Expression and significance of procalcitonin, leukotriene B4, serum amyloid A, and C-reactive protein in children with different types of pneumonia: An observational study.

This study aimed to investigate the expression and significance of serum procalcitonin (PCT), leukotriene B4 (LTB4), Serum amyloid A (SAA), and C-reactive protein (CRP) in children with different types of pneumonia caused by different pathogenic infections. One hundred and one children with pneumonia admitted to The Fifth People Hospital of Zhuhai from July 2019 to June 2020 were enrolled and divided into 38 cases in the bacterial group, 30 cases in the mycoplasma group, and 33 cases in the virus group according to the different types of pathogens. The patients were divided into 42 cases in the noncritical group, 33 cases in the critical group, and 26 cases in the very critical group according to the pediatric clinical illness score (PCIS), and 30 healthy children were selected as the control group during the same period. Comparison of serum PCT, SAA: bacterial group > mycoplasma group > viral group > control group with significant differences (P < .05). Receiver operator characteristic (ROC) analysis showed that the area under the curves (AUCs) of serum PCT, LTB4, SAA, and CRP for the diagnosis of bacterial pneumonia were 1.000, 0.531, 0.969, and 0.833, respectively, and the AUCs for the diagnosis of mycoplasma pneumonia were 0.653, 0.609, 0.547, and 0.652, respectively, and the AUCs for the diagnosis of viral pneumonia were 0.888, 0.570, 0.955, and 1.000, respectively. Comparison of serum PCT, LTB4, SAA: very critical group > critical group > noncritical group > control group, with significant differences (P < .05). Serum PCT, LTB4, and SAA were negatively correlated with PCIS score by Pearson analysis (P < .05). Serum PCT and SAA showed diagnostic value for bacterial pneumonia, and serum SAA and CRP showed diagnostic value for viral pneumonia; serum PCT, LTB4, and SAA correlate with severity of disease and show higher expression with worsening of the condition.

Biomarkers for iron metabolism among patients hospitalized with community-acquired pneumonia caused by infection with SARS-CoV-2, bacteria, and influenza.

Ferritin, the central iron storage protein, has attracted attention as a biomarker of severe COVID-19. Few studies have investigated regulators of iron metabolism in the context of COVID-19. The aim was to evaluate biomarkers for iron metabolism in the acute phase response to community-acquired pneumonia (CAP) caused by SARS-CoV-2 compared with CAP caused by bacteria or influenza virus in hospitalized patients. A cross-sectional study of 164 patients from the Surviving Pneumonia Cohort recruited between January 8, 2019 and May 26, 2020. Blood samples were collected at admission and analyzed for levels of C-reactive protein (CRP), ferritin, soluble transferrin receptor, erythroferrone, and hepcidin. Median (IQR) hepcidin was higher in SARS-CoV-2 with 143.8 (100.7-180.7) ng/mL compared with bacterial and influenza infection with 78.8 (40.1-125.4) and 53.5 (25.2-125.8) ng/mL, respectively. The median ferritin level was more than 2-fold higher in patients with SARS-CoV-2 compared with the other etiologies (p < 0.001). Patients with SARS-CoV-2 had lower levels of erythroferrone and CRP compared with those infected with bacteria. Higher levels of hepcidin and lower levels of erythroferrone despite lower CRP levels among patients with SARS-CoV-2 compared with those infected with bacteria indicate alterations in iron metabolism in patients with SARS-CoV-2 infection.

Cytomegalovirus infection in malignant pleural mesothelioma.

