Functional Status and Quality of Life 6 Months After Extracorporeal Membrane Oxygenation Therapy for COVID-19-Related Pulmonary Failure.

Extracorporeal membrane oxygenation (ECMO) is increasingly used in COVID-19-related pulmonary failure and the number of patients recovering from COVID-19 is growing. Here, we assess survival and recovery 6 months after ECMO for COVID-19. From April 2020 to September 2021, n = 60 (60.5 [51.0-65.0] years, 23.3% female) were treated with venovenous/venoarterial ECMO for COVID-19. 41.7% were weaned off ECMO, survival-to-discharge was 40.0% (n = 24). Age (63.0 [60.0-66.8] vs. 55.0 [43.8-60.0] years, p < 0.001), vasoactive support (97.2% vs. 75.0%, p = 0.013), and pre-ECMO SOFA scores (13.0 [12.0-14.8] vs. 12.0 [10.0-13.8] p = 0.036) correlated with nonsurvival. All patients aged >65 years, with histories of neoplasia, immunocompromise, chronic renal failure, or frailty died. After 6 months, 20 were alive (6-month survival 33.3%, survival conditioned on survival-to-discharge 83.3%), with follow-up in 19. 57.9% showed no relevant, 26.3% moderate, 15.8% severe deficits. Cardiopulmonary status was satisfactory (mMRC level: 84.2% ≤2). 73.7% were independent in daily life. Cognitive impairments were frequent (52.6%). 26.3% showed moderate depression, 15.8% posttraumatic stress disorder. Social and work life were considerably affected. Extracorporeal membrane oxygenation thus can serve as salvage therapy in COVID-19, but advanced age, immunocompromise, histories of neoplasia, and frailty must be considered as relative contraindications. Age, vasoactive support, and SOFA scores assist discriminating in daily practice. Deficits after 6 months are substantial, and efforts need to focus on long-term recovery.

Distinct profiles and kinetics of soluble infammatory markers in patients with acute and chronic HCV-infections and SARS-CoV-2-infections: Implications for the long-term consequences of viral infections?

Background and Aims Viral infections occur acutely but can also progress chronically, with the immune system having a central role in immunopathoge-nesis. The question arises whether all alterations in immune responses are reversible after viral elimination (spontaneously or by therapy). Therefore, the aim of this study is to compare soluble infammatory markers (SIM) during and after infection with SARS-CoV-2 and acute and chronic HCV-infections. Patients and Method Patients with acute HCV (n = 29), chronic HCV (n = 54), SARS-CoV-2 (n = 39) and 31 healthy-controls were included. Blood samples were tested at baseline, end of treatment/infection, and follow-up ( >= 9 months after baseline). IL-12p70, IL-1b, IL-4, IL-5, IL-6, IL-8, TNF, IFN-g, IL-10, IL-22, CXCL-10, MCP-1, MIP-1b, ITAC were quantified using the HD-SP-X Imaging and Analysis SystemTM. Results SIM profiles in patients with acute HCV were substantially elevated at baseline and the decrease during follow-up was considerably less compared to the SARS-CoV-2 cohort. In chronic HCV-patients, viral elimination by therapy resulted in a decrease in SIM, although not always to those of controls. Cirrhotic HCV patients had higher SIM levels after HCV elimination than non-cirrhotic chronic HCV-patients. In the SARS-CoV-2 cohort, most SIM returned to levels of controls 3 months after baseline. Conclusions SIM profiles and kinetics after viral elimination difer between blood-borne acute and chronic HCV- and respiratory SARS-CoV-2-infections. The immunologic imprint 9 months after cured HCV-infection (both acute and chronic) appears to be more pronounced than after SARS-CoV-2-infection. Further analysis is needed to correlate the SIM profle with the clinical pheno-type (long-HepC vs. long-COVID-19).

Potential use of polyphenols in the battle against COVID-19.

The coronavirus disease 2019 (COVID-19) is a public health emergency of international concern. The rising number of cases of this highly transmissible infection has stressed the urgent need to find a potent drug. Although repurposing of known drugs currently provides an accelerated route to approval, there is no satisfactory treatment. Polyphenols, a major class of bioactive compounds in nature, are known for their antiviral activity and pleiotropic effects. The aim of this review is to assess the effects of polyphenols on COVID-19 drug targets as well as to provide a perspective on the possibility to use polyphenols in the development of natural approaches against this viral disease.

