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Mayo Clin Proc ; 95(7): 1354-1368, 2020 07.
Article in English | MEDLINE | ID: covidwho-1500136


OBJECTIVE: To explore the transcriptomic differences between patients with hypertrophic cardiomyopathy (HCM) and controls. PATIENTS AND METHODS: RNA was extracted from cardiac tissue flash frozen at therapeutic surgical septal myectomy for 106 patients with HCM and 39 healthy donor hearts. Expression profiling of 37,846 genes was performed using the Illumina Human HT-12v3 Expression BeadChip. All patients with HCM were genotyped for pathogenic variants causing HCM. Technical validation was performed using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. This study was started on January 1, 1999, and final analysis was completed on April 20, 2020. RESULTS: Overall, 22% of the transcriptome (8443 of 37,846 genes) was expressed differentially between HCM and control tissues. Analysis by genotype revealed that gene expression changes were similar among genotypic subgroups of HCM, with only 4% (1502 of 37,846) to 6% (2336 of 37,846) of the transcriptome exhibiting differential expression between genotypic subgroups. The qRT-PCR confirmed differential expression in 92% (11 of 12 genes) of tested transcripts. Notably, in the context of coronavirus disease 2019 (COVID-19), the transcript for angiotensin I converting enzyme 2 (ACE2), a negative regulator of the angiotensin system, was the single most up-regulated gene in HCM (fold-change, 3.53; q-value =1.30×10-23), which was confirmed by qRT-PCR in triplicate (fold change, 3.78; P=5.22×10-4), and Western blot confirmed greater than 5-fold overexpression of ACE2 protein (fold change, 5.34; P=1.66×10-6). CONCLUSION: More than 20% of the transcriptome is expressed differentially between HCM and control tissues. Importantly, ACE2 was the most up-regulated gene in HCM, indicating perhaps the heart's compensatory effort to mount an antihypertrophic, antifibrotic response. However, given that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses ACE2 for viral entry, this 5-fold increase in ACE2 protein may confer increased risk for COVID-19 manifestations and outcomes in patients with increased ACE2 transcript expression and protein levels in the heart.

Betacoronavirus , Cardiomyopathy, Hypertrophic/genetics , Cardiomyopathy, Hypertrophic/virology , Coronavirus Infections/complications , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/complications , Adolescent , Adult , Aged , Angiotensin-Converting Enzyme 2 , COVID-19 , Cardiomyopathy, Hypertrophic/metabolism , Case-Control Studies , Child , Genotype , Humans , Middle Aged , Myocardium/metabolism , Pandemics , RNA, Messenger/metabolism , Real-Time Polymerase Chain Reaction , SARS-CoV-2 , Young Adult
Ren Fail ; 43(1): 1329-1337, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1493366


BACKGROUND: This study sought to investigate incidence and risk factors for acute kidney injury (AKI) in hospitalized COVID-19. METHODS: In this retrospective study, we enrolled 823 COVID-19 patients with at least two evaluations of renal function during hospitalization from four hospitals in Wuhan, China between February 2020 and April 2020. Clinical and laboratory parameters at the time of admission and follow-up data were recorded. Systemic renal tubular dysfunction was evaluated via 24-h urine collections in a subgroup of 55 patients. RESULTS: In total, 823 patients were enrolled (50.5% male) with a mean age of 60.9 ± 14.9 years. AKI occurred in 38 (40.9%) ICU cases but only 6 (0.8%) non-ICU cases. Using forward stepwise Cox regression analysis, we found eight independent risk factors for AKI including decreased platelet level, lower albumin level, lower phosphorus level, higher level of lactate dehydrogenase (LDH), procalcitonin, C-reactive protein (CRP), urea, and prothrombin time (PT) on admission. For every 0.1 mmol/L decreases in serum phosphorus level, patients had a 1.34-fold (95% CI 1.14-1.58) increased risk of AKI. Patients with hypophosphatemia were likely to be older and with lower lymphocyte count, lower serum albumin level, lower uric acid, higher LDH, and higher CRP. Furthermore, serum phosphorus level was positively correlated with phosphate tubular maximum per volume of filtrate (TmP/GFR) (Pearson r = 0.66, p < .001) in subgroup analysis, indicating renal phosphate loss via proximal renal tubular dysfunction. CONCLUSION: The AKI incidence was very low in non-ICU patients as compared to ICU patients. Hypophosphatemia is an independent risk factor for AKI in patients hospitalized for COVID-19 infection.

Acute Kidney Injury/etiology , COVID-19/complications , Hypophosphatemia/complications , Pneumonia, Viral/complications , Acute Kidney Injury/epidemiology , COVID-19/epidemiology , China/epidemiology , Female , Hospitalization , Humans , Hypophosphatemia/epidemiology , Incidence , Intensive Care Units , Kidney Function Tests , Male , Middle Aged , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Retrospective Studies , Risk Factors , SARS-CoV-2
Dtsch Med Wochenschr ; 146(13-14): 927-932, 2021 Jul.
Article in German | MEDLINE | ID: covidwho-1493274


Acute COVID-19 pneumonia may result in persistent changes with various imaging and histopathological patterns, including organizing pneumonia and pulmonary fibrosis. In addition, SARS-CoV-2 infection is associated with increased risk of pulmonary vascular endothelialitis and thrombosis. Herein, current findings on pulmonary consequences of COVID-19 with implications for clinical management are summarized based on a selective literature review.

