Loss of Y in leukocytes as a risk factor for critical COVID-19 in men

COVID-19 shows an unexplained, strong male bias for severity and mortality. Loss of Y (LOY) in myeloid cells is a risk factor candidate in COVID-19 because of associations with many age-related diseases and its effect on transcription of immune genes. We report the highest levels of LOY in cells that are crucial for the development of severe COVID-19 phenotype, such as low-density neutrophils, granulocytes, and monocytes reaching 46%, 32%, and 29%, respectively, from men with critical COVID-19 (n=139). LOY in sorted subpopulations of leukocytes correlated with increased thrombocyte count, thromboembolic events, invasive mechanical ventilation and a history of vessel disease. In recovered patients, LOY decreased in whole blood and peripheral blood mononuclear cells. Moreover, sc-RNA-seq analysis of CD14+ monocytes from 30 COVID-19 males and 34 controls revealed pervasive transcriptional downregulation in LOY-cells, notably affecting HLA class I and II genes important for antigen presentation. The data support a link between LOY and emergency myelopoiesis as well as the role of LOY in modulation of COVID-19 severity. Our results might also be relevant for other viral infections showing similar male bias.

Serum neopterin levels in relation to mild and severe COVID-19

BackgroundThe COVID-19 pandemic, caused by the coronavirus SARS-CoV-2, is rapidly spreading worldwide. There is limited information about prognostic markers that could help clinicians to identify COVID-19 patients with a poor prognosis. Serum levels of the immune activation marker neopterin has shown to be of prognostic value in patients with SARS. The aim of this study was to investigate whether serum neopterin is associated with the severity of COVID-19. MethodsWe included 34 patients with confirmed COVID-19 between March 3 and March 30, 2020. Fifteen patients had mild disease and did not require hospitalization, whereas 19 patients developed severe COVID-19 requiring intensive care. Concentrations of serum neopterin, tryptophan, and kynurenine were measured at and repeatedly after inclusion. ResultsWe found a more than two-fold higher mean concentration of neopterin in severely ill patients (mean value 42.0 nmol/L (SD 18.2)) compared to patients with mild symptoms (16.9 nmol/L (SD 11.0)). All of the severe cases had elevated neopterin concentrations (>9.1 nmol/L) at the initial sampling with values ranging from 17.2 to 86.7 nmol/L. In comparison, 10 of 15 patients with mild disease had neopterin levels above 9.1 nmol/L, with concentrations in the range from 4.9 to 31.6 nmol/L. Neopterin levels gradually decreased during the course of COVID-19, but severe cases maintained elevated levels for a longer period. Moreover, lower levels of tryptophan and higher levels of kynurenine, indicating an increased tryptophan catabolism, were seen in the group with severe cases. ConclusionsIn conclusion, we found that serum neopterin levels are associated with the severity of COVID-19. Our findings suggest that neopterin could be used as a prognostic marker, but further studies are needed to elucidate how it can be used in clinical praxis.

Serum-IgG responses to SARS-CoV-2 after mild and severe COVID-19 infection and analysis of IgG non-responders

BackgroundTo accurately interpret COVID-19 seroprevalence surveys, knowledge of serum-IgG responses to SARS-CoV-2 with a better understanding of patients who do not seroconvert, is imperative. This study aimed to describe serum-IgG responses to SARS-CoV-2 in a cohort of patients with both severe and mild COVID-19, including extended studies of patients who remained seronegative more than 90 days post symptom onset. ResultsForty-seven patients (mean age 49 years, 38% female) were included. All (15/15) patients with severe symptoms and 29/32 (90.6%) patients with mild symptoms of COVID-19 developed SARS-CoV-2-specific IgG antibodies in serum. Time to seroconversion was significantly shorter (median 11 vs. 22 days, P=0.04) in patients with severe compared to mild symptoms. Of the three patients without detectable IgG-responses after >90 days, all had detectable virus-neutralizing antibodies and in two, spike-protein receptor binding domain-specific IgG was detected with an in-house assay. Antibody titers were preserved during follow-up and all patients who seroconverted, irrespective of the severity of symptoms, still had detectable IgG levels >75 days post symptom onset. ConclusionsPatients with severe COVID-19 both seroconvert earlier and develop higher concentrations of SARS-CoV-2-specific IgG than patients with mild symptoms. Of those patients who not develop detectable IgG antibodies, all have detectable virus-neutralizing antibodies, suggesting immunity. Our results showing that not all COVID-19 patients develop detectable IgG using two validated commercial clinical methods, even over time, are vital for the interpretation of COVID-19 seroprevalence surveys and for estimating the true infection prevalence in populations.