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1.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-335491

ABSTRACT

Purpose: Coronavirus disease 2019 (COVID-19) is a novel cause of Acute Respiratory Distress Syndrome (ARDS). With the increase of ARDS cases during COVID-19 pandemic, the use of non-invasive ventilation (NIV) has grown significantly in the hospital ward. However, there is a lack of evidence to support its efficacy in these patients. Methods We conducted an observational cohort study including adult ARDS COVID-19 patients admitted in a third level COVID-center in Rome, Italy (Jan-Sep 2020). The study analyzed the rate of NIV failure defined by the occurrence of orotracheal intubation and/or death within 28 days from starting NIV, its effectiveness, and its relative risk of death. The factors associated with the outcomes were identified through a logistic regression analysis. Results During the study period, a total of 942 COVID-19 patients were admitted, of which 307 (32.5%) with ARDS at hospitalization. Overall, 224 (23.8%) were treated with NIV. NIV failure occurred in 84 (37.5%) patients. Moderate and severe ARDS had an increased risk of NIV failure within 28 days from starting NIV of 5- (aOR = 5.01, 95% CI 2.08–12.09) and 20-fold (aOR = 19.95, 5.31–74.94) respectively, compared to patients with mild ARDS. A total of 128 patients (13.5%) were admitted to the Intensive Care Unit (ICU). At 28-day from ICU admission, COVID-19 patients treated with NIV without intubation had 96% lower mortality (aOR 0.04, 0.01–0.32) in comparison with patients that underwent orotracheal intubation without prior NIV. Conclusions NIV failure was independently associated with COVID-19 ARDS severity. Starting NIV in COVID-19 patients with already mild ARDS (P/F > 200 mmHg) appears to increase NIV effectiveness and reduce the risk of orotracheal intubation and/or death. Moreover, early NIV treatment seems to reduce the risk of ICU mortality within 28 days from ICU admission.

2.
J Clin Med ; 11(9)2022 May 05.
Article in English | MEDLINE | ID: covidwho-1820313

ABSTRACT

(1) Background: Although COVID-19 is largely a respiratory disease, it is actually a systemic disease that has a wide range of effects that are not yet fully known. The aim of this study was to determine the incidence, predictors and outcome of non-hepatic hyperammonemia (NHH) in COVID-19 in intensive care unit (ICU); (2) Methods: This is a 3-month prospective observational study in a third-level COVID-19 hospital. The authors collected demographic, clinical, severity score and outcome data. Logistic regression analyses were performed to identify predictors of NHH; (3) Results: 156 COVID-19 patients were admitted to the ICU. The incidence of NHH was 12.2% (19 patients). The univariate analysis showed that invasive mechanical ventilation had a 6.6-fold higher risk (OR 6.66, 95% CI 0.86-51.6, p = 0.039) for NHH, while in the multiple regression analysis, there was a 7-fold higher risk for NHH-but it was not statistically significant (OR 7.1, 95% CI 0.90-56.4, p = 0.062). Demographics, clinical characteristics and mortality in the ICU at 28 days did not show a significant association with NHH. (4) Conclusions: The incidence of NHH in ICU COVID-19 patients was not low. NHH did not appear to significantly increase mortality, and all patients with non-hepatic hyperammonemia were successfully treated without further complications. However, the pathogenesis of NHH in ICU patients with COVID-19 remains a topic to be explored with further research.

