[Follow-up of patients after COVID-19 pneumonia. Pulmonary sequelae]. / Seguimiento de los pacientes después de neumonía por COVID-19. Secuelas pulmonares.

Coronavirus disease 2019 (COVID-19) is an infection caused by SARS-CoV-2 that has caused an unprecedented pandemic with a high rate of morbidity and mortality worldwide. Although most cases are mild, there are a considerable number of patients who develop pneumonia or even acute respiratory distress syndrome (ARDS). After having recovered from the initial disease, many patients continue with various symptoms (fatigue, dry cough, fever, dyspnea, anosmia, and chest pain, among others.), which has led to consider the possible existence of "post-COVID-19 syndrome". Although the definition and validity of this syndrome are not clear yet, several studies report that individuals who have recovered from COVID-19 may have persistent symptoms, radiological abnormalities, and compromised respiratory function. Current evidence suggests that there is a large number of pulmonary sequelae after COVID-19 pneumonia (interstitial thickening, ground glass opacities, crazy paving pattern, and bronchiectasis, among others.). Likewise, it seems that pulmonary function tests (spirometry, DLCO, 6MWT, and measurement of maximum respiratory pressures), in addition to high-resolution computed axial tomographies (CAT scan), are useful for the assessment of these post-COVID-19 pulmonary sequelae. This review aims to describe the possible pulmonary sequelae after COVID-19 pneumonia, as well as to suggest diagnostic procedures for their correct assessment and follow-up; thus, allowing proper management by a multidisciplinary medical team.

COVID-19 es la enfermedad causada por el virus SARS-CoV-2, la cual ha ocasionado una pandemia sin precedentes, con gran cantidad de infectados y muertos en el mundo. Aunque la mayoría de los casos son leves, existe una cantidad considerable de pacientes que desarrollan neumonía o, incluso, síndrome de distrés respiratorio agudo (SDRA). Luego de recuperarse del cuadro inicial, muchos pacientes continúan con diversos síntomas (fatiga, tos seca, fiebre, disnea, anosmia, dolor torácico, entre otras), lo que ha llevado a considerar la posible existencia del "síndrome pos-COVID-19". Aunque la definición y validez de este síndrome aún no son claras, varios estudios reportan que los individuos recuperados de la COVID-19 pueden tener persistencia de síntomas, anormalidades radiológicas y compromiso en la función respiratoria. La evidencia actual sugiere que existe gran cantidad de secuelas pulmonares despues de una neumonía por COVID-19 (engrosamiento intersticial, infiltrado en vidrio esmerilado, patrón en empedrado, bronquiectasias, entre otras.). De igual forma, parece ser que las pruebas de función pulmonar (espirometría, prueba de difusión pulmonar de monóxido de carbono, prueba de caminata de seis minutos y la medición de las presiones respiratorias máximas), además de la tomografía axial computarizada de alta resolución, son útiles para evaluar las secuelas pulmonares pos-COVID-19. En esta revisión se pretende describir las posibles secuelas a nivel pulmonar posteriores a neumonía por COVID-19, así como sugerir procedimientos diagnósticos para su correcta evaluación y seguimiento, que permitan el manejo adecuado por parte de un equipo médico multidisciplinario.

COVID-19 and Acute Pulmonary Embolism: A Case Series and Brief Review.

The SARS-CoV-2 virus, or COVID-19, is responsible for the current global pandemic and has resulted in the death of over 400,000 in the United States. Rates of venous thromboembolism have been noted to be much higher in those infected with COVID-19. Here we report a case-series of COVID-19 patients with diverse presentations of pulmonary embolism (PE). We also briefly describe the pathophysiology and mechanisms for pulmonary embolism in COVID-19. These cases indicate a need to maintain a high index of suspicion for PE in patients with COVID-19, as well as the need to consider occult COVID-19 infection in patients with PE in the right clinical circumstance.

Diagnostic Accuracy of D-Dimers for Predicting Pulmonary Embolism in COVID-19-Patients.