Human cytomegalovirus (HCMV) is a highly prevalent herpes virus which persists as a latent infection and has been detected in several different tumor types. HCMV disease is rare but may occur in high-risk settings, often manifesting as a pulmonary infection. To date HCMV has not been investigated in malignant pleural mesothelioma (MPM). In a consecutive case series of 144 MPM patients we evaluated two biomarkers of HCMV: IgG serostatus (defined as positive and negative) and DNAemia (>100 copies/mL of cell free HCMV DNA in serum). Approximately half of the MPM patient population was HCMV IgG seropositive (51%). HCMV DNAemia was highly prevalent (79%) in MPM and independent of IgG serostatus. DNAemia levels consistent with high level current infection (>1000 copies/mL serum) were present in 41% of patients. Neither IgG serostatus nor DNAemia were associated with patient survival. In tissues, we observed that HCMV DNA was present in 48% of tumors (n = 40) and only 29% of normal pleural tissue obtained from individuals without malignancy (n = 21). Our results suggest nearly half of MPM patients have a high level current HCMV infection at the time of treatment and that pleural tissue may be a reservoir for latent HCMV infection. These findings warrant further investigation to determine the full spectrum of pulmonary infections in MPM patients, and whether treatment for high level current HCMV infection may improve patient outcomes.

Longitudinal monitoring of laboratory markers characterizes hospitalized and ambulatory COVID-19 patients.

Early detection of severe forms of COVID-19 is absolutely essential for timely triage of patients. We longitudinally followed-up two well-characterized patient groups, hospitalized moderate to severe (n = 26), and ambulatory mild COVID-19 patients (n = 16) at home quarantine. Human D-dimer, C-reactive protein (CRP), ferritin, cardiac troponin I, interleukin-6 (IL-6) levels were measured on day 1, day 7, day 14 and day 28. All hospitalized patients were SARS-CoV-2 positive on admission, while all ambulatory patients were SARS-CoV-2 positive at recruitment. Hospitalized patients had higher D-dimer, CRP and ferritin, cardiac troponin I and IL-6 levels than ambulatory patients (p < 0.001, p < 0.001, p = 0.016, p = 0.035, p = 0.002 respectively). Hospitalized patients experienced significant decreases in CRP, ferritin and IL-6 levels from admission to recovery (p < 0.001, p = 0.025, and p = 0.001 respectively). Cardiac troponin I levels were high during the acute phase in both hospitalized and ambulatory patients, indicating a potential myocardial injury. In summary, D-dimer, CRP, ferritin, cardiac troponin I, IL-6 are predictive laboratory markers and can largely determine the clinical course of COVID-19, in particular the prognosis of critically ill COVID-19 patients.

Patient hematology during hospitalization for viral pneumonia caused by SARS-CoV-2 and non-SARS-CoV-2 agents: a retrospective study.

BACKGROUND: Hematological comparison of coronavirus disease (COVID-19) and other viral pneumonias can provide insights into COVID-19 treatment. METHODS: In this retrospective case-control single-center study, we compared the data of 126 patients with viral pneumonia during different outbreaks [severe acute respiratory syndrome (SARS) in 2003, influenza A (H1N1) in 2009, human adenovirus type 7 in 2018, and COVID-19 in 2020]. RESULTS: One of the COVID-19 characteristics was a continuous decline in the hemoglobin level. The neutrophil count was related to the aggravation of COVID-19 and SARS. Thrombocytopenia occurred in patients with SARS and severe COVID-19 even at the recovery stage. Lymphocytes were related to the entire course of adenovirus infection, recovery of COVID-19, and disease development of SARS. CONCLUSIONS: Dynamic changes in hematological counts could provide a reference for the pathogenesis and prognosis of pneumonia caused by respiratory viruses in clinics.

Tocilizumab improves survival in severe COVID-19 pneumonia with persistent hypoxia: a retrospective cohort study with follow-up from Mumbai, India.