3.
J Clin Med ; 11(6)2022 Mar 11.
Article in English | MEDLINE | ID: covidwho-1742502

ABSTRACT

BACKGROUND: There is conflicting evidence for how HIV influences COVID-19 infection. The aim of this study was to compare characteristics at presentation and the clinical outcomes of people living with HIV (PLWH) versus HIV-negative patients (non-PLWH) hospitalized with COVID-19. METHODS: Primary endpoint: time until invasive ventilation/death. Secondary endpoints: time until ventilation/death, time until symptoms resolution. RESULTS: A total of 1647 hospitalized patients were included (43 (2.6%) PLWH, 1604 non-PLWH). PLWH were younger (55 vs. 61 years) and less likely to be with PaO2/FiO2 < 300 mmHg compared with non-PLWH. Among PLWH, nadir of CD4 was 185 (75-322) cells/µL; CD4 at COVID-19 diagnosis was 272 cells/µL (127-468) and 77% of these were virologically suppressed. The cumulative probability of invasive mechanical ventilation/death at day 15 was 4.7% (95%CI 1.2-17.3) in PLWH versus 18.9% (16.9-21.1) in non-PLWH (p = 0.023). The cumulative probability of non-invasive/invasive ventilation/death at day 15 was 20.9% (11.5-36.4) in PLWH versus 37.6% (35.1-40.2) in non-PLWH (p = 0.044). The adjusted hazard ratio (aHR) of invasive mechanical ventilation/death of PLWH was 0.49 (95% CI 0.12-1.96, p = 0.310) versus non-PLWH; similarly, aHR of non-invasive/invasive ventilation/death of PLWH was 1.03 (95% CI 0.53-2.00, p = 0.926). CONCLUSION: A less-severe presentation of COVID-19 at hospitalization was observed in PLWH compared to non-PLWH; no difference in clinical outcomes could be detected.

4.
Antibiotics (Basel) ; 11(3)2022 Mar 16.
Article in English | MEDLINE | ID: covidwho-1742295

ABSTRACT

Pulmonary thromboembolism (PTE) has been associated with tuberculosis (TB), but the true incidence is unknown. The aim of our study was to retrospectively evaluate the PTE prevalence in TB patients hospitalized at the National Institute for Infectious Diseases L. Spallanzani during the January 2016-December 2021 period. Retrospective data collection and evaluation were conducted. Among 1801 TB patients, 29 (1.61%) exhibited PTE. Twenty (69%) had comorbidities; eleven (37.9%) had predisposing factors for PTE. Nineteen (65.5%) had extensive TB disease. The commonest respiratory symptoms were cough (37.9%), dyspnea (31%), chest pain (10.3%), and hemoptysis (6.9%). Twenty-five (86.2%) had elevated serum D-dimer levels. An increased prevalence of PTE from 0.6% in the pre-COVID-19 pandemic period to 4.6% in the pandemic period was found. Acute respiratory failure and extensive TB disease increased significantly in the pandemic period. The increase in PTE could be explained by the increased severity of TB in patients in the pandemic period and by increased clinical suspicion and, consequently, increased requests for D-dimer testing, including in patients with non-COVID-19 pneumonia. Patients with extensive pulmonary disease are at high risk of developing PTE. Clinicians should be aware of this potentially life-threatening complication of TB, and patients should receive a thromboembolism risk assessment.

5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-314865

ABSTRACT

Background: More detailed temporal analyses of complete (Full) blood count (CBC) parameters, their evolution and relationship to patient age, gender, co-morbidities and management outcomes in survivors and non-survivors with COVID-19 disease could help identify prognostic clinical biomarkers. Methods: From 29 January 2020 until 28 March 2020, we performed a longitudinal cohort study of COVID-19 inpatients at the Italian National Institute for Infectious Diseases, Rome, Italy. Nine CBC parameters as a continuous variable were studied [neutrophils, lymphocytes, monocytes, platelets, mean platelet volume, red blood cell count, haemoglobin concentration, mean red blood cell volume and red blood cell distribution width (RDW %)]. Model-based punctual estimates and difference between survivors and non-survivors, overall, and by co-morbidities, at specific times after symptoms, with relative 95% CI and P-values were obtained by marginal prediction and ANOVA-style joint tests. All analyses were carried out by STATA 15 statistical package. Main Findings: 379 COVID-19 patients [273 (72% were male;mean age was 61.67 (SD 15.60)] were enrolled and 1,805 measures per parameter were analysed. Neutrophil counts were on average significantly higher in non-survivors than in survivors (P<0.001) and lymphocytes were on average higher in survivors (P<0.001). These differences were time dependent. Reverse temporal trends were observed for lymphocyte and neutrophil counts in survivors and non-survivors. Average platelets counts (P<0.001) and median platelets volume (P<0.001) were significantly different in survivors and in non-survivors. The differences were time dependent and consistent with acute inflammation followed either by recovery or by death. Anaemia with anisocytosis were observed in the later phase of COVID-19 disease in non-survivors only. Mortality was significantly higher in patients with diabetes (p=0.005), obesity (p=0.010), chronic renal failure (p=0.001), COPD (p=0.033) cardiovascular diseases (p=0.001) and those >60 years(p=0.001). Age (p=0.042), obesity (p=0.002), chronic renal failure (p=0.002) and cardiovascular diseases (p=0.009) were independently associated with poor patient clinical outcome at 30 day after symptom onset. Interpretation: Increased neutrophil counts, reduced lymphocyte counts, higher median platelet volume, anemia with anisocytosis, in association with obesity, chronic renal failure, COPD, cardiovascular diseases and age >60 years predict poor prognosis in COVID19 patients.Funding Statement: Ricerca Corrente e Finalizzata Italy Ministry of Health, AIRC (IG2018-21880);Regione Lazio (Gruppi di ricerca, E56C18000460002).Declaration of Interests: The authors declare no competing interest.Ethics Approval Statement: This study was approved by the IRB of Italian National Institute for Infectious Diseases “Lazzaro Spallanzani” (INMI), in Rome (Italy).

