Corrigendum: D-dimer trends elaborate the heterogeneity of risk in hospitalized patients with COVID-19: a multi-national case series from different waves.

[This corrects the article DOI: 10.3389/fmed.2023.1103842.].

D-dimer trends elaborate the heterogeneity of risk in hospitalized patients with COVID-19: A multi-national case series from different waves.

Introduction: Variable D-dimer trends during hospitalization reportedly result in distinct in-hospital mortality. In this multinational case series from the first and second waves, we show the universality of such D-dimer trends. Methods: We reviewed 405 patients with COVID-19 during the first wave admitted to three institutions in the United States, Italy, and Colombia, and 111 patients admitted to the U.S. site during the second wave and 55 patients during the third wave. D-dimer was serially followed during hospitalization. Results: During the first wave, 66 (15%) patients had a persistently-low pattern, 33 (8%) had early-peaking, 70 (16%) had mid-peaking, 94 (22%) had fluctuating, 30 (7%) had late-peaking, and 112 (26%) had a persistently-high pattern. During the second and third waves, similar patterns were observed. D-dimer patterns were significantly different in terms of in-hospital mortality similarly in all waves. Patterns were then classified into low-risk patterns (persistently-low and early-peaking), where no deaths were observed in both waves, high-risk patterns (mid-peaking and fluctuating), and malignant patterns (late-peaking and persistently-high). Overall, D-dimer trends were associated with an increased risk for in-hospital mortality in the first wave (overall: HR: 1.73) and stayed the same during the second (HR: 1.67, p < 0.001) and the third (HR: 4.4, p = 0.001) waves. Conclusion: D-dimer behavior during COVID-19 hospitalization yielded universal categories with distinct mortality risks that persisted throughout all studied waves of infection. Monitoring D-dimer behavior may be useful in the management of these patients.

Disruption of cardio-pulmonary coupling in myopathies: Pathophysiological and mechanistic characterization with special emphasis on nemaline myopathy.

The heart and lung are in continuous reciprocal interaction that creates a functional and anatomical reserve referred to as cardiopulmonary coupling (CPC). Disruption of CPC can occur due to various cardiac or pulmonary pathologies but also can occur in patients with myopathies. Nemaline myopathy (NM) is a skeletal muscle heterogeneous disorder due to contractile proteins' gene mutations that impact lung and cardiac mechanics and thus is expected to adversely affect CPC in a complex manner. We present a case of NM and we review the literature on cardiac and pulmonary effects of myopathy-related disruption of CPC.

Association between right ventricular dysfunction and in-hospital mortality in surges of SARS-CoV-2 infection attributed to the Alpha, Delta, and Omicron variants.

Background: Right ventricular (RV) dysfunction in acute COVID-19 was reported to be associated with poor prognosis. We studied the association between parameters of RV dysfunction and in-hospital mortality during the surges caused by different SARS-CoV-2 variants. Methods: In a retrospective single-center study, we enrolled 648 consecutive patients hospitalized with COVID-19 [66 (10 %) hospitalized during the alpha variant surge, 433 (67 %) during the delta variant surge, and 149 (23 %), during the omicron variant surge]. Patients were reported from a hospital with an underreported population of mostly African American and Hispanic patients. Patients were followed for a median of 11 days during which in-hospital death occurred in 155 (24 %) patients [Alpha wave: 25 (38 %), Delta Wave: 112 (26 %), Omicron wave: 18 (12 %), p < 0.001]. Results: RV dysfunction occurred in 210 patients (alpha: 32 %, 26 %, delta: 29 %, and omicron: 49 %, p < 0.001) and was associated with higher mortality across waves, however, independently predicted in-hospital mortality in the Alpha (HR = 5.1, 95 % CI: 2.06-12.5) and Delta surges (HR = 1.6, 95 % CI: 1.11-2.44), but not in the Omicron surge. When only patients with RV dysfunction were compared, the mortality risk was found to decrease significantly from the Alpha (HR = 13.6, 95 % CI: 3.31-56.3) to the delta (HR = 1.93, 95 % CI: 1.25-2.96) and to the Omicron waves (HR = 11, 95 % CI: 0.6-20.8). Conclusions: RV dysfunction continues to occur in all strains of the SARS-CoV-2 virus, however, the mortality risk decreased from wave to wave likely due to evolution of better therapeutics, increase rate of vaccination, or viral mutations resulting in decrease virulence.Registration number of clinical studies: BronxCare Hospital center institutional review board under the number 05 13 21 04.

Anticoagulation for hypercoagulability in severe critical COVID-19: A case series of fading and fatal cycles of microthrombosis.

