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1.
J Nucl Med ; 63(7): 1058-1063, 2022 07.
Article in English | MEDLINE | ID: covidwho-1923992

ABSTRACT

During the coronavirus disease 2019 (COVID-19) pandemic, Long COVID syndrome, which impairs patients through cognitive deficits, fatigue, and exhaustion, has become increasingly relevant. Its underlying pathophysiology, however, is unknown. In this study, we assessed cognitive profiles and regional cerebral glucose metabolism as a biomarker of neuronal function in outpatients with long-term neurocognitive symptoms after COVID-19. Methods: Outpatients seeking neurologic counseling with neurocognitive symptoms persisting for more than 3 mo after polymerase chain reaction (PCR)-confirmed COVID-19 were included prospectively between June 16, 2020, and January 29, 2021. Patients (n = 31; age, 53.6 ± 2.0 y) in the long-term phase after COVID-19 (202 ± 58 d after positive PCR) were assessed with a neuropsychologic test battery. Cerebral 18F-FDG PET imaging was performed in 14 of 31 patients. Results: Patients self-reported impaired attention, memory, and multitasking abilities (31/31), word-finding difficulties (27/31), and fatigue (24/31). Twelve of 31 patients could not return to the previous level of independence/employment. For all cognitive domains, average group results of the neuropsychologic test battery showed no impairment, but deficits (z score < -1.5) were present on a single-patient level mainly in the domain of visual memory (in 7/31; other domains ≤ 2/31). Mean Montreal Cognitive Assessment performance (27/30 points) was above the cutoff value for detection of cognitive impairment (<26 points), although 9 of 31 patients performed slightly below this level (23-25 points). In the subgroup of patients who underwent 18F-FDG PET, we found no significant changes of regional cerebral glucose metabolism. Conclusion: Long COVID patients self-report uniform symptoms hampering their ability to work in a relevant fraction. However, cognitive testing showed minor impairments only on a single-patient level approximately 6 mo after the infection, whereas functional imaging revealed no distinct pathologic changes. This clearly deviates from previous findings in subacute COVID-19 patients, suggesting that underlying neuronal causes are different and possibly related to the high prevalence of fatigue.


Subject(s)
COVID-19 , Cerebrum , Glucose , COVID-19/complications , COVID-19/psychology , Cerebrum/metabolism , Fatigue , Fluorodeoxyglucose F18/metabolism , Glucose/metabolism , Humans , Middle Aged , Neuropsychological Tests , Positron-Emission Tomography
2.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-322709

ABSTRACT

SARS-CoV-2 spike mRNA vaccines mediate protection from severe disease as early as 10 days post prime vaccination, when specific antibodies are hardly detectable and still lack neutralizing activity. Vaccine-induced T cells, especially CD8+ T cells, may thus be the main mediators of protection at this early stage. The details of antigen-specific CD8+ T cell induction after prime/boost vaccination, their comparison to naturally induced CD8+ T cell responses and their association with other arms of vaccine-induced adaptive immunity remain, however, incompletely understood. Here, we show on a single epitope level that both, a stable memory precursor pool of spike-specific CD8+ T cells and fully functional spike-specific effector CD8+ T cell populations, are vigorously mobilized as early as one week after prime vaccination when CD4+ T cell and spike-specific antibody responses are still weak and neutralizing antibodies are lacking. Boost vaccination after 3 weeks induced a full-fledged recall expansion generating highly differentiated CD8+ effector T cells, however, neither the functional capacity nor the memory precursor T cell pool was affected. Compared to natural infection, vaccine-induced early memory T cells exhibited similar frequencies and functional capacities but a different subset distribution dominated by effector memory T cells at the expense of self-renewing and multipotent central memory T cells. Our results indicate that spike-specific CD8+ T cells may represent the major correlate of early protection after SARS-CoV-2 mRNA/bnt162b2 prime vaccination that precede other effector arms of vaccine-induced adaptive immunity and are stably maintained after boost vaccination.

3.
J Nucl Med ; 63(7): 1058-1063, 2022 07.
Article in English | MEDLINE | ID: covidwho-1470742

ABSTRACT

During the coronavirus disease 2019 (COVID-19) pandemic, Long COVID syndrome, which impairs patients through cognitive deficits, fatigue, and exhaustion, has become increasingly relevant. Its underlying pathophysiology, however, is unknown. In this study, we assessed cognitive profiles and regional cerebral glucose metabolism as a biomarker of neuronal function in outpatients with long-term neurocognitive symptoms after COVID-19. Methods: Outpatients seeking neurologic counseling with neurocognitive symptoms persisting for more than 3 mo after polymerase chain reaction (PCR)-confirmed COVID-19 were included prospectively between June 16, 2020, and January 29, 2021. Patients (n = 31; age, 53.6 ± 2.0 y) in the long-term phase after COVID-19 (202 ± 58 d after positive PCR) were assessed with a neuropsychologic test battery. Cerebral 18F-FDG PET imaging was performed in 14 of 31 patients. Results: Patients self-reported impaired attention, memory, and multitasking abilities (31/31), word-finding difficulties (27/31), and fatigue (24/31). Twelve of 31 patients could not return to the previous level of independence/employment. For all cognitive domains, average group results of the neuropsychologic test battery showed no impairment, but deficits (z score < -1.5) were present on a single-patient level mainly in the domain of visual memory (in 7/31; other domains ≤ 2/31). Mean Montreal Cognitive Assessment performance (27/30 points) was above the cutoff value for detection of cognitive impairment (<26 points), although 9 of 31 patients performed slightly below this level (23-25 points). In the subgroup of patients who underwent 18F-FDG PET, we found no significant changes of regional cerebral glucose metabolism. Conclusion: Long COVID patients self-report uniform symptoms hampering their ability to work in a relevant fraction. However, cognitive testing showed minor impairments only on a single-patient level approximately 6 mo after the infection, whereas functional imaging revealed no distinct pathologic changes. This clearly deviates from previous findings in subacute COVID-19 patients, suggesting that underlying neuronal causes are different and possibly related to the high prevalence of fatigue.