6.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-322655

ABSTRACT

(1) Background: Benefits and timing of percutaneous dilatational tracheostomy (PDT) in Intensive Care Unit (ICU) COVID-19 patients are still controversial. PDT is considered a high risk procedure for transmission of SARS CoV-2 to health care workers (HCWs). The present study analyzed optimal timing of PDT, clinical outcomes of patients undergoing PDT and safety of HCWs performing PDT. (2) Methods: 133 COVID-19 patients underwent PDT in our ICU from April 1, 2020 to March 31, 2021, 23 patients were excluded and 110 patients were enrolled. A trained medical team was dedicated to the PDT procedure. Demographic, clinical history and outcome data were collected. Patients who underwent PDT were stratified into two groups: early group, PDT ≤12 days from orotracheal-intubation (OTI) and late group, &gt;12 days from OTI;HCW surveillance program was performed. (3) Results: Early group included 57 patients and late group included 53 patients. Early group patients showed shorter ICU length of stay and fewer days of mechanical ventilation than the late group (p&lt;0.001). At day 7 after tracheostomy, early group patients required fewer intravenous anesthetic drugs and experienced an improvement of ventilation parameters, PaO2/FiO2-Ratio, PEEP and FiO2 (p&lt;0.001). No difference in case fatality ratio between the two groups was reported. No SARS-CoV-2 infection was reported in HCWs performing PDT. (4) Conclusions: PDT was safe and effective for COVID-19 patients, since it improved respiratory support parameters, reduced ICU length of stay and duration of mechanical ventilation, and optimized the weaning process. The procedure was safe for all HCWs involved in the dedicated medical team. The development of standardized early PDT protocols should be implemented and PDT procedure could be considered as first line approach in ICU COVID-19 requiring prolonged mechanical ventilation.

7.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-317624

ABSTRACT

Tuberculosis (TB) is top infectious disease killer caused by a single organismresponsible for 1.5 million deaths in 2018. Both COVID 19 and the pandemic responseare risking to affect control measures for TB and continuity of essential services forpeople affected by this infection in western countries and even more in developingcountries. Knowledges about concomitant pulmonary TB and COVID-19 are extremelylimited. The double burden of these two diseases can have devastating effects. Herewe describe from both the clinical and the immunological point of view a case of apatient with in vitro immune cell anergy affected by bilateral cavitary pulmonary TB andsubsequent COVID-19-associated pneumonia with a worst outcome. COVID-19 can bea precipitating factor in TB respiratory failure and, during ongoing SARS COV 2 pandemic, clinicians must be aware of this possible coinfection in differential diagnosisof patients with active TB and new or worsening chest imaging

