Circulating Mitochondrial DNA is an Early Indicator of Severe Illness and Mortality from COVID-19 (preprint)

Mitochondrial DNA (MT-DNA) are intrinsically inflammatory nucleic acids released by damaged solid organs. Whether the appearance of cell-free MT-DNA is linked to poor COVID-19 outcomes remains undetermined. Here, we quantified circulating MT-DNA in prospectively collected, cell-free plasma samples from 97 subjects with COVID-19 at the time of hospital presentation. Circulating MT-DNA were sharply elevated in patients who eventually died, required ICU admission or intubation. Multivariate regression analysis revealed that high circulating MT-DNA levels is an independent risk factor for all of these outcomes after adjusting for age, sex and comorbidities. Additionally, we found that circulating MT-DNA has a similar or superior area-under-the curve when compared to clinically established measures of systemic inflammation, as well as emerging markers currently of interest as investigational targets for COVID-19 therapy. These results show that high circulating MT-DNA levels is a potential indicator for poor COVID-19 outcomes.

AIDS and COVID-19 are two diseases separated by a common lymphocytopenia (preprint)

HIV and SARS-CoV-2 are responsible for two of the most dangerous and life-threatening infectious diseases of our times. To better analyze the difference in the immunological response elicited by the two infections, we compare the alterations in the lymphocyte subpopulations, measured by flow cytometry analysis (FCA) in both AIDS and COVID-19 patients, referred to our University Hospital. A total of 184 HIV infected patients were retrospectively examined and the results of FCA collected and compared to those obtained in 110 SARS-CoV-2 infected patients, examined during the actual outbreak. We observe a comparable reduction in B cells in both diseases and a more severe reduction in the total amount of T cells in COVID-19 as compared to AIDS patients. The analysis of the T cells subpopulations indicates that there is a comparable reduction in the CD4+ cells count. Conversely, a remarkable difference between them is observed in the CD8+ counts. In AIDS patients the CD8+ cells are slightly higher than normal, while in COVID-19 patients the CD8+ cell count is markedly reduced. As a result, the CD4+/CD8+ ratios, is very low in AIDS and higher than normal in COVID-19 patients. The NK cells are reduced in both diseases, but SARS-CoV-2 infection causes a more severe reduction compared to HIV infection. In conclusion, both HIV and SARS-CoV-2 viruses induce major changes in the lymphocytes count, with remarkable similarities and differences between them. The total absolute numbers of T cells and, in particular of the CD8+ subpopulation, are lower in COVID-19 patients compared to AIDS ones, while the CD4+ are reduced in both at similar levels. These results indicate that the host immune system reacts differently to the two infection, but they are responsible of a comparable dropping effect on the serum levels of CD4+ T cell population. The meaning of the similarities and of the differences in terms of T cells activation and serum depletion are discussed. The knowledge on how the immune system reacts to these two infections will be useful to better define their mechanism of action and to design specific preventive and therapeutic approaches.