Impaired Antibody-Dependent Cellular Cytotoxicity in a Spanish Cohort of Patients With COVID-19 Admitted to the ICU

Abstract

SARS-CoV-2 infection causes COVID-19, ranging from mild to critical disease in symptomatic subjects. It is essential to better understand the immunologic responses occurring in patients with the most severe outcomes. In this study, parameters related to the humoral immune response elicited against SARS-CoV-2 were analysed in 61 patients with different presentations of COVID-19 who were recruited in Hospitals and Primary Healthcare Centres in Madrid, Spain, during the first pandemic peak between April and June 2020. Subjects were allocated as mild patients without hospitalization, severe patients hospitalized or critical patients requiring ICU assistance. Critical patients showed significantly enhanced levels of B cells with memory and plasmablast phenotypes, as well as higher levels of antibodies against SARS-CoV-2 with neutralization ability, which were particularly increased in male gender. Despite all this, antibody-dependent cell-mediated cytotoxicity was defective in these individuals. Besides, patients with critical COVID-19 also showed increased IgG levels against herpesvirus such as CMV, EBV, HSV-1 and VZV, as well as detectable CMV and EBV viremia in plasma. Altogether, these results suggest an enhanced but ineffectual immune response in patients with critical COVID-19 that allowed latent herpesvirus reactivation. These findings should be considered during the clinical management of these patients due to the potential contribution to the most severe disease during SARS-CoV-2 infection.

High-affinity FcγRIIIa genetic variants and potent NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC) responses contributing to severe COVID-19

“… 9 , 17 Another ex vivo study analyzed the potential of peripheral blood mononuclear cells derived from patients with COVID-19 to induce an ADCC response against rituximab-coated Raji cells. 18 The authors found a considerably defective ADCC response in hospitalized patients with COVID-19, which also shows exhaustion of ADCC mediating cells in these patients. Combined, these and our data show that the SARS-CoV-2-specific antibody-mediated ADCC responses may contribute to the immune exhaustion in patients with COVID-19.…”

Machine learning assisted analysis on TCR profiling data from COVID-19-convalescent and healthy individuals unveils cross-reactivity between SARS-CoV-2 and a wide spectrum of pathogens and other diseases

“…Cellular cross-reactivity against EBV and SARS-CoV-2 has not been studied to date. However, there have been reports associating the clinical manifestation of COVID-19 with reactivation of EBV infection and correlating it with severe disease progression, thus underpinning a possible entanglement [70][71][72] . Cross-reactivity between SARS-CoV-2 and HIV has also been reported in studies describing false positive HIV results in COVID-19 patients.…”

Herpes Simplex Virus 1 (HSV-1) Reactivation in Critically Ill COVID-19 Patients: A Brief Narrative Review

“…In some studies, PCR testing was repeated periodically [ 14 , 16 , 17 , 56 ]. Regarding serology, anti-HSV-1 IgG levels in patients with severe and critical COVID-19 have been reported to be 4.6 and 6 times higher than in healthy subjects, respectively [ 59 ]. In the same study, anti-HSV-1 IgG levels in patients with critical COVID-19 were two times higher than in patients with mild COVID-19 [ 59 ].…”