Novel clinical and immunological features associated with persistent post-acute sequelae of COVID-19 after six months of follow-up: a pilot study.

BACKGROUND: Currently, there is scant information regarding the features associated to the persistence of post-COVID-19 syndrome, which is the main aim of the present study. METHODS: A cohort study of 102 COVID-19 patients was conducted. The post-COVID-19 symptoms were assessed by a standardised questionnaire. Lymphocyte immunophenotyping was performed by flow cytometry and chemokines/cytokines, neutrophil extracellular traps, the tripartite motif 63, anti-cellular, and anti-SARS-CoV-2 IgG antibodies were addressed in serum. The primary outcome was the persistence of post-COVID-19 syndrome after six months follow-up. RESULTS: Thirteen patients (12.7%) developed the primary outcome and had a more frequent history of post-COVID-19 syndrome 3 months after infection onset (p = .044), increased levels of IL-1α (p = .011) and IP-10 (p = .037) and increased CD57 expression in CD8+ T cells (p = .003). There was a trend towards higher levels of IFN-γ (p = .051), IL-1ß (p = .062) and IL-6 (p = .087). The history of post COVID-19 in the previous 3 months, obesity, baseline serum MIP-1α and IP-10, and CD57 expression in CD8+ T cells were independently associated with the persistence of post-COVID-19 syndrome. CONCLUSION: Our data suggest an important relationship between a pro-inflammatory state mediated through metabolic pathways related to obesity and increased cellular senescence as a key element in the persistence of post-COVID-19 syndrome at six months of follow-up.

Clinical and immunological features associated to the development of a sustained immune humoral response in COVID-19 patients: Results from a cohort study.

Background: Until now, most of the research addressing long-term humoral responses in coronavirus disease 2019 (COVID-19) had only evaluated the serum titers of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgGs, without the assessment of the baseline antiviral clinical and immune profile, which is the aim of this study and may be the key factor leading to a broad and sustained antibody response. Methods: We included 103 patients with COVID-19. When the patients sought medical attention (baseline), a blood sample was drawn to perform immunophenotype of lymphocytes by flow cytometry. The patients were assessed 15 days after baseline and then every month until the third month, followed by a last visit 6 months after recruitment. We evaluated the anti-SARS-COV-2 IgG at all time points, and the serum levels of cytokines, chemokines, anti-cellular (AC) antibodies and neutrophil extracellular traps were also assessed during the follow-up. The primary outcome of the study was the presence of a sustained immune humoral response, defined as an anti-SARS-CoV-2 IgG titer >4.99 arbitrary units/mL in at least two consecutive measures. We used generalized lineal models to assess the features associated with this outcome and to assess the effect of the changes in the cytokines and chemokines throughout time on the development of a sustained humoral immune response. Results: At baseline the features associated to a sustained immune humoral response were the diagnosis of critical disease, absolute number of lymphocytes, serum IP-10, IL-4, IL-2, regulatory T cells, CD8+ T cells, and positive AC antibodies. Critical illness and the positivity of AC antibodies were associated with a sustained humoral immune response after 3 months, whilst critical illness and serum IL-13 were the explanatory variables after 6 months. Conclusion: A sustained immune humoral response is strongly related to critical COVID-19, which is characterized by the presence of AC antibodies, quantitative abnormalities in the T cell compartment, and the serum cytokines and chemokines during acute infection and throughout time.

Pituitary dysfunction in granulomatosis with polyangiitis.

Granulomatosis with polyangiitis (GPA) is a necrotizing granulomatous vasculitis of small vessels that affect the pituitary gland in less than 1% of cases being exceptionally rare. To describe the clinical, biochemical, radiological findings, treatment, and outcomes of 4 patients with GPA-related hypophysitis. A systematic review of published cases with the same diagnosis is presented as well. A cross-sectional case series of patients with hypophysitis due to GPA from 1981 to 2018 at a third level specialty center. Literature review was performed searching in seven different digital databases for terms "granulomatosis with polyangiitis" and "pituitary gland" or "hypophysitis," including in the analysis all published cases between 1950 and 2019 with a minimum follow-up of 6 months. We found 197 patients with GPA in our institution of whom 4 patients (2.0%) had pituitary involvement. Clinical characteristics and outcomes are described. We also reviewed 7 case series, and 36 case reports describing pituitary dysfunction related to GPA from 1953 to 2019, including the clinical picture of an additional 74 patients. Pituitary dysfunction due to GPA is rare. Treatment is targeted to control systemic manifestations; nevertheless, the outcome of the pituitary function is poor. Central diabetes insipidus, particularly in younger women with other systemic features, should raise suspicion of GPA.Key Points• Involvement of the pituitary gland is an uncommon manifestation in GPA patients. The presence of central diabetes insipidus in the setting of systemic symptoms should prompt its suspicion.• In patients with pituitary involvement due to GPA, affection of other endocrine glands is rare, neither concomitant nor in different times during the disease course. This may arise the hypothesis of a local or regional pathogenesis affection of the gland.• There is no consensus on the best therapy strategy for GPA hypophysitis. Although the use of glucocorticoids with CYC is the most common drug combination, no differences in the outcome of the pituitary function and GPA disease course are seen with other immunosuppressants.• Poor prognosis regarding pituitary function is expected due to possible permanent pituitary tissue damage that results in the need of permanent hormonal replacement.