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1.
PLoS Genet ; 18(3): e1010042, 2022 03.
Article in English | MEDLINE | ID: covidwho-1793655

ABSTRACT

In November 2021, the COVID-19 pandemic death toll surpassed five million individuals. We applied Mendelian randomization including >3,000 blood proteins as exposures to identify potential biomarkers that may indicate risk for hospitalization or need for respiratory support or death due to COVID-19, respectively. After multiple testing correction, using genetic instruments and under the assumptions of Mendelian Randomization, our results were consistent with higher blood levels of five proteins GCNT4, CD207, RAB14, C1GALT1C1, and ABO being causally associated with an increased risk of hospitalization or respiratory support/death due to COVID-19 (ORs = 1.12-1.35). Higher levels of FAAH2 were solely associated with an increased risk of hospitalization (OR = 1.19). On the contrary, higher levels of SELL, SELE, and PECAM-1 decrease risk of hospitalization or need for respiratory support/death (ORs = 0.80-0.91). Higher levels of LCTL, SFTPD, KEL, and ATP2A3 were solely associated with a decreased risk of hospitalization (ORs = 0.86-0.93), whilst higher levels of ICAM-1 were solely associated with a decreased risk of respiratory support/death of COVID-19 (OR = 0.84). Our findings implicate blood group markers and binding proteins in both hospitalization and need for respiratory support/death. They, additionally, suggest that higher levels of endocannabinoid enzymes may increase the risk of hospitalization. Our research replicates findings of blood markers previously associated with COVID-19 and prioritises additional blood markers for risk prediction of severe forms of COVID-19. Furthermore, we pinpoint druggable targets potentially implicated in disease pathology.


Subject(s)
Blood Proteins/metabolism , COVID-19/blood , COVID-19/pathology , Biomarkers/analysis , Biomarkers/blood , Blood Proteins/analysis , Blood Proteins/genetics , COVID-19/diagnosis , COVID-19/mortality , Causality , Genome-Wide Association Study , Hospitalization , Humans , Mendelian Randomization Analysis , Mortality , Pandemics , Polymorphism, Single Nucleotide , Prognosis , Proteome/analysis , Proteome/genetics , Proteome/metabolism , Respiratory Insufficiency/blood , Respiratory Insufficiency/diagnosis , Respiratory Insufficiency/mortality , Respiratory Insufficiency/pathology , Risk Factors , SARS-CoV-2/physiology , Severity of Illness Index
2.
Biol Sex Differ ; 12(1): 63, 2021 11 22.
Article in English | MEDLINE | ID: covidwho-1528694

ABSTRACT

BACKGROUND: Several biomarkers have been identified to predict the outcome of COVID-19 severity, but few data are available regarding sex differences in their predictive role. Aim of this study was to identify sex-specific biomarkers of severity and progression of acute respiratory distress syndrome (ARDS) in COVID-19. METHODS: Plasma levels of sex hormones (testosterone and 17ß-estradiol), sex-hormone dependent circulating molecules (ACE2 and Angiotensin1-7) and other known biomarkers for COVID-19 severity were measured in male and female COVID-19 patients at admission to hospital. The association of plasma biomarker levels with ARDS severity at admission and with the occurrence of respiratory deterioration during hospitalization was analysed in aggregated and sex disaggregated form. RESULTS: Our data show that some biomarkers could be predictive both for males and female patients and others only for one sex. Angiotensin1-7 plasma levels and neutrophil count predicted the outcome of ARDS only in females, whereas testosterone plasma levels and lymphocytes counts only in males. CONCLUSIONS: Sex is a biological variable affecting the choice of the correct biomarker that might predict worsening of COVID-19 to severe respiratory failure. The definition of sex specific biomarkers can be useful to alert patients to be safely discharged versus those who need respiratory monitoring.