IMPORTANCE: Proinflammatory and hypercoagulable states with marked elevation seen in D-Dimer levels have been accurately described in patients infected by the SARS- Cov2 even without pulmonary embolism (PE). OBJECTIVES: To compare D-dimers values in patients infected by the novel Coronavirus 2019 (COVID-19) with and without PE and to establish an optimal D-dimer cut-off to predict the occurrence of PE, which guides pulmonary computed tomography angiography (CTPA) indication. METHODS: We retrospectively enrolled all COVID-19-patients admitted between October first and November 22th, 2020, at the University Hospital Center of Mohammed VI, Oujda (Morocco), suspected to have PE and underwent a CTPA. Demographic characteristics and blood test results were compared between PE-positive and PE-negative. The receiver operating characteristics (ROC) curve was constructed to establish an optimal D-Dimer cut-off to predict the occurrence of PE. RESULTS: The study population consisted of 84 confirmed COVID-19-patients. The mean age was 64.93 years (SD 14.19). PE was diagnosed on CTPA in 31 (36.9%) patients. Clinical symptoms and in-hospital outcomes were similar in both groups except that more men had PE (p = .025). The median value of D-dimers in the group of patients with PE was significantly higher (14 680[IQR 33620-3450]ng/mL compared to the group of patients without PE 2980[IQR 6870-1600]ng/mL [P < .001]. A D-dimer at 2600 ng/mL was the optimal cut-off for predicting PE with a sensitivity of 90.3%, and AUC was .773[CI 95%, .667 -.876). CONCLUSION: A D-dimer cut-off value of 2600 ng/mL is a significant predictor of PE in COVID-19-patients with a sensitivity of 90.3%.

On-admission versus in-hospital thromboembolism due to COVID-19 infection. What is the particular characteristic of those with early thrombotic events?

INTRODUCTION: Increasing evidence has declared a hypercoagulable state in the coronavirus 2019 infection (COVID-19), while the etiology has remained a question. For the first time, the current study has aimed to compare the contributors of thromboembolism among those whose primary manifestations of COVID-19 were thrombosis vs the patients with a thrombotic event during the period of hospitalization. MATERIAL AND METHODS: This case-control study has been conducted on 267 COVID-19 patients, including 59, 48, and 160 ones with an on-admission, in-hospital, and without a thrombotic event, respectively. The events were defined as deep vein thrombosis (DVT), ischemic cerebrovascular accidents (CVA), pulmonary thromboembolism (PTE), or acute myocardial infarction (AMI). The demographic, physical examination, clinical and laboratory assessments of the groups were compared. RESULTS: The DVT (OR: 5.18; 95% CI: 1.01-26.7), AMI (OR: 11.1; 95% CI: 2.36-52.3), and arterial thrombosis (OR: 5.93; 95% CI: 0.63-55.8) were significantly associated with an on-admission thrombosis compared to those who presented in-hospital events. Lower levels of oxygen saturation were the only significant predictor index inversely associated with on-admission thrombosis compared to those with an event during the hospital admission period. CONCLUSION: PTE development was the most common in-hospital thrombotic event, whereas other thromboembolism types were remarkably more often among cases with on-admission events. Oxygen saturation was the only predictor of premature thrombosis that was inversely associated with outpatient events.

Comparison of Outcomes in Patients With COVID-19 and Thrombosis Versus Those Without Thrombosis.

The occurrence of venous thromboembolisms in patients with COVID-19 has been established. We sought to evaluate the clinical impact of thrombosis in patients with COVID-19 over the span of the pandemic to date. We analyzed patients with COVID-19 with a diagnosis of thrombosis who presented to the MedStar Health system (11 hospitals in Washington, District of Columbia, and Maryland) during the pandemic (March 1, 2020, to March 31, 2021). We compared the clinical course and outcomes based on the presence or absence of thrombosis and then, specifically, the presence of cardiac thrombosis. The cohort included 11,537 patients who were admitted for COVID-19. Of these patients, 1,248 had noncardiac thrombotic events and 1,009 had cardiac thrombosis (myocardial infarction) during their hospital admission. Of the noncardiac thrombotic events, 562 (45.0%) were pulmonary embolisms, 480 (38.5%) were deep venous thromboembolisms, and 347 (27.8%) were strokes. In the thrombosis arm, the mean age of the cohort was 64.5 ± 15.3 years, 53.3% were men, and the majority were African-American (64.9%). Patients with thrombosis tended to be older with more co-morbidities. The in-hospital mortality rate was significantly higher (16.0%) in patients with COVID-19 with concomitant non-cardiac thrombosis than in those without thrombosis (7.9%, p <0.001) but lower than in patients with COVID-19 with cardiac thrombosis (24.7%, p <0.001). In conclusion, patients with COVID-19 with thrombosis, especially cardiac thrombosis, are at higher risk for in-hospital mortality. However, this prognosis is not as grim as for patients with COVID-19 and cardiac thrombosis. Efforts should be focused on early recognition, evaluation, and intensifying antithrombotic management for these patients.

