Cytokine storm intervention in the early stages of COVID-19 pneumonia.

Clinical intervention in patients with corona virus disease 2019 (COVID-19) has demonstrated a strong upregulation of cytokine production in patients who are critically ill with SARS-CoV2-induced pneumonia. In a retrospective study of 41 patients with COVID-19, most patients with SARS-CoV-2 infection developed mild symptoms, whereas some patients later developed aggravated disease symptoms, and eventually passed away because of multiple organ dysfunction syndrome (MODS), as a consequence of a severe cytokine storm. Guidelines for the diagnosis and treatment of SARS-CoV-2 infected pneumonia were first published January 30th, 2020; these guidelines recommended for the first time that cytokine monitoring should be applied in severely ill patients to reduce pneumonia related mortality. The cytokine storm observed in COVID-19 illness is also an important component of mortality in other viral diseases, including SARS, MERS and influenza. In view of the severe morbidity and mortality of COVID-19 pneumonia, we review the current understanding of treatment of human coronavirus infections from the perspective of a dysregulated cytokine and immune response.

Genome-wide analysis of an avirulent strain that induces protective immunity against challenge with virulent Streptococcus suis serotype 2.

BACKGROUND: It was previously reported in China that two recent large-scale outbreaks of Streptococcus suis serotype 2 (S. suis 2) infections in human were caused by two highly virulent S. suis 2 strains, from which a novel genomic island (GEI), associated with disease onset and progression and designated 89 K, was identified. Here, an avirulent strain, 05HAS68, was isolated from a clinically healthy pig. RESULTS: By comparing the genomes of this avirulent strain with virulent strains, it was found that massive genomic rearrangements occurred, resulting in alterations in gene expression that caused enormous single gene gain and loss. Important virulent genes were lost, such as extracellular protein factor (ef) and suilysin (sly) and larger mutants, such as muramidase-released protein (mrp). Piglets vaccinated with the avirulent strain, 05HAS68, had increased TNF-α and IFN-γ levels in the peripheral blood and were fully protected from challenge infection with the most virulent S. suis 2 strain, 05ZYH33. Transfusion of T cells and plasma from vaccinated pigs resulted in protection of recipient animals against the 05ZYH33 challenge. CONCLUSION: These results suggest that analysis genome of the avirulent strains are instrumental in the development of vaccines and for the functional characterization of important of genetic determinants.

Study of the biological features of in vitro cultured γδ T cells.

The aim of the present study was to investigate the biological features of in vitro cultured γδ T cells. The γδ T cells were in vitro cultured and on different culture days cell proliferation, phenotype, killing activity and the secretion of cytokines were analyzed. Cell numbers were counted by an automated cell counter, phenotype of the cells and cytokines were analyzed by flow cytometry, and killing activities of the cells against gastric cancer SGC-7901 cells were tested using the cell counting kit-8. From days 7 to 14, in vitro cultured γδ T cells enter the exponential phase. On day 14, maximum proliferation fold was observed, and on day 10, the maximum specific growth rate µmax was achieved. Flow phenotype cluster of differentiation 3+-T-cell receptor γδ+ of the γδ T cells in the first 7-17 days achieved a higher proportion and showed no significant differences between 10 days. Secretion of the cytokines interferon-γ and tumor necrosis factor-α gradually increased in the first 7-14 days. The maximum was achieved on day 14, and subsequently began to decrease. The cytolytic activity of the γδ T cells to kill the SGC-7901 cells in the first 7-14 days had an improved killing effect, a slight decline from the first 17 days; in the effector cell to target cell (E:T) ratio 20:1, 10:1 and 5:1 conditions, γδ T cells kill SGC-7901 cells more effectively than 1:1 and 1:2. In conclusion, γδ T cells cultured in the first 7-14 days are suitable for clinical transfusion, and the optimal transfusion time is day 10. An E:T ratio >5:1 is preferred.