Subject(s)
Biomarkers/blood , COVID-19/complications , Hospitalization , Respiratory Distress Syndrome/complications , Respiratory Distress Syndrome/diagnosis , Respiratory Insufficiency/complications , Respiratory Insufficiency/diagnosis , Sex Characteristics , Adult , Angiotensin-Converting Enzyme 2/blood , Angiotensins/blood , COVID-19/blood , Estradiol/blood , Female , Humans , Male , Middle Aged , Respiratory Distress Syndrome/blood , Respiratory Insufficiency/blood , SARS-CoV-2 , Testosterone/blood
3.
J Endocrinol Invest ; 45(4): 753-762, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1520532

ABSTRACT

PURPOSE: Hypogonadism was described in high number of male subjects with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this study, we investigated whether low testosterone (T) values may influence the clinical presentation and outcome of SARS-CoV-2-related pneumonia in a large population of adult males with coronavirus disease 19 (COVID-19). METHODS: Two hundred twenty one adult males hospitalized for COVID-19 at the IRCCS Humanitas Research Hospital, Rozzano-Milan (Italy) were consecutively evaluated for arterial partial pressure oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio, serum T and inflammatory parameters at study entry, need of ventilation during hospital stay and in-hospital mortality. RESULTS: Subjects low T values (< 8 nmol/L; 176 cases) were significantly older (P = 0.001) and had higher serum interleukin-6 (P = 0.001), C-reactive protein (P < 0.001), lactate dehydrogenase (P < 0.001), ferritin (P = 0.012), lower P/F ratio (P = 0.001), increased prevalence of low T3 syndrome (P = 0.041), acute respiratory insufficiency (P < 0.001), more frequently need of ventilation (P < 0.001) and higher mortality rate (P = 0.009) compared to subjects with higher T values. In the multivariable regression analyses, T values maintained significant associations with acute respiratory insufficiency (odds ratio [OR] 0.85, 95% confidence interval [CI] 0.79-0.94; P < 0.001 and in-hospital mortality (OR 0.80, 95% CI 0.69-0.95; P = 0.009), independently of age, comorbidities, thyroid function and inflammation. CONCLUSION: Low T levels values are associated with unfavorable outcome of COVID-19. Prospective studies are needed to evaluate the long-term outcomes of hypogonadism related to COVID-19 and the clinical impact of T replacement during and after acute illness.


Subject(s)
COVID-19/complications , Respiratory Insufficiency/etiology , Testosterone/blood , Adult , Aged , Aged, 80 and over , Biomarkers/blood , COVID-19/blood , COVID-19/mortality , Hospitalization , Humans , Italy/epidemiology , Male , Middle Aged , Respiratory Insufficiency/blood , Respiratory Insufficiency/mortality , Survival Rate
4.
Chest ; 161(3): 710-727, 2022 03.
Article in English | MEDLINE | ID: covidwho-1491838

