Timing and outcomes of noninvasive ventilation in 307 ARDS COVID-19 patients: an observational study in an Italian third level COVID-19 hospital (preprint)

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.

Outcomes and Timing of Bedside Percutaneous Tracheostomy of COVID-19 Patients Over a Year in Intensive Care Unit (preprint)

(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, >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<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<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.

COVID-19 Disease - Temporal Analyses of Complete Blood Count Parameters Over Course of Illness, and Relationship to Patient Demographics and Management Outcomes in Survivors and Non-Survivors: A Longitudinal Descriptive Cohort Study (preprint)

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).

Concurrent cavitary pulmonary tuberculosisand COVID-19 pneumonia with in vitro immune cell anergy:a case report. (preprint)

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

Spectrum of innate and adaptive immune response to SARS CoV 2 infection across asymptomatic, mild and severe cases; a longitudinal cohort study (preprint)

Background: SARS-CoV-2 is a novel coronavirus, not encountered before by humans. The wide spectrum of clinical expression of SARS-CoV-2 illness suggests that individual immune responses to SARS-CoV-2 play a crucial role in determining the clinical course after first infection. Immunological studies have focussed on patients with moderate to severe disease, demonstrating excessive inflammation in tissues and organ damage. We have studied the individual response to SARS-CoV-2 of asympromatic, mild and severe COVID-19 patients in order to investigate the role of innnate and adaptive immunity in determining the clinical course after first infection. Methods: To understand the basis of the protective immune response in COVID-19, we performed a longitudinal follow-up analysis of innate and adaptive immunity in 64 adults with a spectrum of clinical presentations: (28 healthy SARS-CoV-2-negative contacts of COVID-19 cases; 20 asymptomatic SARS-CoV-2-infected cases; 8 patients with mild COVID-19 disease and 8 cases of severe COVID-19 disease). Results: Our data show that high frequency of NK cells and early and transient increase of specific IgA and, to a lower extent, IgG are associated to asymptomatic SARS-CoV-2 infection. By contrast, monocyte expansion and high and persistent levels of IgA and IgG, produced relatively late in the course of the infection, characterize severe disease. Modest increase of monocytes and rapidly declining antibodies are detected in mild COVID-19. Conclusions: The importance of innate NK cells and the short-lived antibody response of asymptomatic individuals and patients with mild disease suggest that only severe COVID-19 may result in protective memory established by the adaptive immune response.