Analysis of autopsy tissues obtained from patients who died from COVID-19 showed kidney tropism for SARS-COV-2, with COVID-19-related renal dysfunction representing an overlooked problem even in patients lacking previous history of chronic kidney disease. This study aimed to corroborate in a substantial sample of consecutive acutely ill COVID-19 hospitalized patients the efficacy of estimated GFR (eGFR), assessed at hospital admission, to identify acute renal function derangement and the predictive role of its association with in-hospital death and need for mechanical ventilation and admission to intensive care unit (ICU). We retrospectively analyzed charts of 764 patients firstly admitted to regular medical wards (Division of Internal Medicine) for symptomatic COVID-19 between March 6th and May 30th, 2020 and between October 1st, 2020 and March 15th, 2021. eGFR values were calculated with the 2021 CKD-EPI formula and assessed at hospital admission and discharge. Baseline creatinine and GFR values were assessed by chart review of patients’ medical records from hospital admittance data in the previous year. The primary outcome was in-hospital mortality, while ARDS development and need for non-invasive ventilation (NIV) and invasive mechanical ventilation (IMV) were the secondary outcomes. SARS-COV-2 infection was diagnosed in 764 patients admitted with COVID-19 symptoms. A total of 682 patients (age range 23–100 years) were considered for statistical analysis, 310 needed mechanical ventilation and 137 died. An eGFR value <60 mL/min/1.73 m² was found in 208 patients, 181 met KDIGO AKI criteria; eGFR values at hospital admission were significantly lower with respect to both hospital discharge and baseline values (p < 0.001). In multivariate analysis, an eGFR value <60 mL/min/1.73 m² was significantly associated with in-hospital mortality (OR 2.6, 1.7–4.8, p = 0.003); no association was found with both ARDS and need for mechanical ventilation. eGFR was non-inferior to both IL-6 serum levels and CALL Score in predicting in-hospital death (AUC 0.71, 0.68–0.74, p = 0.55). eGFR calculated at hospital admission correlated well with COVID-19-related kidney injury and eGFR values < 60 mL/min/1,73 m² were independently associated with in-hospital mortality, but not with both ARDS or need for mechanical ventilation.

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Despite Tocilizumab is now recognized as a concrete therapeutic option in patients with severe SARS-CoV-2 related respiratory failure, literature lacks about factors influencing the response to it in this context. Therefore, the aim of our study was to provide evidence about predictors of poor outcome in Tocilizumab treated patients in the real-world practice. We retrospectively analyzed clinical, laboratory and chest computer tomography (CCT) data of patients firstly admitted in non Intensive Care Units (ICU) and suffering from severe respiratory failure, who were treated with the IL-6 antagonist Tocilizumab. We compared patients who died and/or required admission to ICU with oro-tracheal intubation (OTI) with those who did not. Two hundreds and eighty-seven patients (29.9% females) with mean age ± SD 64.1 ± 12.6 years were the study population. In-hospital mortality was 18.8%, while the composite endpoint in-hospital mortality and/or ICU admission with OTI occurred in 23.7%. At univariate analysis, patients who died and/or were admitted to ICU with OTI were significantly older and co-morbid, had significantly higher values of creatinine, C-reactive protein (CRP) and procalcitonin and lower lymphocytes count, PaO2/FiO2 ratio (P/F) and room air pulsossimetry oxygen saturation (RAO₂S) at hospital admission. Computed tomography ground glass opacities (CT-GGO) involving the pulmonary surface ≥ 50% were found in 55.4% of patients who died and/or were admitted to ICU with OTI and in 21.5% of patients who did not (p=0.0001). At multivariate analysis, age ≥ 65 years (OR 17.3, 95% CI: 3.7-81.0), procalcitonin ≥ 0.14 (OR 9.9, 95%CI: 1.7-56.1), RAO₂S ≤ 90% (OR 4.6, 95%CI: 1.2-17.0) and CCT-GGO involvement ≥ 50% (OR 5.1, 95%CI: 1.2-21.0) were independent risk factors associated with death and/or ICU admission with OTI. Tocilizumab has shown to improve outcome in patients with severe respiratory failure associated to SARS-CoV-2 related pneumonia. In our multicentre study focusing on Tocilizumab treated severe COVID-19 patients, age ≥ 65 years, procalcitonin ≥ 0.14 ng/mL, RAO₂S ≤ 90% and CCT-GGO involvement ≥ 50% were independent factors associated with poor outcome.