ABSTRACT

BACKGROUND: Pulmonary vascular microthrombi are a proposed mechanism of COVID-19 respiratory failure. We hypothesized that early administration of tissue plasminogen activator (tPA) followed by therapeutic heparin would improve pulmonary function in these patients. RESEARCH QUESTION: Does tPA improve pulmonary function in severe COVID-19 respiratory failure, and is it safe? STUDY DESIGN AND METHODS: Adults with COVID-19-induced respiratory failure were randomized from May14, 2020 through March 3, 2021, in two phases. Phase 1 (n = 36) comprised a control group (standard-of-care treatment) vs a tPA bolus (50-mg tPA IV bolus followed by 7 days of heparin; goal activated partial thromboplastin time [aPTT], 60-80 s) group. Phase 2 (n = 14) comprised a control group vs a tPA drip (50-mg tPA IV bolus, followed by tPA drip 2 mg/h plus heparin 500 units/h over 24 h, then heparin to maintain aPTT of 60-80 s for 7 days) group. Patients were excluded from enrollment if they had not undergone a neurologic examination or cross-sectional brain imaging within the previous 4.5 h to rule out stroke and potential for hemorrhagic conversion. The primary outcome was Pao2 to Fio2 ratio improvement from baseline at 48 h after randomization. Secondary outcomes included Pao2 to Fio2 ratio improvement of > 50% or Pao2 to Fio2 ratio of ≥ 200 at 48 h (composite outcome), ventilator-free days (VFD), and mortality. RESULTS: Fifty patients were randomized: 17 in the control group and 19 in the tPA bolus group in phase 1 and eight in the control group and six in the tPA drip group in phase 2. No severe bleeding events occurred. In the tPA bolus group, the Pao2 to Fio2 ratio values were significantly (P < .017) higher than baseline at 6 through 168 h after randomization; the control group showed no significant improvements. Among patients receiving a tPA bolus, the percent change of Pao2 to Fio2 ratio at 48 h (16.9% control [interquartile range (IQR), -8.3% to 36.8%] vs 29.8% tPA bolus [IQR, 4.5%-88.7%]; P = .11), the composite outcome (11.8% vs 47.4%; P = .03), VFD (0.0 [IQR, 0.0-9.0] vs 12.0 [IQR, 0.0-19.0]; P = .11), and in-hospital mortality (41.2% vs 21.1%; P = .19) did not reach statistically significant differences when compared with those of control participants. The patients who received a tPA drip did not experience benefit. INTERPRETATION: The combination of tPA bolus plus heparin is safe in severe COVID-19 respiratory failure. A phase 3 study is warranted given the improvements in oxygenation and promising observations in VFD and mortality. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT04357730; URL: www. CLINICALTRIALS: gov.


Subject(s)
COVID-19/complications , Pandemics , Respiratory Insufficiency/drug therapy , SARS-CoV-2 , Thrombosis/complications , Tissue Plasminogen Activator/administration & dosage , Adolescent , Adult , Aged , COVID-19/blood , COVID-19/epidemiology , Cross-Sectional Studies , Female , Fibrinolytic Agents/administration & dosage , Follow-Up Studies , Humans , Male , Middle Aged , Partial Thromboplastin Time , Respiratory Insufficiency/blood , Respiratory Insufficiency/etiology , Retrospective Studies , Thrombosis/blood , Thrombosis/drug therapy , Treatment Outcome , Young Adult
5.
PLoS One ; 16(10): e0258754, 2021.
Article in English | MEDLINE | ID: covidwho-1477539

ABSTRACT

Continuous positive airway pressure (CPAP) has been successfully applied to patients with COVID-19 to prevent endotracheal intubation. However, experience of CPAP application in pregnant women with acute respiratory failure (ARF) due to SARS-CoV-2 pneumonia is scarce. This study aimed to describe the natural history and outcome of ARF in a cohort of pregnant women with SARS-CoV-2 pneumonia, focusing on the feasibility of helmet CPAP (h-CPAP) application and the variables related to ARF worsening. A retrospective, observational study enrolling 41 consecutive pregnant women hospitalised for SARS-CoV-2 pneumonia in a tertiary care center between March 2020 and March 2021. h-CPAP was applied if arterial partial pressure of oxygen to fraction of inspired oxygen ratio (PaO2/FiO2) was inferior to 200 and/or patients had respiratory distress despite adequate oxygen supplementation. Characteristics of patients requiring h-CPAP vs those in room air or oxygen only were compared. Twenty-seven (66%) patients showed hypoxemic ARF requiring oxygen supplementation and h-CPAP was needed in 10 cases (24%). PaO2/FiO2 was significantly improved during h-CPAP application. The device was well-tolerated in all cases with no adverse events. Higher serum C reactive protein and more extensive (≥3 lobes) involvement at chest X-ray upon admission were observed in the h-CPAP group. Assessment of temporal distribution of cases showed a substantially increased rate of CPAP requirement during the third pandemic wave (January-March 2021). In conclusion, h-CPAP was feasible, safe, well-tolerated and improved oxygenation in pregnant women with moderate-to-severe ARF due to SARS-CoV-2 pneumonia. Moderate-to-severe ARF was more frequently observed during the third pandemic wave.