Testosterone suppression combined with high dose estrogen as potential treatment of SARS-CoV-2. A mini review.

Compared to females, males experience severe acute respiratory syndrome due to COVID-19 (SARS-CoV-2) more often, and also die more frequently from COVID-19. Testosterone has inhibitory and estrogens have favorable effects on the immune system. Both ACE2 and TMPRSS2 are specific host-cellular proteins stimulating viral entry in cells and SARS-CoV-2. Both proteins can be suppressed by inhibition of testosterone levels and by stimulation of estrogen levels. Therefore, both androgen-deprivation therapy (ADT) and estrogen therapy (ET) may decrease COVID-19 virus cell entry. Literature was searched for evidence of COVID-19 treatment benefits with estrogens, progesterone, androgen deprivation, and anti-androgens. Data supporting the effect of ADT on SARS-CoV-2 are sparse and inconsistent. The benefit of anti-androgen therapy is inconsistent. Data on the effect of ET were not found. Indirect estrogen data related to menopausal hormone therapy and hormonal contraception are favorable. In a small study, progesterone had some beneficial effects. The combination of ADT and ET (ADET) has never been studied as a treatment option for SARS-CoV-2. Based on the mode of action of the combination, it is hypothesized that ADET may be an effective and safe treatment of SARS-CoV-2, to be confirmed in a clinical trial.

Large thrombus in transit in a COVID-19 patient.

The course of COVID-19 patients may be complicated by thromboembolic events. We report on a 48-year-old female COVID-19 patient who underwent surgical removal of a large intracardiac thrombus. As per our centre protocol, critically ill COVID-19 patients are anticoagulated by the direct thrombin inhibitor Argatroban with close monitoring of anti-IIa activity. An intra-atrial thrombus formation fixed in a patent foramen ovale but also large mobile portions in both atria was diagnosed 4 days after weaning and removal of the jugular and femoral extracorporeal membrane oxygenation cannulas. The thrombus was removed surgically via median sternotomy and on cardiopulmonary bypass. The thrombus had a bizarre appearance with several finger-like appendices, and histological analysis revealed a mixed picture of acute and chronic thrombus portions. This case highlights the risk of life-threatening thrombus formation in COVID-19 patients despite therapeutic thrombin inhibition.

Cerebrospinal fluid findings in COVID-19: a multicenter study of 150 lumbar punctures in 127 patients.

BACKGROUND: Comprehensive data on the cerebrospinal fluid (CSF) profile in patients with COVID-19 and neurological involvement from large-scale multicenter studies are missing so far. OBJECTIVE: To analyze systematically the CSF profile in COVID-19. METHODS: Retrospective analysis of 150 lumbar punctures in 127 patients with PCR-proven COVID-19 and neurological symptoms seen at 17 European university centers RESULTS: The most frequent pathological finding was blood-CSF barrier (BCB) dysfunction (median QAlb 11.4 [6.72-50.8]), which was present in 58/116 (50%) samples from patients without pre-/coexisting CNS diseases (group I). QAlb remained elevated > 14d (47.6%) and even > 30d (55.6%) after neurological onset. CSF total protein was elevated in 54/118 (45.8%) samples (median 65.35 mg/dl [45.3-240.4]) and strongly correlated with QAlb. The CSF white cell count (WCC) was increased in 14/128 (11%) samples (mostly lympho-monocytic; median 10 cells/µl, > 100 in only 4). An albuminocytological dissociation (ACD) was found in 43/115 (37.4%) samples. CSF L-lactate was increased in 26/109 (24%; median 3.04 mmol/l [2.2-4]). CSF-IgG was elevated in 50/100 (50%), but was of peripheral origin, since QIgG was normal in almost all cases, as were QIgA and QIgM. In 58/103 samples (56%) pattern 4 oligoclonal bands (OCB) compatible with systemic inflammation were present, while CSF-restricted OCB were found in only 2/103 (1.9%). SARS-CoV-2-CSF-PCR was negative in 76/76 samples. Routine CSF findings were normal in 35%. Cytokine levels were frequently elevated in the CSF (often associated with BCB dysfunction) and serum, partly remaining positive at high levels for weeks/months (939 tests). Of note, a positive SARS-CoV-2-IgG-antibody index (AI) was found in 2/19 (10.5%) patients which was associated with unusually high WCC in both of them and a strongly increased interleukin-6 (IL-6) index in one (not tested in the other). Anti-neuronal/anti-glial autoantibodies were mostly absent in the CSF and serum (1509 tests). In samples from patients with pre-/coexisting CNS disorders (group II [N = 19]; including multiple sclerosis, JC-virus-associated immune reconstitution inflammatory syndrome, HSV/VZV encephalitis/meningitis, CNS lymphoma, anti-Yo syndrome, subarachnoid hemorrhage), CSF findings were mostly representative of the respective disease. CONCLUSIONS: The CSF profile in COVID-19 with neurological symptoms is mainly characterized by BCB disruption in the absence of intrathecal inflammation, compatible with cerebrospinal endotheliopathy. Persistent BCB dysfunction and elevated cytokine levels may contribute to both acute symptoms and 'long COVID'. Direct infection of the CNS with SARS-CoV-2, if occurring at all, seems to be rare. Broad differential diagnostic considerations are recommended to avoid misinterpretation of treatable coexisting neurological disorders as complications of COVID-19.