Acute Respiratory Distress Syndrome (ARDS) caused by COVID-19 is substantially different from ARDS caused by other diseases and its treatment is dissimilar and challenging. As many studies showed conflicting results regarding the use of Non-invasive ventilation in COVID-19-associated ARDS, no unquestionable indications by operational guidelines were reported. The aim of this study was to estimate the use and success rate of Helmet (h) Continuous Positive Airway Pressure (CPAP) in COVID-19-associated ARDS in medical regular wards patients and describe the predictive risk factors for its use and failure. In our monocentric retrospective observational study, we included patients admitted for COVID-19 in medical regular wards. hCPAP was delivered when supplemental conventional or high-flow nasal oxygen failed to achieve respiratory targets. The primary outcomes were hCPAP use and failure rate (including the need to use Bilevel (BL) PAP or oro-tracheal intubation (OTI) and death during ventilation). The secondary outcome was the rate of in-hospital death and OTI. We computed a score derived from the factors independently associated with hCPAP failure. Out of 701 patients admitted with COVID-19 symptoms, 295 were diagnosed with ARDS caused by COVID-19 and treated with hCPAP. Factors associated with the need for hCPAP use were the PaO₂/FiO₂ ratio < 270, IL-6 serum levels over 46 pg/mL, AST > 33 U/L, and LDH > 570 U/L; age > 78 years and neuropsychiatric conditions were associated with lower use of hCPAP. Failure of hCPAP occurred in 125 patients and was associated with male sex, polypharmacotherapy (at least three medications), platelet count < 180 × 10⁹/L, and PaO₂/FiO₂ ratio < 240. The computed hCPAP-f Score, ranging from 0 to 11.5 points, had an AUC of 0.74 in predicting hCPAP failure (significantly superior to Call Score), and 0.73 for the secondary outcome (non-inferior to IL-6 serum levels). In conclusion, hCPAP was widely used in patients with COVID-19 symptoms admitted to medical regular wards and developing ARDS, with a low OTI rate. A score computed combining male sex, multi-pharmacotherapy, low platelet count, and low PaO₂/FiO₂ was able to predict hCPAP failure in hospitalized patients with ARDS caused by COVID-19.

Heme is a member of the porphyrins family of cyclic tetrapyrroles and influences various cell processes and signalling pathways. Enzyme deficiencies in the heme biosynthetic pathway provoke rare human inherited metabolic diseases called porphyrias. Protein levels and activity of enzymes involved in the heme biosynthetic pathway and especially 5′-Aminolevulinate Synthase 1 are featured by 24-h rhythmic oscillations driven by the biological clock. Heme biosynthesis and circadian pathways intermingle with mutual modulatory roles. Notably, heme is a ligand of important cogs of the molecular clockwork, which upon heme binding recruit co-repressors and inhibit the transcription of numerous genes enriching metabolic pathways and encoding functional proteins bringing on crucial cell processes. Herein, we assessed mRNA levels of circadian genes in patients suffering from porphyrias and found several modifications of core clock genes and clock-controlled genes expression, associated with metabolic and electrolytic changes. Overall, our results show an altered expression of circadian genes accompanying heme biosynthesis disorders and confirm the need to deepen the knowledge of the mechanisms through which the alteration of the circadian clock circuitry could take part in determining signs and symptoms of porphyria patients and then again could represent a target for innovative therapeutic strategies.