Coronavirus disease 2019 (COVID-19) poses an increased risk for severe illness and suboptimal vaccination responses in patients with kidney disease, in which oxidative stress may be involved. ...Oxidative stress can be reliably measured by determining circulating free thiols (R–SH, sulfhydryl groups), since R–SH are rapidly oxidized by reactive species. In this study, we aimed to examine the association between serum free thiols and the ability to mount a humoral immune response to SARS-CoV-2 vaccination in kidney patients.
Serum free thiol concentrations were measured in patients with chronic kidney disease stages 4/5 (CKD G4/5) (n = 46), on dialysis (n = 43), kidney transplant recipients (KTR) (n = 73), and controls (n = 50). Baseline serum free thiol and interferon-γ-induced protein-10 (IP-10) – a biomarker of the interferon response – were analyzed for associations with seroconversion rates and SARS-CoV-2 spike (S1)-specific IgG concentrations after two doses of the mRNA-1273 vaccine.
Albumin-adjusted serum free thiol concentrations were significantly lower in patients with CKD G4/5 (P < 0.001), on dialysis (P < 0.001), and KTR (P < 0.001), as compared to controls. Seroconversion rates after full vaccination were markedly reduced in KTR (52.1%) and were significantly associated with albumin-adjusted free thiols (OR = 1.76, P = 0.033). After adjustment for MMF use, hemoglobin, and eGFR, this significance was not sustained (OR = 1.49, P = 0.241).
KTR show suboptimal serological responses to SARS-CoV-2 vaccination, which is inversely associated with serum R–SH, reflecting systemic oxidative stress. Albeit this association was not robust to relevant confounding factors, it may at least partially be involved in the inability of KTR to generate a positive serological response after SARS-CoV-2 vaccination.
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•Kidney transplant recipients (KTR) show reduced humoral immune responses to COVID-19 vaccination.•Systemic oxidative stress is present in patients with kidney disease and KTR, which is most prominent in CKD (4–5) patients.•Serum free thiols (R–SH, sulfhydryl groups) reflect the systemic redox status in health and disease.•R-SH associates with anti-S1 SARS-CoV-2 IgG titers in KTR, but the association was not robust to clinical confounding factors.
Hydrogen sulfide (H
S) is one of the three main gasotransmitters that are endogenously produced in humans and are protective against oxidative stress. Recent findings from studies focusing on ...coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), shifted our attention to a potentially modulatory role of H
S in this viral respiratory disease.
H
S levels at hospital admission may be of importance since this gasotransmitter has been shown to be protective against lung damage through its antiviral, antioxidant, and anti-inflammatory actions. Furthermore, many COVID-19 cases have been described demonstrating remarkable clinical improvement upon administration of high doses of N-acetylcysteine (NAC). NAC is a renowned pharmacological antioxidant substance acting as a source of cysteine, thereby promoting endogenous glutathione (GSH) biosynthesis as well as generation of sulfane sulfur species when desulfurated to H
S.
Combining H
S physiology and currently available knowledge of COVID-19, H
S is hypothesized to target three main vulnerabilities of SARS-CoV-2: (i) cell entry through interfering with functional host receptors, (ii) viral replication through acting on RNA-dependent RNA polymerase (RdRp), and (iii) the escalation of inflammation to a potentially lethal hyperinflammatory cytokine storm (toll-like receptor 4 TLR4 pathway and NLR family pyrin domain containing 3 NLRP3 inflammasome).
Dissecting the breakdown of NAC reveals the possibility of increasing endogenous H
S levels, which may provide a convenient rationale for the application of H
S-targeted therapeutics. Further randomized-controlled trials are warranted to investigate its definitive role.
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.
COVID-19 is of special concern to immunocompromised individuals, including organ transplant recipients. However, the exact implications of COVID-19 for the immunocompromised host remain unclear. ...Existing theories regarding this matter are controversial and mainly based on clinical observations. Here, the postmortem histopathology, immunopathology, and viral presence in various tissues of a kidney transplant recipient with COVID-19 were compared to those of 2 nontransplanted patients with COVID-19 matched for age, sex, length of intensive care unit stay, and admission period in the pandemic. None of the tissues of the kidney transplant recipient demonstrated the presence of SARS-CoV-2. In lung tissues of both controls, some samples showed viral positivity with high Ct values with quantitative reverse transcription polymerase chain reaction. The lungs of the kidney transplant recipient and controls demonstrated similar pathology, consisting of acute fibrinous and organizing pneumonia with thrombosis and an inflammatory response with T cells, B cells, and macrophages. The kidney allograft and control kidneys showed a similar pattern of interstitial lymphoplasmacytic infiltration. No myocarditis could be observed in the hearts of the kidney transplant recipient and controls, although all cases contained scattered lymphoplasmacytic infiltrates in the myocardium, pericardium, and atria. The brainstems of the kidney transplant recipient and controls showed a similar pattern of lymphocytic inflammation with microgliosis. This research report highlights the possibility that, based on the results obtained from this single case, at time of death, the immune response in kidney transplant recipients with long-term antirejection immunosuppression use prior to severe illness is similar to nontransplanted deceased COVID-19 patients.
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 (
= 0.014), indicating oxidative stress. Serum free thiols were positively associated with albumin (St. β = 0.710,
0.001) and inversely associated with CRP (St. β = -0.434,
= 0.027), and showed significant discriminative ability to differentiate subjects with COVID-19 from healthy controls (AUC = 0.69,
= 0.011), which was slightly higher than the discriminative performance of CRP concentrations regarding COVID-19 diagnosis (AUC = 0.66,
= 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.
Background: 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. Methods: 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. Findings: 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). Interpretation: 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. Funding: This study was funded by Mr. Hosam and Wasim s. El Helou.
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