procedural volume in 2020, using a specialty-wide, community-based registry. Materials & Methods: The American Urological Association Quality (AQUA) Registry collects data via automated extraction from electronic health record systems at 157 urology practices representing 3,165 providers (roughly one-quarter of US urologists) across 48 US states and territories. We analyzed trends in care delivery from February 2020 to July 2020 based on patient, practice, and local/regional demographic and pandemic response features. The primary outcomes were mean visit volume and procedure volume per practice per week, and we compared each week to the corresponding week in 2019. Results: There were 2,750,001 patients in our cohort, accounting for 8,953,832 outpatient visits and 1,570,161 procedures. We found large (>40%) declines in outpatient visits from March to April 2020 across all demographic groups and US states, regardless of timing of stay-at-home orders. Visits recovered through May and early June, but began falling again by early July (see Figure). Non-urgent visits and procedures decreased more (39–47%) than visits for urgent diagnoses (29–43%);surgical procedures for non-urgent conditions also decreased more (37–53%) than those for potentially urgent conditions (13–21%). African American and Hispanic patients had smaller decreases in visits compared with Asian and Caucasian patients, but also slower recoveries back to baseline. Medicare-insured patients (mostly over 65 years old) had the steepest declines (50%) while those on Medicaid (generally low-income) had among the lowest percentage of recovery to baseline (84.4%). Practices in zip codes with lower median incomes, higher poverty levels, and lower urologist to population ratios had smaller decreases in outpatient visits. (Figure Presented) Conclusions: This study provides timely, real-world evidence on the magnitude of decline in the provision of urological care across demographic groups and practice settings, and demonstrates a differential impact on the utilization of urologic health services by sociodemographic strata and specific diagnoses.

Pre-test probability for SARS-Cov-2-related infection score: The PARIS score.

INTRODUCTION: In numerous countries, large population testing is impossible due to the limited availability of RT-PCR kits and CT-scans. This study aimed to determine a pre-test probability score for SARS-CoV-2 infection. METHODS: This multicenter retrospective study (4 University Hospitals) included patients with clinical suspicion of SARS-CoV-2 infection. Demographic characteristics, clinical symptoms, and results of blood tests (complete white blood cell count, serum electrolytes and CRP) were collected. A pre-test probability score was derived from univariate analyses of clinical and biological variables between patients and controls, followed by multivariate binary logistic analysis to determine the independent variables associated with SARS-CoV-2 infection. RESULTS: 605 patients were included between March 10th and April 30th, 2020 (200 patients for the training cohort, 405 consecutive patients for the validation cohort). In the multivariate analysis, lymphocyte (<1.3 G/L), eosinophil (<0.06 G/L), basophil (<0.04 G/L) and neutrophil counts (<5 G/L) were associated with high probability of SARS-CoV-2 infection but no clinical variable was statistically significant. The score had a good performance in the validation cohort (AUC = 0.918 (CI: [0.891-0.946]; STD = 0.014) with a Positive Predictive Value of high-probability score of 93% (95%CI: [0.89-0.96]). Furthermore, a low-probability score excluded SARS-CoV-2 infection with a Negative Predictive Value of 98% (95%CI: [0.93-0.99]). The performance of the score was stable even during the last period of the study (15-30th April) with more controls than infected patients. CONCLUSIONS: The PARIS score has a good performance to categorize the pre-test probability of SARS-CoV-2 infection based on complete white blood cell count. It could help clinicians adapt testing and for rapid triage of patients before test results.

The storm that was delayed: the deterioration of an in-hospital diabetes process-of-care metric during the COVID-19 pandemic

Background/Aims Networked glucose blood monitoring has been demonstrated as a useful process of care for improving glycaemia and clinical outcomes in hospital inpatients. However, these benefits are partly reliant on the accurate entry of patients' medical record numbers by healthcare staff. This study assessed the accuracy of such data entry, comparing the periods before and after the onset of the COVID-19 pandemic. Methods This retrospective observational study analysed glucose meter medical record number entries at a large hospital in Victoria, Australia. The study period spanned from September 2019, when the networked blood glucose monitoring system was introduced, to July 2020. The proportion of inaccurate entries were presented as a percentage of the total number of entries and comparisons were made between the pre-COVID-19 and post-COVID-19 onset periods. Data were analysed using an interrupted time series methodology and presented using a Quasipoisson distribution. Results A gradual decrease in the percentage of accurate medical record number entries was observed following the introduction of the networked blood glucose monitoring system. This decline in accuracy decreased further following the onset of COVID-19, despite the hospital serving a relatively low number of patients with the virus. Conclusions The ongoing decrease in accuracy of data entry into the networked blood glucose monitoring system is thought to be a result of insufficient training and time constraints, which were exacerbated by the COVID-19 pandemic because of protocol changes and furloughed staff. It is recommended that accurate use of the networked blood glucose monitoring system is allocated more regular training in hospital wards.