8.
Int J Infect Dis ; 113 Suppl 1: S82-S87, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1575296

ABSTRACT

OBJECTIVES: The interaction of COVID-19 and tuberculosis (TB) are still poor characterized. Here we evaluated the immune response specific for Micobacterium tuberculosis (Mtb) and SARS-CoV-2 using a whole-blood-based assay-platform in COVID-19 patients either with TB or latent TB infection (LTBI). METHODS: We evaluated IFN-γ level in plasma from whole-blood stimulated with Mtb antigens in the Quantiferon-Plus format or with peptides derived from SARS-CoV-2 spike protein, Wuhan-Hu-1 isolate (CD4-S). RESULTS: We consecutively enrolled 63 COVID-19, 10 TB-COVID-19 and 11 LTBI-COVID-19 patients. IFN-γ response to Mtb-antigens was significantly associated to TB status and therefore it was higher in TB-COVID-19 and LTBI-COVID-19 patients compared to COVID-19 patients (p ≤ 0.0007). Positive responses against CD4-S were found in 35/63 COVID-19 patients, 7/11 LTBI-COVID-19 and only 2/10 TB-COVID-19 patients. Interestingly, the responders in the TB-COVID-19 group were less compared to COVID-19 and LTBI-COVID-19 groups (p = 0.037 and 0.044, respectively). Moreover, TB-COVID-19 patients showed the lowest quantitative IFN-γ response to CD4-S compared to COVID-19-patients (p = 0.0336) and LTBI-COVID-19 patients (p = 0.0178). CONCLUSIONS: Our data demonstrate that COVID-19 patients either TB or LTBI have a low ability to build an immune response to SARS-CoV-2 while retaining the ability to respond to Mtb-specific antigens.


Subject(s)
COVID-19 , Coinfection , Tuberculosis , Antigens, Bacterial/immunology , Antigens, Viral/immunology , COVID-19/immunology , Humans , Interferon-gamma/immunology , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Tuberculosis/immunology
9.
J Clin Med ; 10(23)2021 Nov 29.
Article in English | MEDLINE | ID: covidwho-1566682

ABSTRACT

(1) Background: COVID-19 is a novel cause of acute respiratory distress syndrome (ARDS). Indeed, with the increase of ARDS cases due to the COVID-19 pandemic, there has also been an increase in the incidence of cases with pneumothorax (PNX) and pneumomediastinum (PNM). However, the incidence and the predictors of PNX/PMN in these patients are currently unclear and even conflicting. (2) Methods: The present observational study analyzed the incidence of barotrauma (PNX/PNM) in COVID-19 patients with moderate-severe ARDS hospitalized in a year of the pandemic, also focusing on the three waves occurring during the year, and treated with positive-pressure ventilation (PPV). We collected demographic and clinical data. (3) Results: During this period, 40 patients developed PNX/PNM. The overall incidence of barotrauma in all COVID-19 patients hospitalized in a year was 1.6%, and in those with moderate-severe ARDS in PPV was 7.2% and 3.8 events per 1000 positive-pressure ventilator days. The incidence of barotrauma in moderate-severe ARDS COVID-19 patients during the three waves was 7.8%, 7.4%, and 8.7%, respectively. Treatment with noninvasive respiratory support alone was associated with an incidence of barotrauma of 9.1% and 2.6 events per 1000 noninvasive ventilator days, of which 95% were admitted to the ICU after the event, due to a worsening of respiratory parameters. The incidence of barotrauma of ICU COVID-19 patients in invasive ventilation over a year was 5.8% and 2.7 events per 1000 invasive ventilator days. There was no significant difference in demographics and clinical features between the barotrauma and non-barotrauma group. The mortality was higher in the barotrauma group (17 patients died, 47.2%) than in the non-barotrauma group (170 patients died, 37%), although this difference was not statistically significant (p = 0.429). (4) Conclusions: The incidence of PNX/PNM in moderate-severe ARDS COVID-19 patients did not differ significantly between the three waves over a year, and does not appear to be very different from that in ARDS patients in the pre-COVID era. The barotrauma does not appear to significantly increase mortality in COVID-19 patients with moderate-severe ARDS if protective ventilation strategies are applied. Attention should be paid to the risk of barotrauma in COVID-19 patients in noninvasive ventilation because the event increases the probability of admission to the intensive care unit (ICU) and intubation.

