Altered bioenergetics and mitochondrial dysfunction of monocytes in patients with COVID-19 pneumonia
EMBO MOLECULAR MEDICINE
Authors: Gibellini, Lara; De Biasi, Sara; Paolini, Annamaria; Borella, Rebecca; Boraldi, Federica; Mattioli, Marco; Lo Tartaro, Domenico; Fidanza, Lucia; Caro-Maldonado, Alfredo; Meschiari, Marianna; Iadisernia, Vittorio; Bacca, Erica; Riva, Giovanni; Cicchetti, Luca; Quaglino, Daniela; Guaraldi, Giovanni; Busani, Stefano; Girardis, Massimo; Mussini, Cristina; Cossarizza, Andrea
In patients infected by SARS-CoV-2 who experience an exaggerated inflammation leading to pneumonia, monocytes likely play a major role but have received poor attention. Thus, we analyzed peripheral blood monocytes from patients with COVID-19 pneumonia and found that these cells show signs of altered bioenergetics and mitochondrial dysfunction, had a reduced basal and maximal respiration, reduced spare respiratory capacity, and decreased proton leak. Basal extracellular acidification rate was also diminished, suggesting reduced capability to perform aerobic glycolysis. Although COVID-19 monocytes had a reduced ability to perform oxidative burst, they were still capable of producing TNF and IFN-gamma in vitro. A significantly high amount of monocytes had depolarized mitochondria and abnormal mitochondrial ultrastructure. A redistribution of monocyte subsets, with a significant expansion of intermediate/pro-inflammatory cells, and high amounts of immature monocytes were found, along with a concomitant compression of classical monocytes, and an increased expression of inhibitory checkpoints like PD-1/PD-L1. High plasma levels of several inflammatory cytokines and chemokines, including GM-CSF, IL-18, CCL2, CXCL10, and osteopontin, finally confirm the importance of monocytes in COVID-19 immunopathogenesis.
Guillain-Barre syndrome associated with SARS-CoV-2 infection: A systematic review and individual participant data meta-analysis
JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM
Authors: Hasan, Imran; Saif-Ur-Rahman, K. M.; Hayat, Shoma; Papri, Nowshin; Jahan, Israt; Azam, Rufydha; Ara, Gulshan; Islam, Zhahirul
Several published reports have described a possible association between Guillain-Barre syndrome (GBS) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. This systematic review aimed to summarize and meta-analyze the salient features and prognosis of SARS-CoV-2-associated GBS. We searched the PubMed (Medline), Web of Science and Cochrane databases for articles published between 01 January 2020 and 05 August 2020 using SARS-CoV-2 and GBS-related keywords. Data on sociodemographic characteristics, antecedent symptoms, clinical, serological and electrophysiological features, and hospital outcomes were recorded. We included 45 articles from 16 countries reporting 61 patients with SARS-CoV-2-associated GBS. Most (97.7%) articles were from high- and upper-middle-income countries. Forty-two (68.9%) of the patients were male; median (interquartile range) age was 57 (49-70) years. Reverse transcriptase polymerase chain reaction for SARS-CoV-2 was positive in 90.2% of patients. One report of SARS-CoV-2-associated familial GBS was found which affected a father and daughter of a family. Albuminocytological dissociation in cerebrospinal fluid was found in 80.8% of patients. The majority of patients (75.5%) had a demyelinating subtype of GBS. Intravenous immunoglobulin and plasmapheresis were given to 92.7% and 7.3% of patients, respectively. Around two-thirds (65.3%) of patients had a good outcome (GBS-disability score <= 2) on discharge from hospital. Two patients died in hospital. SARS-CoV-2-associated GBS mostly resembles the classical presentations of GBS that respond to standard treatments. Extensive surveillance is required in low- and lower-middle-income countries to identify and report similar cases/series. Further large-scale case-control studies are warranted to strengthen the current evidence. PROSPERO Registration Number CRD42020201673.