Autoantibodies against apolipoprotein A‐1 after COVID‐19 predict symptoms persistence

Abstract

Background SARS‐CoV‐2 infection triggers different auto‐antibodies, including anti‐apolipoprotein A‐1 IgGs (AAA1), which could be of concern as mediators of persistent symptoms. We determined the kinetics of AAA1 response over after COVID‐19 and the impact of AAA1 on the inflammatory response and symptoms persistence. Methods All serologies were assessed at one, three, six and twelve months in 193 hospital employees with COVID‐19. ROC curve analyses and logistic regression models (LRM) were used to determine the prognostic accuracy of AAA1 and their association with patient‐reported COVID‐19 symptoms persistence at 12 months. Interferon (IFN)‐α and‐γ production by AAA1‐stimulated human monocyte‐derived macrophages (HMDM) was assessed in vitro. Results AAA1 seropositivity was 93% at one month and declined to 15% at 12 months after COVID‐19. Persistent symptoms at 12 months were observed in 45.1% of participants, with a predominance of neurological (28.5%), followed by general (15%) and respiratory symptoms (9.3%). Over time, strength of correlations between AAA1 and anti‐SARS‐COV2 serologies decreased, but remained significant. From the 3 rd month on, AAA1 levels predicted persistent respiratory symptoms (area under the curves 0.72‐0.74; p < 0.001), independently of disease severity, age and gender (adjusted odds ratios 4.81–4.94; p = 0.02), while anti‐SARS‐CoV‐2 serologies did not. AAA1 increased IFN‐α production by HMDMs ( p = 0.03), without affecting the IFN‐γ response. Conclusion COVID‐19 induces a marked though transient AAA1 response, independently predicting one‐year persistence of respiratory symptoms. By increasing IFN‐α response, AAA1 may contribute to persistent symptoms. If and how AAA1 levels assessment could be of use for COVID‐19 risk stratification remains to be determined.

Prevalence and clinical presentation of long COVID in children: a systematic review

“…A persistent proinflammatory state could explain organ damage and prolonged symptoms, such as fatigue, headache, and smell impairment [ 46 , 48 ]. Moreover, several types of autoantibodies are produced during SARS-CoV-2 infection due to a molecular mimicry mechanism between self-antigens and spike epitopes [ 51 ]. Autoantibodies against G-protein coupled receptors (GPCRs) have been associated with post COVID-19 condition.…”

Overview of autoantibodies in COVID‐19 convalescents

“…Importantly, these autoantibodies were previously shown to be an independent predictor of cardiovascular complications and mortality in different groups of patients and worse outcomes in individuals with existing cardiovascular disease 68–70 . However, the study analyzing the seroprevalence of anti‐apolipoprotein A‐1 antibodies in COVID‐19 convalescents did not relate their presence to cardiovascular outcomes, advocating further research in this area 54 …”

“…Another group of autoantibodies important in the context of cardiovascular function demonstrated in COVID-19 convalescents includes IgG anti-apolipoprotein A-1 antibodies, which were found in some patients to persist to at least 1-year postinfection, although their seroprevalence generally decreased over the time. 54 Importantly, these autoantibodies were previously shown to be an independent predictor of cardiovascular complications and mortality in different groups of patients and worse outcomes in individuals with existing cardiovascular disease. [68][69][70] However, the study analyzing the seroprevalence of anti-apolipoprotein A-1 antibodies in COVID-19 convalescents did not relate their presence to cardiovascular outcomes, advocating further research in this area.…”

“…[68][69][70] However, the study analyzing the seroprevalence of anti-apolipoprotein A-1 antibodies in COVID-19 convalescents did not relate their presence to cardiovascular outcomes, advocating further research in this area. 54 Moreover, selected studies identified antiphospholipid antibodies in COVID-19 convalescents, including autoantibodies against β2-glycoprotein (Table 2). Interestingly, although their presence correlated with COVID-19 severity, 51 the postinfection observations reveal that they may also occur in patients with the mild disease.…”

COVID-19, post-acute COVID-19 syndrome (PACS, “long COVID”) and post-COVID-19 vaccination syndrome (PCVS, “post-COVIDvac-syndrome”): Similarities and differences

“…Autoantibodies were detected during the acute phase of COVID-19 [316] , [317] , [318] , [319] , [320] , [321] , [322] , [323] , [324] , [325] , [326] , [327] , [328] , [329] , [330] , [331] , [332] , [333] , months afterwards (predicting PACS symptoms) [334] , [335] , in PACS [336] , [337] , [338] , [339] , [340] , and in PCVS [295] , [298] , [341] , [342] , [343] , [344] , [345] , [346] , [347] , [348] , [349] , [350] , [351] , [352] , [353] , [354] , [355] , [356] , [357] , [358] , [359] , [360] , [361] , [362] , [363] , [364] , [365] . In the absence of PCVS after COVID-19 vaccination, autoantibodies are generally not present [366] , [367] , [368] .…”