The Antiviral Effect of Nirmatrelvir/Ritonavir during COVID-19 Pandemic Real-World Data.

INTRODUCTION: Vaccination against SARS-CoV-2 and the prevalence of Omicron variants have reduced the risk of the severe clinical progress of COVID-19. However, the risk of breakthrough infections has increased, and early administration of an effective antiviral treatment is significant in order to prevent the severe progression of COVID-19 in vulnerable patients with comorbidities. PATIENTS AND METHODS: Adults with confirmed SARS-CoV-2 infection were included in a matched-pair retrospective study based on age, gender, comorbidities and vaccination status. They were divided into two groups: group A (n = 200) consisted of outpatients at increased risk of severe clinical progress who were treated with nirmatrelvir/ritonavir and group B (n = 200) consisted of non-hospitalized patients who did not receive antiviral treatment. Demographic data, clinical outcome (death, intubation), days of hospitalization, time for recovery, adverse events and treatment compliance were reported. RESULTS: The median age (75.24 ± 13.12 years in the study group and 76.91 ± 14.02 years in the comparison group) and the proportion of males (59% vs. 60.5%, respectively) were similar between the two groups. A total of 6.5% of patients in group A and 10.5% in group B were unvaccinated against SARS-CoV-2. Three patients from group A (1.5%) and one hundred eleven (55.5%) from group B required hospitalization. The duration of hospitalization (3 days vs. 10 days in group B, p < 0.001) and the total time needed for recovery (5 days vs. 9 days, p < 0.001) was shorter in the study group. A rebound of SARS-CoV-2 infection within 8-12 days after diagnosis was documented in 6.5% of patients in group A and 8% of patients in group B. CONCLUSION: Oral treatment with nirmatrelvir/ritonavir in high-risk non-hospitalized patients was safe and effective in preventing the severe clinical progress of COVID-19 pneumonia. Early administration of antiviral agents in vulnerable outpatients combined with a full vaccination scheme is significant in order to avoid hospitalization and severe clinical outcomes.

Impact of SARS-CoV-2 on pregnancy outcomes (Review)

The impact of the pandemic outbreak associated with coronavirus 2019 disease (COVID-19) on pregnant women is of interest to obstetricians and gynecologists due to the vulnerability of this target group. In pregnant women and their infants, an exceptional clinical management is warranted. Current epidemiological findings provide information regarding the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on pregnant patients and potential adverse perinatal outcomes. Overall, these findings are a strong indication that an increased antenatal surveillance for pregnant patients infected with COVID-19 is warranted. The aim of the present narrative review was to summarize the data obtained to date regarding the health of women during pregnancy, as well as that of the fetus associated with the risk of severe infection due to COVID-19. The present review aimed to provide further insight into the effects of this pandemic on pregnancy, also providing the experience of the authors on this matter as an example.

Complement and tissue factor-enriched neutrophil extracellular traps are key drivers in COVID-19 immunothrombosis.

Emerging data indicate that complement and neutrophils contribute to the maladaptive immune response that fuels hyperinflammation and thrombotic microangiopathy, thereby increasing coronavirus 2019 (COVID-19) mortality. Here, we investigated how complement interacts with the platelet/neutrophil extracellular traps (NETs)/thrombin axis, using COVID-19 specimens, cell-based inhibition studies, and NET/human aortic endothelial cell (HAEC) cocultures. Increased plasma levels of NETs, tissue factor (TF) activity, and sC5b-9 were detected in patients. Neutrophils of patients yielded high TF expression and released NETs carrying active TF. Treatment of control neutrophils with COVID-19 platelet-rich plasma generated TF-bearing NETs that induced thrombotic activity of HAECs. Thrombin or NETosis inhibition or C5aR1 blockade attenuated platelet-mediated NET-driven thrombogenicity. COVID-19 serum induced complement activation in vitro, consistent with high complement activity in clinical samples. Complement C3 inhibition with compstatin Cp40 disrupted TF expression in neutrophils. In conclusion, we provide a mechanistic basis for a pivotal role of complement and NETs in COVID-19 immunothrombosis. This study supports strategies against severe acute respiratory syndrome coronavirus 2 that exploit complement or NETosis inhibition.

The Activin/Follistatin Axis Is Severely Deregulated in COVID-19 and Independently Associated With In-Hospital Mortality.

BACKGROUND: Activins are members of the transforming growth factor-ß superfamily implicated in the pathogenesis of several immunoinflammatory disorders. Based on our previous studies demonstrating that overexpression of activin-A in murine lung causes pathology sharing key features of coronavirus disease 2019 (COVID-19), we hypothesized that activins and their natural inhibitor follistatin might be particularly relevant to COVID-19 pathophysiology. METHODS: Activin-A, activin-B, and follistatin were retrospectively analyzed in 574 serum samples from 263 COVID-19 patients hospitalized in 3 independent centers, and compared with demographic, clinical, and laboratory parameters. Optimal scaling with ridge regression was used to screen variables and establish a prediction model. RESULT: The activin/follistatin axis was significantly deregulated during the course of COVID-19, correlated with severity and independently associated with mortality. FACT-CLINYCoD, a scoring system incorporating follistatin, activin-A, activin-B, C-reactive protein, lactate dehydrogenase, intensive care unit admission, neutrophil/lymphocyte ratio, age, comorbidities, and D-dimers, efficiently predicted fatal outcome (area under the curve [AUC], 0.951; 95% confidence interval, .919-.983; P <10-6). Two validation cohorts indicated similar AUC values. CONCLUSIONS: This study demonstrates a link between activin/follistatin axis and COVID-19 mortality and introduces FACT-CLINYCoD, a novel pathophysiology-based tool that allows dynamic prediction of disease outcome, supporting clinical decision making.