Immune and inflammatory responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contribute to disease severity of coronavirus disease 2019 (COVID-19). However, the utility of specific immune-based biomarkers to predict clinical outcome remains elusive. Here, we analyzed levels of 66 soluble biomarkers in 175 Italian patients with COVID-19 ranging from mild/moderate to critical severity and assessed type I IFN–, type II IFN–, and NF-κB–dependent whole-blood transcriptional signatures. A broad inflammatory signature was observed, implicating activation of various immune and nonhematopoietic cell subsets. Discordance between IFN-α2a protein and IFNA2 transcript levels in blood suggests that type I IFNs during COVID-19 may be primarily produced by tissue-resident cells. Multivariable analysis of patients’ first samples revealed 12 biomarkers (CCL2, IL-15, soluble ST2 [sST2], NGAL, sTNFRSF1A, ferritin, IL-6, S100A9, MMP-9, IL-2, sVEGFR1, IL-10) that when increased were independently associated with mortality. Multivariate analyses of longitudinal biomarker trajectories identified 8 of the aforementioned biomarkers (IL-15, IL-2, NGAL, CCL2, MMP-9, sTNFRSF1A, sST2, IL-10) and 2 additional biomarkers (lactoferrin, CXCL9) that were substantially associated with mortality when increased, while IL-1α was associated with mortality when decreased. Among these, sST2, sTNFRSF1A, IL-10, and IL-15 were consistently higher throughout the hospitalization in patients who died versus those who recovered, suggesting that these biomarkers may provide an early warning of eventual disease outcome.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as coronavirus disease (COVID-19), is a major pandemic challenging health care systems around the world. The optimal management of patients infected with COVID-19 is still unclear, although the consensus is moving toward the need of a biphasic approach. During the first phase of the disease (from onset of the symptoms up to 7–10 days) viral-induced effects are prominent, with the opportunity to institute antiviral therapy. In the second inflammatory phase of the disease, immunosuppressive strategies (for example with glucocorticoids or anticytokine drugs) may be considered. This latter stage is characterized by the development of progressive lung involvement with increasing oxygen requirements and occasionally signs of the hemophagocytic syndrome. The management of the disease in patients with kidney disease is even more challenging, especially in those who are immunosuppressed or with severe comorbidities. Here we present the therapeutic approach used in Brescia (Italy) for managing patients infected with COVID-19 who underwent kidney transplantation and are receiving hemodialysis. Furthermore, we provide some clinical and physiopathological background, as well as preliminary outcome data of our cohort, to better clarify the pathogenesis of the disease and clinical management.

Immune system aging is becoming a field of increasing public health interest because of prolonged life expectancy, which is not paralleled by an increase in health expectancy. As age progresses, innate and adaptive immune systems undergo changes, which are defined, respectively, as inflammaging and immune senescence. A wealth of available data demonstrates that these two conditions are closely linked, leading to a greater vulnerability of elderly subjects to viral, bacterial, and opportunistic infections as well as lower post-vaccination protection. To face this novel scenario, an in-depth assessment of the immune players involved in this changing epidemiology is demanded regarding the individual and concerted involvement of immune cells and mediators within endogenous and exogenous factors and co-morbidities. This review provides an overall updated description of the changes affecting the aging immune system, which may be of help in understanding the underlying mechanisms associated with the main age-associated infectious diseases.

Objectives:To assess incidence, risk factors, histology, and outcome of severe hepatotoxicity (SH) during antiretroviral treatment (ART). Methods:Seven hundred fifty-five HIV-seropositive patients consecutively prescribed new ART were selected. Liver function tests were assessed at baseline, after 1 month, and every 4 months thereafter. Liver biopsy was recommended in case of SH (i.e., increase in liver enzymes ≥10 times the upper limit of normal or 5 times baseline if markedly abnormal). Results:Twenty-six cases of SH were observed with an incidence of 4.2% personyears. Liver failure (LF) was rarely seen (1.1 per 100 person-years). Liver damage was invariably observed in patients with chronic viral hepatitis. Liver histology showed exacerbation of viral hepatitis in all 16 patients for whom a liver biopsy was available at the time of SH. A direct correlation was found between alanine aminotransferase increase and increase in CD4+ T-cell count in patients with SH (r = 0.53, p < .001). Death occurred during follow-up in 7 of 26 (27%) patients, all of whom showed LF and baseline CD4+ count less than 200 cells/mm3 (7/7 patients = 100% vs. 8/19 patients without LF; p < .01). Relapse of SH was observed after ART was recommenced in 7 of 17 (41%) patients. Five of these 7 patients did not show further SH relapse after treatment with interferon. Conclusions:This study provides estimates of SH and LF in a large populationbased setting where hepatitis C virus coinfection is highly prevalent and provides indications that liver damage may be caused by immune reconstitution and related exacerbation of viral hepatitis. A strict follow-up for hepatotoxicity is mandatory when ART is initiated in patients with <200 CD4+ T cells/mm3. Antihepatitis pre- or comedication could be an effective preventive or curative measure. Manuscript received July 31, 2002; accepted December 17, 2002. Address correspondence and reprint requests to Massimo Puoti, Istituto di Malattie Infettive Spedali Civili. Piazza Spedali Civili. 1 25123 Brescia, Italy; e-mail: [email protected] © 2003 Lippincott Williams & Wilkins, Inc.