Sustained cellular immune dysregulation in individuals recovering from SARS-CoV-2 infection

Abstract

SARS-CoV-2 causes a wide spectrum of clinical manifestations and significant mortality. Studies investigating underlying immune characteristics are needed to understand disease pathogenesis and inform vaccine design. In this study, we examined immune cell subsets in hospitalized and non-hospitalized individuals. In hospitalized patients, many adaptive and innate immune cells were decreased in frequency compared to healthy and convalescent individuals, with the exception of B lymphocytes which increased. Our findings show increased frequencies of T-cell activation markers (CD69, OX40, HLA-DR and CD154) in hospitalized patients, with other T-cell activation/exhaustion markers (PD-L1 and TIGIT) remaining elevated in hospitalized and nonhospitalized individuals. B cells had a similar pattern of activation/exhaustion, with increased frequency of CD69 and CD95 during hospitalization, followed by an increase in PD1 frequencies in non-hospitalized individuals. Interestingly, many of these changes were found to increase over time in non-hospitalized longitudinal samples, suggesting a prolonged period of immune dysregulation following SARS-CoV-2 infection. Changes in T-cell activation/exhaustion in nonhospitalized patients were found to positively correlate with age. Severely infected individuals had increased expression of activation and exhaustion markers. These data suggest a prolonged period of immune dysregulation following SARS-CoV-2 infection highlighting the need for additional studies investigating immune dysregulation in convalescent individuals.

SARS-CoV-2-specific peripheral T follicular helper cells correlate with neutralizing antibodies and increase during convalescence

“…A delay in pTfh response formation could be due to the T-cell dysfunction that occurs in SARS-CoV-2 infection. Many groups have described significant T-cell dysfunction in acute SARS-CoV-2 infection (4, 5, 39), and our group has recently illustrated that this dysfunction is sustained during convalescence, even in non-hospitalized individuals (6). These high magnitude pTfh responses could also be the result of persistent antigen exposure, as several groups have reported prolonged detection of SARS-CoV-2 by PCR (40, 41).…”

“…In SARS-CoV-2 infection, initial studies reported significant lymphopenia in hospitalized patients (3). An elevation of both activation and exhaustion markers on T cells in both severe and mild disease has also been described (4)(5)(6). More recently, data on antigen-specific T-cell responses in individuals recovered from SARS-CoV-2 infection has emerged.…”

Distinct Characteristics of COVID-19 Infection in Children

“…ACE2 is highly expressed in alveolar epithelium, heart, renal tubules and intestinal epithelial cells (7)(8)(9). Severe complications of COVID-19, such as multiple organ dysfunction syndromes (MODS) and acute respiratory distress syndrome (ARDS), might be caused by dysregulated immune response and cytokine storms (10)(11)(12). Recently, many severe cases presenting persistent fever and the involvement of two or more organ systems in children with COVID-19 have been reported, which is termed as multisystem inflammatory syndrome (MIS-C).…”

The Role of Immunogenetics in COVID-19

“…Thus, immunosenescence represents a further potential contributor to the insurgence of fatal complications in COVID-19 [ 8 , 62 , 63 ]. Lymphopenia and accumulation of immune cells showing immunophenotypic and functional signs of exhaustion were commonly documented in COVID-19 patients, correlating with age and severity [ 43 , 68 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 ]. This strong resemblance to immunosenescence makes COVID-19 a possible scenario to deepen the knowledge about the molecular basis affecting normal immune cell metabolism/lifespan/turnover and to determine the importance of genetic variants and epigenetic modifications behind the appearance of inflammaging and immunosenescence [ 66 , 85 , 86 , 87 , 88 ].…”