RESUMEN
Background Hypercoagulability is a major pathologic event in COVID-19. Factor VIII plays an important role in hemostasis, and high levels of factor VIII have been shown to be associated with an increased risk of thrombosis and severe disease. Little is known about the impact of COVID-19 on clinical outcomes in patients with hemophilia A. Methodology Retrospective data of adult male patients with COVID-19 with and without hemophilia A were retrieved from the TriNetX database (Cambridge, USA). The 1:1 propensity score-matching was performed to balance baseline characteristics. Patients were matched for age, race, body mass index, and medical comorbidities. Thirty-day outcomes were assessed. Results We identified 1,758 patients with pre-existing hemophilia A diagnosis prior to COVID-19 diagnosis and 5,191,908 comparators. After 1:1 propensity score matching, groups were balanced on demographics and comorbidities. All-cause mortality rates were similar between the two groups (HR 0.805; 95% CI 0.467-1.389). The frequency of severe infection, ICU admission, and composite thrombotic events did not differ between the groups. Patients with hemophilia A were hospitalized more frequently than those without a history of hemophilia A (19.2% vs. 14.4%; p<0.05). Additionally, gastrointestinal (GI) bleeding and composite bleeding events occurred more frequently in patients with hemophilia A (3.2% vs. 2.2%; p<0.05 and 4.0% vs. 2.8%; p<0.05, respectively). Conclusions The mortality of individuals with hemophilia A due to COVID-19 is comparable to the general population but with higher risks of hospitalization and bleeding.
RESUMEN
Nosocomial infections pose an imminent challenge to hospitalized Coronavirus disease-19 (COVID-19) patients due to complex interplay of dysregulated immune response combined with immunomodulator therapy. In the pre-pandemic era, immunomodulatory therapy has shown benefit in certain autoimmune conditions with untamed inflammatory response. Efforts to recapitulate these immunomodulatory effects in COVID-19 patients has gained impetus and were followed by NIH COVID-19 expert panel recommendations. The current NIH guideline recommends interleukin-6 inhibitors (tocilizumab and sarilumab) and Janus kinase inhibitors (baricitinib and tofacitinib). Several landmark research trials like COVAVTA, EMPACTA, REMDACTA, STOP-COVID and COV BARRIER have detailed the various effects associated with administration of immunomodulators. The historical evidence of increased infection among patients receiving immunomodulators for autoimmune conditions, raised concerns regarding administration of immunomodulators in COVID-19 patients. The aim of this review article is to provide a comprehensive update on the currently available literature surrounding this issue. We reviewed 40 studies out of which 37 investigated IL-6 inhibitors and 3 investigated JAK inhibitors. Among the studies reviewed, the reported rates of nosocomial infections among the COVID-19 patients treated with immunomodulators were similar to patients receiving standard of care for COVID-19. However, these studies were not powered to assess the side effect profile of these medications. Immunomodulators, by dampening the pyrogenic response and inflammatory markers may delay detection of infections among the patients. This underscores the importance of long-term surveillance which are necessary to discover the potential risks associated with these agents.