Subject(s)
COVID-19 , Continuous Positive Airway Pressure , Oxygen/administration & dosage , Pregnancy Complications, Infectious , Respiratory Insufficiency , SARS-CoV-2/metabolism , Tertiary Care Centers , Acute Disease , Adult , COVID-19/blood , COVID-19/therapy , Female , Humans , Oxygen/blood , Pregnancy , Pregnancy Complications, Infectious/blood , Pregnancy Complications, Infectious/therapy , Protein C/metabolism , Respiratory Insufficiency/blood , Respiratory Insufficiency/therapy , Retrospective Studies
6.
Int J Mol Sci ; 22(19)2021 Sep 26.
Article in English | MEDLINE | ID: covidwho-1438630

ABSTRACT

A high incidence of thromboembolic events associated with high mortality has been reported in severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infections with respiratory failure. The present study characterized post-transcriptional gene regulation by global microRNA (miRNA) expression in relation to activated coagulation and inflammation in 21 critically ill SARS-CoV-2 patients. The cohort consisted of patients with moderate respiratory failure (n = 11) and severe respiratory failure (n = 10) at an acute stage (day 0-3) and in the later course of the disease (>7 days). All patients needed supplemental oxygen and severe patients were defined by the requirement of positive pressure ventilation (intubation). Levels of D-dimers, activated partial thromboplastin time (aPTT), C-reactive protein (CRP), and interleukin (IL)-6 were significantly higher in patients with severe compared with moderate respiratory failure. Concurrently, next generation sequencing (NGS) analysis demonstrated increased dysregulation of miRNA expression with progression of disease severity connected to extreme downregulation of miR-320a, miR-320b and miR-320c. Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis revealed involvement in the Hippo signaling pathway, the transforming growth factor (TGF)-ß signaling pathway and in the regulation of adherens junctions. The expression of all miR-320 family members was significantly correlated with CRP, IL-6, and D-dimer levels. In conclusion, our analysis underlines the importance of thromboembolic processes in patients with respiratory failure and emphasizes miRNA-320s as potential biomarkers for severe progressive SARS-CoV-2 infection.


Subject(s)
COVID-19/complications , COVID-19/genetics , MicroRNAs/genetics , Respiratory Insufficiency/etiology , Respiratory Insufficiency/genetics , Aged , Aged, 80 and over , Blood Coagulation , COVID-19/blood , Disease Progression , Down-Regulation , Female , Humans , Inflammation/blood , Inflammation/etiology , Inflammation/genetics , Male , MicroRNAs/blood , Middle Aged , Respiratory Insufficiency/blood , SARS-CoV-2/isolation & purification , Severity of Illness Index
7.
Lancet Respir Med ; 9(8): 933-936, 2021 08.
Article in English | MEDLINE | ID: covidwho-1413072

ABSTRACT

The 2012 Berlin definition of acute respiratory distress syndrome (ARDS) provided validated support for three levels of initial arterial hypoxaemia that correlated with mortality in patients receiving ventilatory support. Since 2015, high-flow nasal oxygen (HFNO) has become widely used as an effective therapeutic support for acute respiratory failure, most recently in patients with severe COVID-19. We propose that the Berlin definition of ARDS be broadened to include patients treated with HFNO of at least 30 L/min who fulfil the other criteria for the Berlin definition of ARDS. An expanded definition would make the diagnosis of ARDS more widely applicable, allowing patients at an earlier stage of the syndrome to be recognised, independent of the need for endotracheal intubation or positive-pressure ventilation, with benefits for the testing of early interventions and the study of factors associated with the course of ARDS. We identify key questions that could be addressed in refining an expanded definition of ARDS, the implementation of which could lead to improvements in clinical practice and clinical outcomes for patients.


