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Coronavirus disease 2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been recently recognized as a systemic disorder inducing a prothrombotic state. The molecular mechanisms underlying the hypercoagulable state seen in patients with COVID-19 is still incompletely understood, although it presumably involves the close link between inflammatory and hemostatic systems. The laboratory coagulation monitoring of severely ill COVID-19 patients is mandatory to identify those patients at increased thrombotic risk and to modulate thromboprophylaxis accordingly. In this review, we summarize the current understanding on the pathogenesis, epidemiology, clinical and laboratory features and management of coagulopathy associated with COVID-19.

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An imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) may contribute to liver fibrosis in patients with hepatitis C (HCV) infection. We measured the circulating levels of different MMPs and TIMPs in HCV monoinfected and HIV/HCV coinfected patients and evaluated the potential for anti-HCV therapy to modulate MMP and TIMP levels in HCV subjects. We analyzed 83 plasma samples from 16 HCV monoinfected patients undergoing dual or triple anti-HCV therapy, 15 HIV/HCV coinfected patients with undetectable HIV load, and 10 healthy donors (HD). Levels of MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-10, TIMP-1, and TIMP-2 were measured by a SearchLight Multiplex Immunoassay Kit. MMP-2 and MMP-9 were the highest expressed MMPs among all the analyzed samples and their levels significantly increased in HCV monoinfected and HIV/HCV coinfected subjects compared to HD. TIMP-1 levels were significantly higher in HCV and HIV/HCV subjects compared to HD and were correlated with liver stiffness. These findings raise the possibility of using circulating TIMP-1 as a non-invasive marker of liver fibrosis in HCV infection. A longitudinal study demonstrated that MMP-9 levels significantly decreased (40% reduction from baseline) in patients receiving dual as well as triple direct-acting antivirals (DAA) anti-HCV therapy, which had no effect on MMP-2, TIMP-1, and TIMP-2. As the dysregulation of MMP-2 and MMP-9 may reflect inflammatory processes in the liver, the decrease of MMP-9 following HCV protease inhibitor treatment suggests a positive effect on the reduction of liver inflammation.

Background. Ivermectin has received particular attention as a potential treatment for COVID-19. However, the evidence to support its clinical efficacy is controversial. Objectives. We undertook a new systematic review of ivermectin for the treatment and prophylaxis of COVID-19, including new primary studies, outcomes other than mortality, and grading the quality of the available evidence following the Cochrane guidance for methodology. Methods. We searched electronic databases, repository databases, and clinical trial registries (up to June 2021). The measure of treatment effect was risk difference (RD) with 95% confidence intervals (CIs). The GRADE system was used to assess the certainty of the evidence. Results. The review includes 11 RCTs (2436 participants). The certainty of the available evidence was quite low or very low due to risk of bias, inconsistency, and imprecision. When the analysis was limited to patients with baseline mild or moderate disease (8 reports, 1283 patients), there were no differences in mortality between ivermectin and control groups (low level of certainty); in patients with baseline severe diseases (3 reports, 304 patients), the use of ivermectin significantly decreased mortality compared to the controls (RD −0.17; 95% CIs, −0.24/−0.10; p = 0.00001; low level of certainty). In terms of disease progression (to severe pneumonia, admission to intensive care unit, and/or mechanical ventilation), the results were much the same. At day 14, the rate of patients with a negative RT-PCR test was 21% higher (from 5 to 36% higher) for ivermectin recipients than it was for the controls (low quality of evidence). Three studies (736 subjects) indicated that prophylaxis with ivermectin increased the likelihood of preventing COVID-19 compared to controls (low quality of evidence). Serious adverse events were rarely reported. Conclusions. There is limited evidence for the benefit of ivermectin for COVID-19 treatment and prophylaxis, and most of this evidence is of low quality. Further evidence is needed to fine-tune potential indications and optimal treatment protocols for ivermectin as a treatment for COVID-19.

There is little information available on the possible toxic effects that antiretroviral (ARV) drugs used for the treatment of human immunodeficiency virus (HIV)-infected subjects, may have on the central nervous system (CNS) resident cells. Moreover, it remains unclear whether the efficacy of the ARV drugs may also be due to their ability to exert extravirological effects on factors responsible for the development of HIV brain injury, e.g., matrix metalloproteinases (MMPs). This study investigates the toxicity of three different ARV drugs and on their ability to modulate levels and expression of gelatinases A (MMP-2) and B (MMP-9) in astrocytes. Primary cultures of rat astrocytes were activated by exposure to lipopolysaccaride (LPS) and simultaneously treated with darunavir, maraviroc, or raltegravir, used alone or in combination. Among the tested drugs, maraviroc was the less toxic for astrocytes. At toxic concentration (TC ), the studied drugs induced the production of reactive oxygen species (ROS), suggesting that the oxidative stress may represent a mechanism of ARV toxicity. As assessed by gelatin zymography and RT-PCR, the single antiretroviral drugs reduced levels and expression of both MMP-2 and MMP-9 through the inhibition of the signaling transduction pathway of extracellular signal-regulated kinase1/2, which is involved in the regulation of MMP-9 gene. A synergistic inhibition of MMP-2 and MMP-9 was observed with combinations of the studied ARV drugs. The present results indicate that maraviroc, darunavir, and raltegravir, through their ability to inhibit MMP-2 and MMP-9 at doses non-toxic for astrocytes, might have a great potential for the management of HIV-associated neurological complications.

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In this systematic review, we evaluate the efficacy and safety of blood components treated with pathogen reduction technologies (PRTs). We searched the Medline, Embase, Scopus, Ovid, and Cochrane Library to identify RCTs evaluating PRTs. Risk of bias assessment and the Mantel–Haenszel method for data synthesis were used. We included in this review 19 RCTs evaluating 4332 patients (mostly oncohematological patients) receiving blood components treated with three different PRTs. Compared with standard platelets (St-PLTs), the treatment with pathogen-reduced platelets (PR-PLTs) does not increase the occurrence of bleeding events, although a slight increase in the occurrence of severe bleeding events was observed in the overall comparison. No between-groups difference in the occurrence of serious adverse events was observed. PR-PLT recipients had a lower 1 and 24 h CI and CCI. The number of patients with platelet refractoriness and alloimmunization was significantly higher in PR-PLT recipients compared with St-PLT recipients. PR-PLT recipients had a higher number of platelet and RBC transfusions compared with St-PLT recipients, with a shorter transfusion time interval. The quality of evidence for these outcomes was from moderate to high. Blood components treated with PRTs are not implicated in serious adverse events, and PR-PLTs do not have a major effect on the increase in bleeding events. However, treatment with PRTs may require a greater number of transfusions in shorter time intervals and may be implicated in an increase in platelet refractoriness and alloimmunization.