Comparison between Patients Hospitalized with Influenza and COVID-19 at a Tertiary Care Center.

BACKGROUND: Widespread reports suggest the characteristics and disease course of coronavirus disease 2019 (COVID-19) and influenza differ, yet detailed comparisons of their clinical manifestations are lacking. OBJECTIVE: Comparison of the epidemiology and clinical characteristics of COVID-19 patients during the pandemic with those of influenza patients in previous influenza seasons at the same hospital DESIGN: Admission rates, clinical measurements, and clinical outcomes from confirmed COVID-19 cases between March 1 and April 30, 2020, were compared with those from confirmed influenza cases in the previous five influenza seasons (8 months each) beginning September 1, 2014. SETTING: Large tertiary care teaching hospital in Boston, MA PARTICIPANTS: Laboratory-confirmed COVID-19 and influenza inpatients MEASUREMENTS: Patient demographics and medical history, mortality, incidence and duration of mechanical ventilation, incidences of vasopressor support and renal replacement therapy, and hospital and intensive care admissions. RESULTS: Data was abstracted from medical records of 1052 influenza patients and 582 COVID-19 patients. An average of 210 hospital admissions for influenza occurred per 8-month season compared to 582 COVID-19 admissions over 2 months. The median weekly number of COVID-19 patients requiring mechanical ventilation was 17 (IQR: 4, 34) compared to a weekly median of 1 (IQR: 0, 2) influenza patient (p=0.001). COVID-19 patients were significantly more likely to require mechanical ventilation (31% vs 8%) and had significantly higher mortality (20% vs. 3%; p<0.001 for all). Relatively more COVID-19 patients on mechanical ventilation lacked pre-existing conditions compared with mechanically ventilated influenza patients (25% vs 4%, p<0.001). Pneumonia/ARDS secondary to the virus was the predominant cause of mechanical ventilation in COVID-19 patients (94%) as opposed to influenza (56%). LIMITATION: This is a single-center study which could limit generalization. CONCLUSION: COVID-19 resulted in more weekly hospitalizations, higher morbidity, and higher mortality than influenza at the same hospital.

Determining extent of COVID-19 pneumonia on CT based on biological variables.

INTRODUCTION: Covid-19 pneumonia CT extent correlates well with outcome including mortality. However, CT is not widely available in many countries. This study aimed to explore the relationship between Covid-19 pneumonia CT extent and blood tests variations. The objective was to determine for the biological variables correlating with disease severity the cut-off values showing the best performance to predict the parenchymal extent of the pneumonia. METHODS: Bivariate correlations were calculated between biological variables and grade of disease extent on CT. Receiving Operating Characteristic curve analysis determined the best cutoffs for the strongest correlated biological variables. The performance of these variables to predict mild (<10%) or severe pneumonia (>50% of parenchyma involved) was evaluated. RESULTS: Correlations between biological variables and disease extent was evaluated in 168 patients included in this study. LDH, lymphocyte count and CRP showed the strongest correlations (with 0.67, -0.41 and 0.52 correlation coefficient, respectively). Patients were split into a training and a validation cohort according to their centers. If one variable was above/below the following cut-offs, LDH>380, CRP>80 or lymphocyte count <0.8G/L, severe pneumonia extent on CT was detected with 100% sensitivity. Values above/below all three thresholds were denoted in 73% of patients with severe pneumonia extent. The combination of LDH<220 and CRP<22 was associated with mild pneumonia extent (<10%) with specificity of 100%. DISCUSSION: LDH showed the strongest correlation with the extent of Covid-19 pneumonia on CT. Combined with CRP±lymphocyte count, it helps predicting parenchymal extent of the pneumonia when CT scan is not available.