Caffeoylquinic acids: chemistry, biosynthesis, occurrence, analytical challenges, and bioactivity.

Caffeoylquinic acids (CQAs) are specialized plant metabolites we encounter in our daily life. Humans consume CQAs in mg-to-gram quantities through dietary consumption of plant products. CQAs are considered beneficial for human health, mainly due to their anti-inflammatory and antioxidant properties. Recently, new biosynthetic pathways via a peroxidase-type p-coumaric acid 3-hydroxylase enzyme were discovered. More recently, a new GDSL lipase-like enzyme able to transform monoCQAs into diCQA was identified in Ipomoea batatas. CQAs were recently linked to memory improvement; they seem to be strong indirect antioxidants via Nrf2 activation. However, there is a prevalent confusion in the designation and nomenclature of different CQA isomers. Such inconsistencies are critical and complicate bioactivity assessment since different isomers differ in bioactivity and potency. A detailed explanation regarding the origin of such confusion is provided, and a recommendation to unify nomenclature is suggested. Furthermore, for studies on CQA bioactivity, plant-based laboratory animal diets contain CQAs, which makes it difficult to include proper control groups for comparison. Therefore, a synthetic diet free of CQAs is advised to avoid interferences since some CQAs may produce bioactivity even at nanomolar levels. Biotransformation of CQAs by gut microbiota, the discovery of new enzymatic biosynthetic and metabolic pathways, dietary assessment, and assessment of biological properties with potential for drug development are areas of active, ongoing research. This review is focused on the chemistry, biosynthesis, occurrence, analytical challenges, and bioactivity recently reported for mono-, di-, tri-, and tetraCQAs.

Maintenance of Acute Stroke Care Service During the COVID-19 Pandemic Lockdown.

[Figure: see text].

Pakistani perspective, preparation and response to COVID-19: A review

The recent 2020 emerging infection of COVID-19 was initiated from Wuhan China. At first, it spread around China and now reached more than 213 countries around the globe including Pakistan. The nurses and doctors play an important role before and during the pandemics, nursing plays a leading role in preparation for the outbreak. The clinical symptoms of COVID-19 are very similar to respiratory diseases. Every day the number of laboratory-confirmed cases associated with deaths increasing regularly in different countries around the world. Natural infections of coronavirus are seven (229E, NL63, OC43, HKUI, SARS, MERS and COVID-19). Out of seven four are mild upper respiratory infection, and SARS-CoV, MERS-CoV and COVID-19 are known for their high mortality rate. Among them, COVID-19 is an emerging viral infection responsible for pandemics. Fortunately, the mortality rate of COVID-19 is low as compared to SARS and MERS, the majority of cases are recovered in almost all the countries. The death rate toll of COVID-19 is high even after its mortality because COVID-19 causes a pandemic, while the other can't. Currently, COVID-19 influenced a large segment of the world population, which let to public health emergencies around the world, and an international concern, putting all the health organizations to high alert. The present review is on preparation, response, general continent, virology, epidemiology, clinical presentations, diagnosis, treatment and control of COVID-19 regarding Pakistan.

