Early predictors of clinical outcomes of COVID-19 outbreak in Milan, Italy

Ciceri, Fabio; Castagna, Antonella; Rovere‐Querini, Patrizia; Cobelli, Francesco De; Ruggeri, Annalisa; Galli, Laura; Conte, Caterina; Lorenzo, Rebecca De; Poli, Andrea; Ambrosio, Alberto; Signorelli, Carlo; Bossi, E; Fazio, Maria; Tresoldi, Cristina; Colombo, Sergio; Monti, Giacomo; Fominskiy, Evgeny; Franchini, Stefano; Spessot, Marzia; Martinenghi, C; Carlucci, Michele; Beretta, Luigi; Scandroglio, Anna Maria; Clementi, Massimo; Locatelli, Massimo; Tresoldi, Moreno; Scarpellini, Paolo; Martino, Gianvito; Bosi, Emanuele; Dagna, Lorenzo; Lazzarin, Adriano; Landoni, Giovanni; Zangrillo, Alberto

doi:10.1016/j.clim.2020.108509

Cited by 265 publications

(306 citation statements)

References 19 publications

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“…Lymphocytes play an important role in immune status and inflammatory response. When a virus infects the lymphocytes, this leads to a decrease in lymphocytes (especially cytotoxic lymphocytes) and makes a body more vulnerable with an increasing risk of bacterial infections [1,2,[10][11][12]16,17]. Several studies have shown an important role of lymphocytes in COVID-19 patients [5][6][7][10][11][12][13].…”

Section: Lymphocyte Countmentioning

confidence: 99%

“…As several studies already examined the influence of COVID-19 on routine hematology parameters in their country [3][4][5][6][7][8][9][10][11][12][13], the aim of this study was to confirm or reject these findings in our hospital and to investigate whether there is a specific time period after disease onset in which predictions of outcome can be made based on routine hematology parameters.…”

Section: Introductionmentioning

confidence: 96%

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The influence of COVID-19 on routine hematological parameters of hospitalized patients

Blomme

Smets

Ranst

et al. 2020

Acta Clinica Belgica

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Objectives: Coronavirus disease 2019 (COVID-19) was first discovered in Wuhan, China, in December 2019, and soon spread around the entire world. As no effective treatment is known, prediction of disease severity is very important in order to estimate a patients outcome. Aim of this study was to evaluate routine hematology parameters in time after admission. Methods: Data from routine blood analyses from confirmed COVID-19 cases admitted to the University Hospital of Leuven in Belgium were collected. COVID-19 patients (n = 197) were assigned to three groups: a 'non-ICU' group, a 'ICU' group and a 'deceased' group. A control group of 60 Influenza A (non-COVID-19) patients was also included. The parameters evaluated were platelet count (PLT, 10 9 /L), hemoglobin concentration (Hb, g/dL), leukocyte count (LEU, 10 9 /L), neutrophil count (NEU, %), eosinophil count (EO, %), lymphocyte count (LYM, %) and monocyte count (MONO, %). Results: Deceased COVID-19 patients had significant lower platelet count, higher leukocyte/ neutrophil count, and lower eosinophil/lymphocyte/monocyte count compared to recovered patients. Especially lymphocyte count showed important differences; they were significantly lower between day 9 and 12 after admission making this time window important in predicting clinical worsening of a patient. Conclusion: Patients with COVID-19 with poor outcome showed significant differences in results of routine hematological parameters compared with patients that recovered. Especially lymphocyte count can be helpful in the prediction of a patients outcome.

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Section: Lymphocyte Countmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

The influence of COVID-19 on routine hematological parameters of hospitalized patients

Blomme

Smets

Ranst

et al. 2020

Acta Clinica Belgica

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“…In that study, dyspnea, hemoptysis, and unconsciousness were clinical predictors of critical illness [ 23 ]. While several clinical predictors for severe COVID-19 (dyspnea [ 24 ], old age [ 25 ], type II diabetes [ 26 ], obesity [ 27 ], possibly hypertension [ 28 ], history of cancer [ 29 ], cardiovascular disease [ 30 ], or increased ratios of CD4/CD8 [ 31 ], neutrophils/lymphocytes [ 32 ], and CRP/lymphocytes [ 33 ]) have been identified, no study has assessed clinical predictors for SARS-CoV-2 positivity. This knowledge is important for the upcoming phase, when the ratio of patients affected to patients tested will remain low in most test centers.…”

Section: Discussionmentioning

confidence: 99%

COVID-19 Triage and Test Center: Safety, Feasibility, and Outcomes of Low-Threshold Testing

