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1.
Eur J Clin Nutr ; 2022 Aug 26.
Article in English | MEDLINE | ID: covidwho-2016683

ABSTRACT

BACKGROUND/OBJECTIVES: The aim of this post-hoc analysis was to evaluate if epicardial adipose tissue (EAT) quantity and quality, as evaluated by computed tomography (CT), have a different role in the risk of mortality and pulmonary embolism in critically ill COVID-19 patients admitted to an intensive care unit (ICU). SUBJECTS/METHODS: CT derived EAT volume and density, as well as anthropometric and blood biomarkers, were evaluated in a sample of 138 subjects, 109 men and 29 women, for whom CT images and information on pulmonary embolism were available from a total of 313 subjects who were consecutively admitted to the ICU for COVID-19 from the REINSURE-ARDS prospective registry. RESULTS: A total of 28 patients (20.3%) died during the first 28 days after ICU admission. 26 subjects out of 138 had pulmonary embolism (18.8%). Age, weight, BMI, IL-6 levels and pulmonary embolism prevalence were significantly higher across EAT volume tertiles. Subjects who died in the first 28 days from ICU admission were older, had higher EAT volume, D-dimer, LDH and IL-6 level. After adjustment for age and gender, participants in tertile 3 of EAT volume had lower survival at 28 days from ICU admission as compared to subjects in the tertile 1, HR 2.95 (95% C.I. 1.02-8.49), but after adjusting for potential confounders the relation was no longer significant. No relation between EAT density and mortality was observed. From a binary logistic regression, subjects in tertile 3 of EAT volume and in tertile 1 of EAT density showed a 4 times and 3.6 times increased risk of pulmonary embolism, respectively. CONCLUSIONS: ICU subjects affected by severe COVID-19 with higher EAT volume and low EAT density should be carefully monitored and managed with a prompt and aggressive approach, to prevent serious and life-threatening consequences and the increase of hospital treatment costs.

2.
Updates Surg ; 74(4): 1247-1252, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1748398

ABSTRACT

The spread of COVID-19 has overwhelmed medical facilities across the globe, with patients filling beds in both regular wards and in intensive care units. The repurposing of hospital facilities has resulted in a dramatic decrease in the capacity of hospitals-in terms of available beds, surgical facilities, and medical and nursing staff- to care for oncology patients. The Italian National Board of Bioethics provided precise and homogeneous guidelines for the allocation of the scarce resources available. In our experience, strictly following these general guidelines and not considering the clinical vocation of each single health care center did not allow us to resume usual activities but generated further confusion in resource allocation. To face the scarcity of available resources and guarantee our patients fair access to the health care system we created a surgical triage with four fundamental steps. We took into consideration " well defined and widely accepted clinical prognostic factors " as stated by the Italian Society of Anesthesia and Resuscitation. We were able to draw up a list of patients giving priority to those who theoretically should have a greater chance of overcoming their critical situation. The age criterion has also been used in the overall evaluation of different cure options in each case, but it has never been considered on its own or outside the other clinical parameters. Although not considered acceptable by many we had to forcefully adopt the criterion of comparison between patients to give priority to those most in need of immediate care.

3.
J Ultrasound Med ; 41(10): 2547-2556, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-1630846

ABSTRACT

OBJECTIVES: Lung ultrasound (LUS) holds the promise of an accurate, radiation-free, and affordable diagnostic and monitoring tool in coronavirus disease 2019 (COVID-19) pneumonia. We sought to evaluate the usefulness of LUS in the diagnosis of patients with respiratory distress and suspicion of interstitial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia, in comparison to other imaging modalities. METHODS: This was a multicenter, retrospective study. LUS was performed, on Emergency Department (ED) arrival of patients presenting for possible COVID-19 evaluation, by trained emergency physicians, before undergoing conventional radiologic examination or while waiting for the report. Scans were performed using longitudinal transducer orientation of the lung regions. CXR was interpreted by radiologists staffing ED radiology. Subjects were divided into two group based on molecular test results. LUS findings were compared to COVID test results, nonlaboratory data, and other imaging for each patient. Categorical variables were expressed as percentages and continuous variables as median ± standard error. RESULTS: A total of 479 patients were enrolled, 87% diagnosed with SARS-CoV-2 by molecular testing. COVID positive and COVID negative patients differed with respect to sex, presence of fever, and white blood cells count. Most common findings on lung point of care ultrasound (POCUS) for COVID-positive patients were B-lines, irregular pleural lines, and small consolidation. Normal chest X-ray was found in 17.89% of cases. CONCLUSIONS: This 479 patient cohort, with COVID-19, found LUS to be noninferior to chest X-ray (CXR) for diagnostic accuracy. In this study, COVID-positive patients are most likely to show B lines and sub-pleural consolidations on LUS examination.