Subject(s)
COVID-19 , Oxygen Inhalation Therapy/methods , Respiratory Insufficiency , COVID-19/blood , COVID-19/diagnosis , COVID-19/therapy , Early Diagnosis , Humans , Patient Selection , Respiratory Insufficiency/blood , Respiratory Insufficiency/diagnosis , Respiratory Insufficiency/therapy , SARS-CoV-2 , Severity of Illness Index , Time-to-Treatment/standards
8.
J Med Virol ; 93(9): 5416-5424, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1363679

ABSTRACT

The kinetics of IgG antibodies after coronavirus disease 2019 (COVID-19) remain poorly understood. We investigated factors influencing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG antibody levels and time to seronegativation during the follow-up of severe and critically ill patients. We retrospectively reviewed serological evaluations drawn during the follow-up of severe or critical laboratory-proven COVID-19 patients hospitalized at a large academic hospital. Specific IgG titers were measured using a chemiluminescent assay targeting anti-spike and anti-nucleocapsid protein IgG. The influence of time, demographic factors, clinical and paraclinical characteristics, and COVID-19 therapeutics on IgG levels were assessed through linear regression using a mixed-effect model, and delay until IgG negativation through a Weibull regression model. The cohort included 116 patients with a total of 154 IgG measurements drawn at a median of 79 days after diagnosis. IgG antibodies were increased with age (p = 0.005) and decreased significantly over time (p = 0.0002). Using elapsed time and age as covariates, we demonstrated higher IgG levels in patients with a higher body mass index (BMI) (p = 0.0026) and lower IgG levels in immunocompromised patients (p = 0.032). A high BMI was further found to delay and immunodeficiency to hasten significantly seronegativation, whereas no significant effect was observed with corticosteroids. These data highlight the waning over time of IgG antibodies after severe or critical COVID-19. Age, BMI, and immunosuppression also appear to influence the IgG kinetics, while short-term corticotherapy does not. Those data improve the understanding of SARS-CoV-2 serology while further research should determine the determinants of long-term seroprotection.


Subject(s)
Antibodies, Viral/blood , COVID-19/immunology , Immunocompromised Host , Immunoglobulin G/blood , Respiratory Insufficiency/immunology , SARS-CoV-2/immunology , Adrenal Cortex Hormones/therapeutic use , Aged , Body Mass Index , COVID-19/blood , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19 Serological Testing , Convalescence , Female , Humans , Hydroxychloroquine/therapeutic use , Male , Middle Aged , Respiratory Insufficiency/blood , Respiratory Insufficiency/diagnosis , Respiratory Insufficiency/drug therapy , Retrospective Studies , Sensitivity and Specificity , Severity of Illness Index , Time Factors
9.
Chest ; 160(2): e189-e193, 2021 08.
Article in English | MEDLINE | ID: covidwho-1333295

ABSTRACT

CASE PRESENTATION: A 57-year-old man who had been intubated and placed on venovenous extracorporeal membrane oxygenation for hypoxemic respiratory failure due to COVID-19 pneumonia was transferred to our facility. He underwent anticoagulation with IV heparin titrated to an anti-Factor Xa goal of 0.1 to 0.3 international unit/mL. Over extracorporeal membrane oxygenation days 13 to 17, his WBC count rose from 17,500 to 47,000 cells/µL. He simultaneously experienced the development of fluid-refractory shock that required multiple vasopressors and received stress-dose hydrocortisone when his WBC was 30,000 cells/µL. He remained afebrile and was started on broad-spectrum antimicrobials that included antifungal and anthelminthic therapy.