BACKGROUND: Cytokine storm triggered by Severe Coronavirus Disease 2019 (COVID-19) is associated with high mortality. With high Interleukin -6 (IL-6) levels reported in COVID-19 related deaths in China, IL-6 is considered to be the key player in COVID-19 cytokine storm. Tocilizumab, a monoclonal antibody against IL-6 receptor, is used on compassionate grounds for treatment of COVID-19 cytokine storm. The aim of this study was to assess effect of tocilizumab on mortality due to COVID-19 cytokine storm. METHOD: This retrospective, observational study included patients of severe COVID-19 pneumonia with persistent hypoxia (defined as saturation 94% or less on supplemental Oxygen of 15 L per minute through non-rebreathing mask or PaO2/FiO2 ratio of less than 200) who were admitted to a tertiary care center in Mumbai, India, between 31st March to 5th July 2020. In addition to standard care, single Inj. Tocilizumab 400 mg was given intravenously to 151 consecutive COVID-19 patients with persistent hypoxia, from 13th May to 5th July 2020. These 151 patients were retrospectively analysed and compared with historic controls, ie consecutive COVID-19 patients with persistent hypoxia, defined as stated above (N = 118, from our first COVID-19 admission on 31st March to 12th May 2020 i.e., till tocilizumab was available in hospital). Univariate and multivariate Cox regression analysis was performed for identifying predictors of survival. Statistical analysis was performed using IBM SPSS version 26. RESULTS: Out of 269 (151 in tocilizumab group and 118 historic controls) patients studied from 31st March to 5th July 2020, median survival in the tocilizumab group was significantly longer than in the control group; 18 days (95% CI, 11.3 to 24.7) versus 9 days (95% CI, 5.7 to 12.3); log rank p 0.007. On multivariate Cox regression analysis, independent predictors of survival were use of tocilizumab (HR 0.621, 95% CI 0.427-0.903, P 0.013) and higher oxygen saturation. CONCLUSION: Tocilizumab may improve survival in severe COVID-19 pneumonia with persistent hypoxia. Randomised controlled trials on use of tocilizumab as rescue therapy in patients of severe COVID-19 pneumonia with hypoxia (PaO2/FiO2 less than 200) due to hyperinflammatory state, are warranted.

Adenovirus viremia may predict adenovirus pneumonia severity in immunocompetent children.

BACKGROUND: Previous studies have demonstrated an association between adenovirus viremia and disease severity in immunocompromised children. However, few studies have focused on this association in immunocompetent children. This study explored the association between adenovirus viremia and adenovirus pneumonia severity in immunocompetent children. METHODS: We performed a retrospective, observational study of immunocompetent children with adenovirus pneumonia admitted to Shenzhen Children's Hospital in Shenzhen, China. Pneumonia was classified as severe or mild based on the Chinese guideline for the classification of pneumonia severity. Serum samples from all the children included in the study were tested for adenovirus DNA with a quantitative polymerase chain reaction. Clinical manifestations, laboratory examinations, and disease severity were compared between children with severe and mild pneumonia. RESULTS: A total of 111 immunocompetent children with adenovirus pneumonia (60 severe, 51 mild) were included. The median age was 40 months, and 64 patients were male. Five patients were admitted to the intensive care unit, and two underwent endotracheal intubation. All patients were discharged after recovery or improvement. Univariate analysis and binary logistic regression analysis showed that leukocytosis (OR = 1.1; 95% CI: 1.0 to 1.2; P = 0.033), co-infection with Mycoplasma pneumoniae (OR = 5.0; 95% CI: 2.1 to 12.3; P <  0.001), and high blood viral load (OR = 1.5; 95% CI: 1.2 to 2.0; P = 0.001) may be risk factors for severe adenovirus pneumonia. CONCLUSIONS: Leukocytosis, co-infection with Mycoplasma pneumoniae, and high blood viral load may be risk factors for severe adenovirus pneumonia in immunocompetent children. Blood viral load may predict pneumonia severity.

Integration of heparin-binding protein and interleukin-6 in the early prediction of respiratory failure and mortality in pneumonia by SARS-CoV-2 (COVID-19).