Subject(s)
COVID-19 , Pneumonia , COVID-19/diagnostic imaging , Humans , Lung/diagnostic imaging , Retrospective Studies , SARS-CoV-2 , Ultrasonography/methods
4.
Cell Death Differ ; 29(2): 420-438, 2022 02.
Article in English | MEDLINE | ID: covidwho-1406388

ABSTRACT

Inflammatory responses rapidly detect pathogen invasion and mount a regulated reaction. However, dysregulated anti-pathogen immune responses can provoke life-threatening inflammatory pathologies collectively known as cytokine release syndrome (CRS), exemplified by key clinical phenotypes unearthed during the SARS-CoV-2 pandemic. The underlying pathophysiology of CRS remains elusive. We found that FLIP, a protein that controls caspase-8 death pathways, was highly expressed in myeloid cells of COVID-19 lungs. FLIP controlled CRS by fueling a STAT3-dependent inflammatory program. Indeed, constitutive expression of a viral FLIP homolog in myeloid cells triggered a STAT3-linked, progressive, and fatal inflammatory syndrome in mice, characterized by elevated cytokine output, lymphopenia, lung injury, and multiple organ dysfunctions that mimicked human CRS. As STAT3-targeting approaches relieved inflammation, immune disorders, and organ failures in these mice, targeted intervention towards this pathway could suppress the lethal CRS inflammatory state.


Subject(s)
COVID-19/physiopathology , Cytokine Release Syndrome/etiology , Cytokine Release Syndrome/metabolism , Inflammation/metabolism , STAT3 Transcription Factor/metabolism , Aged , Aged, 80 and over , Animals , COVID-19/metabolism , Caspase 8/metabolism , Cytokines/immunology , Cytokines/metabolism , Female , Humans , Male , Mice , Mice, Inbred C57BL , Middle Aged , SARS-CoV-2/immunology , STAT3 Transcription Factor/genetics , Signal Transduction
5.
Sci Rep ; 11(1): 17730, 2021 09 06.
Article in English | MEDLINE | ID: covidwho-1397894

ABSTRACT

The efficacy of non-invasive ventilation (NIV) in acute respiratory failure secondary to SARS-CoV-2 infection remains controversial. Current literature mainly examined efficacy, safety and potential predictors of NIV failure provided out of the intensive care unit (ICU). On the contrary, the outcomes of ICU patients, intubated after NIV failure, remain to be explored. The aims of the present study are: (1) investigating in-hospital mortality in coronavirus disease 2019 (COVID-19) ICU patients receiving endotracheal intubation after NIV failure and (2) assessing whether the length of NIV application affects patient survival. This observational multicenter study included all consecutive COVID-19 adult patients, admitted into the twenty-five ICUs of the COVID-19 VENETO ICU network (February-April 2020), who underwent endotracheal intubation after NIV failure. Among the 704 patients admitted to ICU during the study period, 280 (40%) presented the inclusion criteria and were enrolled. The median age was 69 [60-76] years; 219 patients (78%) were male. In-hospital mortality was 43%. Only the length of NIV application before ICU admission (OR 2.03 (95% CI 1.06-4.98), p = 0.03) and age (OR 1.18 (95% CI 1.04-1.33), p < 0.01) were identified as independent risk factors of in-hospital mortality; whilst the length of NIV after ICU admission did not affect patient outcome. In-hospital mortality of ICU patients intubated after NIV failure was 43%. Days on NIV before ICU admission and age were assessed to be potential risk factors of greater in-hospital mortality.


