Immunometabolic interference between cancer and COVID-19.

Even though cancer patients are generally considered more susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the mechanisms driving their predisposition to severe forms of coronavirus disease 2019 (COVID-19) have not yet been deciphered. Since metabolic disorders are associated with homeostatic frailty, which increases the risk of infection and cancer, we asked whether we could identify immunometabolic pathways intersecting with cancer and SARS-CoV-2 infection. Thanks to a combined flow cytometry and multiomics approach, here we show that the immunometabolic traits of COVID-19 cancer patients encompass alterations in the frequency and activation status of circulating myeloid and lymphoid subsets, and that these changes are associated with i) depletion of tryptophan and its related neuromediator tryptamine, ii) accumulation of immunosuppressive tryptophan metabolites (i.e., kynurenines), and iii) low nicotinamide adenine dinucleotide (NAD+) availability. This metabolic imbalance is accompanied by altered expression of inflammatory cytokines in peripheral blood mononuclear cells (PBMCs), with a distinctive downregulation of IL-6 and upregulation of IFNγ mRNA expression levels. Altogether, our findings indicate that cancer not only attenuates the inflammatory state in COVID-19 patients but also contributes to weakening their precarious metabolic state by interfering with NAD+-dependent immune homeostasis.

Long-term prognostic impact of subclinical myocardial dysfunction in patients recovered from COVID-19.

BACKGROUND: Cardiovascular sequelae may occur in patients recovered from coronavirus disease 2019 (COVID-19). Recent studies have detected a considerable incidence of subclinical myocardial dysfunction-assessed with speckle-tracking echocardiography-and of long-COVID symptoms in these patients. This study aimed to define the long-term prognostic role of subclinical myocardial dysfunction and long-COVID condition in patients recovered from COVID-19 pneumonia. METHODS: We prospectively followed up 110 patients hospitalized at our institution due to COVID-19 pneumonia in April 2020 and then recovered from SARS-CoV-2 infection. A 7-month clinical and echocardiographic evaluation was performed, followed by a 21-month clinical follow-up. The primary outcome was major adverse cardiovascular events (MACE), a composite of myocardial infarction, stroke, heart failure hospitalization, and all-cause mortality. RESULTS: A subclinical myocardial dysfunction-defined as an impairment of left ventricular global longitudinal strain (≥-18%)-was identified at a 7-month follow-up in 37 patients (34%), was associated with an increased risk of long-term MACE with a good discriminative power (area under the curve: .73) and resulted in a strong independent predictor of extended MACE in multivariate regression analyses. Long-COVID condition was not associated with a worse long-term prognosis, instead. CONCLUSIONS: In patients recovered from COVID-19 pneumonia, a subclinical myocardial dysfunction is present in one-third of the whole population at 7-month follow-up and is associated with a higher risk of MACE at long-term follow-up. Speckle-tracking echocardiography is a promising tool to optimize the risk-stratification in patients recovered from COVID-19 pneumonia, while the definition of a long-COVID condition has no prognostic relevance.

When Outcomes Diverge: Age and Cardiovascular Risk as Determinants of Mortality and ICU Admission in COVID-19.

BACKGROUND: Hospital mortality and admission to the Intensive Care Unit (ICU) are markers of disease severity in COVID-19 patients. Cardiovascular co-morbidities are one of the main determinants of negative outcomes. In this study we investigated the impact of cardiovascular co-morbidities on mortality and admission to the ICU in first-wave COVID-19 patients. METHODS: A multicenter, retrospective, cohort study. A total of 1077 patients were analyzed for mortality and ICU admission. Cardiovascular risk factors were explored as determinants of the outcomes after correction for other confounders. RESULTS: In the multivariable model, after correction for age, only a history of heart failure remained independently associated (p = 0.0013) with mortality (hazard ratio 2.22, 95% confidence interval 1.37 to 3.62). Age showed a mortality risk increase of 8% per year (hazard ratio 1.08, 95% confidence interval 1.05 to 1.10, p = 0.001). The transition from ward to the ICU had, as a single determinant, the age, but in a reversed fashion (hazard ratio 0.96, 95% confidence interval 0.94 to 0.98, p = 0.0002). CONCLUSIONS: Once adjusted for the main determinant of mortality (age) heart failure only remained independently associated with mortality. Admission to the ICU was less likely for elderly patients. This may reflect the catastrophic impact of the first wave of COVID-19 pandemic in terms of ICU bed availability in Lombardy, leading to a selection process for ICU admission.

