Objective We aimed to describe the associations of age and sex with the risk of COVID-19 in different severity stages ranging from infection to death. Design Systematic review and meta-analysis. Data sources PubMed and Embase through 4 May 2020. Study selection We considered cohort and case-control studies that evaluated differences in age and sex on the risk of COVID-19 infection, disease severity, intensive care unit (ICU) admission and death. Data extraction and synthesis We screened and included studies using standardised electronic data extraction forms and we pooled data from published studies and data acquired by contacting authors using random effects meta-analysis. We assessed the risk of bias using the Newcastle-Ottawa Scale. Results We screened 11.550 titles and included 59 studies comprising 36.470 patients in the analyses. The methodological quality of the included papers was high (8.2 out of 9). Men had a higher risk for infection with COVID-19 than women (relative risk (RR) 1.08, 95% CI 1.03 to 1.12). When infected, they also had a higher risk for severe COVID-19 disease (RR 1.18, 95% CI 1.10 to 1.27), a higher need for intensive care (RR 1.38, 95% CI 1.09 to 1.74) and a higher risk of death (RR 1.50, 95% CI 1.18 to 1.91). The analyses also showed that patients aged 70 years and above have a higher infection risk (RR 1.65, 95% CI 1.50 to 1.81), a higher risk for severe COVID-19 disease (RR 2.05, 95% CI 1.27 to 3.32), a higher need for intensive care (RR 2.70, 95% CI 1.59 to 4.60) and a higher risk of death once infected (RR 3.61, 95% CI 2.70 to 4.84) compared with patients younger than 70 years. Conclusions Meta-analyses on 59 studies comprising 36.470 patients showed that men and patients aged 70 and above have a higher risk for COVID-19 infection, severe disease, ICU admission and death. PROSPERO registration number CRD42020180085.

https://bmjopen.bmj.com/content/bmjopen/11/1/e044640.full.pdf

Demographic risk factors for COVID-19 infection, severity, ICU admission and death: a meta-analysis of 59 studies.

Background Troponin elevation is common in hospitalized COVID-19 patients, but underlying aetiologies are ill-defined. We used multi-parametric cardiovascular magnetic resonance (CMR) to assess myocardial injury in recovered COVID-19 patients. Methods and results One hundred and forty-eight patients (64 ± 12 years, 70% male) with severe COVID-19 infection [all requiring hospital admission, 48 (32%) requiring ventilatory support] and troponin elevation discharged from six hospitals underwent convalescent CMR (including adenosine stress perfusion if indicated) at median 68 days. Left ventricular (LV) function was normal in 89% (ejection fraction 67% ± 11%). Late gadolinium enhancement and/or ischaemia was found in 54% (80/148). This comprised myocarditis-like scar in 26% (39/148), infarction and/or ischaemia in 22% (32/148) and dual pathology in 6% (9/148). Myocarditis-like injury was limited to three or less myocardial segments in 88% (35/40) of cases with no associated LV dysfunction; of these, 30% had active myocarditis. Myocardial infarction was found in 19% (28/148) and inducible ischaemia in 26% (20/76) of those undergoing stress perfusion (including 7 with both infarction and ischaemia). Of patients with ischaemic injury pattern, 66% (27/41) had no past history of coronary disease. There was no evidence of diffuse fibrosis or oedema in the remote myocardium (T1: COVID-19 patients 1033 ± 41 ms vs. matched controls 1028 ± 35 ms; T2: COVID-19 46 ± 3 ms vs. matched controls 47 ± 3 ms). Conclusions During convalescence after severe COVID-19 infection with troponin elevation, myocarditis-like injury can be encountered, with limited extent and minimal functional consequence. In a proportion of patients, there is evidence of possible ongoing localized inflammation. A quarter of patients had ischaemic heart disease, of which two-thirds had no previous history. Whether these observed findings represent pre-existing clinically silent disease or de novo COVID-19-related changes remain undetermined. Diffuse oedema or fibrosis was not detected.

/pdf/patterns-of-myocardial-injury-in-recovered-troponin-positive-4ly8auks4n.pdf

Patterns of myocardial injury in recovered troponin-positive COVID-19 patients assessed by cardiovascular magnetic resonance.

Special Article - Acute myocardial injury in patients hospitalized with COVID-19 infection: A review.