Subject(s)
COVID-19/therapy , Intensive Care Units/statistics & numerical data , Intubation, Intratracheal/methods , Noninvasive Ventilation/methods , Respiratory Insufficiency/therapy , Aged , COVID-19/complications , COVID-19/virology , Female , Hospital Mortality , Humans , Logistic Models , Male , Middle Aged , Multivariate Analysis , Outcome Assessment, Health Care/methods , Outcome Assessment, Health Care/statistics & numerical data , Respiratory Insufficiency/etiology , Risk Factors , SARS-CoV-2/physiology
6.
Lorenzoni, Giulia, Sella, Nicolò, Boscolo, Annalisa, Azzolina, Danila, Bartolotta, Patrizia, Pasin, Laura, Pettenuzzo, Tommaso, De Cassai, Alessandro, Baratto, Fabio, Toffoletto, Fabio, De Rosa, Silvia, Fullin, Giorgio, Peta, Mario, Rosi, Paolo, Polati, Enrico, Zanella, Alberto, Grasselli, Giacomo, Pesenti, Antonio, Navalesi, Paolo, Gregori, Dario, Tocco, Martina, Pretto, Chiara, Tamburini, Enrico, Fregolent, Davide, Pirelli, Pier Francesco, Marchesin, Davide, Perona, Matteo, Franchetti, Nicola, Paolera, Michele Della, Simoni, Caterina, Falcioni, Tatiana, Tresin, Alessandra, Schiavolin, Chiara, Schiavi, Aldo, Vathi, Sonila, Sartori, Daria, Sorgato, Alice, Pistollato, Elisa, Linassi, Federico, Gianoli, Sara, Gaspari, Silvia, Gruppo, Francesco, Maggiolo, Alessandra, Giurisato, Elena, Furlani, Elisa, Calore, Alvise, Serra, Eugenio, Pittarello, Demetrio, Tiberio, Ivo, Bond, Ottavia, Michieletto, Elisa, Muraro, Luisa, Peralta, Arianna, Persona, Paolo, Petranzan, Enrico, Zarantonello, Francesco, Graziano, Alessandro, Piasentini, Eleonora, Bernardi, Lorenzo, Pianon, Roberto, Mazzon, Davide, Poole, Daniele, Badii, Flavio, Bosco, Enrico, Agostini, Moreno, Trevisiol, Paride, Farnia, Antonio, Altafini, Lorella, Calò, Mauro Antonio, Meggiolaro, Marco, Lazzari, Francesco, Martinello, Ivan, Papaccio, Francesco, di Gregorio, Guido, Bonato, Alfeo, Sgarabotto, Camilla, Montacciani, Francesco, Alessandra, Parnigotto, Gagliardi, Giuseppe, Ferraro, Gioconda, Ongaro, Luigi, Baiocchi, Marco, Danzi, Vinicio, Zanatta, Paolo, Donadello, Katia, Gottin, Leonardo, Sinigaglia, Ezio, da Ros, Alessandra, Marchiotto, Simonetta, Bassanini, Silvia, Zamperini, Massimo, Daroui, Ivan, Mosaner, Walter.
Journal of Anesthesia, Analgesia and Critical Care ; 1(1):3-3, 2021.
Article in English | BioMed Central | ID: covidwho-1388853
7.
Front Cell Infect Microbiol ; 11: 683409, 2021.
Article in English | MEDLINE | ID: covidwho-1370984

ABSTRACT

Objective: To investigate the presence of bacteria and fungi in bronchial aspirate (BA) samples from 43 mechanically ventilated patients with severe COVID-19 disease. Methods: Detection of SARS-CoV-2 was performed using Allplex 2019-nCoV assay kits. Isolation and characterisation of bacteria and fungi were carried out in BA specimens treated with 1X dithiothreitol 1% for 30 min at room temperature, using standard culture procedures. Results: Bacterial and/or fungal superinfection was detected in 25 out of 43 mechanically ventilated patients, generally after 7 days of hospitalisation in an intensive care unit (ICU). Microbial colonisation (colony forming units (CFU) <1000 colonies/ml) in BA samples was observed in 11 out of 43 patients, whereas only 7 patients did not show any signs of bacterial or fungal growth. Pseudomonas aeruginosa was identified in 17 patients. Interestingly, 11 out of these 17 isolates also showed carbapenem resistance. The molecular analysis demonstrated that resistance to carbapenems was primarily related to OprD mutation or deletion. Klebsiella pneumoniae was the second most isolated pathogen found in 13 samples, of which 8 were carbapenemase-producer strains. Conclusion: These data demonstrate the detection of bacterial superinfection and antimicrobial resistance in severe SARS-CoV-2-infected patients and suggest that bacteria may play an important role in COVID-19 evolution. A prospective study is needed to verify the incidence of bacterial and fungal infections and their influence on the health outcomes of COVID-19 patients.


