PMC8637609_01
Blood pressure (systolic, diastolic, mmHg) before (A), during (B), and after treatment with BC 007 (C): a reduction of the diastolic blood pressure was observed after the elimination of functional active G-protein-coupled receptor autoantibodies [GPCR-AAb; w-week; dotted line: individual target level of systolic (red) and diastolic (blue) blood pressure].
fmed-08-754667-g0001.jpg
PMC8637609_01_fmed-08-754667-g0001.jpg
F1
In addition, diastolic blood pressure was increased (Figure 1). In addition to that, previously elevated diastolic blood pressure was lowered (Figure 1).
Measurement of ocular parameters (capillary microcirculation, A-D; intraocular pressure, E): Capillary microcirculation of the macula and peripapillary region, scanned by optical coherence tomography-angiography (OCT-A): vessel density (VD) was monitored in the three layers of the macula (superficial vascular plexus, SVP, A; intermediate capillary plexus, ICP, B; deep capillary plexus, DCP, C) and peripapillary region (D). Vessel density of the macula was reduced after COVID-19 infection compared to the preexisting data of 2018. After treatment with BC 007, the VD increased in all the three layers of the macula and peripapillary region, being stable over at least during the observation period of 4 weeks (gray: range of VD in normal eyes, dotted line: reference level of VD after COVID-19 infection). Data of the left eye are shown as the quality of the OCT-A scans of the right eye were not exploitable due to a hindered fixation of the patient by the presence of cataract. (E) Intraocular pressure (IOP, mmHg; measured by Goldmann applanation tonometry) was monitored before and after treatment with BC 007; reference data of 2018 (EGR, ISSN 2191-5008, CS-2011; NTC00494923) were presented: IOP was reduced after treatment with BC 007, as IOP level was stable, yet without IOP lowering eye drops (antiglaucomatous eyes drop before treatment with BC 007: Tafluprost 15 mug/ml, once a day; after treatment with BC 007: without IOP lowering local therapy); w-week; 1st COVID-19 infection: 04/2020; assumed 2nd COVID-19 infection: turn of the year 2021.
fmed-08-754667-g0002.jpg
PMC8637609_01_fmed-08-754667-g0002.jpg
F2
Optical coherence tomography-angiography (OCT-A) (Spectralis II OCT-A, Heidelberg Engineering, Heidelberg, Germany) yielded an impaired capillary microcirculation in the macula and peripapillary region compared to normative data (Figures 2A-D). Retinal capillary microcirculation was measured by OCT-A as retinal vessel density serves as a correlate for the systemic microcirculation (Figures 2A-D). The improvement of the retinal microcirculation, observed shortly after the infusion of BC 007, was continuously increasing at days 1 and 2 and remained at a constantly increased level in ex ante comparison during the observation period of 4 weeks (Figures 2A-D). As a positive side effect, we observed a lowering of the intraocular pressure (IOP) in both eyes (Figure 2E).
Autoantibodies (AAbs) against G-protein coupled receptors (ss2-AAb, AT-1-AAb, alpha1-AAb, MAS-AAb, and M2-AAb) before (at the day of infusion, before the treatment, single star) and after treatment with BC 007 [after 2 h (double star), 1 day, 2 days, and 1-4 weeks]: functional activity of the positive and negative chronotrope effect of the different AAbs were reduced even after 2 h and functionally inactive at least over the observation period of 4 weeks (cut-off 1.8 beats/15 s); w-week.
fmed-08-754667-g0003.jpg
PMC8637609_01_fmed-08-754667-g0003.jpg
F3
Seropositivity for ss2-AAb, AT-1-AAb, alpha1-AAb, MAS-AAb, and M2-AAb was evaluated (Figure 3). The patient remained seronegative for ss2-AAb, AT-1-AAb, alpha1-AAb, MAS-AAb, and M2-AAb as long as 4 weeks after the infusion of BC 007 (Figure 3).
Chronic fatigue syndrome (CFS) was assessed by the Canadian Criteria, Chalder Fatigue Scale, and the Bell Score before and after treatment with BC 007: CFS was reduced after treatment with BC 007, being absent after 4 weeks; the lower is the Canadian Criteria and Chalder Fatigue Scale, the lower is the CFS; the higher the Bell Score, the lower is the CFS; w, week; the range of the scores:Canadian Criteria Score: 0 (best)-34 (worst): Chalder Fatigue Scale: 0 (best)-33 (worst); Bell Score: 100 (best)-0 (worst).
fmed-08-754667-g0004.jpg
PMC8637609_01_fmed-08-754667-g0004.jpg
F4
Chronic fatigue symptoms were assessed by three standardized scores (Canadian Criteria, Chalder Fatigue Scale, and the Bell Score; Figure 4). Corresponding to the increased retinal capillary microcirculation, the fatigue symptoms of the patient improved steadily (Figure 4).