Subject(s)
COVID-19/blood , COVID-19/therapy , Extracorporeal Membrane Oxygenation , Respiratory Insufficiency/blood , Respiratory Insufficiency/therapy , Humans , Leukocyte Count , Male , Middle Aged , Respiratory Insufficiency/etiology
10.
Int Immunopharmacol ; 98: 107874, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1267706

ABSTRACT

BACKGROUND: Following positive experience on the use of blood ozonation in SARS-CoV-2, the CORMOR randomized trial was designed to evaluate the adjuvant role of oxygen/ozone therapy in mild to moderate SARS-CoV-2 pneumonia. METHODS: The trial (ClinicalTrial.gov NCT04388514) was conducted in four different Italian centers (April-October 2020). Patients were treated according to best available standard of care (SoC) therapy, with or without O3-autohemotherapy (O3-AHT). RESULTS: A total of 92 patients were enrolled: SoC + O3-AHT (48 patients) were compared to the SoC treatment (44 patients). The two groups differed in steroids therapy administration (72.7% in SoC arm vs. 50.0% in O3-AHT arm; p = 0.044). Steroid therapy was routinely started when it was subsequently deemed as effective for the treatment of COVID-19 disease. No significant differences in mortality rates, length of hospital stay, mechanical ventilation requirement and ICU admission were observed. Clinical improvement in patients with pneumonia was assessed according to a specifically designed score (decrease in SIMEU class, improvement in radiology imaging, improvement in PaO2/FiO2, reduction in LDH and requirement of oxygen therapy ≤ 5 days). Score assessment was performed on day-3 (T3) and day-7 (TEnd) of O3-AHT treatment. A significant increase in the score was reported at TEnd, in the O3-AHT treatment arm (0 [0-1] in the SoC arm vs. 2 [1-3] the O3-AHT arm; p = 0.018). No adverse events related O3-AHT treatment was observed. CONCLUSION: In mild-to-moderate pneumonia due to SARS-CoV-2, adjuvant oxygen/ozone therapy did not show any effect on mortality, or mechanical intubation but show a clinical improvement a day 7 from randomization in a composite clinical endpoint. Larger Randomized prospective studies alone or in combination with steroids are needed to confirm our results.


Subject(s)
COVID-19/therapy , Lung/physiopathology , Ozone/administration & dosage , Respiratory Insufficiency/therapy , Aged , COVID-19/blood , COVID-19/mortality , COVID-19/physiopathology , Female , Hospital Mortality , Humans , Italy , Length of Stay , Lung/virology , Male , Middle Aged , Ozone/adverse effects , Ozone/blood , Prospective Studies , Respiration, Artificial , Respiratory Insufficiency/blood , Respiratory Insufficiency/mortality , Respiratory Insufficiency/physiopathology , Severity of Illness Index , Time Factors , Treatment Outcome
12.
Am J Physiol Lung Cell Mol Physiol ; 321(1): L213-L218, 2021 07 01.
Article in English | MEDLINE | ID: covidwho-1234311

ABSTRACT

The renin-angiotensin system (RAS) is fundamental to COVID-19 pathobiology, due to the interaction between the SARS-CoV-2 virus and the angiotensin-converting enzyme 2 (ACE2) coreceptor for cellular entry. The prevailing hypothesis is that SARS-CoV-2-ACE2 interactions lead to an imbalance of the RAS, favoring proinflammatory angiotensin II (ANG II)-related signaling at the expense of the anti-inflammatory ANG-(1-7)-mediated alternative pathway. Indeed, multiple clinical trials targeting this pathway in COVID-19 are underway. Therefore, precise measurement of circulating RAS components is critical to understand the interplay of the RAS on COVID-19 outcomes. Multiple challenges exist in measuring the RAS in COVID-19, including improper patient controls, ex vivo degradation and low concentrations of angiotensins, and unvalidated laboratory assays. Here, we conducted a prospective pilot study to enroll 33 patients with moderate and severe COVID-19 and physiologically matched COVID-19-negative controls to quantify the circulating RAS. Our enrollment strategy led to physiological matching of COVID-19-negative and COVID-19-positive moderate hypoxic respiratory failure cohorts, in contrast to the severe COVID-19 cohort, which had increased severity of illness, prolonged intensive care unit (ICU) stay, and increased mortality. Circulating ANG II and ANG-(1-7) levels were measured in the low picomolar (pM) range. We found no significant differences in circulating RAS peptides or peptidases between these three cohorts. The combined moderate and severe COVID-19-positive cohorts demonstrated a mild reduction in ACE activity compared with COVID-19-negative controls (2.2 ± 0.9 × 105 vs. 2.9 ± 0.8 × 105 RFU/mL, P = 0.03). These methods may be useful in designing larger studies to physiologically match patients and quantify the RAS in COVID-19 RAS augmenting clinical trials.