Cardiovascular magnetic resonance characterization of myocardial injury in recovered COVID-19 patients with elevated troponins during hospital stay

Aims Despite being a common finding in hospitalized COVID-19 patients, cardiac troponin elevation remains a nonspecific detection of myocardial injury and further in-hospital investigation into the cause of myocardial injury is rarely done. COVID-19 patients with myocardial injury show a significantly higher in-hospital mortality rate compared with those without myocardial injury and among those with myocardial injury, greater degrees of troponin elevation are associated with higher mortality rates. There are still many questions regarding possible cardiovascular sequelae and prognostic significance in these patients. Being able to distinguish between inflammatory and ischaemic causes of myocardial injury cardiovascular magnetic resonance (CMR) is the non-invasive modality of choice to investigate myocardial involvement in these patients. Presented are the preliminary single-centre results from a multicentre study aimed to characterize the prevalence, type and extent of COVID-19-related cardiovascular sequelae using CMR imaging. Methods and results In this single-centre prospective observational cohort study, patients hospitalized with confirmed COVID-19 and at least one value of high sensitivity I troponin (hs-Tnl) >99th percentile during hospitalization were eligible for follow-up contrast-enhanced CMR imaging. Patients with any standard CMR contraindications were excluded. Images were acquired using a standardized myocarditis protocol including late gadolinium enhancement (LGE) and T1 and T2 mapping. Cutoff values of 1015 ms and 50 ms were used for abnormal T1 and T2 measurements, respectively. Of the 21 patients (65 ± 11.85 years) who underwent imaging, 15 (71.4%) were male. The mean follow-up duration from the date of confirmed COVID-19 diagnosis was 169 ± 19 days. The mean left ventricular ejection fraction was 64.1 ± 13.87 and 3 (14.3%) patients had evidence of wall motion abnormalities. LGE was seen in 9/20 (45.0%) patients, reflecting myocardial fibrosis. Increased native T1 signal representing myocardial fibrosis and/or oedema was seen in 9/20 (45.0%) patients. While increased native T2 signal, being more specific for oedema was observed in 3/20 (15.0%) patients. Considering CMR findings, 6 (28.6%) patients showed evidence of previous myocarditis. Conclusions In this single centre Italian study of patients hospitalized with COVID-19 and elevated cardiac enzymes, myocarditis-like injury was evident in about a quarter of the patients. Whether these findings will lead to long-term cardiac complications is still to be confirmed.

CMR prevalence of subclinical myocardial damage in non-hospitalized COVID-19 patients: are we looking for a needle in a haystack?

Aims Subclinical myocardial damage is not uncommon in COVID-19 patients, likely reflecting a combination of direct viral toxicity with the activation of an uncontrolled autoimmune response usually developing during the cytokine storm phase. Whilst myocardial involvement in hospitalized patients has been extensively described in literature, no data are currently available for non-hospitalized individuals. Present study aimed to explore prevalence and impact on patients’ management of myocardial damage detected with CMR, in a cohort of consecutive non-hospitalized SARS-CoV-2 infection patients. Methods and results We conducted a single centre prospective observational study on 31 consecutive patients with previous COVID-19 who underwent CMR between October 2020 and June 2021 without requiring hospital admission. Myocarditis was defined by CMR according to the revised Lake Louise Criteria (LLC), if at least one criterion was positive: T2-based marker for myocardial oedema and T1-based marker for associated myocardial injury. Our patients’ cohort included 31 individuals with a mean age of 42.5 ± 17.4 years (20 males;64.5%) with mean follow-up time of 365.8 ± 89 days between first positive PCR and last clinical evaluation. CMR evidence of cardiac involvement was observed in six patients (19.3%)—including two acute (of which one with pericardial inflammation), one subacute and three healed myocarditis. CMR abnormalities were associated with a higher percentage of palpitations (83% vs. 24%, P = 0.013) and chest pain (66% vs. 16%, P = 0.026) during the active phase of COVID-19. In all CMR positive cases, a tailored therapeutic approach was established consisting with the administration of cardioactive therapy with beta-blockers. All cases were uneventful during the follow-up period. Conclusions Our data showed a 19.3% prevalence of unexpected/subclinical myocardial involvement in a cohort of 31 consecutive non-hospitalized patients with previous SARS-CoV-2 infection. CMR findings were retrospectively associated with cardiac symptoms during the acute phase and yielded a change in clinical and therapeutic management in all positive cases. A better knowledge of symptomatic course of COVID-19 could help physicians to adequately select individuals in which CMR may show signs of cardiac damage.