Clinical improvement of Long-COVID is associated with reduction in autoantibodies, lipids, and inflammation following therapeutic apheresis.

In the aftermath of the COVID-19 pandemic, we are witnessing an unprecedented wave of post-infectious complications. Most prominently, millions of patients with Long-Covid complain about chronic fatigue and severe post-exertional malaise. Therapeutic apheresis has been suggested as an efficient treatment option for alleviating and mitigating symptoms in this desperate group of patients. However, little is known about the mechanisms and biomarkers correlating with treatment outcomes. Here, we have analyzed in different cohorts of Long-Covid patients specific biomarkers before and after therapeutic apheresis. In patients that reported a significant improvement following two cycles of therapeutic apheresis, there was a significant reduction in neurotransmitter autoantibodies, lipids, and inflammatory markers. Furthermore, we observed a 70% reduction in fibrinogen, and following apheresis, erythrocyte rouleaux formation and fibrin fibers largely disappeared as demonstrated by dark field microscopy. This is the first study demonstrating a pattern of specific biomarkers with clinical symptoms in this patient group. It may therefore form the basis for a more objective monitoring and a clinical score for the treatment of Long-Covid and other postinfectious syndromes.

Parosmia as a predictor of a better olfactory function in COVID-19: a multicentric longitudinal study for upper respiratory tract infections.

PURPOSE: This study aimed to evaluate the course of olfactory dysfunction [OD] due to upper respiratory tract infections [URTI] especially for COVID-19 [C19] in a multicentric design and to investigate possible predictors for the outcome. METHODS: In a multicentric study, patients (n = 147, of which 96 were women) with OD due to URTI, including C19 and non-C19 were evaluated at two visits with a standardized medical history and "Sniffin' Sticks" extended psychophysical testing to examine the course and possible predictors for improvement of olfactory function. RESULTS: C19 patients showed better overall olfactory function (p < 0.001) compared to non-C19. Olfactory function (p < 0.001) improved over 3.5 ± 1.2 months in a comparable fashion for C19 and non-C19 comparable over time (p = 0.20) except for a more pronounced improvement of odour threshold (p = 0.03) in C19. C19 patients with parosmia exhibited a higher probability of clinically relevant improvement of odour threshold, a better threshold in the second visit, and tended to have a better TDI-score at the second visit. Further possible predictors for an improving olfactory function were younger age, female gender, and had lower scores in olfactory tests at the first visit. CONCLUSIONS: Patients with C19 and non-C19 URTI exhibit a similar improvement over 3-4 months except for the odour threshold, with a better TDI in both visits for C19. For C19 a better prognosis in terms of olfactory recovery was found for younger patients with parosmia and lower olfactory scores at the first visit. Still, for many patients with olfactory loss, an improvement that is experienced as complete may only occur over months and possibly years.

Long-Term Treatment and Transfusion of Normal Blood Components Following Tolerance Induction in Patients with Anti-IgA Anaphylactic Reactions.

BACKGROUND: In general, patients with significant anti-Ig-A do not tolerate intravenous (i.v.) administration of normal blood products. Here, we present our experiences in the induction of immune tolerance (IIT) and long-term treatment in a series of such patients affected in such a way. The question whether blood components from IgA-deficient donors are required will be discussed. METHODS: Ten adult patients (4 females and 6 males; age ranging from 36 to 75 years) with anti-IgA were included in this study. All patients required long-term treatment with blood components. One patient had IgA deficiency and paroxysmal nocturnal hemoglobinuria (PNH), and all other patients had common variable immunodeficiency (CVID). The particle gel immunoassay was used for the detection of anti-IgA. Immune tolerance to IgA was induced by controlled subcutaneous (s.c.) and/or i.v. infusions of IgG preparations. RESULTS: Prior to IIT, anti-IgA was detectable in plasma samples of all patients and significantly diminished or abolished by controlled s.c. and/or i.v. infusions of IgG. Multiple transfusions with normal blood components could be repeatedly performed with the patient suffering from PNH without any complications. As long as i.v. IgG (IVIgG) infusions were consequently administered as individually required (intervals 2-8 weeks), none of the patients developed reactions during observation (up to 10 years). However, interruption of treatment and re-exposure to IVIgG resulted in adverse reactions. CONCLUSION: Patients with significant anti-IgA can be safely desensitized and tolerate long-term IgG substitutions independent of the IgA concentration of the used blood component.

Absence of Type I Interferon Autoantibodies or Significant Interferon Signature Alterations in Adults With Post-COVID-19 Syndrome.

Genetic defects in the interferon (IFN) system or neutralizing autoantibodies against type I IFNs contribute to severe COVID-19. Such autoantibodies were proposed to affect post-COVID-19 syndrome (PCS), possibly causing persistent fatigue for >12 weeks after confirmed SARS-CoV-2 infection. In the current study, we investigated 128 patients with PCS, 21 survivors of severe COVID-19, and 38 individuals who were asymptomatic. We checked for autoantibodies against IFN-α, IFN-ß, and IFN-ω. Few patients with PCS had autoantibodies against IFNs but with no neutralizing activity, indicating a limited role of type I IFNs in PCS pathogenesis. In a subset consisting of 28 patients with PCS, we evaluated IFN-stimulated gene activity and showed that it did not correlate with fatigue. In conclusion, impairment of the type I IFN system is unlikely responsible for adult PCS.

SARS-CoV-2 Leads to Significantly More Severe Olfactory Loss than Other Seasonal Cold Viruses.

The aim of this study was to investigate whether COVID-associated olfactory impairment differs from olfactory disorders due to other upper respiratory tract infections. We investigated the frequency of a SARS-CoV-2 infection among subjects presenting with a subjective olfactory impairment to a corona outpatient clinic between October 2020 and March 2021. Olfactory and gustatory loss were tested psychophysically, and the type of infection, SARS-CoV-2 versus 14 other common cold viruses, was assessed with nasopharyngeal swabs. Differences between the smell impairment caused by the pathogens were compared. Out of the 2120 patients, 314 reported sudden smell and/or taste loss (14%). In 68.9% of them, olfactory and in 25.6%, gustatory dysfunction could be confirmed by psychophysical testing. Of those with a psychophysically determined loss of smell, 61% were tested positive for SARS-CoV-2. SARS-CoV-2 led to a significantly more severe loss of smell and more qualitative olfactory disorders than other pathogens. Apart from rhinorrhea, shortness of breath and sore throat accompanying cold symptoms do not differ significantly between the viruses indicating the particular importance of smell loss in the differential diagnosis of seasonal colds. Multiplex-PCR in non-COVID patients revealed that only 27% of them had rhinoviruses, whereas the remainder were no further identified pathogens. Olfactory screening significantly increases diagnostic accuracy in COVID-19 patients compared to subjective assessment of olfactory loss.