Subject(s)
Angiotensin II/blood , Angiotensin I/blood , Angiotensin-Converting Enzyme 2/blood , COVID-19/blood , Peptide Fragments/blood , Renin-Angiotensin System , Respiratory Insufficiency/blood , SARS-CoV-2/metabolism , Adult , Aged , COVID-19/pathology , COVID-19/physiopathology , Female , Humans , Male , Middle Aged , Pilot Projects , Respiratory Insufficiency/pathology , Respiratory Insufficiency/physiopathology
13.
J Endocrinol Invest ; 44(10): 2285-2293, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1118298

ABSTRACT

PURPOSE: Hypovitaminosis D has emerged as potential risk factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the general population with variable effects on the outcome of the coronavirus disease-19 (COVID-19). The aim of this retrospective single-center study was to investigate the impact of hypovitaminosis D and secondary hyperparathyroidism on respiratory outcomes of COVID-19. METHODS: Three-hundred-forty-eight consecutive patients hospitalized for COVID-19 at the IRCCS Humanitas Research Hospital, Rozzano, Milan (Italy) were evaluated for arterial partial pressure oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio, serum 25hydroxy-vitamin D [25(OH)D], parathyroid hormone (PTH) and inflammatory parameters at study entry and need of ventilation during the hospital stay. RESULTS: In the entire population, vitamin D deficiency (i.e., 25(OH)D values < 12 ng/mL) was significantly associated with acute hypoxemic respiratory failure at the study entry [adjusted odds ratio (OR) 2.48, 95% confidence interval 1.29-4.74; P = 0.006], independently of age and sex of subjects, serum calcium and inflammatory parameters. In patients evaluated for serum PTH (97 cases), secondary hyperparathyroidism combined with vitamin D deficiency was significantly associated with acute hypoxemic respiratory failure at study entry (P = 0.001) and need of ventilation during the hospital stay (P = 0.031). CONCLUSION: This study provides evidence that vitamin D deficiency, when associated with secondary hyperparathyroidism, may negatively impact the clinical outcome of SARS-CoV-2-related pneumonia.


Subject(s)
COVID-19/complications , Hyperparathyroidism/complications , Respiratory Insufficiency/complications , Vitamin D Deficiency/complications , Adult , Aged , Aged, 80 and over , COVID-19/blood , COVID-19/therapy , Female , Humans , Hyperparathyroidism/blood , Male , Middle Aged , Respiratory Insufficiency/blood , Respiratory Insufficiency/therapy , Retrospective Studies , Treatment Outcome , Vitamin D Deficiency/blood
15.
Sci Rep ; 10(1): 21697, 2020 12 10.
Article in English | MEDLINE | ID: covidwho-1059940

