Long COVID (LC) affects approximately 10% of individuals post-SARS-CoV-2 infection, with symptoms persisting beyond 12 weeks. The underlying mechanisms remain unclear, and current models often focus on pre-existing comorbidities. This cohort study aimed to identify robust biomarkers and clarify LC pathogenesis through a comprehensive analysis performed in 32 LC individuals 26 months post-infection compared with 35 fully recovered individuals recruited between March and July 2022. Blood and fecal samples were collected, and multiple parameters associated with immune dysfunction, endothelial damage, bacterial translocation, and coagulation alterations, alongside signs of viral persistence and sociodemographic and clinical features, were analyzed. Although viral RNA was undetected on blood or stool, elevated plasma IgG against the nucleocapsid may indicate frequent reinfections, greater infection severity, or delayed immune normalization. Increased levels of prothrombin, thrombin, fibrinogen, sEPCR, and CRP pointed to persistent endothelial dysfunction and coagulation imbalance. Lower levels of the bactericidal protein REG3A suggest potential disruptions in mucosal immune response. We found no major differences in traditional comorbidities, highlighting that LC may stem from distinct pathogenic mechanisms beyond pre-existing conditions. Importantly, our study revealed impaired humoral immunity and identified an association between vaccine heterogeneity and increased LC risk, emphasizing the relevance of consistent vaccination strategies. A Random Forest model using the measured biomarkers achieved 100% accuracy in classifying LC individuals, reinforcing their diagnostic potential. These findings support a multifactorial model of LC involving immune dysregulation and persistent endothelial damage that led to coagulation abnormalities and a pro-thrombotic profile, supporting that LC is more closely related to a sustained, uncontrolled inflammatory response rather than immunodeficiency, and underscoring the value of multidimensional biomarker profiling for guiding clinical management and prevention strategies.

Griscelli syndrome (GS) is a rare genetic disorder that is classified into three distinct types. Partial oculocutaneous albinism is common to all three types. In addition, neurological abnormalities and immunodeficiency are seen in types 1 and 2, respectively. Hemophagocytic lymphohistiocytosis (HLH) is common in GS-2. We present a case of a four-year-old boy who presented with features of albinism, recurrent infections, and hepatosplenomegaly. His complete blood count (CBC) revealed pancytopenia, and bone marrow biopsy showed prominent hemophagocytic activity. Serum ferritin was elevated, and fibrinogen was low. The diagnostic criteria for HLH were met. Hair shaft microscopy revealed large, irregularly spaced clumps of melanin in the medulla. A diagnosis of GS-2 was made. Unfortunately, the patient died before mutation analysis could be performed. Along with this case report, we have included a literature review of 42 cases from 33 case reports and case series. We also propose a diagnostic approach to three hematological disorders associated with albinism, Chediak-Higashi syndrome (CHS), Hermansky-Pudlak syndrome (HPS), and GS.

Complement factor I (CFI) deficiency is a rare primary immunodeficiency that disrupts the classical and alternative complement pathways, potentially causing severe recurrent infections and autoimmune manifestations in pediatric patients. However, the coexistence of both pathways in a pediatric patient is extremely uncommon. We report a seven-year-old patient with a rare primary immunodeficiency disorder who presented with recurrent middle ear infections, paronychia, gastrointestinal infections, and respiratory infections. Genetic testing revealed a previously unreported homozygous variant in the CFI gene (c.848A>G; p.D283G). Immunological testing showed a decrease in complement C3, CFI, and CFH levels in the patient. Interestingly, the patient presented with IgA vasculitis, with renal pathology showing deposits of immune complexes containing IgA, IgG, IgM, and C1q. By considering the child's condition and genetic test results, the child was treated symptomatically and received regular peritoneal dialysis treatment. Subsequently, the child's condition improved compared to before and was discharged from the hospital. This case highlights the importance of considering CFI deficiency in children with recurrent infections and abnormalities in both the classical and alternative complement pathways. Our findings expand the known phenotypic spectrum of CFI deficiency and contribute to understanding genotype-phenotype correlations in complement disorders.

Disseminated intravascular Coagulation (DIC) is a thrombotic microangiopathy which may complicate a number of severe disease processes including sepsis. Development of microvascular thromboses results in consumption of coagulation factors and platelets and ultimate bleeding. Patients with HIV infection (PWH) often present with baseline dysregulation of the coagulation system which may increase severity and derangement of DIC presentation. Previously, we have shown that HIV is a significant risk factor for development of DIC. We conducted a retrospective record review of all DIC screens submitted to our tertiary coagulation laboratory in Johannesburg, South Africa, over a one year period and compared the laboratory presentation of DIC in PWH with presentation of DIC in patients without HIV infection. Over the year, 246 patients fulfilled the International Society of Thrombosis and Haemostasis (ISTH) diagnostic criteria for DIC- 108 were confirmed HIV-infected and 77 were confirmed uninfected. PWH and DIC presented at a significantly earlier age (41 vs 46 years respectively, p<0.02). The prothrombin time was significantly more prolonged (30.1s vs 26.s), the d-dimer levels were substantially higher (5.89mg/L vs 4.52mg/L) and the fibrinogen (3.92g/L vs 1.73g/L) and platelet levels (64.8 vs 114.8x109/l) were significantly lower in PWH. PWH also showed significant synthetic liver dysfunction and higher background inflammation. PWH who fulfil the diagnostic criteria for DIC show significantly more dysregulation of the haemostatic system. This may reflect baseline abnormalities including endothelial dysfunction in the context of inflammation and liver dysfunction.

Coagulation abnormalities are common complications of human immunodeficiency virus (HIV) infection. Highly active antiretroviral treatment (HAART) decreased the mortality of HIV but increased coagulopathies. HIV-related thrombocytopenia, prolonged prothrombin time (PT), activated partial thromboplastin time (APTT), and high D-dimer level commonly manifested in patients with HIV. Thus, this study is aimed to compare coagulation parameters of HAART-treated and HAART-naïve HIV-infected patients with HIV-seronegative controls. A systematic literature search was conducted using the databases PubMed/MEDLINE, Embase, Web of Science, and Google Scholar of studies published until July 2021. The primary outcome of interest was determining the pooled mean difference of coagulation parameters between HIV-infected patients and seronegative controls. The Joana Briggs Institute (JBI) critical appraisal tool was used for quality appraisal. Statistical analyses were performed using Stata11.0 software. The statistical results were expressed as the effect measured by standardized mean difference (SMD) with their related 95% confidence interval (CI). A total of 7,498 participants (1,144 HAART-naïve patients and 2,270 HAART-treated HIV-infected patients and 3,584 HIV-seronegative controls) from 18 studies were included. HIV-infected patients (both on HAART and HAART-naive) exhibited significantly higher levels of PT than HIV-seronegative controls (SMD = 0.66; 95% CI: 0.53-0.80 and SMD = 1.13; 95% CI: 0.60-2.0, respectively). The value of APTT was significantly higher in patients with HIV on HAART than in seronegative controls. However, the values of PLT count, APTT, and fibrinogen level were significantly higher in seronegative controls. Besides, the level of fibrinogen was significantly higher in HAART-treated than treatment-naïve patients (SMD = 0.32; 95%CI: 0.08, 0.57). Moreover, the level of APTT and PT had no statistical difference between HAART and HAART-naïve HIV-infected patients. This study identified that HIV-infected patients are more likely to develop coagulation abnormalities than HIV-seronegative controls. Therefore, coagulation parameters should be assessed regularly to prevent and monitor coagulation disorders in HIV-infected patients.