BET 1: Everything in graduation: arterial/end-tidal CO2 gradient and the diagnosis of pulmonary embolism.

A short cut review was carried out to establish the diagnostic characteristics of alveolar dead space fraction (AVDSf) in the diagnosis of pulmonary embolism (PE). This is calculated from the arterial and end-tidal CO2 Three papers were selected to answer the clinical question. The author, study type, relevant outcomes, results and weaknesses are tabulated. It is concluded that there is good evidence to support the use of AVDSf within a clinical prediction model to exclude a PE in patients when there is a low pretest probability. However, the specificity is not sufficient to support it as a 'rule in' test.

Severe acute myopathy following SARS-CoV-2 infection: a case report and review of recent literature.

BACKGROUND: SARS-CoV2 virus could be potentially myopathic. Serum creatinine phosphokinase (CPK) is frequently found elevated in severe SARS-CoV2 infection, which indicates skeletal muscle damage precipitating limb weakness or even ventilatory failure. CASE PRESENTATION: We addressed such a patient in his forties presented with features of severe SARS-CoV2 pneumonia and high serum CPK. He developed severe sepsis and acute respiratory distress syndrome (ARDS) and received intravenous high dose corticosteroid and tocilizumab to counter SARS-CoV2 associated cytokine surge. After 10 days of mechanical ventilation (MV), weaning was unsuccessful albeit apparently clear lung fields, having additionally severe and symmetric limb muscle weakness. Ancillary investigations in addition with serum CPK, including electromyogram, muscle biopsy, and muscle magnetic resonance imaging (MRI) suggested acute myopathy possibly due to skeletal myositis. CONCLUSION: We wish to stress that myopathogenic medication in SARS-CoV2 pneumonia should be used with caution. Additionally, serum CPK could be a potential marker to predict respiratory failure in SARS-CoV2 pneumonia as skeletal myopathy affecting chest muscles may contribute ventilatory failure on top of oxygenation failure due to SARS-CoV2 pneumonia.

COVID-19 neuropathology at Columbia University Irving Medical Center/New York Presbyterian Hospital.

Many patients with SARS-CoV-2 infection develop neurological signs and symptoms; although, to date, little evidence exists that primary infection of the brain is a significant contributing factor. We present the clinical, neuropathological and molecular findings of 41 consecutive patients with SARS-CoV-2 infections who died and underwent autopsy in our medical centre. The mean age was 74 years (38-97 years), 27 patients (66%) were male and 34 (83%) were of Hispanic/Latinx ethnicity. Twenty-four patients (59%) were admitted to the intensive care unit. Hospital-associated complications were common, including eight patients (20%) with deep vein thrombosis/pulmonary embolism, seven (17%) with acute kidney injury requiring dialysis and 10 (24%) with positive blood cultures during admission. Eight (20%) patients died within 24 h of hospital admission, while 11 (27%) died more than 4 weeks after hospital admission. Neuropathological examination of 20-30 areas from each brain revealed hypoxic/ischaemic changes in all brains, both global and focal; large and small infarcts, many of which appeared haemorrhagic; and microglial activation with microglial nodules accompanied by neuronophagia, most prominently in the brainstem. We observed sparse T lymphocyte accumulation in either perivascular regions or in the brain parenchyma. Many brains contained atherosclerosis of large arteries and arteriolosclerosis, although none showed evidence of vasculitis. Eighteen patients (44%) exhibited pathologies of neurodegenerative diseases, which was not unexpected given the age range of our patients. We examined multiple fresh frozen and fixed tissues from 28 brains for the presence of viral RNA and protein, using quantitative reverse-transcriptase PCR, RNAscope® and immunocytochemistry with primers, probes and antibodies directed against the spike and nucleocapsid regions. The PCR analysis revealed low to very low, but detectable, viral RNA levels in the majority of brains, although they were far lower than those in the nasal epithelia. RNAscope® and immunocytochemistry failed to detect viral RNA or protein in brains. Our findings indicate that the levels of detectable virus in coronavirus disease 2019 brains are very low and do not correlate with the histopathological alterations. These findings suggest that microglial activation, microglial nodules and neuronophagia, observed in the majority of brains, do not result from direct viral infection of brain parenchyma, but more likely from systemic inflammation, perhaps with synergistic contribution from hypoxia/ischaemia. Further studies are needed to define whether these pathologies, if present in patients who survive coronavirus disease 2019, might contribute to chronic neurological problems.