10.
J Clin Med ; 10(23)2021 Nov 29.
Article in English | MEDLINE | ID: covidwho-1542621

ABSTRACT

(1) Background: COVID-19 is a novel cause of acute respiratory distress syndrome (ARDS). Indeed, with the increase of ARDS cases due to the COVID-19 pandemic, there has also been an increase in the incidence of cases with pneumothorax (PNX) and pneumomediastinum (PNM). However, the incidence and the predictors of PNX/PMN in these patients are currently unclear and even conflicting. (2) Methods: The present observational study analyzed the incidence of barotrauma (PNX/PNM) in COVID-19 patients with moderate-severe ARDS hospitalized in a year of the pandemic, also focusing on the three waves occurring during the year, and treated with positive-pressure ventilation (PPV). We collected demographic and clinical data. (3) Results: During this period, 40 patients developed PNX/PNM. The overall incidence of barotrauma in all COVID-19 patients hospitalized in a year was 1.6%, and in those with moderate-severe ARDS in PPV was 7.2% and 3.8 events per 1000 positive-pressure ventilator days. The incidence of barotrauma in moderate-severe ARDS COVID-19 patients during the three waves was 7.8%, 7.4%, and 8.7%, respectively. Treatment with noninvasive respiratory support alone was associated with an incidence of barotrauma of 9.1% and 2.6 events per 1000 noninvasive ventilator days, of which 95% were admitted to the ICU after the event, due to a worsening of respiratory parameters. The incidence of barotrauma of ICU COVID-19 patients in invasive ventilation over a year was 5.8% and 2.7 events per 1000 invasive ventilator days. There was no significant difference in demographics and clinical features between the barotrauma and non-barotrauma group. The mortality was higher in the barotrauma group (17 patients died, 47.2%) than in the non-barotrauma group (170 patients died, 37%), although this difference was not statistically significant (p = 0.429). (4) Conclusions: The incidence of PNX/PNM in moderate-severe ARDS COVID-19 patients did not differ significantly between the three waves over a year, and does not appear to be very different from that in ARDS patients in the pre-COVID era. The barotrauma does not appear to significantly increase mortality in COVID-19 patients with moderate-severe ARDS if protective ventilation strategies are applied. Attention should be paid to the risk of barotrauma in COVID-19 patients in noninvasive ventilation because the event increases the probability of admission to the intensive care unit (ICU) and intubation.

11.
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
12.
Int J Infect Dis ; 108: 244-251, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1351698

ABSTRACT

OBJECTIVES: To investigate the association between sex hormones and the severity of coronavirus disease 2019 (COVID-19). Furthermore, associations between sex hormones and systemic inflammation markers, viral shedding and length of hospital stay were studied. DESIGN AND METHODS: This case-control study included a total of 48 male patients with COVID-19 admitted to an Italian reference hospital. The 24 cases were patients with PaO2/FiO2 <250 mmHg and who needed ventilatory support during hospitalization (severe COVID-19). The 24 controls were selected in a 1:1 ratio, matched by age, from patients who maintained PaO2/FiO2 >300 mmHg at all times and who may have required low-flow oxygen supplementation during hospitalization (mild COVID-19). For each group, sex hormones were evaluated on hospital admission. RESULTS: Patients with severe COVID-19 (cases) had a significantly lower testosterone level compared with patients with mild COVID-19 (controls). Median total testosterone (TT) was 1.4 ng/mL in cases and 3.5 ng/mL in controls (P = 0.005); median bioavailable testosterone (BioT) was 0.49 and 1.21 in cases and controls, respectively (P = 0.008); and median calculated free testosterone (cFT) was 0.029 ng/mL and 0.058 ng/mL in cases and controls, respectively (P = 0.015). Low TT, low cFT and low BioT were correlated with hyperinflammatory syndrome (P = 0.018, P = 0.048 and P = 0.020, respectively) and associated with longer length of hospital stay (P = 0.052, P = 0.041 and P = 0.023, respectively). No association was found between sex hormone level and duration of viral shedding, or between sex hormone level and mortality rate. CONCLUSIONS: A low level of testosterone was found to be a marker of clinical severity of COVID-19.


Subject(s)
COVID-19 , SARS-CoV-2 , Biomarkers , Case-Control Studies , Humans , Male , Testosterone , Virulence Factors
13.
J Clin Med ; 10(15)2021 Jul 28.
Article in English | MEDLINE | ID: covidwho-1335120