Recent publications on the probable role of heparin-binding protein (HBP) as a biomarker in sepsis prompted us to investigate its diagnostic and prognostic performance in severe COVID-19. HBP and IL-6 were measured by immunoassays at admission and on day 7 in 178 patients with pneumonia by SARS-CoV-2. Patients were classified into non-sepsis and sepsis as per the Sepsis-3 definitions and were followed up for the development of severe respiratory failure (SRF) and for outcome. Results were confirmed by multivariate analyses. HBP was significantly higher in patients classified as having sepsis and was negatively associated with the oxygenation ratio and positively associated with creatinine and lactate. Logistic regression analysis evidenced admission HBP more than 18 ng/ml and IL-6 more than 30 pg/ml as independent risk factors for the development of SRP. Their integration prognosticated SRF with respective sensitivity, specificity, positive predictive value, and negative predictive 59.1%, 96.3%, 83.9%, and 87.8%. Cox regression analysis evidenced admission HBP more than 35 ng/ml and IL-6 more than 30 pg/ml as independent risk factors for 28-day mortality. Their integration prognosticated 28-day mortality with respective sensitivity, specificity, positive predictive value, and negative predictive value 69.2%, 92.7%, 42.9%, and 97.5%. HBP remained unchanged over-time course. A prediction score of the disposition of patients with COVID-19 is proposed taking into consideration admission levels of IL-6 and HBP. Using different cut-offs, the score may predict the likelihood for SRF and for 28-day outcome.

Tumor Necrosis Factor Alpha Gene Polymorphisms Increase Susceptibility to Adenovirus Infection in Children and Are Correlated with Severity of Adenovirus-Associated Pneumonia.

Objective: To study the relationships between single nucleotide polymorphisms (SNPs) in the intron of the tumor necrosis factor α (TNFα) gene and the susceptibility and severity of disease associated with adenovirus infection in children. Methods: Four polymorphic loci of the TNFα gene (rs3093661, rs1800610, rs3093662, and rs3093664) were characterized allelically and genotypically in 320 children with adenovirus-associated pneumonia (AP) and compared with 320 healthy controls. Enzyme-linked immunosorbent assays (ELISAs) were used to detect the plasma TNFα protein levels in all subjects. Results: The TNFα gene rs3093661 locus A allele, the rs1800610 locus A allele, the rs3093662 locus G allele, and the rs3093664 locus G allele were identified as susceptibility alleles for development of AP, and they were also positively correlated with the severity of AP. In children who had the GGAA haplotype, AP susceptibility was significantly reduced (0.28-fold) (95% confidence interval, CI: 0.20-0.40, p < 0.001). Conversely, among the subjects with the AGGG haplotype, their AP susceptibility risk was significantly increased (2.76-fold) (95% CI: 1.77-4.29, p < 0.001); and in the subjects with the AP GGGG haplotype their AP susceptibility risk was significantly increased (2.49-fold) (95% CI: 1.67-3.72, p < 0.001). The TNFα rs3093661, rs1800610, rs3093662, and rs3093664 SNPs were significantly correlated with plasma TNFα levels (p < 0.05). Conclusion: The TNFα gene rs3093661, rs1800610, rs3093662, and rs3093664 loci are associated with AP susceptibility and severity. This relationship might be due to the effect on TNFα levels found in the plasma. Clinical Trial Registration number: LL20190723.

Chembio DPP COVID-19 IgM/IgG Serological Testing: Laboratory Validation, Guidelines, and Recommendations.

