Coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), continues to spread globally despite the worldwide implementation of preventive measures to combat the disease. Although most COVID‐19 cases are characterised by a mild, self‐limiting disease course, a considerable subset of patients develop a more severe condition, varying from pneumonia and acute respiratory distress syndrome (ARDS) to multi‐organ failure (MOF). Progression of COVID‐19 is thought to occur as a result of a complex interplay between multiple pathophysiological mechanisms, all of which may orchestrate SARS‐CoV‐2 infection and contribute to organ‐specific tissue damage. In this respect, dissecting currently available knowledge of COVID‐19 immunopathogenesis is crucially important, not only to improve our understanding of its pathophysiology but also to fuel the rationale of both novel and repurposed treatment modalities. Various immune‐mediated pathways during SARS‐CoV‐2 infection are relevant in this context, which relate to innate immunity, adaptive immunity, and autoimmunity. Pathological findings in tissue specimens of patients with COVID‐19 provide valuable information with regard to our understanding of pathophysiology as well as the development of evidence‐based treatment regimens. This review provides an updated overview of the main pathological changes observed in COVID‐19 within the most commonly affected organ systems, with special emphasis on immunopathology. Current management strategies for COVID‐19 include supportive care and the use of repurposed or symptomatic drugs, such as dexamethasone, remdesivir, and anticoagulants. Ultimately, prevention is key to combat COVID‐19, and this requires appropriate measures to attenuate its spread and, above all, the development and implementation of effective vaccines. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

Oxidative stress has been implicated to play a critical role in the pathophysiology of coronavirus disease 2019 (COVID-19) and may therefore be considered as a relevant therapeutic target. Serum free thiols (R-SH, sulfhydryl groups) comprise a robust marker of systemic oxidative stress, since they are readily oxidized by reactive oxygen species (ROS). In this study, serum free thiol concentrations were measured in hospitalized and non-hospitalized patients with COVID-19 and healthy controls and their associations with relevant clinical parameters were examined. Serum free thiol concentrations were measured colorimetrically (Ellman’s method) in 29 non-hospitalized COVID-19 subjects and 30 age-, sex-, and body-mass index (BMI)-matched healthy controls and analyzed for associations with clinical and biochemical disease parameters. Additional free thiol measurements were performed on seven serum samples from COVID-19 subjects who required hospitalization to examine their correlation with disease severity. Non-hospitalized subjects with COVID-19 had significantly lower concentrations of serum free thiols compared to healthy controls (p = 0.014), indicating oxidative stress. Serum free thiols were positively associated with albumin (St. β = 0.710, p < 0.001) and inversely associated with CRP (St. β = −0.434, p = 0.027), and showed significant discriminative ability to differentiate subjects with COVID-19 from healthy controls (AUC = 0.69, p = 0.011), which was slightly higher than the discriminative performance of CRP concentrations regarding COVID-19 diagnosis (AUC = 0.66, p = 0.042). This study concludes that systemic oxidative stress is increased in patients with COVID-19 compared with healthy controls. This opens an avenue of treatment options since free thiols are amenable to therapeutic modulation.

Post‐COVID‐19 condition (PCC), also known as long COVID, is a complex multiple organ system condition that can develop and persist for months after acute COVID‐19. PCC encompasses a wide range of symptoms, resulting in heterogeneous clinical manifestations. These manifestations likely arise from diverse underlying pathophysiological mechanisms, which, in turn, are influenced by risk factors such as age, sex, and comorbidities. To this end, characterising clinical phenotypes of PCC is essential for deepening our understanding of its (potentially) distinct pathophysiological mechanisms and for advancing diagnostic and patient‐tailored management strategies. PCC is thought to result from a complex interaction of various pathophysiological mechanisms, leading to functional and structural pathological alterations across multiple organ systems. Investigating these alterations is critical to improving our currently incomplete understanding of PCC's complex pathophysiology. This review provides an overview of the main clinical phenotypes of PCC, characterises these phenotypes by examining symptoms and signs, as well as the associated risk factors. The main hypothesised pathophysiological mechanisms are discussed by outlining the current knowledge on PCC pathology, focussing on the most commonly affected organ systems. Current PCC management includes supportive care such as physiotherapy and the repurposing of existing drugs primarily targeting persistence of SARS‐CoV‐2 (e.g. antivirals, monoclonal antibodies) and immune dysfunction (e.g. antiinflammatory drugs, immunomodulators). To date, prevention of SARS‐CoV‐2 infection remains critical, which can be achieved through effective public health measures and vaccination strategies. Finally, this review highlights current knowledge gaps and proposes future research directions to advance the understanding and treatment of PCC. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