Subject(s)
COVID-19 , Pharmaceutical Preparations , Superinfection , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Humans , Intensive Care Units , Microbial Sensitivity Tests , RNA, Viral , Respiration, Artificial , SARS-CoV-2 , Superinfection/drug therapy
8.
Crit Care ; 25(1): 263, 2021 07 28.
Article in English | MEDLINE | ID: covidwho-1331949

ABSTRACT

BACKGROUND: Pathophysiological features of coronavirus disease 2019-associated acute respiratory distress syndrome (COVID-19 ARDS) were indicated to be somewhat different from those described in nonCOVID-19 ARDS, because of relatively preserved compliance of the respiratory system despite marked hypoxemia. We aim ascertaining whether respiratory system static compliance (Crs), driving pressure (DP), and tidal volume normalized for ideal body weight (VT/kg IBW) at the 1st day of controlled mechanical ventilation are associated with intensive care unit (ICU) mortality in COVID-19 ARDS. METHODS: Observational multicenter cohort study. All consecutive COVID-19 adult patients admitted to 25 ICUs belonging to the COVID-19 VENETO ICU network (February 28th-April 28th, 2020), who received controlled mechanical ventilation, were screened. Only patients fulfilling ARDS criteria and with complete records of Crs, DP and VT/kg IBW within the 1st day of controlled mechanical ventilation were included. Crs, DP and VT/kg IBW were collected in sedated, paralyzed and supine patients. RESULTS: A total of 704 COVID-19 patients were screened and 241 enrolled. Seventy-one patients (29%) died in ICU. The logistic regression analysis showed that: (1) Crs was not linearly associated with ICU mortality (p value for nonlinearity = 0.01), with a greater risk of death for values < 48 ml/cmH2O; (2) the association between DP and ICU mortality was linear (p value for nonlinearity = 0.68), and increasing DP from 10 to 14 cmH2O caused significant higher odds of in-ICU death (OR 1.45, 95% CI 1.06-1.99); (3) VT/kg IBW was not associated with a significant increase of the risk of death (OR 0.92, 95% CI 0.55-1.52). Multivariable analysis confirmed these findings. CONCLUSIONS: Crs < 48 ml/cmH2O was associated with ICU mortality, while DP was linearly associated with mortality. DP should be kept as low as possible, even in the case of relatively preserved Crs, irrespective of VT/kg IBW, to reduce the risk of death.


Subject(s)
COVID-19/mortality , Respiration, Artificial , Respiratory Distress Syndrome/mortality , Aged , Female , Humans , Intensive Care Units , Intubation , Italy , Male , Middle Aged , Respiratory Distress Syndrome/virology , Tidal Volume
9.
Infect Dis Ther ; 10(3): 1579-1590, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1274997

ABSTRACT

INTRODUCTION: To better define COVID-19 long-term impact we prospectively analysed patient-centred outcomes, including general health and symptom duration. METHODS: Barthel index (BI), St. George's Respiratory Questionnaire adapted to patients with COVID-19 (aSGRQ) and WHO Clinical Progression Scale (CPS) were measured at enrolment and at 6 weeks from the onset of symptoms. Persistence of most frequently reported symptoms was assessed at 6 weeks and, among symptomatic patients, at 12 weeks from the onset of symptoms. Predictors of impaired general health over time were identified using an ordinal multilevel multivariate model. RESULTS: A total of 448 patients (55% men, median age 56 years) were enrolled. WHO-CPS showed mild, moderate and severe disease in 48%, 42% and 10% of patients at admission and mild disease in all patients at follow-up, respectively. BI and aSGRQ were normal in 96% and 93% patients before COVID-19 but only in 47% and 16% at COVID-19 diagnosis and in 87% and 65% at 6-week follow-up. Male gender was identified by all three assessments as a predictor of impaired general health (BI, OR 2.14, p < 0.0001; aSGRQ, OR 0.53, p = 0.003; WHO-CPS, OR 1.56, p = 0.01). Other predictors included age, ICU admission and comorbidities (e.g. cardiovascular disease and cancer) for BI, hospital admission for aSGRQ, age and presence of comorbidities for WHO-CPS. At 6- and 12-week follow-up, 39% and 20% of patients, respectively, were still reporting symptoms. Fatigue and breathlessness were the most frequently reported symptoms. CONCLUSIONS: Long-term follow-up facilitates the monitoring of health impairment and symptom persistence and can contribute to plan tailored interventions.