ABSTRACT

BACKGROUND: The benefits and timing of percutaneous dilatational tracheostomy (PDT) in Intensive Care Unit (ICU) COVID-19 patients are still controversial. PDT is considered a high-risk procedure for the transmission of SARS-CoV-2 to healthcare workers (HCWs). The present study analyzed the optimal timing of PDT, the clinical outcomes of patients undergoing PDT, and the safety of HCWs performing PDT. METHODS: Of the 133 COVID-19 patients who underwent PDT in our ICU from 1 April 2020 to 31 March 2021, 13 patients were excluded, and 120 patients were enrolled. A trained medical team was dedicated to the PDT procedure. Demographic, clinical history, and outcome data were collected. Patients who underwent PDT were stratified into two groups: an early group (PDT ≤ 12 days after orotracheal intubation (OTI) and a late group (>12 days after OTI). An HCW surveillance program was also performed. RESULTS: The early group included 61 patients and the late group included 59 patients. The early group patients had a shorter ICU length of stay and fewer days of mechanical ventilation than the late group (p < 0.001). On day 7 after tracheostomy, early group patients required fewer intravenous anesthetic drugs and experienced an improvement of the ventilation parameters PaO2/FiO2 ratio, PEEP, and FiO2 (p < 0.001). No difference in the case fatality ratio between the two groups was observed. No SARS-CoV-2 infections were reported in the HCWs performing the PDTs. CONCLUSIONS: PDT was safe and effective for COVID-19 patients since it improved respiratory support parameters, reduced ICU length of stay and duration of mechanical ventilation, and optimized the weaning process. The procedure was safe for all HCWs involved in the dedicated medical team. The development of standardized early PDT protocols should be implemented, and PDT could be considered a first-line approach in ICU COVID-19 patients requiring prolonged mechanical ventilation.

14.
J Transl Med ; 19(1): 272, 2021 06 26.
Article in English | MEDLINE | ID: covidwho-1282262

ABSTRACT

BACKGROUND: Recent studies proposed the whole-blood based IFN-γ-release assay to study the antigen-specific SARS-CoV-2 response. Since the early prediction of disease progression could help to assess the optimal treatment strategies, an integrated knowledge of T-cell and antibody response lays the foundation to develop biomarkers monitoring the COVID-19. Whole-blood-platform tests based on the immune response detection to SARS-CoV2 peptides is a new approach to discriminate COVID-19-patients from uninfected-individuals and to evaluate the immunogenicity of vaccine candidates, monitoring the immune response in vaccine trial and supporting the serological diagnostics results. Here, we aimed to identify in the whole-blood-platform the best immunogenic viral antigen and the best immune biomarker to identify COVID-19-patients. METHODS: Whole-blood was overnight-stimulated with SARS-CoV-2 peptide pools of nucleoprotein-(NP) Membrane-, ORF3a- and Spike-protein. We evaluated: IL-1ß, IL-1Ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12p70, IL-13, IL- 15, IL-17A, eotaxin, FGF, G-CSF, GM-CSF, IFN-γ, IP-10, MCP-1, MIP-1α, MIP-1ß, PDGF, RANTES, TNF-α, VEGF. By a sparse partial least squares discriminant analysis we identified the most important soluble factors discriminating COVID-19- from NO-COVID-19-individuals. RESULTS: We identified a COVID-19 signature based on six immune factors: IFN-γ, IP-10 and IL-2 induced by Spike; RANTES and IP-10 induced by NP and IL-2 induced by ORF3a. We demonstrated that the test based on IP-10 induced by Spike had the highest AUC (0.85, p < 0.0001) and that the clinical characteristics of the COVID-19-patients did not affect IP-10 production. Finally, we validated the use of IP-10 as biomarker for SARS-CoV2 infection in two additional COVID-19-patients cohorts. CONCLUSIONS: We set-up a whole-blood assay identifying the best antigen to induce a T-cell response and the best biomarkers for SARS-CoV-2 infection evaluating patients with acute COVID-19 and recovered patients. We focused on IP-10, already described as a potential biomarker for other infectious disease such as tuberculosis and HCV. An additional application of this test is the evaluation of immune response in SARS-CoV-2 vaccine trials: the IP-10 detection may define the immunogenicity of a Spike-based vaccine, whereas the immune response to the virus may be evaluated detecting other soluble factors induced by other viral-antigens.


