Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly reached pandemic proportions. Given that the main target of SARS-CoV-2 are lungs leading to severe pneumonia with hyperactivation of the inflammatory cascade, we conducted a prospective study to assess alveolar inflammatory status in patients with moderate to severe COVID-19. Methods Diagnostic bronchoalveolar lavage (BAL) was performed in 33 adult patients with SARS-CoV-2 infection by real-time PCR on nasopharyngeal swab admitted to the Intensive care unit (ICU) (n = 28) and to the Intermediate Medicine Ward (IMW) (n = 5). We analyze the differential cell count, ultrastructure of cells and Interleukin (IL)6, 8 and 10 levels. Results ICU patients showed a marked increase in neutrophils (1.24 × 105 ml− 1, 0.85–2.07), lower lymphocyte (0.97 × 105 ml− 1, 0.024–0.34) and macrophages fractions (0.43 × 105 ml− 1, 0.34–1.62) compared to IMW patients (0.095 × 105 ml− 1, 0.05–0.73; 0.47 × 105 ml− 1, 0.28–1.01 and 2.14 × 105 ml− 1, 1.17–3.01, respectively) (p < 0.01). Study of ICU patients BAL by electron transmission microscopy showed viral particles inside mononuclear cells confirmed by immunostaining with anti-viral capsid and spike antibodies. IL6 and IL8 were significantly higher in ICU patients than in IMW (IL6 p < 0.01, IL8 p < 0.0001), and also in patients who did not survive (IL6 p < 0.05, IL8 p = 0.05 vs. survivors). IL10 did not show a significant variation between groups. Dividing patients by treatment received, lower BAL concentrations of IL6 were found in patients treated with steroids as compared to those treated with tocilizumab (p < 0.1) or antivirals (p < 0.05). Conclusions Alveolitis, associated with COVID-19, is mainly sustained by innate effectors which showed features of extensive activation. The burden of pro-inflammatory cytokines IL6 and IL8 in the broncho-alveolar environment is associated with clinical outcome.

The term Long COVID (or Post COVID) describes a condition characterized by persistence of symptoms for at least 12 weeks after the onset of COVID-19. It may last several months but the duration is still matter of observation. The symptoms and the clinical manifestations are clinically heterogeneous and suggesting involvement of multi-organs/systems, including the cardiovascular system. The general recurrent symptoms include fatigue, breathlessness, myalgia, headache, loss of memory, and impaired concentration. Patients report loss of their previous psychophysical performance. Cardiovascular involvement manifests with common symptoms such as palpitations and chest pain, and, less commonly, with events such as late arterial and venous thromboembolisms, heart failure episodes, strokes or transient ischaemic attack, ‘myo-pericarditis’. The diagnostic criteria are mainly based on the narrative of the patients. Measurable biomarkers or instrumental findings or clinical events are not yet framed in a shared diagnostic framework. The open question for clinicians and researchers is whether biomarkers, electrocardiogram, non-invasive imaging, and clinical monitoring should be included in a shared diagnostic protocol aimed at defining the diagnostic path and protecting patients at risk of unexpected events.

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Background:Excessive production of mitochondrial reactive oxygen species (ROS) is a central mechanism for the development of diabetes complications. Recently, hypoxia has been identified to play an additional pathogenic role in diabetes. In this study, we hypothesized that ROS overproduction was secondary to the impaired responses to hypoxia due to the inhibition of hypoxia-inducible factor-1 (HIF-1) by hyperglycemia.Methods:The ROS levels were analyzed in the blood of healthy subjects and individuals with type 1 diabetes after exposure to hypoxia. The relation between HIF-1, glucose levels, ROS production and its functional consequences were analyzed in renal mIMCD-3 cells and in kidneys of mouse models of diabetes.Results:Exposure to hypoxia increased circulating ROS in subjects with diabetes, but not in subjects without diabetes. High glucose concentrations repressed HIF-1 both in hypoxic cells and in kidneys of animals with diabetes, through a HIF prolyl-hydroxylase (PHD)-dependent mechanism. The impaired HIF-1 signaling contributed to excess production of mitochondrial ROS through increased mitochondrial respiration that was mediated by Pyruvate dehydrogenase kinase 1 (PDK1). The restoration of HIF-1 function attenuated ROS overproduction despite persistent hyperglycemia, and conferred protection against apoptosis and renal injury in diabetes.Conclusions:We conclude that the repression of HIF-1 plays a central role in mitochondrial ROS overproduction in diabetes and is a potential therapeutic target for diabetic complications. These findings are timely since the first PHD inhibitor that can activate HIF-1 has been newly approved for clinical use.Funding:This work was supported by grants from the Swedish Research Council, Stockholm County Research Council, Stockholm Regional Research Foundation, Bert von Kantzows Foundation, Swedish Society of Medicine, Kung Gustaf V:s och Drottning Victorias Frimurarestifelse, Karolinska Institute’s Research Foundations, Strategic Research Programme in Diabetes, and Erling-Persson Family Foundation for S-B.C.; grants from the Swedish Research Council and Swedish Heart and Lung Foundation for T.A.S.; and ERC consolidator grant for M.M.