BACKGROUND: On January 30, 2020, WHO declared COVID-19 a pandemic. In this article we describe our experience at Richmond University Medical Center with Chembio serological IgM, IgG testing. METHODS: In this prospective cohort study of patients and hospital employees, we utilized Chembio COVID-19 IgM/IgG serological testing in addition to Cepheid RT-PCR analysis. RESULTS: We evaluated the performance of Chembio serological test for IgM and IgG as an employee screening tool in a community hospital setting. The total number of currently asymptomatic employees screened was 1,866 from the Richmond University Medical Center. The non-exposed group included 1,253 (67.1%) employees with no significant clinical history and non-reactive IgM and IgG antibodies. The convalescent group included 255 (13.7%) of the employees with elevation of IgG only, 18 (1%) employees with past history of positive PCR and COVID-19 who currently have non-reactive IgM and IgG antibodies or demonstrate elevated IgG only, followed by 3 employees (< 1%) with no past clinical history who demonstrated reactive IgM and IgG antibodies and negative follow up by PCR. The reported 14.9% exposure/convalescent rate is lower than the reported 20% by the Department of Health and Governor Andrew Cuomo and may represent a better utilization of personal protective equipment, better hand washing techniques, and better disinfection procedures combined with strict social distancing. CONCLUSIONS: Chembio's performance is satisfactory; however, hospitals must design their own policies addressing: who needs to be screened and who will interpret the results as well as constructing management algorithms for employees with no previous history and current double positive antibodies.

SARS-CoV-2 Cysteine-like Protease Antibodies Can Be Detected in Serum and Saliva of COVID-19-Seropositive Individuals.

Currently, there is a need for reliable tests that allow identification of individuals that have been infected with SARS-CoV-2 even if the infection was asymptomatic. To date, the vast majority of the serological tests for SARS-CoV-2-specific Abs are based on serum detection of Abs to either the viral spike glycoprotein (the major target for neutralizing Abs) or the viral nucleocapsid protein that is known to be highly immunogenic in other coronaviruses. Conceivably, exposure of Ags released from infected cells could stimulate Ab responses that might correlate with tissue damage and, hence, they may have some value as a prognostic indicator. We addressed whether other nonstructural viral proteins, not incorporated into the infectious viral particle, specifically the viral cysteine-like protease, might also be potent immunogens. Using ELISA tests, coating several SARS-CoV-2 proteins produced in vitro, we describe that COVID-19 patients make high titer IgG, IgM, and IgA Ab responses to the Cys-like protease from SARS-CoV-2, also known as 3CLpro or Mpro, and it can be used to identify individuals with positive serology against the coronavirus. Higher Ab titers in these assays associated with more-severe disease, and no cross-reactive Abs against prior betacoronavirus were found. Remarkably, IgG Abs specific for Mpro and other SARS-CoV-2 Ags can also be detected in saliva. In conclusion, Mpro is a potent Ag in infected patients that can be used in serological tests, and its detection in saliva could be the basis for a rapid, noninvasive test for COVID-19 seropositivity.

Correlation between premorbid IL-6 levels and COVID-19 mortality: Potential role for Vitamin D.

There is recent evidence that interleukin-6 (IL-6) levels are elevated in cases of complicated COVID-19, but it is also possible that this cytokine may have a far more important role in the pathogenesis of viral infection. IL-6 is known to be modulated by Vitamin D, and there is preliminary evidence that deficiency of this vitamin is linked to poorer outcomes. To identify whether IL-6 levels prior to infection might predict outcome, early data on COVID-19 mortality from Italy and the UK were compared with previously published results of mean IL-6 levels from these countries as well as from the USA. There was a highly significant correlation (r = 0.9883; p = 0.00025) between age-stratified mortality rates and IL-6 levels from previously published data on healthy individuals. To determine whether Vitamin D may be beneficial at lowering IL-6 levels in patients, a limited analysis of trials examining the relationship between these entities published since 2015 was undertaken. Eight out of 11 studies described a significant lowering effect of Vitamin D on IL-6. Given that IL-6 likely facilitates viral cell entry and replication, levels prior to infection may predict mortality. This provides a rationale for prophylactic and therapeutic measures directed at lowering IL-6, including Vitamin D prescription.

Association of elevated inflammatory markers and severe COVID-19: A meta-analysis.

