Patients with Covid 19 have significantly reduced CH50 activity

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), is a new virus that emerged in China and immediately spread around the world. Evidence has been documented that the immune system is impressively involved in the pathogenesis of this disease, especially in causing inflammation. One of the important components of the immune system is the complement system whose increased activity has been shown in inflammatory diseases and consequently damage caused by the activity of its components. In the present study, serum levels of C3 and C4 factors as well as the activity level of complement system in the classical pathway were measured by CH50 test in patients with SARS-CoV-2. Participants in the study consisted of 53 hospitalized patients whose real-time PCR test was positive for SARS-CoV-2. The mean age of these patients was 42.06 ± 18.7 years, including 40% women and 60% men. The most common symptoms in these patients were cough (70%), fever (59%), dyspnea (53%) and chills (53%), respectively. Analysis of biochemical and hematological test results revealed that 26 (49%) patients had lymphopenia, 34 (64%) patients were positive for C-reactive protein (CRP) and 26 (49%) patients had ESR and LDH levels significantly higher than normal. In addition, 27 patients (51%) had vitamin D deficiency. The mean CH50 activity level in COVID-19 patients was significantly reduced compared to healthy individuals (84.9 versus 169.9 U/ml, p = < 0.0001). Comparison of the mean CH50 activity levels between different subgroups of patients indicated that COVID-19 patients with decreased peripheral blood lymphocyte count and positive CRP had a significant increase in activity compared to the other groups ( p = 0.0002). The serum levels of C3 and C4 factors had no significant change between patients and healthy individuals. Conclusion: The activity level of complement system in the classical pathway decreases in COVID-19 patients compared to healthy individuals, due to increased activity of complement system factors in these patients.

Associations between serum levels of C3, C4, and total classical complement activity in COVID-19 patients at the time of admission and clinical outcome

“…The finding also match earlier findings by Ghazavi et al, which showed that C3 and C4 levels were markedly decreased in severe COVID-19 patients in comparison with non-severe COVID-19 patients [8]. In agreement with our data, Keshavarz et al indicated that mean CH50 activity level in COVID-19 patients is significantly reduced compared to healthy individuals [15].…”

“…However, this study supports the findings from previous observations [6,8,15]. Fang et al in a retrospective cohort study investigated C3 levels in COVID-19 patients [6].…”

“…Conversely, Keshavarz and colleagues showed that serum levels of the C3 and C4 factors have no significant change between patients and healthy individuals [15]. In another study, Zhang et al showed that complement C3 cannot predict disease progression [24].…”

Complement C1s as a diagnostic marker and therapeutic target: Progress and propective

“…Of note, it was shown that up-regulation of C1s led to host cell damage via the classical pathway in a model of SARS-CoV-2 infection ( 59 ). Clinical investigation found that the mean 50% hemolytic complement (CH50) level in COVID-19 patients was significantly lower compared to that in healthy individuals, likely due to sustained CP activation in these SARS-CoV-2 infected patients ( 60 ). Further studies found that antibody-mediated increase of CP activation was highly associated to COVID-19 disease severity ( 61 ), although the downstream effects of this activation may differ depending the disease status of the individual and on the specific antigen targeted ( 62 ).…”

Complement-mediated microvascular injury and thrombosis in the pathogenesis of severe COVID-19: A review

“…In severe cases, SARS-CoV-2 induces a dysregulated immune response that becomes detrimental to the host, described as ‘cytokine storm’ or ‘cytokine release syndrome’[ 7 ]. During cytokine storm, serum levels of complement components 3 and 4 (C3 and C4) and other components of the classical complement pathway as measured by the CH50 assay are decreased due to increased complement factor consumption[ 8 ]. Post-mortem cadaveric analysis of patients with severe SARS-CoV-2 infection has demonstrated thrombotic microangiopathy (TMA) implicating the activation of the complement cascade[ 9 ].…”