Stroke Admissions, Stroke Severity, and Treatment Rates in Urban and Rural Areas During the COVID-19 Pandemic.

Background: Many regions worldwide reported a decline of stroke admissions during the early phase of the coronavirus disease 2019 (COVID-19) pandemic. It remains unclear whether urban and rural regions experienced similar declines and whether deviations from historical admission numbers were more pronounced among specific age, stroke severity or treatment groups. Methods: We used registry datasets from (a) nine acute stroke hospitals in Berlin, and (b) nine hospitals from a rural TeleNeurology network in Northeastern Germany for primary analysis of 3-week-rolling average of stroke/TIA admissions before and during the COVID-19 pandemic. We compared course of stroke admission numbers with regional cumulative severe acute respiratory syndrome coronavirus 2 (Sars-CoV-2) infections. In secondary analyses, we used emergency department logs of the Berlin Charité University hospital to investigate changes in age, stroke severity, and thrombolysis/thrombectomy frequencies during the early regional Sars-CoV-2 spread (March and April 2020) and compared them with preceding years. Results: Compared to past years, stroke admissions decreased by 20% in urban and 20-25% in rural hospitals. Deviations from historical averages were observable starting in early March and peaked when numbers of regional Sars-CoV-2 infections were still low. At the same time, average admission stroke severity and proportions of moderate/severe strokes (NIHSS >5) were 20 and 20-40% higher, respectively. There were no relevant deviations observed in proportions of younger patients (<65 years), proportions of patients with thrombolysis, or number of thrombectomy procedures. Stroke admissions at Charité subsequently rebounded and reached near-normal levels after 4 weeks when the number of new Sars-CoV-2 infections started to decrease. Conclusions: During the early pandemic, deviations of stroke-related admissions from historical averages were observed in both urban and rural regions of Northeastern Germany and appear to have been mainly driven by avoidance of admissions of mildly affected stroke patients.

COVID-19 among heart transplant recipients in Germany: a multicenter survey.

AIMS: Heart transplantation may represent a particular risk factor for severe coronavirus infectious disease 2019 (COVID-19) due to chronic immunosuppression and frequent comorbidities. We conducted a nation-wide survey of all heart transplant centers in Germany presenting the clinical characteristics of heart transplant recipients with COVID-19 during the first months of the pandemic in Germany. METHODS AND RESULTS: A multicenter survey of all heart transplant centers in Germany evaluating the current status of COVID-19 among adult heart transplant recipients was performed. A total of 21 heart transplant patients with COVID-19 was reported to the transplant centers during the first months of the pandemic in Germany. Mean patient age was 58.6 ± 12.3 years and 81.0% were male. Comorbidities included arterial hypertension (71.4%), dyslipidemia (71.4%), diabetes mellitus (33.3%), chronic kidney failure requiring dialysis (28.6%) and chronic-obstructive lung disease/asthma (19.0%). Most patients received an immunosuppressive drug regimen consisting of a calcineurin inhibitor (71.4%), mycophenolate mofetil (85.7%) and steroids (71.4%). Eight of 21 patients (38.1%) displayed a severe course needing invasive mechanical ventilation. Those patients showed a high mortality (87.5%) which was associated with right ventricular dysfunction (62.5% vs. 7.7%; p = 0.014), arrhythmias (50.0% vs. none; p = 0.012), and thromboembolic events (50.0% vs. none; p = 0.012). Elevated high-sensitivity cardiac troponin T- and N-terminal prohormone of brain natriuretic peptide were significantly associated with the severe form of COVID-19 (p = 0.017 and p < 0.001, respectively). CONCLUSION: Severe course of COVID-19 was frequent in heart transplanted patients. High mortality was associated with right ventricular dysfunction, arrhythmias, thromboembolic events, and markedly elevated cardiac biomarkers.

Perspectives from CO+RE: How COVID-19 changed our food systems and food security paradigms.

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