Subject(s)
COVID-19 , Biomarkers , COVID-19 Vaccines , Humans , RNA, Viral , SARS-CoV-2
15.
Front Pharmacol ; 12: 683529, 2021.
Article in English | MEDLINE | ID: covidwho-1247897

ABSTRACT

The outcome of COVID-19 appears to be influenced by vitamin D status of population. Although epidemiological data indicate that COVID-19 produces more severe symptoms and higher mortality in elderly in comparison to young patients and in men in comparison to women to date sex and age differences in vitamin D status in infected patients have not been evaluated yet. In this study we evaluated the levels of circulating 25(OH)D in patients hospitalized for COVID-19 divided accordingly to their sex and age. We also correlated 25(OH)D levels with patient's respiratory status (i.e., PaO2/FiO2 ratio) and with sex hormones plasma levels to analyze the potential relationship of these parameters. We found no significant differences in plasma levels of 25(OH)D between pre- and post-menopausal female patients and age matched male patients. Interestingly, the 25(OH)D plasma levels positively correlated to PaO2/FiO2 ratio only in young patients, regardless of their sex. We also found a significantly positive correlation between 17ß-estradiol and 25(OH)D in elderly women and between testosterone and 25(OH)D in elderly men, supporting the role of sex hormones in maintaining 25(OH)D levels. In conclusion, we suggest that a synergy between vitamin D and sex hormones could contribute to the age-related outcome of COVID-19.

16.
Front Pharmacol ; 12: 621676, 2021.
Article in English | MEDLINE | ID: covidwho-1221961

ABSTRACT

Objectives: No specific treatment has been approved for COVID-19. Lopinavir/ritonavir (LPV/r) and hydroxychloroquine (HCQ) have been used with poor results, and a trial showed advantages of combined antiviral therapy vs. single antivirals. The aim of the study was to assess the effectiveness of the combination of antivirals (LPV/r and HCQ) or their single use in COVID-19 hospitalized patients vs. standard of care (SoC). Methods: Patients ≥18 years with SARS-CoV-2 infection, defined as positive RT-PCR from nasal/oropharyngeal (NP/OP) swab or positive serology, admitted at L. Spallanzani Institute (Italy) were included. Primary endpoint: time to invasive ventilation/death. Secondary endpoint: time to two consecutive negative SARS-CoV-2 PCRs in NP/OP swabs. In order to control for measured confounders, a marginal Cox regression model with inverse probability weights was used. Results: A total of 590 patients were included in the analysis: 36.3% female, 64 years (IQR 51-76), and 91% with pneumonia. Cumulative probability of invasive ventilation/death at 14 days was 21.2% (95% CI 17.6, 24.7), without difference between SOC, LPV/r, hydroxychloroquine, HCQ + LPV/r, and SoC. The risk of invasive ventilation/death in the groups appeared to vary by baseline ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2). Overall cumulative probability of confirmed negative nasopharyngeal swabs at 14 days was 44.4% (95% CI 38.9, 49.9), without difference between groups. Conclusion: In this retrospective analysis, we found no difference in the rate of invasive ventilation/death or viral shedding by different strategies, as in randomized trials performed to date. Moreover, even the combination HCQ + LPV/r did not show advantages vs. SoC.

17.
Clin Infect Dis ; 71(16): 2272-2275, 2020 11 19.
Article in English | MEDLINE | ID: covidwho-1165366

ABSTRACT

Increased production of inflammatory cytokines and myeloid-derived suppressor cells occurs in patients with coronavirus disease 2019. These inversely correlated with perforin-expressing natural killer (NK) and CD3+ T cells. We observed a lower number of perforin-expressing NK cells in intensive care unit (ICU) patients compared with non-ICU patients, suggesting an impairment of the immune cytotoxic arm as a pathogenic mechanism.


Subject(s)
COVID-19/immunology , Inflammation/blood , Killer Cells, Natural/immunology , Perforin/immunology , T-Lymphocytes, Cytotoxic/immunology , Aged , COVID-19/blood , Cytokines/immunology , Female , Humans , Inflammation/complications , Inflammation/immunology , Intensive Care Units/statistics & numerical data , Italy , Lymphocyte Activation/immunology , Male , Middle Aged , SARS-CoV-2
18.
Mediterr J Hematol Infect Dis ; 13(1): e2021016, 2021.
Article in English | MEDLINE | ID: covidwho-1145644