10.
Stem Cell Res Ther ; 12(1): 316, 2021 06 02.
Article in English | MEDLINE | ID: covidwho-1255964

ABSTRACT

Coronavirus disease 2019 (COVID-19) may result in a life-threatening condition due to a hyperactive immune reaction to severe acute respiratory syndrome-coronavirus-2 infection, for which no effective treatment is available. Based on the potent immunomodulatory properties of mesenchymal stromal cells (MSCs), a growing number of trials are ongoing. This prompted us to carry out a thorough immunological study in a patient treated with umbilical cord-derived MSCs and admitted to the Intensive Care Unit for COVID-19-related pneumonia. The exploratory analyses were assessed on both peripheral blood and bronchoalveolar fluid lavage samples at baseline and after cellular infusion by means of single-cell RNA sequencing, flow cytometry, ELISA, and functional assays. Remarkably, a normalization of circulating T lymphocytes count paralleled by a reduction of inflammatory myeloid cells, and a decrease in serum levels of pro-inflammatory cytokines, mostly of interleukin-6 and tumor necrosis factor-α, were observed. In addition, a drop of plasma levels of those chemokines essential for neutrophil recruitment became evident that paralleled the decrease of lung-infiltrating inflammatory neutrophils. Finally, circulating monocytes and low-density gradient neutrophils acquired immunosuppressive function. This scenario was accompanied by an amelioration of respiratory, renal, inflammatory, and pro-thrombotic indexes. Our results provide the first immunological data possibly related to the use of umbilical cord-derived MSCs in severe COVID-19 context.


Subject(s)
COVID-19 , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Humans , SARS-CoV-2 , Umbilical Cord
11.
Front Physiol ; 12: 651167, 2021.
Article in English | MEDLINE | ID: covidwho-1241192

ABSTRACT

BACKGROUND: Muscular fatigue and injury are frequently observed in critically ill COVID-19 patients. The aim of this study was to determine whether different muscle adipose tissue depots are associated with mortality and muscle damage in patients affected by COVID-19 admitted to the ICU. METHODS: CT images were obtained in 153 ICU patients with COVID-19 (121 males and 32 females). Height, weight, body mass index (BMI), C-reactive protein, Creatine PhosphoKinase (CPK), muscle density, and intermuscular adipose tissue (IMAT) were measured. RESULTS: Participants in the highest tertile of IMAT/muscle had the shorter 28-day survival from ICU admission as compared to subjects in the first tertile. Estimates derived from the Cox proportional hazard models, after adjustment for age, sex, and BMI, confirmed the results of the survival analysis (HR 3.94, 95% CI: 1.03-15.09). Participants in the lowest tertile of muscle density had the shorter survival at 28 days from ICU admission as compared to subjects in the highest tertile (HR 3.27, 95% CI: 1.18-4.61), but the relationship was no longer significant when age was included in the model. Subjects in the second muscle density tertile did not show an increased risk.Participants in the highest tertile of IMAT/muscle and those in the lowest tertile of muscle density showed both significantly higher CPK adjusted for weight values as evaluated during the first 8 days of hospitalization. CONCLUSION: Our data seem to suggest that higher levels of IMAT/muscle and low muscle density are both associated with higher risk of ICU mortality and muscle injury as evaluated with CPK level.

12.
Nat Commun ; 12(1): 1428, 2021 03 05.
Article in English | MEDLINE | ID: covidwho-1118806

ABSTRACT

Since the beginning of the SARS-CoV-2 pandemic, COVID-19 appeared as a unique disease with unconventional tissue and systemic immune features. Here we show a COVID-19 immune signature associated with severity by integrating single-cell RNA-seq analysis from blood samples and broncho-alveolar lavage fluids with clinical, immunological and functional ex vivo data. This signature is characterized by lung accumulation of naïve lymphoid cells associated with a systemic expansion and activation of myeloid cells. Myeloid-driven immune suppression is a hallmark of COVID-19 evolution, highlighting arginase-1 expression with immune regulatory features of monocytes. Monocyte-dependent and neutrophil-dependent immune suppression loss is associated with fatal clinical outcome in severe patients. Additionally, our analysis shows a lung CXCR6+ effector memory T cell subset is associated with better prognosis in patients with severe COVID-19. In summary, COVID-19-induced myeloid dysregulation and lymphoid impairment establish a condition of 'immune silence' in patients with critical COVID-19.