Our study aimed to assess the existing evidence on whether severe coronavirus disease 2019 (COVID-19) is associated with elevated inflammatory markers.The PubMed, Embase, Web of Science, Scopus, Chinese National Knowledge Infrastructure, WanFang, and China Science and Technology Journal databases were searched to identify studies published between January 1 and April 21, 2020 that assayed inflammatory markers in COVID-19 patients. Three reviewers independently examined the literature, extracted relevant data, and assessed the risk of publication bias before including the meta-analysis studies.Fifty-six studies involving 8719 COVID-19 patients were identified. Meta-analysis showed that patients with severe disease showed elevated levels of white blood cell count (WMD: 1.15, 95% CI: 0.78-1.52), C-reactive protein (WMD: 38.85, 95% CI: 31.19-46.52), procalcitonin (WMD: 0.08, 95% CI: 0.06-0.11), erythrocyte sedimentation rate (WMD: 10.15, 95% CI: 5.03-15.46), interleukin-6 (WMD: 23.87, 95% CI: 15.95-31.78), and interleukin-10 (WMD: 2.12, 95% CI: 1.97-2.28). Similarly, COVID-19 patients who died during follow-up showed significantly higher levels of white blood cell count (WMD: 4.11, 95% CI: 3.25-4.97), C-reactive protein (WMD: 74.18, 95% CI: 56.63-91.73), procalcitonin (WMD: 0.26, 95% CI: 0.11-0.42), erythrocyte sedimentation rate (WMD: 10.94, 95% CI: 4.79-17.09), and interleukin-6 (WMD: 59.88, 95% CI: 19.46-100.30) than survivors.Severe COVID-19 is associated with higher levels of inflammatory markers than a mild disease, so tracking these markers may allow early identification or even prediction of disease progression.

Hematological changes in patients with COVID­19 (Review).

In December 2019, an emergence of pneumonia was detected in patients infected with a novel coronavirus (CoV) in Wuhan (Hubei, China). The International Committee on Taxonomy of Viruses named the virus severe acute respiratory syndrome­CoV­2 and the disease CoV disease­19 (COVID­19). Patients with COVID­19 present with symptoms associated with respiratory system dysfunction and hematological changes, including lymphopenia, thrombocytopenia and coagulation disorders. However, to the best of our knowledge, the pathogenesis of COVID­19 remains unclear. Therefore, understanding the mechanisms underlying the hematological changes that manifest during COVID­19 may aid in the development of treatments and may improve patient prognosis.

Vitamin D Supplementation Associated to Better Survival in Hospitalized Frail Elderly COVID-19 Patients: The GERIA-COVID Quasi-Experimental Study.

BACKGROUND: The objective of this quasi-experimental study was to determine whether bolus vitamin D supplementation taken either regularly over the preceding year or after the diagnosis of COVID-19 was effective in improving survival among hospitalized frail elderly COVID-19 patients. METHODS: Seventy-seven patients consecutively hospitalized for COVID-19 in a geriatric unit were included. Intervention groups were participants regularly supplemented with vitamin D over the preceding year (Group 1), and those supplemented with vitamin D after COVID-19 diagnosis (Group 2). The comparator group involved participants having received no vitamin D supplements (Group 3). Outcomes were 14-day mortality and highest (worst) score on the ordinal scale for clinical improvement (OSCI) measured during COVID-19 acute phase. Potential confounders were age, gender, functional abilities, undernutrition, cancer, hypertension, cardiomyopathy, glycated hemoglobin, number of acute health issues at admission, hospital use of antibiotics, corticosteroids, and pharmacological treatments of respiratory disorders. RESULTS: The three groups (n = 77; mean ± SD, 88 ± 5years; 49% women) were similar at baseline (except for woman proportion, p = 0.02), as were the treatments used for COVID-19. In Group 1 (n = 29), 93.1% of COVID-19 participants survived at day 14, compared to 81.2% survivors in Group 2 (n = 16) (p = 0.33) and 68.7% survivors in Group 3 (n = 32) (p = 0.02). While considering Group 3 as reference (hazard ratio (HR) = 1), the fully-adjusted HR for 14-day mortality was HR = 0.07 (p = 0.017) for Group 1 and HR = 0.37 (p = 0.28) for Group 2. Group 1 had longer survival time than Group 3 (log-rank p = 0.015), although there was no difference between Groups 2 and 3 (log-rank p = 0.32). Group 1, but not Group 2 (p = 0.40), was associated with lower risk of OSCI score ≥5 compared to Group 3 (odds ratio = 0.08, p= 0.03). CONCLUSIONS: Regular bolus vitamin D supplementation was associated with less severe COVID-19 and better survival in frail elderly.