COPD patients have increased risk of severe pneumonia and poor outcomes when they develop COVID-19. This may be related to poor underlying lung reserves or increased expression of ACE-2 receptor in small airways.https://bit.ly/37dSB8l

https://erj.ersjournals.com/content/erj/56/2/2002108.full.pdf

COVID-19 and COPD.

Patients with cardiovascular disease and, namely, heart failure are more susceptible to coronavirus disease 2019 (COVID-19) and have a more severe clinical course once infected. Heart failure and myocardial damage, shown by increased troponin plasma levels, occur in at least 10% of patients hospitalized for COVID-19 with higher percentages, 25% to 35% or more, when patients critically ill or with concomitant cardiac disease are considered. Myocardial injury may be elicited by multiple mechanisms, including those occurring with all severe infections, such as fever, tachycardia, adrenergic stimulation, as well as those caused by an exaggerated inflammatory response, endotheliitis and, in some cases, myocarditis that have been shown in patients with COVID-19. A key role may be that of the renin-angiotensin-aldosterone system. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects human cells binding to angiotensin-converting enzyme 2 (ACE2), an enzyme responsible for the cleavage of angiotensin II into angiotensin 1-7, which has vasodilating and anti-inflammatory effects. Virus-mediated down-regulation of ACE2 may increase angiotensin II stimulation and contribute to the deleterious hyper-inflammatory reaction of COVID-19. On the other hand, ACE2 may be up-regulated in patients with cardiac disease and treated with ACE inhibitors or angiotensin receptor blockers. ACE2 up-regulation may increase the susceptibility to COVID-19 but may be also protective vs. angiotensin II-mediated vasoconstriction and inflammatory activation. Recent data show the lack of untoward effects of ACE inhibitors or angiotensin receptor blockers for COVID-19 infection and severity. Prospective trials are needed to ascertain whether these drugs may have protective effects.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/ejhf.1871

COVID 19 and heart failure: from infection to inflammation and angiotensin II stimulation. Searching for evidence from a new disease

Objective We sought to explore the prevalence and immediate clinical implications of acute myocardial injury in a cohort of patients with covid-19 in a region of China where medical resources are less stressed than in Wuhan (the epicentre of the pandemic). Methods We prospectively assessed the medical records, laboratory results, chest CT images and use of medication in a cohort of patients presenting to two designated covid-19 treatment centres in Sichuan, China. Outcomes of interest included death, admission to an intensive care unit (ICU), need for mechanical ventilation, treatment with vasoactive agents and classification of disease severity. Acute myocardial injury was defined by a value of high-sensitivity troponin T (hs-TnT) greater than the normal upper limit. Results A total of 101 cases were enrolled from January to 10 March 2020 (average age 49 years, IQR 34–62 years). Acute myocardial injury was present in 15.8% of patients, nearly half of whom had a hs-TnT value fivefold greater than the normal upper limit. Patients with acute myocardial injury were older, with a higher prevalence of pre-existing cardiovascular disease and more likely to require ICU admission (62.5% vs 24.7%, p=0.003), mechanical ventilation (43.5% vs 4.7%, p Conclusion Acute myocardial injury is common in patients with covid-19 and is associated with adverse prognosis.

https://heart.bmj.com/content/heartjnl/106/15/1154.full.pdf

Acute myocardial injury is common in patients with COVID-19 and impairs their prognosis.

The effects of intravenous lidocaine on the refractory periods of the atrium, AV node and right ventricular myocardium were studied using His bundle recordings and the extrastimulus technique with and without atrial and ventricular pacing The drug was administered in an intravenous bolus dose of 1 mg/Kg followed by an infusion of 100 micrograms/Kg/min The AH, HV intervals and resting sinus cycle length as well as functional and effective refractory periods of atrium, AV node and right ventricle were measured before and 5 min afrer bolus injection of lidocaine Neither of the refractory periods nor AH and HV intervals changed significantly following administration of lidocaine The result of this first study in children is in agreement with previous reports of the effects of lidocaine on the cardiac conduction system in adults

Suspected Hydroxychloroquine-Induced Sinus Bradycardia and QTc Prolongation in a Patient with COVID-19

A right‐to‐left shunt (RLS) can mediate the hypoxic state, and hypoxemia is relevant for the development of drug‐resistant epilepsy (DRE). The objective of this study was to identify the relationship between RLS and DRE and further investigate the contribution of RLS to the oxygenation state in patients with epilepsy (PWEs).