Subject(s)
COVID-19/immunology , SARS-CoV-2/immunology , Aged , Aged, 80 and over , CD8-Positive T-Lymphocytes/immunology , COVID-19/blood , Case-Control Studies , Cytokines/immunology , Female , Humans , Male , Middle Aged , Monocytes/immunology , Myeloid Cells/immunology , Neutrophils/immunology , T-Lymphocytes/immunology
13.
Nutr Metab Cardiovasc Dis ; 31(3): 762-768, 2021 03 10.
Article in English | MEDLINE | ID: covidwho-1065504

ABSTRACT

BACKGROUND AND AIMS: Recent studies show that obesity is a risk factor for hospital admission and for critical care need in patients with coronavirus disease 2019 (COVID-19). The aim was to determine whether obesity is a risk factor for unfavourable health outcomes in patients affected by COVID-19 admitted to ICU. METHODS AND RESULTS: 95 consecutive patients with COVID-19 (78 males and 18 females) were admitted to ICU and included in the study. Height, weight, BMI, Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, CRP, CPK, ICU and hospital length of stay and comorbidities were evaluated. Participants with obesity had a lower 28 day survival rate from ICU admission than normal weight subjects. Cox proportional hazard model-derived estimates, adjusted for age, gender and comorbidity, confirmed the results of the survival analysis (HR:5.30,95%C.I.1.26-22.34). Obese subjects showed longer hospital and ICU stay as compared with normal weight counterpart.Subjects with obesity showed significantly higher CRP and CPK levels than normal weight subjects. CONCLUSION: In individuals with obesity, careful management and prompt intervention in case of suspected SARS-CoV-2 infection is necessary to prevent the progression of the disease towards severe outcomes and the increase of hospital treatment costs.


Subject(s)
COVID-19/epidemiology , COVID-19/mortality , Obesity/epidemiology , APACHE , Adult , Aged , Aged, 80 and over , Body Mass Index , Critical Illness , Female , Hospitalization/statistics & numerical data , Humans , Intensive Care Units , Length of Stay/statistics & numerical data , Male , Middle Aged , Obesity/mortality , Proportional Hazards Models , Risk Factors , SARS-CoV-2 , Severity of Illness Index
14.
J Clin Invest ; 130(12): 6409-6416, 2020 12 01.
Article in English | MEDLINE | ID: covidwho-1011054

ABSTRACT

BACKGROUNDPatients with coronavirus disease 2019 (COVID-19) develop pneumonia generally associated with lymphopenia and a severe inflammatory response due to uncontrolled cytokine release. These mediators are transcriptionally regulated by the JAK/STAT signaling pathways, which can be disabled by small molecules.METHODSWe treated a group of patients (n = 20) with baricitinib according to an off-label use of the drug. The study was designed as an observational, longitudinal trial and approved by the local ethics committee. The patients were treated with 4 mg baricitinib twice daily for 2 days, followed by 4 mg per day for the remaining 7 days. Changes in the immune phenotype and expression of phosphorylated STAT3 (p-STAT3) in blood cells were evaluated and correlated with serum-derived cytokine levels and antibodies against severe acute respiratory syndrome-coronavirus 2 (anti-SARS-CoV-2). In a single treated patient, we also evaluated the alteration of myeloid cell functional activity.RESULTSWe provide evidence that patients treated with baricitinib had a marked reduction in serum levels of IL-6, IL-1ß, and TNF-α, a rapid recovery of circulating T and B cell frequencies, and increased antibody production against the SARS-CoV-2 spike protein, all of which were clinically associated with a reduction in the need for oxygen therapy and a progressive increase in the P/F (PaO2, oxygen partial pressure/FiO2, fraction of inspired oxygen) ratio.CONCLUSIONThese data suggest that baricitinib prevented the progression to a severe, extreme form of the viral disease by modulating the patients' immune landscape and that these changes were associated with a safer, more favorable clinical outcome for patients with COVID-19 pneumonia.TRIAL REGISTRATIONClinicalTrials.gov NCT04438629.FUNDINGThis work was supported by the Fondazione Cariverona (ENACT Project) and the Fondazione TIM.


Subject(s)
Azetidines/administration & dosage , COVID-19 , Off-Label Use , Purines/administration & dosage , Pyrazoles/administration & dosage , SARS-CoV-2 , Sulfonamides/administration & dosage , Aged , Aged, 80 and over , B-Lymphocytes/immunology , B-Lymphocytes/metabolism , B-Lymphocytes/pathology , COVID-19/blood , COVID-19/immunology , COVID-19/pathology , Cytokines/blood , Cytokines/immunology , Female , Humans , Longitudinal Studies , Male , Middle Aged , SARS-CoV-2/immunology , SARS-CoV-2/metabolism , Severity of Illness Index , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , T-Lymphocytes/pathology
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