interleukin-8 and Convalescence

The systemic processes involved in the manifestation of life-threatening COVID-19 and in disease recovery are still incompletely understood, despite investigations focusing on the dysregulation of immune responses after SARS-CoV-2 infection. To define hallmarks of severe COVID-19 in acute disease (n = 58) and in disease recovery in convalescent patients (n = 28) from Hannover Medical School, we used flow cytometry and proteomics data with unsupervised clustering analyses. In our observational study, we combined analyses of immune cells and cytokine/chemokine networks with endothelial activation and injury. ICU patients displayed an altered immune signature with prolonged lymphopenia but the expansion of granulocytes and plasmablasts along with activated and terminally differentiated T and NK cells and high levels of SARS-CoV-2-specific antibodies. The core signature of seven plasma proteins revealed a highly inflammatory microenvironment in addition to endothelial injury in severe COVID-19. Changes within this signature were associated with either disease progression or recovery. In summary, our data suggest that besides a strong inflammatory response, severe COVID-19 is driven by endothelial activation and barrier disruption, whereby recovery depends on the regeneration of the endothelial integrity.

Topics: Antibodies, Viral; Biomarkers; Blood Proteins; C-Reactive Protein; Chemokine CXCL10; Chemokine CXCL9; Cluster Analysis; Convalescence; COVID-19; Cytokine Release Syndrome; Disease Progression; Endothelium, Vascular; Granulocytes; Hematopoietic Cell Growth Factors; Hepatocyte Growth Factor; Humans; Intensive Care Units; Interleukin-12 Subunit p40; Interleukin-6; Interleukin-8; Killer Cells, Natural; Lectins, C-Type; Lymphopenia; Plasma Cells; SARS-CoV-2; Survival Analysis; T-Lymphocytes

This case series describes three patients affected by severe acute respiratory syndrome coronavirus 2, who developed polyradiculoneuritis as a probable neurological complication of coronavirus disease 2019 (COVID-19). A diagnosis of Guillain Barré syndrome was made on the basis of clinical symptoms, cerebrospinal fluid analysis, and electroneurography. In all of them, the therapeutic approach included the administration of intravenous immunoglobulin (0.4 gr/kg for 5 days), which resulted in the improvement of neurological symptoms. Clinical neurophysiology revealed the presence of conduction block, absence of F waves, and in two cases, a significant decrease in amplitude of compound motor action potential cMAP. Due to the potential role of inflammation on symptoms development and prognosis, interleukin-6 (IL-6) and IL-8 levels were measured in serum and cerebrospinal fluid during the acute phase, while only serum was tested after recovery. Both IL-6 and IL-8 were found increased during the acute phase, both in the serum and cerebrospinal fluid, whereas 4 months after admission (at complete recovery), only IL-8 remained elevated in the serum. These results confirm the inflammatory response that might be linked to peripheral nervous system complications and encourage the use of IL-6 and IL-8 as prognostic biomarkers in COVID-19.

Topics: Action Potentials; Acute Disease; Aged; Anti-Bacterial Agents; Biomarkers; Convalescence; COVID-19; COVID-19 Drug Treatment; Darunavir; Drug Combinations; Guillain-Barre Syndrome; Humans; Hydroxychloroquine; Immunoglobulins, Intravenous; Interleukin-6; Interleukin-8; Lopinavir; Male; Neural Conduction; Peripheral Nervous System; Prognosis; Respiratory Insufficiency; Ritonavir; SARS-CoV-2

Haematological and cytokine alterations in malaria are a broad and controversial subject in the literature. However, few studies have simultaneously evaluated various cytokines in a single patient group during the acute and convalescent phases of infection. The aim of this study was to sequentially characterise alterations in haematological patters and circulating plasma cytokine and chemokine levels in patients infected with Plasmodium vivax or Plasmodium falciparum from a Brazilian endemic area during the acute and convalescent phases of infection. During the acute phase, thrombocytopaenia, eosinopaenia, lymphopaenia and an increased number of band cells were observed in the majority of the patients. During the convalescent phase, the haematologic parameters returned to normal. During the acute phase, P. vivax and P. falciparum patients had significantly higher interleukin (IL)-6, IL-8, IL-17, interferon-γ, tumour necrosis factor (TNF)-α, macrophage inflammatory protein-1β and granulocyte-colony stimulating factor levels than controls and maintained high levels during the convalescent phase. IL-10 was detected at high concentrations during the acute phase, but returned to normal levels during the convalescent phase. Plasma IL-10 concentration was positively correlated with parasitaemia in P. vivax and P. falciparum-infected patients. The same was true for the TNF-α concentration in P. falciparum-infected patients. Finally, the haematological and cytokine profiles were similar between uncomplicated P. falciparum and P. vivax infections.

Topics: Acute Disease; Adult; Brazil; Case-Control Studies; Chemokine CCL4; Chemokines; Convalescence; Cytokines; Female; Granulocyte Colony-Stimulating Factor; Hematocrit; Humans; Inflammation; Interferon-gamma; Interleukin-10; Interleukin-12; Interleukin-17; Interleukin-1beta; Interleukin-4; Interleukin-6; Interleukin-8; Malaria, Falciparum; Malaria, Vivax; Male; Parasitemia; Plasmodium falciparum; Plasmodium vivax; Statistics, Nonparametric; Tumor Necrosis Factor-alpha

Japanese encephalitis (JE) virus infection induces infiltration of neutrophils in neural as well as extraneural tissues in patients. As interleukin-8 (IL-8) has inflammatory properties, the present study was undertaken to investigate the IL-8 concentrations in cerebrospinal fluid (CSF) and serum from patients with JE and correlate them with neutrophil counts. IL-8 was measured in the CSF or serum of 30 patients with confirmed JE. The majority (92%) of the acute CSF samples showed raised levels of IL-8 with raised numbers of polymorphonuclear leucocytes. Similarly, significantly higher serum IL-8 concentrations were detected in the acute phase of illness than in convalescent JE patients or normal healthy controls. Twenty-one of 25 patients with high concentrations of IL-8 showed significantly increased neutrophil counts in acute phase sera. A gradual decline in neutrophil counts was observed in the convalescent phase of patients who recovered. There was a significant correlation between IL-8 level and the severity of illness, as all severely ill and fatal cases showed higher levels of IL-8 in acute CSF or serum than the levels found in those who recovered. IL-8 concentrations remained high for a longer period in patients with prolonged severe illness than in those who made a complete recovery.

Topics: Acute Disease; Adolescent; Adult; Child; Child, Preschool; Convalescence; Encephalitis, Japanese; Humans; Interleukin-8; Leukocyte Count; Neutrophils