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/epi4.12710

Relationship between right‐to‐left shunt, hypoxia, and epilepsy


 The therapeutic efficacy of CAR-T cells in solid tumors, unlike in hematologic tumor, is greatly limited by the insufficient infiltration and persistence of CAR-T cells as well as the immunosuppressive tumor microenvironment. The aim of this study was to overcome these obstacles by introducing an αPDL1/CD28 switch-receptor construct and by seeking combinatorial strategies for CAR-T cells in solid tumors. We found that in non-transduction T cells, the cytokine release and T cell proliferation were repressed in response to PD-L1 protein, while T cells that express αPDL1/CD28 switch-receptor showed enhanced functions, indicating that αPDL1/CD28 could revert PD-L1 inhibition into CD28 costimulation. CAR-T cells with αPDL1/CD28 switch-receptor showed better effector function than that of unitary CAR-T in vitro studies and significant responses in tumor-bearing mice, with more effector memory T cells infiltrated in the tumor. On this basis, PD-1 inhibitor can further enhance the efficacy and persistence of αPDL1/CD28 CAR-T cells, especially in PDL1+ tumor models. We found in vitro studies that radiotherapy increased the expression of T-cell recruiting chemokines and promoted CAR-T cell transmigration. In tumor-bearing mice, synergistic anti-tumor efficacy of mice treated with radiotherapy and αPDL1/CD28 CAR-T cells was further observed. Finally, triple therapy with radiotherapy and anti-PD1 plus αPDL1/CD28 CAR-T cells maximized antitumor responses and induced complete cures in the tumor-bearing mice. Our study suggests that αPDL1/CD28 augments the function of CAR-T cells, and the combinatorial regime of αPDL1/CD28 CAR-T cells, radiotherapy and anti-PD1 in solid tumors could be further investigated.
 Citation Format: Limei Yin, Wenbo Wang, Zhuoran Yao, Jianxin Xue, Ruizhan Tong, Hui Wang, Shuangsi Liao, Laduona Wang, Yue Zheng, Feifei Na, Min Yu, Xuanwei Zhang, Youling Gong, Meijuan Huang, Xianming Mo, Chong Chen, You Lu. CAR-T cells with αPDL1/CD28 switch-receptor synergize radiotherapy and anti-PD1 therapy in solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5569.

Abstract 5569: CAR-T cells with αPDL1/CD28 switch-receptor synergize radiotherapy and anti-PD1 therapy in solid tumors

An abnormal aortic sinus (37 mm) and ascending aorta (42 mm) were detected in a 67-year-old man 9 years ago (Panel A). It showed a progressive widening (53 mm) with moderate aortic regurgitation (Panels B and C) in 2 years of follow-up. Then Aortic valve replacement and ascending aortoplasty were performed (Panels D–F). Intraoperatively, the aortic wall and leaves were thickened, showing fibrous changes but no inflammatory reaction. However, the aortic root began to sink down slightly to left ventricular outflow tract (LVOT) in the first year after surgery, with a normal function of the prosthetic valve and no perivalvular leakage (Panels G–I). A regular follow-up was suggested. In the 6th year after surgery, the patient suddenly suffered from chest tightness, palpitations, and even syncope. Transthoracic echocardiography showed the aortic root sinking was aggravated, which caused LVOT disappearing and severe mitral valve stenosis (Panels J–L, see Supplementary material online, Movies 1–3). Mitral valve replacement and floating Bentall with LVOT reconstruction were performed, and postoperative and 1 monthly follow-up showed normal prosthetic valve function (Panels M–O). 

Hui Wang

Papers

Acute myocardial injury is common in patients with COVID-19 and impairs their prognosis.

Suspected Hydroxychloroquine-Induced Sinus Bradycardia and QTc Prolongation in a Patient with COVID-19

Relationship between right‐to‐left shunt, hypoxia, and epilepsy

Abstract 5569: CAR-T cells with αPDL1/CD28 switch-receptor synergize radiotherapy and anti-PD1 therapy in solid tumors

Aortic root 'sink down' caused mitral stenosis after aortic valve replacement: a rare presentation of Bechet's disease.