COVID-19 has raised special concern for patients with β-thalassemia major (β-TM) due to frequent comorbidities, regular blood transfusions, and iron overload. However, the exact implications of COVID-19 for patients with β-TM remain uncertain. We aimed to explore the COVID-19 incidence and severity, and the serological response to SARS-CoV-2 infection and vaccination in patients with β-TM. Patients with β-TM (n = 105) and age-matched healthy controls, all individuals of all control groups were health care workers of the hospital, were prospectively enrolled at the haematology department of Al-Shifa hospital in the Gaza Strip from January 1st, 2021 to December 31st, 2021. Data on COVID-19 incidence and severity were analysed, with Alpha, Beta, and Delta SARS-CoV-2 variants dominating at that time. Anti-SARS-CoV-2 IgG antibody levels were measured and compared between study groups. Patients with β-TM showed a higher incidence of SARS-CoV-2 infection than the general population (61.9% vs. 7.1%, p < 0.0001). Most patients with β-TM had asymptomatic (70.8%) or mild disease (26.1%), with no fatalities recorded. COVID-19 illness was more severe among female than male patients with β-TM. Anti-SARS-CoV-2 IgG antibodies were significantly higher in symptomatic patients with β-TM than controls post-infection (geometric mean ÷ geometric standard deviation 1299.0 ÷ 3.3 vs. 555.7 ÷ 2.4 AU/mL, p = 0.009) and post-vaccination (8404.0 ÷ 3.9 vs. 2785.6 ÷ 5.0 AU/mL, p = 0.015). Similar responses were observed when comparing splenectomised to non-splenectomised (both asymptomatic and symptomatic) patients with β-TM post-infection (595.4 ÷ 3.9 vs. 280.7 ÷ 3.5 AU/mL, p = 0.005) and post-vaccination (13,778.2 ÷ 3.2 vs. 4961.8 ÷ 4.1 AU/mL, p = 0.045). This distinctive β-TM cohort exhibited a high susceptibility to SARS-CoV-2 infection but mild disease course. Our findings support favourable serological responses to SARS-CoV-2 infection and to vaccination in patients with β-TM, indicating a potential interplay between iron availability and COVID-19-related immunity. This study was funded by Mr. Hosam and Wasim s. El Helou.

Understanding temporal patterns and determinants of RNA shedding is important to comprehend SARS‐CoV‐2 transmission and improve biosafety/isolation guidelines. Nonhospitalized SARS‐CoV‐2‐infected individuals and household members were enrolled between March 2020 and June 2021 and followed prospectively ≥ 3 weeks during acute disease and at 3‐, 6‐, 12‐, and 18‐months to obtain (para)clinical data and biospecimens. Flow cytometry‐based surrogate assay (FlowSA) detected viable SARS‐CoV‐2. Determinants of long RNA shedding ( ≥ 21 days) were investigated. RNA shedding median duration was 14 days (IQR 8.0–21.0) for nasopharyngeal/throat (NPT) and 7 days (IQR 1.0–27.0) for feces— but 20 days (IQR 7.0–27.8) when excluding individuals positive at a single timepoint (25.2%). Among 17 NPT long shedders with FlowSA results, 12 (70.6%) demonstrated viable virus. NPT long shedding was independently positively associated with endocrine disease and chills. Fecal long shedding was independently inversely associated with age, female sex, and fatigue, but positively with vomiting. No associations with long‐term COVID‐19‐related complaints were observed. Finally, fecal long shedders demonstrated higher anti‐spike(S1) IgG levels over 18‐month follow‐up than non‐long shedders (p = 0.006). (Long) SARS‐CoV‐2 RNA shedding in NPT and feces associates with age and acute—but not prolonged—symptoms. The roles of prolonged infectious shedding and fecal shedding in transmission and immunity remain unclear.

Coronavirus disease 2019 (COVID‐19) is of special concern to patients with chronic obstructive pulmonary disease (COPD), given their susceptibility to exacerbations caused by respiratory tract infections. As the susceptibility of acquiring a SARS‐CoV‐2 infection in COPD remains unclear, this study explored the airway expression of SARS‐CoV‐2 entry‐associated proteins in the lungs of COPD patients in comparison to non‐COPD controls. Immunohistochemical staining of lung tissue was performed to investigate the expression profiles of SARS‐CoV‐2 entry‐associated proteins in the bronchial epithelium of 27 COPD patients and 40 non‐COPD controls. In addition, the associations between these expression profiles with lung function in COPD patients and smoking status in non‐COPD controls were examined. COPD patients demonstrated smoking‐independent lower expression of HSPA5, NRP1, BSG, TMPRSS2, and ITGB6 in airway epithelium as compared to non‐COPD controls. No significant differences were observed for Furin, CTSL, ADAM17, and ITGA5. BSG percentage area expression was significantly negatively associated with lung function in COPD patients. Moreover, the study revealed smoking‐associated differences for Furin, HSPA5, ADAM17, BSG, ITGA5, and ITGB6 within non‐COPD controls, with lower airway epithelial expression (except for Furin) in ever‐smokers than in never‐smokers. To conclude, this study showed a lower expression of a specific set of SARS‐CoV‐2 entry‐associated proteins in the bronchial epithelium of COPD patients compared with non‐COPD controls, while other factors showed similar expression levels. The consequences of these findings on COVID‐19 susceptibility remain uncertain. Although reduced expression of entry factors may suggest less cellular availability for viral entry, it could be speculated that the similar expression levels of other factors, together with impaired airway clearance in COPD, may still facilitate infection, thereby providing potential mechanistic insight into COVID‐19 susceptibility in this patient population. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.