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) is mainly a respiratory tract disease and acute respiratory failure with diffuse microvascular pulmonary thrombosis are critical aspects of the morbidity and mortality of this new syndrome. PURPOSE: The aim of our study was to investigate, in severe COVID-19 hospitalized patients, the P-selectin plasma concentration as a biomarker of endothelial dysfunction and platelet activation. METHODS: 46 patients with severe or critical SARS-CoV-2 infection were included in the study. Age-matched patients then were divided in those requiring admission to the intensive care unit (ICU, ICU cases) vs those not requiring ICU hospitalization (non-ICU cases). Blood samples of severe COVID-19 patients were collected at the time of hospital admission. The quantification of soluble P-selectin was performed by ELI, assay. RESULTS: Our study showed a higher P-selectin plasma concentration in patients with Covid-19, regardless of ICU admission, compared to the normal reference values and compared to ten contextually sampled healthy donors (HD); (COVID-19): median 65.2 (IQRs: 45.1-81.1) vs. HD: 40.3 (IQRs: 24.3-48.7), p=0023. Moreover, results showed a significant reduction of P-sele din after platelets removal in HD, in contrast, both ICU and non-ICU COVID-19 patients showed similar high levels of P-selectin with and without platelets. CONCLUSION: Elevation of P-selectin suggests a central role of platelet endothelium interaction as part of the multifaced pathogenic mechanism of COVID-19 leading to the local activation of hemostatic system forming pulmonary thrombi. Further work is necessary to determine the therapeutic role of antiplatelets agents or of the anti P-selectin antibody Crizanlizumab.

19.
Antibiotics (Basel) ; 10(3)2021 Mar 08.
Article in English | MEDLINE | ID: covidwho-1143446

ABSTRACT

BACKGROUND: The WHO advised that the impact of COVID-19 pandemic on TB services was estimated to be dramatic due to the disruption of TB services. METHODS: A retrospective data collection and evaluation was conducted to include all the patients hospitalized for TB at INMI from 9 March to 31 August 2020 (lockdown period and three months thereafter). For the purpose of the study, data from patients hospitalized in the same period of 2019 were also collected. RESULTS: In the period of March-August 2019, 201 patients were hospitalized with a diagnosis of TB, while in the same period of 2020, only 115 patients, with a case reduction of 43%. Patients with weight loss, acute respiratory failure, concurrent extrapulmonary TB, and higher Timika radiographic scores were significantly more frequently hospitalized during 2020 vs. 2019. The median patient delay was 75 days (IQR: 40-100) in 2020 compared to 30 days (IQR: 10-60) in 2019 (p < 0.01). Diagnostic delays in 2020 remain significant in the multiple logistic model (AOR = 6.93, 95%CI: 3.9-12.3). CONCLUSIONS: Our experience suggests that COVID-19 pandemic had an impact on TB patient care in terms of higher diagnostic delay, reduction in hospitalization, and a greater severity of clinical presentations.

20.
Int J Infect Dis ; 105: 532-539, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1116859

ABSTRACT

BACKGROUND: Limited data are available about the predictors and outcomes associated with prolonged SARS-CoV-2 RNA shedding (VS). METHODS: A retrospective study including COVID-19 patients admitted to an Italian hospital between March 1 and July 1, 2020. Predictors of viral clearance (VC) and prolonged VS from the upper respiratory tract were assessed by Poisson regression and logistic regression analyses. The causal relation between VS and clinical outcomes was evaluated through an inverse probability weighted Cox model. RESULTS: The study included 536 subjects. The median duration of VS from symptoms onset was 18 days. The estimated 30-day probability of VC was 70.2%. Patients with comorbidities, lymphopenia at hospital admission, or moderate/severe respiratory disease had a lower chance of VC. The development of moderate/severe respiratory failure, delayed hospital admission after symptoms onset, baseline comorbidities, or D-dimer >1000ng/mL at admission independently predicted prolonged VS. The achievement of VC doubled the chance of clinical recovery and reduced the probability of death/mechanical ventilation. CONCLUSIONS: Respiratory disease severity, comorbidities, delayed hospital admission and inflammatory markers negatively predicted VC, which resulted to be associated with better clinical outcomes. These findings highlight the importance of prompt hospitalization of symptomatic patients, especially where signs of severity or comorbidities are present.


Subject(s)
COVID-19/virology , RNA, Viral/analysis , Respiratory System/virology , SARS-CoV-2/isolation & purification , Virus Shedding , Adult , Aged , Cohort Studies , Female , Humans , Male , Middle Aged , Proportional Hazards Models , Severity of Illness Index , Time Factors
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