Significance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population.

No abstract

Background Despite the vast majority of individuals succumbing to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are elderly, infection fatality rate (IFR) estimates for the age group 70 years older are still scarce. To this end we assessed SARS-CoV-2 seroprevalence among retired blood donors and combined it with national COVID-19 survey data to provide reliable population-based IFR estimates for this age group. Methods We identified 60,926 retired blood donors age 70 years or older in the rosters of three region-wide Danish blood banks and invited them to fill in a questionnaire on COVID-19 related symptoms and behaviours. Among 24,861 (40.8%) responders, we invited a random sample of 3,200 individuals for blood testing. Overall, 1,201 (37.5%) individuals were tested for SARS-CoV-2 antibodies (Wantai) and compared to 1,110 active blood donors age 17-69 years. Seroprevalence 95% confidence intervals (CI) were adjusted for assay sensitivity and specificity. Results Among retired (age 70 years or older) and active (age 17-69 years) blood donors, adjusted seroprevalences were 1.4% (95% CI: 0.3%-2.5%) and 2.5% (95% CI: 1.3%-3.8%), respectively. Using available population data on COVID-19 related fatalities, IFRs for patients age 70 years or older and for 17-69 years were estimated at 5.4% (95% CI: 2.7%–6.4%) and 0.083% (95% CI: 0.054%-0.18%), respectively. Only 52.4% of SARS-CoV-2 seropositive retired blood donors reported having been sick since the start of the pandemic. Conclusion COVID-19 IFR in the age group above 69 years is estimated to be 65 times as high as the IFR for people age 18-69 years.

MicroRNAs are small regulatory RNAs that are deregulated in a wide variety of human cancers, including different types of B-cell lymphoma. Nevertheless, the feasibility of circulating microRNA for early diagnosis of B-cell lymphoma has not been established. To address the possibility of detecting specific circulating microRNAs years before a B-cell lymphoma is diagnosed, we studied the plasma expression of microRNA first in pre-treatment samples from patients with diffuse large B-cell lymphoma and subsequently in repository samples from blood donors who later developed B-cell lymphomas. In addition, we studied the microRNA expression in the diagnostic lymphoma biopsy. The most strongly induced (miR-326) and suppressed (miR-375) plasma microRNA at diagnosis, when compared with healthy blood donors, were also substantially up-or down-regulated in plasma repository samples taken from several months to up to two years before the blood donors were diagnosed with B-cell lymphoma. Importantly, at these time points the donors had no signs of disease and felt healthy enough to donate blood. In conclusion, this first study of plasma microRNA profiles from apparently healthy individuals, taken several years before B-cell lymphoma diagnosis, suggests that plasma microRNA profiles may be predictive of lymphoma development. B cell lymphomas are the most common hematological cancer in adults with reported annual incidence rates of around 21/100,000 persons in DK 1. A wide variety of B-cell lymphoma subtypes are recognized by the WHO classification, the most common of which are diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL) 2. Despite significant improvements in outcome, DLBCL as such still carry considerable mortality with an overall three year survival of around 75% 3. Accordingly, there is a need for biomarkers that are readily applicable in the clinic to facilitate early detection and treatment of patients. Circulating microRNAs may be of potential interest in this regard. MicroRNAs are small RNA strands, consisting of 18 to 23 nucleotides, that regulate the activity of messenger RNA (mRNA) 4. They are detectable-and have been shown to be quite stable in plasma samples despite the presence of RNases 5,6. Therefore, microRNAs have attracted considerable attention in recent years, and multiple studies have repeatedly demonstrated that they are dysregulated in virtually all malignancies 7. In particular, aberrant serum levels of different microRNAs have been reported in patients with various types of lymphoma 8-13 .