ABSTRACT

In SARS-CoV-2 infection there is an urgent need to identify patients that will progress to severe COVID-19 and may benefit from targeted treatment. In this study we analyzed plasma cytokines in COVID-19 patients and investigated their association with respiratory failure (RF) and treatment in Intensive Care Unit (ICU). Hospitalized patients (n = 34) with confirmed COVID-19 were recruited into a prospective cohort study. Clinical data and blood samples were collected at inclusion and after 2-5 and 7-10 days. RF was defined as PaO2/FiO2 ratio (P/F) < 40 kPa. Plasma cytokines were analyzed by a Human Cytokine 27-plex assay. COVID-19 patients with RF and/or treated in ICU showed overall increased systemic cytokine levels. Plasma IL-6, IL-8, G-CSF, MCP-1, MIP-1α levels were negatively correlated with P/F, whereas combinations of IL-6, IP-10, IL-1ra and MCP-1 showed the best association with RF in ROC analysis (AUC 0.79-0.80, p < 0.05). During hospitalization the decline was most significant for IP-10 (p < 0.001). Elevated levels of pro-inflammatory cytokines were present in patients with severe COVID-19. IL-6 and MCP-1 were inversely correlated with P/F with the largest AUC in ROC analyses and should be further explored as biomarkers to identify patients at risk for severe RF and as targets for improved treatment strategies.


Subject(s)
COVID-19/blood , Chemokine CCL2/blood , Interleukin-6/blood , Respiratory Insufficiency/blood , SARS-CoV-2/metabolism , Adult , Aged , Aged, 80 and over , Biomarkers/blood , COVID-19/complications , Female , Humans , Male , Middle Aged , Prospective Studies , Respiratory Insufficiency/etiology , Severity of Illness Index
17.
Eur J Clin Microbiol Infect Dis ; 40(7): 1405-1412, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1053011

ABSTRACT

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.


Subject(s)
Antimicrobial Cationic Peptides/blood , COVID-19/blood , Interleukin-6/blood , Respiratory Insufficiency/blood , Adult , Biomarkers/blood , Blood Proteins , COVID-19/diagnosis , COVID-19/mortality , COVID-19/physiopathology , Female , Humans , Male , Pneumonia, Viral/blood , Pneumonia, Viral/diagnosis , Pneumonia, Viral/mortality , Pneumonia, Viral/physiopathology , Predictive Value of Tests , Prognosis , Respiratory Insufficiency/diagnosis , Respiratory Insufficiency/mortality , Respiratory Insufficiency/physiopathology , SARS-CoV-2/isolation & purification , Sepsis/blood , Sepsis/diagnosis , Sepsis/mortality , Sepsis/physiopathology
18.
Ann Neurol ; 89(3): 610-616, 2021 03.
Article in English | MEDLINE | ID: covidwho-1044305

ABSTRACT

There is emerging evidence for multifarious neurological manifestations of coronavirus disease 2019 (COVID-19), but little is known regarding whether they reflect structural damage to the nervous system. Serum neurofilament light chain (sNfL) is a specific biomarker of neuronal injury. We measured sNfL concentrations of 29 critically ill COVID-19 patients, 10 critically ill non-COVID-19 patients, and 259 healthy controls. After adjusting for neurological comorbidities and age, sNfL concentrations were higher in patients with COVID-19 versus both comparator groups. Higher sNfL levels were associated with unfavorable short-term outcome, indicating that neuronal injury is common and pronounced in critically ill patients. ANN NEUROL 2021;89:610-616.


Subject(s)
COVID-19/blood , Neurofilament Proteins/blood , Adult , Aged , Aged, 80 and over , COVID-19/physiopathology , COVID-19/therapy , Case-Control Studies , Critical Illness , Female , Glasgow Outcome Scale , Hospital Mortality , Humans , Hyponatremia/blood , Hyponatremia/therapy , Intensive Care Units , Length of Stay/statistics & numerical data , Male , Middle Aged , Organ Dysfunction Scores , Pulmonary Edema/blood , Pulmonary Edema/therapy , Respiration, Artificial/statistics & numerical data , Respiratory Insufficiency/blood , Respiratory Insufficiency/therapy , Respiratory Tract Infections/blood , Respiratory Tract Infections/therapy , SARS-CoV-2 , Shock, Cardiogenic/blood , Shock, Cardiogenic/therapy
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