Real world use of Tixagevimab/Cilgavimab pre-exposure prophylaxis of COVID-19 in immunocompromised individuals: data from the OCTOPUS study. (preprint)

We report real world use over time in immunocompromised subjects receiving tixagevimab/cilgavimab (T/C) pre-exposure prophylaxis (PrEP). Observational study on participants receiving T/C PrEP stratified: never had COVID-19 (NoC), hybrids (H) and breakthrough infections (BTIs) if COVID-19 before or after PrEP, respectively. Anti-RBD IgG and BA.5 neutralizing antibodies (nAbs), mucosal IgG, T-cell immunity at the administration of T/C (T0), 3 (T1), 6 (T2), and 9 (T3) months after, were measured. Comparison of markers in each group across timepoints, Poisson regression model for BTIs incidence rate ratios were performed. N=231 participants: median age 63 years (IQR 54.0-73.0), 84% hematological disease, median vaccine dose of three. N=72 NoC, 103 H and 56 (24%) BTIs, mostly mild/moderate, IR 4.2 (95%CI 3.2-5.4) BTIs/100 patients-months, no factors associated with. A significant increase of anti-RBD IgG at T1 was observed in all the groups, with a decline at T2. GMTs of anti-BA.5 nAbs were low at T1 for all the groups and around/below the cut off. No changes of IFN-γ. Overall, a mucosal response was observed at T1. An incidence of 24% of mild/moderate BTIs was observed. Anti-RBD IgG levels persistence was ensured, BA.5 nAbs were low/undetectable, cellular T immunity remained stable.

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.

The Evolution of Clinical and Scientific Evidence-Based Management Guidelines for COVID-19 Disease: A Longitudinal Descriptive Analysis (preprint)

In January 2020, the novel Coronavirus Disease-2019 (COVID-19) epidemic spread to Italy. The ensuing high rates of patients with pulmonary disease due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections, overwhelmed the Italian health services. Management of inpatients was based on World Health Organization (WHO) and other public health bodies’ and specialist societies’ clinical, diagnostic and therapeutic protocols developed with very low-quality evidence base at that time. Over time, management guidelines and protocols were progressively modified and adapted based on the evolving first hand clinical management experience, and the evidence, which has slowly accumulated from clinical large cohort studies and clinical trials. As of August 9th, 2020, there have been 250.103 confirmed COVID-19 cases (with 35.203 deaths) reported from Italy. We present chronological evolution of the clinical and scientific evidence-based management guidelines to date, and their influence on the health care workers management of patients with COVID-19 disease.Funding Statement: This research was supported by funds to National Institute for Infectious Diseases ‘Lazzaro Spallanzani’ IRCCS from Line one-Ricerca Corrente ‘Infezioni Emergenti e Riemergenti’ and by Progetto COVID 2020 12371675 both funded by Italian Ministry of Health and from European Commission – Horizon 2020 (EXSCALATE4CoV).Sir Zumla and Prof Ippolito are co-PIs of the Pan-African Network on Emerging and Re-Emerging Infections (PANDORA-ID-NET – https://www.pandora-id.net/) funded by the European and Developing Countries Clinical Trials Partnership. Sir Zumla is in receipt of a National Institutes of Health Research senior investigator award.Declaration of Interests: EN received grants from Gilead science for educational purpose. Al other authors have no conflicts of interest to declareEthics Approval Statement: The authors stated that Ethical approval was not required.