COVID-19/complications , Cryptogenic Organizing Pneumonia/complications , Pneumonia, Viral/complications , Pulmonary Fibrosis/complications , Acute Disease , COVID-19/diagnostic imaging , COVID-19/therapy , Cryptogenic Organizing Pneumonia/diagnostic imaging , Cryptogenic Organizing Pneumonia/therapy , Follow-Up Studies , Humans , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/therapy , Pulmonary Fibrosis/diagnostic imaging , Pulmonary Fibrosis/therapy
Sci Rep ; 11(1): 21259, 2021 10 28.
Article in English | MEDLINE | ID: covidwho-1493217


Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently a serious public health concern worldwide. Notably, co-infection with other pathogens may worsen the severity of COVID-19 symptoms and increase fatality. Here, we show that co-infection with influenza A virus (IAV) causes more severe body weight loss and more severe and prolonged pneumonia in SARS-CoV-2-infected hamsters. Each virus can efficiently spread in the lungs without interference by the other. However, in immunohistochemical analyses, SARS-CoV-2 and IAV were not detected at the same sites in the respiratory organs of co-infected hamsters, suggesting that either the two viruses may have different cell tropisms in vivo or each virus may inhibit the infection and/or growth of the other within a cell or adjacent areas in the organs. Furthermore, a significant increase in IL-6 was detected in the sera of hamsters co-infected with SARS-CoV-2 and IAV at 7 and 10 days post-infection, suggesting that IL-6 may be involved in the increased severity of pneumonia. Our results strongly suggest that IAV co-infection with SARS-CoV-2 can have serious health risks and increased caution should be applied in such cases.

COVID-19/complications , Orthomyxoviridae Infections/complications , Pneumonia, Viral/complications , SARS-CoV-2 , Animals , COVID-19/pathology , COVID-19/virology , Coinfection/pathology , Disease Models, Animal , Female , Humans , Interleukin-6/blood , Lung/diagnostic imaging , Lung/pathology , Mesocricetus , Orthomyxoviridae/pathogenicity , Orthomyxoviridae Infections/pathology , Orthomyxoviridae Infections/virology , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , SARS-CoV-2/pathogenicity , SARS-CoV-2/physiology , Severity of Illness Index , Virus Replication
Int J Rehabil Res ; 43(3): 285-286, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-1483689


We report, to the best of our knowledge, the first case of a probable COVID-19 infection in a 28-year-old man with Charcot-Marie-Tooth disease. The diagnosis was established through a remote interaction with the patient after early discharge from outpatient therapy due to upcoming traveling restrictions. The COVID-19 disease appeared mild, without major respiratory problems, and no obvious neuromuscular deterioration was reported or observed. Telerehabilitation provided an opportunity to continue with hand rehabilitation after tendon transfer surgery, perform an ad-hoc online evaluation, and advise the patient how to prevent the spread of infection and cope with restrictions limiting outpatient visits. This experience seems valuable for further development of telerehabilitation in anticipation of future pandemics or adversarial events since it allows reaching out to patients unable to travel and overcomes the need for regular outpatient visits.

Betacoronavirus , Charcot-Marie-Tooth Disease/surgery , Coronavirus Infections/complications , Pneumonia, Viral/complications , Telerehabilitation , Adult , COVID-19 , Charcot-Marie-Tooth Disease/complications , Humans , Male , Pandemics , SARS-CoV-2
J Med Ethics ; 46(8): 505-507, 2020 08.
Article in English | MEDLINE | ID: covidwho-1467731


COVID-19 is reducing the ability to perform surgical procedures worldwide, giving rise to a multitude of ethical, practical and medical dilemmas. Adapting to crisis conditions requires a rethink of traditional best practices in surgical management, delving into an area of unknown risk profiles. Key challenging areas include cancelling elective operations, modifying procedures to adapt local services and updating the consenting process. We aim to provide an ethical rationale to support change in practice and guide future decision-making. Using the four principles approach as a structure, Medline was searched for existing ethical frameworks aimed at resolving conflicting moral duties. Where insufficient data were available, best guidance was sought from educational institutions: National Health Service England and The Royal College of Surgeons. Multiple papers presenting high-quality, reasoned, ethical theory and practice guidance were collected. Using this as a basis to assess current practice, multiple requirements were generated to ensure preservation of ethical integrity when making management decisions. Careful consideration of ethical principles must guide production of local guidance ensuring consistent patient selection thus preserving equality as well as quality of clinical services. A critical issue is balancing the benefit of surgery against the unknown risk of developing COVID-19 and its associated complications. As such, the need for surgery must be sufficiently pressing to proceed with conventional or non-conventional operative management; otherwise, delaying intervention is justified. For delayed operations, it is our duty to quantify the long-term impact on patients' outcome within the constraints of pandemic management and its long-term outlook.

Coronavirus Infections/complications , Decision Making/ethics , Ethics, Medical , General Surgery/ethics , Health Equity/ethics , Pandemics/ethics , Patient Selection/ethics , Pneumonia, Viral/complications , Betacoronavirus , COVID-19 , Coronavirus Infections/virology , Cost-Benefit Analysis , England , Ethical Analysis , Ethical Theory , Humans , Informed Consent/ethics , Moral Obligations , Pneumonia, Viral/virology , Practice Guidelines as Topic , Principle-Based Ethics , Risk Assessment , SARS-CoV-2 , State Medicine , Surgeons , Surgical Procedures, Operative
Dtsch Arztebl Int ; 117(29-30): 492, 2020 07 20.
Article in English | MEDLINE | ID: covidwho-1456276