The Chemokine MIG is Associated with an Increased Risk of COVID-19 Mortality in Mexican Patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emergent viral disease in which the host inflammatory response modulates the clinical outcome. Severe outcomes are associated with an exacerbation of inflammation in which chemokines play an important role as the attractants of immune cells to the tissues. OBJECTIVE: To evaluate the relationship of the chemokines IL-8, RANTES, MIG, MCP-1, and IP-10 with COVID-19 severity and outcomes in Mexican patients. METHODS: We analyzed the serum levels of IL-8, RANTES, MIG, MCP-1 and IP-10 in 148 COVID-19 hospitalized patients classified as mild (n=20), severe (n=61), and critical (n=67), as well as in healthy individuals (n=10), by flow cytometry bead array assay. RESULTS: Chemokine levels were higher in patients than in the healthy individuals, but only MIG, MCP-1, and IP-10 increased according to the disease severity, showing the highest levels in the critical group. MIG, MCP-1, and IP-10 levels were also higher in COVID-19 patients with comorbidities such as renal disease, type 2 diabetes, and hypertension. Moreover, elevated MIG levels seem to be related to organic failure/shock, and an increased risk of death. CONCLUSIONS: Our results suggest that the increased levels of MCP-1, IP-10, and especially MIG might be useful in predicting severe COVID-19 outcomes and could be promising therapeutic targets.

Self-correction of chromosomally abnormal embryos in culture and implications for stem cell production.

OBJECTIVE: To ascertain whether embryos classified by preimplantation genetic diagnosis (PGD) for infertility as abnormal and then plated to obtain stem cells would self-correct partially or totally in culture, producing disomic stem cells. DESIGN: Prospective study to determine the chromosome status of embryos on day 3 and 6, as well as cultured cells derived from inner cell masses from the same embryos when cultured up to day 12. SETTING: Research laboratory. PATIENT(S): Patients undergoing PGD of aneuploidy. INTERVENTION(S): Of 142 embryos classified by PGD for aneuploidy as abnormal, 50 were cultured to the blastocyst stage. At that stage a fraction of the embryos underwent trophectoderm biopsy to reconfirm the PGD diagnosis. After further co-culture with feeders up to day 12, 34 embryos attached to the feeder cells. Of those, 24 were analyzed by fluorescence in situ hybridization (FISH) and the rest for the expression of Oct-4, SSEA-3, SSEA-4, TRA1-60, and TRA1-80. MAIN OUTCOME MEASURE(S): Disomic cells obtained from trisomic embryos. RESULT(S): Analysis by FISH of day-12 cultures showed that 7 were totally normal, 6 were mostly abnormal, and 11 had experienced some chromosome normalization, having between 21% and 88% normal cells. Day-12 culture was positive for Oct-4 expression by reverse transcriptase polymerase chain reaction analysis and for SSEA-3, SSEA-4, TRA1-60, and TRA1-80 by immunocytochemistry. CONCLUSION(S): Chromosome self-normalization occurs in a significant proportion of chromosomally abnormal embryos, possibly because of the loss of a chromosome in trisomic cells after blastocyst stage. Thus chromosomally abnormal embryos are a potential source of disomic stem cells. Not all chromosomally abnormal embryos self-corrected. Abnormal stem cells that might be derived could be used as models to study the effect of chromosomal abnormalities on human development.