The role of immune suppression in COVID-19 hospitalization: clinical and epidemiological trends over three years of SARS-CoV-2 epidemic

Specific immune suppression types have been associated with a greater risk of severe COVID-19 disease and death. We analyzed data from patients >17 years that were hospitalized for COVID-19 at the “Fondazione IRCCS Ca′ Granda Ospedale Maggiore Policlinico” in Milan (Lombardy, Northern Italy). The study included 1727 SARS-CoV-2-positive patients (1,131 males, median age of 65 years) hospitalized between February 2020 and November 2022. Of these, 321 (18.6%, CI: 16.8–20.4%) had at least one condition defining immune suppression. Immune suppressed subjects were more likely to have other co-morbidities (80.4% vs. 69.8%, p < 0.001) and be vaccinated (37% vs. 12.7%, p < 0.001). We evaluated the contribution of immune suppression to hospitalization during the various stages of the epidemic and investigated whether immune suppression contributed to severe outcomes and death, also considering the vaccination status of the patients. The proportion of immune suppressed patients among all hospitalizations (initially stable at <20%) started to increase around December 2021, and remained high (30–50%). This change coincided with an increase in the proportions of older patients and patients with co-morbidities and with a decrease in the proportion of patients with severe outcomes. Vaccinated patients showed a lower proportion of severe outcomes; among non-vaccinated patients, severe outcomes were more common in immune suppressed individuals. Immune suppression was a significant predictor of severe outcomes, after adjusting for age, sex, co-morbidities, period of hospitalization, and vaccination status (OR: 1.64; 95% CI: 1.23–2.19), while vaccination was a protective factor (OR: 0.31; 95% IC: 0.20–0.47). However, after November 2021, differences in disease outcomes between vaccinated and non-vaccinated groups (for both immune suppressed and immune competent subjects) disappeared. Since December 2021, the spread of the less virulent Omicron variant and an overall higher level of induced and/or natural immunity likely contributed to the observed shift in hospitalized patient characteristics. Nonetheless, vaccination against SARS-CoV-2, likely in combination with naturally acquired immunity, effectively reduced severe outcomes in both immune competent (73.9% vs. 48.2%, p < 0.001) and immune suppressed (66.4% vs. 35.2%, p < 0.001) patients, confirming previous observations about the value of the vaccine in preventing serious disease

Hypoxic ischemic brain injury: animal models reveal new mechanisms of melatonin-mediated neuroprotection

: Oxidative stress (OS) and inflammation play a key role in the development of hypoxic-ischemic (H-I) induced brain damage. Following H-I, rapid neuronal death occurs during the acute phase of inflammation, and activation of the oxidant-antioxidant system contributes to the brain damage by activated microglia. So far, in an animal model of perinatal H-I, it was showed that neuroprostanes are present in all brain damaged areas, including the cerebral cortex, hippocampus and striatum. Based on the interplay between inflammation and OS, it was demonstrated in the same model that inflammation reduced brain sirtuin-1 expression and affected the expression of specific miRNAs. Moreover, through proteomic approach, an increased expression of genes and proteins in cerebral cortex synaptosomes has been revealed after induction of neonatal H-I. Administration of melatonin in the experimental treatment of brain damage and neurodegenerative diseases has produced promising therapeutic results. Melatonin protects against OS, contributes to reduce the generation of pro-inflammatory factors and promotes tissue regeneration and repair. Starting from the above cited aspects, this educational review aims to discuss the inflammatory and OS main pathways in H-I brain injury, focusing on the role of melatonin as neuroprotectant and providing current and emerging evidence

Synthetic scheme of compounds 23, 24, 33, 34, 35, 38.

<p>Reagents and conditions: i) from <b>1</b> for <b>23</b>, from <b>5</b> for <b>24</b>, from <b>32</b> for <b>33</b>: H₂SO₄, MeOH, reflux, 1 h; ii) from <b>32</b>: Py · SO₃, DMF dry, 120°C, 25 min; iii) CH₃I, anhydrous K₂CO₃, dry DMF, reflux, 1.5 h; iv) 1N NaOH, EtOH.</p

Synthetic scheme of compounds 36, 37.

<p>Reagents and conditions: i) Lindlar catalyst, H₂, pyridine, MeOH, r.t., 16 h; ii) 1N NaOH, EtOH/THF (1:1), r.t., 12 h.</p

Global anti-biofilm performance of ZA-related compounds and structures with the most significant anti-biofilm performance.

<p>Global anti-biofilm performance value of each ZA-related compound calculated as (sum of cell adhesion codes of all concentrations)-(sum of planktonic growth codes of all concentrations). Values equal to 0 were considered without anti-biofilm performance, below 0 were considered globally able to exert an anti-biofilm activity, and above 0 were considered able to improve biofilm performance. Yellow: no anti-biofilm performance; Light orange: little anti-biofilm performance; Medium orange: moderate anti-biofilm performace; Dark orange: optimal anti-biofilm performance; Light green: little improvement of anti-biofilm performance; Medium green: moderate improvement of anti-biofilm performance; Dark green: optimal improvement of anti-biofilm performance.</p

Structural formula of zosteric acid (ZA) and cinnamic acid (4).

<p>Structural formula of zosteric acid (ZA) and cinnamic acid (4).</p

Structures of cinnamic acid analogues used in the present study.

<p>Structures of cinnamic acid analogues used in the present study.</p

Fluorescence analysis of matrix functionalization.

<p>A) Emission spectrum (λ_exc 380 nm) of 5 mM <i>p</i>-ACA in 0.4 M NaHCO₃, 1 M NaCl (pH 8,3). B) Emission spectra (λ_exc 350 nm) of suspensions of <i>p</i>-ACA/matrix (50 μl, drained volume; solid line) and EA/matrix (50 μl, drained volume; dashed line) in 2 mL of 0.4 M NaHCO₃, 1 M NaCl (pH 8,3). A. U., arbitrary units.</p

Synthetic scheme of compounds 23, 24, 33, 34, 35, 38.

<p>Reagents and conditions: i) from <b>1</b> for <b>23</b>, from <b>5</b> for <b>24</b>, from <b>32</b> for <b>33</b>: H₂SO₄, MeOH, reflux, 1 h; ii) from <b>32</b>: Py · SO₃, DMF dry, 120°C, 25 min; iii) CH₃I, anhydrous K₂CO₃, dry DMF, reflux, 1.5 h; iv) 1N NaOH, EtOH.</p