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Pneumonia with severe respiratory failure represents the principal cause of death in COVID-19, where hyper-inflammation plays an important role in lung damage. An effective treatment aiming at reducing the inflammation without preventing virus clearance is thus urgently needed. Tocilizumab, an anti-soluble IL-6 receptor monoclonal antibody, has been proposed for treatment of patients with COVID-19.
A retrospective cohort study at the Montichiari Hospital, Brescia, Italy, was conducted. We included consecutive patients with COVID-19 related pneumonia at the early stage of respiratory failure, all treated with a standard protocol (hydroxychloroquine 400 mg daily, lopinavir 800 mg plus ritonavir 200 mg per day). We compared survival rate and clinical status in a cohort of patients who received additional treatment with tocilizumab once (either 400 mg intravenous or 324 mg subcutaneous) with a retrospective cohort of patients who did not receive tocilizumab (referred to as the standard treatment group). All outcomes were assessed at the end of the follow-up, that correspond to death or complete recovery and discharge from the hospital.
158 patients were included, 90 of which received tocilizumab. 34 out of 68 (50%) patients in the standard treatment group and 7 out of 90 (7.7%) in the tocilizumab group died. Tocilizumab significantly improved survival compared to standard care (multivariate HR 0.057; 95% C.I=0.017- 0.187, p < 0.001). No differences between the two administration routes of tocilizumab were observed. No tocilizumab-related infections and/or side effects were observed.
Early treatment with tocilizumab could be helpful to prevent excessive hyper-inflammation and death in COVID-19 related pneumonia. Low dose administration of tocilizumab is not associated with adverse events.
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Italy's severe COVID-19 outbreak was addressed by a lockdown that gradually increased in space, time and intensity. The effectiveness of the lockdown has not been precisely assessed with respect to the intensity of mobility restriction and the time until the outbreak receded.
We used processed mobile phone tracking data to measure mobility restriction, and related those data to the number of new SARS-CoV-2 positive cases detected on a daily base in the three most affected Italian regions, Lombardy, Veneto and Emilia-Romagna, from February 1 through April 6, 2020, when two subsequent lockdowns with increasing intensity were implemented by the Italian government.
During the study period, mobility restriction was inversely related to the daily number of newly diagnosed SARS-CoV-2 positive cases only after the second, more effective lockdown, with a peak in the curve of diagnosed cases of infection occurring 14 to 18 days from lockdown in the three regions and 9 to 25 days in the included provinces. An effective reduction in transmission must have occurred nearly immediately after the tighter lockdown, given the lag time of around 10 days from asymptomatic infection to diagnosis. The period from lockdown to peak was shorter in the areas with the highest prevalence of the infection. This effect was seen within slightly more than one week in the most severely affected areas.
It appears that the less rigid lockdown led to an insufficient decrease in mobility to reverse an outbreak such as COVID-19. With a tighter lockdown, mobility decreased enough to bring down transmission promptly below the level needed to sustain the epidemic.
No funding sources have been used for this work.
No funding sources have been used for this work.
COVID-19 mortality disproportionately affects the Black population in the United States (US). To explore this association a cohort study was undertaken.
We assembled a cohort of 505,992 patients receiving ambulatory care at Bronx Montefiore Health System (BMHS) between 1/1/18 and 1/1/20 to evaluate the relative risk of hospitalization and death in two time-periods, the pre-COVID time-period (1/1/20-2/15/20) and COVID time-period (3/1/20-4/15/20). COVID testing, hospitalization and mortality were determined with the Black and Hispanic patient population compared separately to the White population using logistic modeling. Evaluation of the interaction of pre-COVID and COVID time periods and race, with respect to mortality was completed.
A total of 9,286/505,992 (1.8%) patients were hospitalized during either or both pre-COVID or COVID periods. Compared to Whites the relative risk of hospitalization of Black patients did not increase in the COVID period (p for interaction=0.12). In the pre- COVID period, compared to Whites, the odds of death for Blacks and Hispanics adjusted for comorbidity was statistically equivalent. In the COVID period compared to Whites the adjusted odds of death for Blacks was 1.6 (95% CI 1.2-2.0,
=0.001). There was a significant increase in Black mortality risk from pre-COVID to COVID periods (p for interaction=0.02). Adjustment for relevant clinical and social indices attenuated but did not fully explain the observed difference in Black mortality.
The BMHS COVID experience demonstrates that Blacks do have a higher mortality with COVID incompletely explained by age, multiple reported comorbidities and available metrics of sociodemographic disparity.
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Identification of effective treatments in severe cases of COVID-19 requiring mechanical ventilation represents an unmet medical need. Our aim was to determine whether the administration of adipose-tissue derived mesenchymal stromal cells (AT-MSC) is safe and potentially useful in these patients.
Thirteen COVID-19 adult patients under invasive mechanical ventilation who had received previous antiviral and/or anti-inflammatory treatments (including steroids, lopinavir/ritonavir, hydroxychloroquine and/or tocilizumab, among others) were treated with allogeneic AT-MSC. Ten patients received two doses, with the second dose administered a median of 3 days (interquartile range-IQR- 1 day) after the first one. Two patients received a single dose and another patient received 3 doses. learn more Median number of cells per dose was 0.98×10
(IQR 0.50×10
) AT-MSC/kg of recipient's body weight. Potential adverse effects related to cell infusion and clinical outcome were assessed. Additional parameters analyzed included changes in imaging, analytical and inflammatory parameters.
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