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Objective: To evaluate the need for cardiac monitoring in unselected patients recovered from COVID-19 and to estimate the risk of heart complications after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)., Materials and Methods: During March 2020 and January 2021, 106 patients who had recovered from SARS-CoV-2 (alpha and beta variants) were enrolled in prospective observational cohort study CoSuBr (Covid Survivals in Brno). The diagnosis was based on a reverse transcription-polymerase chain reaction swab test of the upper respiratory tract. Demographic parameters, patient history, clinical evaluation, cardiac biomarkers, ECG and echocardiography were recorded during three visits (Visit 1 at least 6 weeks after infection, Visit 2 three months later, and Visit 3 one year after Visit 1)., Results: 58.5% of the study group ( n = 106) were female, while the mean age was 46 years (range 18-77 years). The mean time interval between the onset of infection and the follow-up visit was 107 days. One quarter (24.5%) of the patients required hospitalization during the acute phase of the disease; the rest recovered at home. 74% suffered a mild form of the disease, with 4.8, 18.1, and 2.9% suffering moderate, severe, and critical forms, respectively. At the time of enrolment, 64.2% of the patients reported persistent symptoms, while more than half of the whole group (50.9%) mentioned at least one symptom of possible cardiac origin (breathing problems, palpitations, exercise intolerance, fatigue). In the 1-year follow-up after COVID-19 infection, left ventricle ejection fraction showed no significant decrease [median (IQR) change was -1.0 (-6.0; 4.0)%, p = 0.150], and there were no changes of troponin (mean change -0.1 ± 1.72 ng/L; p = 0.380) or NT-proBNP [median (IQR) change 2.0 (-20.0; 29.0) pg/mL; p = 0.315]. There was a mild decrease in right ventricle end diastolic diameter (-mean change 2.3 ± 5.61 mm, p < 0.001), while no right ventricle dysfunction was detected. There was very mild progress in left ventricle diastolic diameter [median (IQR) change 1.0 (-1.0; 4.0) mm; p = 0.001] between V1 and V3, mild enlargement of the left atrium (mean change 1.2 ± 4.17 mm; p = 0.021) and a non-significant trend to impairment of left ventricle diastolic dysfunction. There was a mild change in pulmonary artery systolic pressure [median (IQR) change 3.0 (-2.0; 8.0) mmHg; p = 0.038]., Conclusion: Despite a lot of information regarding cardiac impairment due to SARS-CoV2, our study does not suggest an increased risk for developing clinically significant heart changes during the 1-year follow-up. Based on our results, routine echocardiography and biomarkers collection is currently not recommended after COVID-19 recovery., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Matejova, Radvan, Bartecku, Kamenik, Koc, Horinkova, Sykorova, Stepanova and Kala.)

The cellular pathology of schizophrenia and the potential of antipsychotics to target underlying neuronal dysfunctions are still largely unknown. We employed glutamatergic neurons derived from induced pluripotent stem cells (iPSC) obtained from schizophrenia patients with known histories of response to clozapine and healthy controls to decipher the mechanisms of action of clozapine, spanning from molecular (transcriptomic profiling) and cellular (electrophysiology) levels to observed clinical effects in living patients. Glutamatergic neurons derived from schizophrenia patients exhibited deficits in intrinsic electrophysiological properties, synaptic function and network activity. Deficits in K + and Na + currents, network behavior, and glutamatergic synaptic signaling were restored by clozapine treatment, but only in neurons from clozapine-responsive patients. Moreover, neurons from clozapine-responsive patients exhibited a reciprocal dysregulation of gene expression, particularly related to glutamatergic and downstream signaling, which was reversed by c lozapine treatment. Only neurons from clozapine responders showed return to normal function and transcriptomic profile. Our results underscore the importance of K + and Na + channels and glutamatergic synaptic signaling in the pathogenesis of schizophrenia and demonstrate that clozapine might act by normalizing perturbances in this signaling pathway. To our knowledge this is the first study to demonstrate that schizophrenia iPSC-derived neurons exhibit a response phenotype correlated with clinical response to an antipsychotic. This opens a new avenue in the search for an effective treatment agent tailored to the needs of individual patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hribkova, Svoboda, Bartecku, Zelinkova, Horinkova, Lacinova, Piskacek, Lipovy, Provaznik, Glover, Kasparek and Sun.)