Pathophysiology of SARS-CoV-2: the Mount Sinai COVID-19 autopsy experience.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated clinical syndrome COVID-19 are causing overwhelming morbidity and mortality around the globe and disproportionately affected New York City between March and May 2020. Here, we report on the first 100 COVID-19-positive autopsies performed at the Mount Sinai Hospital in New York City. Autopsies revealed large pulmonary emboli in six cases. Diffuse alveolar damage was present in over 90% of cases. We also report microthrombi in multiple organ systems including the brain, as well as hemophagocytosis. We additionally provide electron microscopic evidence of the presence of the virus in our samples. Laboratory results of our COVID-19 cohort disclose elevated inflammatory markers, abnormal coagulation values, and elevated cytokines IL-6, IL-8, and TNFα. Our autopsy series of COVID-19-positive patients reveals that this disease, often conceptualized as a primarily respiratory viral illness, has widespread effects in the body including hypercoagulability, a hyperinflammatory state, and endothelial dysfunction. Targeting of these multisystemic pathways could lead to new treatment avenues as well as combination therapies against SARS-CoV-2 infection.

COVID-19 infection in symptomatic pregnant women at the midpoint of the pandemic in Spain: a retrospective analysis.

OBJECTIVES: Determine the strengths and weakness of a symptomatic screening for COVID-19 in pregnant women. Analyze the clinical presentation, management, and outcomes. DESIGN: Descriptive retrospective observational study. SETTING: Mancha-Centro Hospital (Spain). MATERIAL AND METHODS: Population: Symptomatic pregnant women with confirmed diagnosis of COVID-19. Between the 12th of March and 17th of April 2020, all the symptomatic pregnancies were screened with diagnostic test for SARS-CoV-2. Data collection was done by reviewing the medical records and telephone interviews. MAIN OUTCOME MEASURES: Clinical characteristics, management, treatment, and obstetric and neonatal outcomes. RESULTS: Twenty patients with positive COVID-19 diagnostic test out of thirty-four suspected. The most common symptoms were fever (70%), cough (65%) and myalgia (35%). A unique symptom of presentation in 20% of cases. COVID-19 pneumonia was diagnosed in 30% by chest X-ray and one case had pulmonary embolism associated diagnosed by CT-Scan. Thromboprophylaxis was indicated in 16 out of 20 patients. Eight women finished their pregnancy during the observation period. Type of birth: 25% natural birth, 12.5% assisted vaginal delivery and 62.5% caesarean section. We had three severe cases, two of them with intensive care support. All neonates had negative test for COVID 19 infection. CONCLUSIONS: We recommend universal screening of all pregnant woman for COVID-19 during the pandemic because of the limits of the symptomatic screening seen in this studio and the ratio of asymptomatic pregnancies with positive test for COVID-19 recently published.

Haemophagocytic lymphohistiocytosis and liver failure-induced massive hyperferritinaemia in a male COVID-19 patient.

The authors present the case of a 58-year-old man with the unique combination of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and, later on, haemophagocytic lymphohistiocytosis admitted to the intensive care unit. During his ICU stay the patient developed a variety of complications including acute respiratory distress syndrome, pulmonary embolism, right heart failure and suspected HLH leading to multiorgan failure and death. Despite the proven diagnosis of haemophagocytic lymphohistiocytosis, the excessively high ferritin levels of the patient did not seem fully explained by this diagnosis. Therefore, the authors want to highlight different causes of hyperferritinaemia in critically ill patients and underline the importance of differential diagnoses when interpreting continuously rising ferritin levels.

COVID-19 and Respiratory System Disorders: Current Knowledge, Future Clinical and Translational Research Questions.

The severe acute respiratory syndrome coronavirus-2 emerged as a serious human pathogen in late 2019, causing the disease coronavirus disease 2019 (COVID-19). The most common clinical presentation of severe COVID-19 is acute respiratory failure consistent with the acute respiratory distress syndrome. Airway, lung parenchymal, pulmonary vascular, and respiratory neuromuscular disorders all feature in COVID-19. This article reviews what is known about the effects of severe acute respiratory syndrome coronavirus-2 infection on different parts of the respiratory system, clues to understanding the underlying biology of respiratory disease, and highlights current and future translation and clinical research questions.