Comparison Between Influenza and COVID-19 at a Tertiary Care Center (preprint)

ABSTRACT Background: Widespread reports suggest the characteristics and disease course of coronavirus disease 2019 (COVID-19) and influenza differ, yet detailed comparisons of their clinical manifestations are lacking. Objective: Comparison of the epidemiology and clinical characteristics of COVID-19 patients with those of influenza patients in previous seasons at the same hospital Design: Admission rates, clinical measurements, and clinical outcomes from confirmed COVID-19 cases between March 1 and April 30, 2020 were compared with those from confirmed influenza cases in the previous five influenza seasons (8 months each) beginning September 1, 2014. Setting: Large tertiary care teaching hospital in Boston, Massachusetts Participants: Laboratory-confirmed COVID-19 and influenza inpatients Measurements: Patient demographics and medical history, mortality, incidence and duration of mechanical ventilation, incidences of vasopressor support and renal replacement therapy, hospital and intensive care admissions. Results: Data was abstracted from medical records of 1052 influenza patients and 583 COVID-19 patients. An average of 210 hospital admissions for influenza occurred per 8-month season compared to 583 COVID-19 admissions over two months. The median weekly number of COVID-19 patients requiring mechanical ventilation was 17 (IQR: 4, 34) compared to a weekly median of 1 (IQR: 0, 2) influenza patient (p=0.001). COVID-19 patients were significantly more likely to require mechanical ventilation (31% vs 8%), and had significantly higher mortality (20% vs. 3%; p<0.001 for all). Relatively more COVID-19 patients on mechanical ventilation lacked pre-existing conditions compared with mechanically ventilated influenza patients (25% vs 4%, p<0.001). Limitation: This is a single-center study which could limit generalization. Conclusion: COVID-19 resulted in more hospitalizations, higher morbidity, and higher mortality than influenza at the same hospital.

Pre-test probability for SARS-Cov-2-related Infection Score: the PARIS score (preprint)

BackgroundDiagnostic tests for SARS-CoV-2 infection (mostly RT-PCR and Computed Tomography) are not widely available in numerous countries, expensive and with imperfect performance MethodsThis multicenter retrospective study aimed to determine a pre-test probability score for SARS-CoV-2 infection based on clinical and biological variables. Patients were recruited from emergency and infectious disease departments and were divided into a training and a validation cohort. Demographic characteristics, clinical symptoms, and results of blood tests (complete white blood cell count, serum electrolytes and CRP) were collected. The pre-test probability score was derived from univariate analyses between patients and controls, followed by multivariate binary logistic analysis to determine the independent variables associated with SARS-CoV-2 infection. Points were assigned to each variable to create the PARIS score. ROC curve analysis determined the area under the curve (AUC). FindingsOne hundred subjects with clinical suspicion of SARS-CoV-2 infection were included in the training cohort, and 300 other consecutive individuals were included in the validation cohort. Low lymphocyte (<1{middle dot}3 G/L), eosinophil (<0{middle dot}06G/L), basophil (<0{middle dot}04G/L) and neutrophil counts (<5G/L) were associated with a high probability of SARS-CoV-2 infection. No clinical variable was statistically significant. The score had a good performance in the validation cohort (AUC=0.889 (CI: [0.846-0.932]; STD=0.022) with a sensitivity and Positive Predictive Value of high-probability score of 80{middle dot}3% and 92{middle dot}3% respectively. Furthermore, a low-probability score excluded SARS-CoV-2 infection with a Negative Predictive Value of 99.5%. InterpretationThe PARIS score based on complete white blood cell count has a good performance to categorize the pre-test probability of SARS-CoV-2 infection. It could help clinicians avoid diagnostic tests in patients with a low-probability score and conversely keep on testing individuals with high-probability score but negative RT-PCR or CT. It could prove helpful in countries with a low-availability of PCR and/or CT during the current period of pandemic. FundingNone Putting research into contextO_ST_ABSEvidence before this studyC_ST_ABSIn numerous countries, large population testing is impossible due to the limited availability and costs of RT-PCR kits and CT-scan. Furthermore, false-negativity of PCR or CT as well as COVID-19 pneumonia mimickers on CT may lead to inaccurate diagnoses. Pre-test probability combining clinical and biological features has proven to be a particularly useful tool, already used in clinical practice for management of patients with a suspicion of pulmonary embolism. Added value of this studyThis retrospective study including 400 patients with clinical suspicion of SARS-CoV-2 infection was composed of a training and a validation cohort. The pre-test probability score (PARIS score) determines 3 levels of probability of SARS-CoV2 infection based on white blood cell count (lymphocyte, eosinophil, basophil and neutrophil cell count). Implications of the available evidenceThis pre-test probability may help to adapt SARS-CoV-2 infection diagnostic tests. The high negative predictive value (99{middle dot}5%) of the low probability category may help avoid further tests, especially during a pandemic with overwhelmed resources. A high probability score combined with typical CT features can be considered sufficient for diagnosis confirmation.