Prognostic factors in hospitalized patients diagnosed with SARS-CoV-2 infection, Bogotá, Colombia / [Factores pronósticos en pacientes hospitalizados con diagnóstico de infección por SARS-CoV-2 en Bogotá, Colombia].

Introduction: Infection with the new SARS-Cov-2 coronavirus is a worldwide public health emergency; its diagnosis is based on molecular tests, while its prognosis depends on the patient's history and on some paraclinical tests. In Colombia, forecasts are not yet counted. Objective: To assess the factors associated with the development of severe disease in hospitalized patients diagnosed with SARS-CoV-2 infection, as well as the prognostic factors for the outcome of mortality. Materials and methods: We conducted an ambispective cohort study in hospitalized patients at the Fundación Cadioinfantil from March to June, 2020. Results: Of the 104 patients analyzed, 31.7% (n=33) had a severe presentation and 9.6% (n=10) had a mortality outcome. For mortality, the most important prognostic factor was the development of severe disease followed by age over 60 years and malnutrition. For the development of the severe disease, prognostic factors were a history of hemodialysis (HR=135), diabetes (HR=4.4), and an increased level of lactate dehydrogenase (LDH) (HR=1,004), while the lymphocyte count over 1,064 was a protective factor (HR=0.9). In the classification of patients, the National Early Warning Score (NEWS2) score in the high and low-risk categories corresponded to the best performance. There was no difference between the treatments administered. Conclusions: The most important prognostic factors for mortality were being over 60 years of age, hypertension, diabetes, and cirrhosis, while for the development of severe disease they were chronic kidney disease with hemodialysis, NEWS2 with high risk at admission, increased levels of LDH and C reactive protein (CRP), and leukocytosis.

Introducción. La infección por el nuevo coronavirus SARS-Cov-2 es una emergencia de salud pública en todo el mundo; su diagnóstico se basa en pruebas moleculares, en tanto que su pronóstico depende de los antecedentes del paciente y de algunos exámenes paraclínicos. En Colombia aún no se cuenta con datos de pronóstico en una población local. Objetivo. Evaluar los factores asociados con el desarrollo de la enfermedad grave en pacientes hospitalizados con diagnóstico de infección por SARS-CoV-2, así como los factores pronósticos de la mortalidad. Materiales y métodos. Se hizo un estudio de cohorte ambispectivo en pacientes hospitalizados en la Fundación Cardioinfantil entre marzo y junio de 2020. Resultados. De los 104 pacientes analizados, en el 31,7 % (n=33) la infección fue grave y en el 9,6 % (n=10) se produjo la muerte. El factor pronóstico más importante de la mortalidad fue el desarrollo de la enfermedad grave, seguido de una edad de más de 60 años y la desnutrición. Para el desarrollo de la enfermedad grave los factores pronósticos fueron los antecedentes de hemodiálisis (hazard ratio, HR=135), diabetes (HR=4,4) y el aumento en el nivel de la lactato deshidrogenasa (LDH) (HR=1,004), en tanto que un conteo de linfocitos superior a 1.064 fue un factor protector (HR=0,9). El puntaje del National Early Warning Score (NEWS2) correspondiente a las categorías de alto y bajo riesgo fue el que mejor rendimiento tuvo. No hubo diferencia entre los tratamientos administrados. Conclusiones. Los factores pronósticos más importantes para la mortalidad fueron tener más de 60 años, hipertensión, diabetes y cirrosis, en tanto que para el desarrollo de la enfermedad grave fueron la enfermedad renal crónica con hemodiálisis, un puntaje de NEWS2 de alto riesgo al ingreso, y aumento en los niveles de LDH y proteína C reactiva, y leucocitosis.