Mansella

Rueegg

Widmer

et al. 2020

JCM

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This prospective observational study evaluated the safety and feasibility of a low threshold testing process in a Triage and Test Center (TTC) during the early course of the coronavirus disease 19 (COVID-19) pandemic. In addition, we aimed to identify clinical predictors for a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) swab result. Patients underwent informal triage, standardized history taking, and physician evaluation, only where indicated. Patients were observed for 30 days. Safety was the primary outcome and was defined as a COVID-19-related 30 day re-presentation rate <5% and mortality rate <1% in patients presenting to the TTC. Feasibility was defined as an overruling of informal triage <5%. Among 4815 presentations, 572 (11.9%) were tested positive for SARS-CoV-2, and 4774 were discharged. Mortality at 30-days was 0.04% (2 patients, one of which related to COVID-19). Fever (OR 2.03 [95% CI 1.70;2.42]), myalgia (OR 1.94 [1.63;2.31]), chills (OR 1.77 [1.44;2.16]), headache (OR 1.61 [1.34;1.94]), cough (OR 1.50 [1.24;1.83]), weakness (OR 1.46 [1.21;1.76]), and confusion (OR 1.39 [1.06;1.80]) were associated with test positivity. Re-presentation rate was 8% overall and 1.4% in COVID-19 related re-presentation (69 of 4774). The overruling rate of informal triage was 1.5%. According to our study, a low-threshold testing process in a TTC appeared to be safe (low re-presentation and low mortality) and is feasible (low overruling of informal triage). A COVID-19 diagnosis based on clinical parameters only does not appear possible.

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“…By 7 August 2020 there were >1,90,00,000 cumulative cases globally and >7,00,000 deaths with ∼5% mortality rate in outcome cases. The main risk factors include older age, comorbidities, low lymphocyte count and high RALE (radiographical assessment of lung edema) ( Ciceri et al, 2020 ). The average incubation period of this virus is 2 to 14 days (mainly 3 to 7 days), but it may be enhanced in people with histories of long-term use of glucocorticoids ( Han et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Denovo designing, retrosynthetic analysis, and combinatorial synthesis of a hybrid antiviral (VTAR-01) to inhibit the interaction of SARS-CoV2 spike glycoprotein with human angiotensin-converting enzyme 2

Tiwari

2020

Biology Open

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SARS-like coronavirus (SARS-CoV2) has emerged as a global threat to humankind and is rapidly spreading. The infectivity, pathogenesis, and infection of this virus are dependent on the interaction of SARS-CoV2 spike protein with human ACE2 (hACE2). Spike protein contains a receptor-binding domain (RBD) that recognizes hACE-2. In the present study, we are reporting a denovo designed novel hybrid antiviral ‘VT-AR-01’ molecule that binds at the interface of RBD-hACE2 interaction. A series of antiviral molecules were tested for binding at the interface of RBD-hACE2 interaction. In-silico screening, molecular mechanics, molecular dynamics simulation (MDS) analysis suggest ribavirin, ascorbate, lopinavir, and hydroxychloroquine have strong interaction at RBD-hACE2 interface. These four molecules were used for denovo fragment-based antiviral design. Denovo designing, docking, and MDS analysis identified a ‘VTAR’ hybrid molecule that has better interaction with this interface as compared to all antiviral used to design it. We have further used retrosynthetic analysis and combinatorial synthesis to design 100 variants of VT-AR molecules. Retrosynthetic analysis and combinatorial synthesis, along with docking and MDS, identified VT-AR-01 that interact with the interface of the RBD-ACE2 complex. MDS analysis confirmed its interaction with the RBD-ACE2 interface by involving Glu35 and Lys353 of ACE2, as well as Gln493 and Ser494 of RBD. Interaction of spike protein with ACE2 is essential for pathogenesis and infection of this virus; hence, this in-silico designed hybrid antiviral molecule (VT-AR-01) that binds at the interface of RBD-hACE2 may be further developed to control the infection of SARS-CoV2.

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Early predictors of clinical outcomes of COVID-19 outbreak in Milan, Italy

Cited by 265 publications

References 19 publications

The influence of COVID-19 on routine hematological parameters of hospitalized patients

The influence of COVID-19 on routine hematological parameters of hospitalized patients

COVID-19 Triage and Test Center: Safety, Feasibility, and Outcomes of Low-Threshold Testing

Denovo designing, retrosynthetic analysis, and combinatorial synthesis of a hybrid antiviral (VTAR-01) to inhibit the interaction of SARS-CoV2 spike glycoprotein with human angiotensin-converting enzyme 2

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