The pathophysiology of the COVID-19 involves a systemic hypercoagulable state and systemic micro-thrombosis which can cause fatal consequences. Despite that anticoagulation seems an intuitive therapeutic option, the US National Institute of Health has issued a warning against its use in critically ill patients. We present five cases of imaging-proven or clinically suspected hypercoagulability with hemodynamic compromise despite therapeutic anticoagulation. We describe the patients with thoughts on links between pathophysiology and the laboratory values, clinical course, and imaging studies in each case. All patients presented to the hospital with symptoms and chest imaging suggestive of COVID-19 pneumonia. All patients presented with severe hypoxia requiring mechanical ventilation, and received full anticoagulation for treatment of hypercoagulable state suggested by elevated D-dimer. All but one patient received alteplase for thrombolytic therapy of suspected massive pulmonary embolism (PE). On the basis of this case series, hypercoagulability in COVID-19 is a late manifestation of the disease that persists despite anticoagulation, is cyclic in nature based on D-dimer despite thrombolysis, and is fatal if it rebounds. The use of anticoagulation and thrombolysis in these patients seemed harmful or non-beneficial. Early intervention before D-dimer elevation and hemodynamic compromise may benefit in preventing thromboembolic burden. .

Combined atrioventricular longitudinal strain rate during isovolumic contraction predicts pulmonary capillary wedge pressure in patients with systolic dysfunction.

BACKGROUND: Reportedly, mitral annular velocities derived by tissue Doppler imaging (TDI)-during isovolumic contraction (IVV) can predict pulmonary capillary wedge pressure (PCWP) in heart failure patients with depressed ejection fraction (EF). We investigated the use of color TDI-derived left atrial (LA) and left ventricular (LV) longitudinal strain rate (SR) during isovolumic contraction (IC) to predict the invasively measured PCWP. METHODS AND RESULTS: Forty patients referred with symptoms of heart failure were prospectively studied [age: 56±8 years, 12 (30%) females, and mean LVEF: 51±14%]. PCWP was measured invasively immediately after echocardiography. Mitral annular IVV was measured for all patients and SR during the IC and ejection were measured for the LV (LVSR-IC, LVSR-Ej) as well as the LA (LASR-IC, and LASR-Ej). Atrioventricular SR during IC and Ej (AVSR-IC, AVSR-Ej) was calculated as the sum of the LV and LA values. Patients were classified and compared based on their EF into 19 (49%) with EF≥55%, and 21 (51%) with EF<55%. No significant differences were noted for age, sex, risk factors, and medications between both patients with EF≥55% and EF<55%. Compared to EF≥55%, patients with EF<55% had lower IVV (4.63±1.2 vs. 7.01±1.9 cm/s, P<0.001), LVSR-Ej (1±0.3 vs. 1.2±0.2, P=0.03), LASR-IC (1.3±0.6 vs. 1.9±1, P=0.03), LASR-Ej (1.5±0.5 vs. 2.6±1.3 s-1, P=0.001), AVSR-IC (2±0.8 vs. 2.7±1.06 s-1, P=0.023), and AVSR-Ej (2.5±0.6 vs. 3.9±1.1 s-1, <0.001). LVSR-IC, LVSR-Ej, LASR-IC, AVSR-IC, and IVV correlated with PCWP in only in EF<55%, with the strongest correlation noted for AVSR-IC (r=-0.72, <0.001). Other correlates with PCWP in EF<55% were E/e' and left atrial volume (r=0.47, 0.7, P=0.04, 0.001; respectively). Multivariate regression revealed that in patients with EF<55% AVSR-IC was the only independent predictor of PCWP. Finally, IVV correlated with LVSR-IC and LASR-IC and this correlation became strongest with AVSR-IC (r=0.77, 0.001). CONCLUSION: The combined LV and LA longitudinal SR during IC as represented by AVSR-IC showed a strong correlation with PCWP in patients with depressed EF. The correlation between mitral annular IVV and PCWP in those patients can be a product of this combination and may a function of atrioventricular mechanical coupling.

COVID-19 in the Healthy Patient Population: Demographic and Clinical Phenotypic Characterization and Predictors of In-Hospital Outcomes.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) can infect patients in any age group including those with no comorbid conditions. Understanding the demographic, clinical, and laboratory characteristics of these patients is important toward developing successful treatment strategies. Approach and Results: In a retrospective study design, consecutive patients without baseline comorbidities hospitalized with confirmed COVID-19 were included. Patients were subdivided into ≤55 and >55 years of age. Predictors of in-hospital mortality or mechanical ventilation were analyzed in this patient population, as well as subgroups. Stable parameters in overall and subgroup models were used to construct a cluster model for phenotyping of patients. Of 1207 COVID-19-positive patients, 157 met the study criteria (80≤55 and 77>55 years of age). Most reliable predictors of outcomes overall and in subgroups were age, initial and follow-up d-dimer, and LDH (lactate dehydrogenase) levels. Their predictive cutoff values were used to construct a cluster model that produced 3 main clusters. Cluster 1 was a low-risk cluster and was characterized by younger patients who had low thrombotic and inflammatory features. Cluster 2 was intermediate risk that also consisted of younger population that had moderate level of thrombosis, higher inflammatory cells, and inflammatory markers. Cluster 3 was a high-risk cluster that had the most aggressive thrombotic and inflammatory feature. CONCLUSIONS: In healthy patient population, COVID-19 remains significantly associated with morbidity and mortality. While age remains the most important predictor of in-hospital outcomes, thromboinflammatory interactions are also associated with worse clinical outcomes regardless of age in healthy patients.