Characteristics and outcomes of diabetic patients infected by the SARS-CoV-2.

Diabetes is considered a risk factor for complications due to COVID-19. In order to clarify this association, we are exploring the characteristics, the clinical signs, the outcomes and death in diabetic patients with COVID-19. In this retrospective observational study we are evaluating the demographic characteristics, the comorbidities of the patients, the clinical signs of the infection, the signs of clinical severity, the biological assessment at admission, the treatment, the outcomes and the deaths of 133 patients with COVID-19, of which 25 (19,4%) had diabetes. In the compared COVID-19 patients, with and without diabetes, the patients with diabetes were older, had higher blood pressure and more cardio-vascular diseases. Severe forms were more present in diabetic patients (56% versus 27.1%). Weight loss was higher in diabetic patients (6kg versus 3kg). Biologically, diabetic patients had higher levels of C-reactive protein (28 versus 5.8mg/l), procalcitonin (0.28 versus 0,13ng/l), ferritin (501 versus 140ng/ml), lactic dehydrogenase (268 versus 226IU/l) and of D. dimer (665 versus 444µg/l). Diabetic patients required more oxygen therapy (60% versus 26.9%), more mechanical ventilation (20% versus 8.3%) and more frequent admission to the intensive care unit (60% versus 27.8%). They presented more thromboembolic complications (12% versus 9%) but there were not significant differences in the other outcomes and in death rates. The excess of morbidity and mortality due to diabetes was still not fully clarified; the role of demographic factors, the interaction of mediations with ACE-2 receptors and the role of co-morbidities will all need to be studied in order to identify the patient at risk profile, i.e. who can develop severe forms of the diseases and more outcomes. The early identification of a possible hyper inflammation could be very valuable. More attention should be paid to patients with COVID-19 with diabetes because they are at a high risk of complications.

Treatment of Cytokine Storm in COVID-19 Patients With Immunomodulatory Therapy.

Observational evidence suggests that excessive inflammation with cytokine storm may play a critical role in development of acute respiratory distress syndrome (ARDS) in COVID-19. We report the emergency use of immunomodulatory therapy utilizing an extracorporeal selective cytopheretic device (SCD) in two patients with elevated serum interleukin (IL)-6 levels and refractory COVID-19 ARDS requiring extracorporeal membrane oxygenation (ECMO). The two patients were selected based on clinical criteria and elevated levels of IL-6 (>100 pg/ml) as a biomarker of inflammation. Once identified, emergency/expanded use permission for SCD treatment was obtained and patient consented. Six COVID-19 patients (four on ECMO) with severe ARDS were also screened with IL-6 levels less than 100 pg/ml and were not treated with SCD. The two enrolled patients' PaO2/FiO2 ratios increased from 55 and 58 to 200 and 192 at 52 and 50 hours, respectively. Inflammatory indices also declined with IL-6 falling from 231 and 598 pg/ml to 3.32 and 116 pg/ml, respectively. IL-6/IL-10 ratios also decreased from 11.8 and 18 to 0.7 and 0.62, respectively. The two patients were successfully weaned off ECMO after 17 and 16 days of SCD therapy, respectively. The results observed with SCD therapy on these two critically ill COVID-19 patients with severe ARDS and elevated IL-6 is encouraging. A multicenter clinical trial is underway with an FDA-approved investigational device exemption to evaluate the potential of SCD therapy to effectively treat COVID-19 intensive care unit patients.