Subject(s)
COVID-19 , Cerebrum , Glucose , COVID-19/complications , COVID-19/psychology , Cerebrum/metabolism , Fatigue , Fluorodeoxyglucose F18/metabolism , Glucose/metabolism , Humans , Middle Aged , Neuropsychological Tests , Positron-Emission Tomography
4.
Dtsch Med Wochenschr ; 146(17): e65-e73, 2021 Sep.
Article in German | MEDLINE | ID: covidwho-1368971

ABSTRACT

BACKGROUND: Increasing evidence suggests that some patients suffer from persistent symptoms for months after recovery from acute COVID-19. However, the clinical phenotype and its pathogenesis remain unclear. We here present data on complaints and results of a diagnostic workup of patients presenting to the post-COVID clinic at the University Medical Center Freiburg. METHODS: Retrospective data analysis of persistently symptomatic patients presenting to our clinic at least 6 months after onset of acute COVID-19. All patients were assessed by a doctor and routine laboratory analysis was carried out. Quality of life was assessed using SF-36 questionnaire. In case of specific persisting symptoms, further organ-specific diagnostic evaluation was performed, and patients were referred to respective departments/specialists. FINDINGS: 132 Patients (58 male, 74 female; mean age 53.8 years) presented to our clinic at least 6 months after COVID-19. 79 (60 %) had been treated as outpatients and 53 (40 %) as inpatients. Most common complaints were persistent fatigue (82 %) and dyspnea on exertion (61 %). Further common complaints were impairments of concentration (54 %), insomnia (43 %), and impairments of smell or taste (35 %). Quality of life was reduced in all sections of the SF-36 questionnaire, yielding a reduced working capacity. Significant pathological findings in laboratory, echocardiographic and radiological work-up were rare. Impairments in lung function tests were more common in previously hospitalized patients. CONCLUSION: Patients presenting 6 months after onset of acute COVID-19 suffer from a diverse spectrum of symptoms with impaired quality of life, also referred to as Long COVID or Post-Acute Sequelae of SARS-CoV-2 infection (PASC). Further research is needed to determine the frequency of these post-COVID syndromes and their pathogenesis, natural course and treatment options. Evaluation and management should be multi-disciplinary.


Subject(s)
COVID-19/complications , SARS-CoV-2/immunology , Adult , Aged , Aged, 80 and over , Anosmia , Antibodies, Viral/blood , COVID-19/epidemiology , Dyspnea , Fatigue , Female , Follow-Up Studies , Germany/epidemiology , Humans , Male , Middle Aged , Quality of Life , Retrospective Studies , Sleep Initiation and Maintenance Disorders , Surveys and Questionnaires , Taste Disorders , Young Adult
5.
Nature ; 597(7875): 268-273, 2021 09.
Article in English | MEDLINE | ID: covidwho-1328849

ABSTRACT

SARS-CoV-2 spike mRNA vaccines1-3 mediate protection from severe disease as early as ten days after prime vaccination3, when neutralizing antibodies are hardly detectable4-6. Vaccine-induced CD8+ T cells may therefore be the main mediators of protection at this early stage7,8. The details of their induction, comparison to natural infection, and association with other arms of vaccine-induced immunity remain, however, incompletely understood. Here we show on a single-epitope level that a stable and fully functional CD8+ T cell response is vigorously mobilized one week after prime vaccination with bnt162b2, when circulating CD4+ T cells and neutralizing antibodies are still weakly detectable. Boost vaccination induced a robust expansion that generated highly differentiated effector CD8+ T cells; however, neither the functional capacity nor the memory precursor T cell pool was affected. Compared with natural infection, vaccine-induced early memory T cells exhibited similar functional capacities but a different subset distribution. Our results indicate that CD8+ T cells are important effector cells, are expanded in the early protection window after prime vaccination, precede maturation of other effector arms of vaccine-induced immunity and are stably maintained after boost vaccination.


Subject(s)
CD8-Positive T-Lymphocytes/cytology , CD8-Positive T-Lymphocytes/immunology , COVID-19 Vaccines/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Vaccination , Vaccines, Synthetic/immunology , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , B-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/immunology , COVID-19/virology , Cells, Cultured , Epitopes, T-Lymphocyte/immunology , Humans , Immunization, Secondary , Immunologic Memory/immunology , SARS-CoV-2/chemistry , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology , Time Factors
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