Anti-chemokine antibodies after SARS-CoV-2 infection correlate with favorable disease course (preprint)

Infection by SARS-CoV-2 leads to diverse symptoms, which can persist for months. While antiviral antibodies are protective, those targeting interferons and other immune factors are associated with adverse COVID-19 outcomes. Instead, we discovered that antibodies against specific chemokines are omnipresent after COVID-19, associated with favorable disease, and predictive of lack of long COVID symptoms at one year post infection. Anti-chemokine antibodies are present also in HIV-1 and autoimmune disorders, but they target different chemokines than those in COVID-19. Finally, monoclonal antibodies derived from COVID-19 convalescents that bind to the chemokine N-loop impair cell migration. Given the role of chemokines in orchestrating immune cell trafficking, naturally arising anti-chemokine antibodies associated with favorable COVID 19 may be beneficial by modulating the inflammatory response and thus bear therapeutic potential.

Low-PEEP Mechanical Ventilation and P/F Ratio Evolution in COVID-19 Patients (preprint)

Background Critically ill COVID-19 patients are burdened by high mortality. Evaluation to improve patients’ management was performed using strict patient criteria for Intensive Care Unit (ICU) admission, a low- positive end-expiratory pressure (PEEP) setting and standard thromboembolism treatment. Objectives of this study was to report the effects of this strategy on P/F-ratio evolution during mechanical ventilation (MV), ICU length of stay (LOS) and MV length.Methods A retrospective analysis was conducted on all consecutive patients with acute respiratory distress due to COVID-19 pneumonia admitted into ICU from March 2nd to January 15th, 2021. Patients were treated with a low-PEEP strategy (PEEP 10 cmH2O if BMI < 30 Kg m-2, PEEP 12 cmH2O if BMI 30-50 Kg m-2, PEEP 15 cmH2O if BMI > 50 Kg m-2) and therapeutic anticoagulation in case of thrombosis or D-dimer greater than 1’500 ng ml-1.Results 79 patients were on invasive MV. Average applied PEEP was 11 ± 2.9 cmH2O for BMI < 30 Kg m-2, 16 ± 3.18 cmH2O for BMI > 30 Kg m-2. After low-PEEP application, patients’ P/F ratio presented daily improvement from admission during next 72 hours (p<0.001; CI 99%) that resulted statistically significant for each single day after oro-tracheal intubation (OTI). Median ICU length of stay (LOS) was 15 days (10–28); median duration of MV was 12 days (8–26). The ICU mortality rate was 31.6%.Conclusions A combination of low-PEEP treatment resulted in P/F persistent daily ratio improvement during first 72 hours after OTI. A low-PEEP strategy could be beneficial in hemodynamic than respiratory terms.

Reduced mortality and shorten ICU stay in SARS-COV-2 pneumonia: a low PEEP strategy (preprint)

Background Intensive Care Unit (ICU) management of COVID-19 patients with severe hypoxemia is associated with high mortality. We implemented a "care map", as a standardized multidisciplinary approach to improve patients monitoring using: uniform patient selection for ICU admission, a low-PEEP strategy and a pharmacologic strategic thromboembolism management. Methods A standardized protocol for managing COVID-19 patients and ICU admissions was implemented through accurate Early Warning Score (EWS) monitoring and thromboembolism prophylaxis at hospital admission. Dyspnea, mental confusion or SpO2 less than 85% were criteria for ICU admission. Ventilation approach employed low PEEP values (about 10 cmH2O in presence of lung compliance > 40 mL/cmH2O) and FiO2 as needed. In presence of lower lung compliance (< 40 mL/cmH2O) PEEP value was increased to about 14 cmH2O. Results From March 16th to April 12nd 2020, 41 COVID-19 patients were admitted to our ICU from a total of 310 patients. 83% (34) of them needed mechanical ventilation. The ventilation approach chosen employed low PEEP value based on BMI (PEEP 11+/- 3.8 (10-12) cmH2O if BMI < 30 Kg/m2; PEEP 15+/- 3.26 (12-18) cmH2O if BMI >30 Kg/m2). To date, ten patients (24%) died, four (9.7%) received mechanical ventilation, two were transferred to another hospital and 25 (60.9%) were discharged from ICU after a median of nine days. Discussion A multimodal approach for COVID-19 patients is mandatory. The knowledge of this multi-organ disease is growing rapidly, requiring improvements in the standard of care. Our approach implements an accurate pre-ICU monitoring and strict selection for ICU admission, and allows to reduce mechanical ventilation, ICU stay and mortality. Funding No funding has been required.