Pulmonary thrombosis in Covid-19: before, during and after hospital admission.

Disordered coagulation, endothelial dysfunction, dehydration and immobility contribute to a substantially elevated risk of deep venous thrombosis, pulmonary embolism (PE) and systemic thrombosis in coronavirus disease 2019 (Covid-19). We evaluated the prevalence of pulmonary thrombosis and reported RV (right ventricular) dilatation/dysfunction associated with Covid-19 in a tertiary referral Covid-19 centre. Of 370 patients, positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 39 patients (mean age 62.3 ± 15 years, 56% male) underwent computed tomography pulmonary angiography (CTPA), due to increasing oxygen requirements or refractory hypoxia, not improving on oxygen, very elevated D-dimer or tachycardia disproportionate to clinical condition. Thrombosis in the pulmonary vasculature was found in 18 (46.2%) patients. However, pulmonary thrombosis did not predict survival (46.2% survivors vs 41.7% non-survivors, p = 0.796), but RV dilatation was less frequent among survivors (11.5% survivors vs 58.3% non-survivors, p = 0.002). Over the following month, we observed four Covid-19 patients, who were admitted with high and intermediate-high risk PE, and we treated them with UACTD (ultrasound-assisted catheter-directed thrombolysis), and four further patients, who were admitted with PE up to 4 weeks after recovery from Covid-19. Finally, we observed a case of RV dysfunction and pre-capillary pulmonary hypertension, associated with Covid-19 extensive lung disease. We demonstrated that pulmonary thrombosis is common in association with Covid-19. Also, the thrombotic risk in the pulmonary vasculature is present before and during hospital admission, and continues at least up to four weeks after discharge, and we present UACTD for high and intermediate-high risk PE management in Covid-19 patients.

Adrenal haemorrhage as a complication of COVID-19 infection.

We report an unusual complication of COVID-19 infection in a 53-year-old Caucasian man. He presented with shortness of breath, fever and pleuritic chest pain. A CT pulmonary angiogram (CTPA) demonstrated acute bilateral pulmonary embolism and bilateral multifocal parenchymal ground glass change consistent with COVID-19 (SARS-CoV-2) infection. Right adrenal haemorrhage was suspected on the CTPA which was confirmed on triple-phase abdominal CT imaging. A short Synacthen test revealed normal adrenal function. He was treated initially with an intravenous heparin infusion, which was changed to apixaban with a planned outpatient review in 3 months' time. He made an uncomplicated recovery and was discharged. Follow-up imaging nearly 5 months later showed near complete resolution of the right adrenal haemorrhage with no CT evidence of an underlying adrenal lesion.

Beyond the clot: perfusion imaging of the pulmonary vasculature after COVID-19.

A compelling body of evidence points to pulmonary thrombosis and thromboembolism as a key feature of COVID-19. As the pandemic spread across the globe over the past few months, a timely call to arms was issued by a team of clinicians to consider the prospect of long-lasting pulmonary fibrotic damage and plan for structured follow-up. However, the component of post-thrombotic sequelae has been less widely considered. Although the long-term outcomes of COVID-19 are not known, should pulmonary vascular sequelae prove to be clinically significant, these have the potential to become a public health problem. In this Personal View, we propose a proactive follow-up strategy to evaluate residual clot burden, small vessel injury, and potential haemodynamic sequelae. A nuanced and physiological approach to follow-up imaging that looks beyond the clot, at the state of perfusion of lung tissue, is proposed as a key triage tool, with the potential to inform therapeutic strategies.

Cardiovascular Manifestations and Mechanisms in Patients with COVID-19.

Coronavirus disease 2019 (COVID-19) patients with pre-existing cardiovascular disease (CVD) or with cardiovascular complications have a higher risk of mortality. The main cardiovascular complications of COVID-19 include acute cardiac injury, acute myocardial infarction (AMI), myocarditis, arrhythmia, heart failure, shock, and venous thromboembolism (VTE)/pulmonary embolism (PE). COVID-19 can cause cardiovascular complications or deterioration of coexisting CVD through direct or indirect mechanisms, including viral toxicity, dysregulation of the renin-angiotensin-aldosterone system (RAAS), endothelial cell damage and thromboinflammation, cytokine storm, and oxygen supply-demand mismatch. We systematically review cardiovascular manifestations, histopathology, and mechanisms of COVID-19, to help to formulate future research goals and facilitate the development of therapeutic management strategies.