Meta-Analysis of Glucocorticoids for Covid-19 Patients Not Receiving Oxygen

Background: Glucocorticoids reduce mortality in hospitalized patients with severe and critical coronavirus disease 2019 (Covid-19), although a possible harm was documented in patients with Covid-19 not requiring oxygen. Methods: We searched Embase, BioMed Central, medRxiv, bioRxiv, PubMed, and the Cochrane Central Register of Controlled Trials for any randomized trial or matched study ever performed on adult patients with Covid-19 not receiving oxygen therapy treated with intravenous or oral glucocorticoids versus any comparator (standard therapy or placebo);there were no restrictions on dose or time of administration. The primary end point was all-cause mortality at the longest available follow-up. Results: Five randomized trials and one propensity-matched study involving 6634 hospitalized patients not on oxygen were finally included (3704 received glucocorticoids and 2930 received standard treatment). The overall mortality of patients treated with glucocorticoids was significantly higher than the mortality of patients in the control group (509 of 3704 [14%] in the glucocorticoid group vs. 294 of 2930 [10%] in the control group;odds ratio, 1.56 [95% confidence interval, 1.27 to 1.92], with three articles reporting mortality events and contributing to the combined odds ratio;P<0.001;number needed to harm=27). Conclusions: Glucocorticoid use likely increases mortality in hospitalized patients with Covid-19 not receiving oxygen, with a number needed to harm of 27. (PROSPERO number CRD42022342996.)

Microvascular lung vessels obstructive thromboinflammatory syndrome in patients with COVID-19: Insights from lung intravascular optical coherence tomography.

Background: Microvascular lung vessels obstructive thromboinflammatory syndrome has been proposed as a possible mechanism of respiratory failure in COVID-19 patients. However, it has only been observed in post-mortem studies and has never been documented in vivo, probably because of a lack of CT scan sensitivity in small pulmonary arteries. The aim of the present study was to assess the safety, tolerability, and diagnostic value of optical coherence tomography (OCT) for the assessment of patients with COVID-19 pneumonia for pulmonary microvascular thromboinflammatory syndrome. Methods: The COVID-OCT trial was a multicenter, open-label, prospective, interventional clinical study. Two cohorts of patients were included in the study and underwent pulmonary OCT evaluation. Cohort A consisted of patients with COVID-19 with a negative CT scan for pulmonary thrombosis and elevated thromboinflammatory markers (D-dimer > 10,000 ng/mL or 5,000 < D-dimer < 10,000 ng/mL and one of: C-reactive Protein > 100 mg/dL, IL-6 > 6 pg/mL, or ferritin > 900 ng/L). Cohort B consisted of patients with COVID-19 and a CT scan positive for pulmonary thrombosis. The primary endpoints of the study were: (i) to evaluate the overall safety of OCT investigation in patients with COVID-19 pneumonia, and (ii) to report on the potential value of OCT as a novel diagnostic tool for the diagnosis of microvascular pulmonary thrombosis in COVID-19 patients. Results: A total of 13 patients were enrolled. The mean number of OCT runs performed in each patient was 6.1 ± 2.0, both in ground glass and healthy lung areas, achieving a good evaluation of the distal pulmonary arteries. Overall, OCT runs identified microvascular thrombosis in 8 patients (61.5%): 5 cases of red thrombus, 1 case of white thrombus, and 2 cases of mixed thrombus. In Cohort A, the minimal lumen area was 3.5 ± 4.6 mm2, with stenosis of 60.9 ± 35.9% of the area, and the mean length of thrombus-containing lesions was 5.4 ± 3.0 mm. In Cohort B, the percentage area obstruction was 92.6 ± 2.6, and the mean thrombus-containing lesion length was 14.1 ± 13.9 mm. No peri-procedural complications occurred in any of the 13 patients. Conclusion: OCT appears to be a safe and accurate method of evaluating the distal pulmonary arteries in hospitalized COVID-19 patients. Here, it enabled the first in vivo documentation of distal pulmonary arterial thrombosis in patients with elevated thromboinflammatory markers, even when their CT angiogram was negative for pulmonary thrombosis. Clinical trial registration: ClinicalTrial.gov, identifier NCT04410549.

Short-Course of Methylprednisolone Improves Respiratory Functional Parameters After 120 Days in Hospitalized COVID-19 Patients (Metcovid Trial): A Randomized Clinical Trial.

Background: The use of corticosteroids may help control the cytokine storm occurring in acute respiratory failure due to the severe form of COVID-19. We evaluated the postacute effect of corticosteroids used during the acute phase, such as impairment in pulmonary function parameters, on day 120 (D120)-follow-up, in participants who survived over 28 days. Methods: This is a parallel, double-blind, randomized, placebo-controlled phase IIb clinical trial carried out between April 18 and October 9, 2020, conducted in hospitalized patients with clinical-radiological suspicion of COVID-19, aged 18 years or older, with SpO2 ≤ 94% on room air or requiring supplementary oxygen, or under invasive mechanical ventilation (IMV) in a referral center in Manaus, Western Brazilian Amazon. Intravenous methylprednisolone (MP) (0.5 mg/kg) was given two times daily for 5 days to these patients. The primary outcome used for this study was pulmonary function testing at day 120 follow-up visit. Results: Out of the total of surviving patients at day 28 (n = 246) from the Metcovid study, a total of 118 underwent satisfactory pulmonary function testing (62 in the placebo arm and 56 in the MP arm). The supportive treatment was similar between the placebo and MP groups (seven [11%] vs. four [7%]; P = 0.45). At hospital admission, IL-6 levels were higher in the MP group (P < 0.01). Also, the need for ICU (P = 0.06), need for IMV (P = 0.07), and creatine kinase (P = 0.05) on admission also tended to be higher in this group. In the univariate analysis, forced expiratory volume on 1st second of exhalation (FEV1) and forced vital capacity (FVC) at D120 follow-up were significantly higher in patients in the MP arm, being this last parameter also significantly higher in the multivariate analysis independently of IMV and IL-6 levels on admission. Conclusion: The use of steroids for at least 5 days in severe COVID-19 was associated with a higher FVC, which suggests that hospitalized COVID-19 patients might benefit from the use of MP in its use in the long-term, with less pulmonary restrictive functions, attributed to fibrosis. Trial Registration: ClinicalTrials.gov, Identifier: NCT04343729.

Efficacy and safety of IL-6 inhibitors in patients with COVID-19 pneumonia: a systematic review and meta-analysis of multicentre, randomized trials.

PURPOSE: COVID-19 is characterized by dysregulated immune response, respiratory failure and a relevant mortality rate among hospitalized patients. Interleukin-6 (IL-6) is involved in COVID-19-associated cytokine storm, and several trials investigated whether its inhibition could improve patients' outcome. We performed a meta-analysis of randomized trials (RCT) to test this hypothesis. MATERIALS AND METHODS: Two independent investigators searched PubMed, Scopus, ClnicalTrials.gov and medRxiv up to September 1st, 2021. Inclusion criteria were: administration of tocilizumab or sarilumab; COVID-19 adult patients with pneumonia; and being a RCT. Primary outcome was mortality at the longest follow-up. Secondary outcomes included intubation rate and incidence of adverse events. Two independent investigators extracted data from eligible trials. RESULTS: Of the 763 studies assessed, 15 RCTs were included (9,320 patients), all were multicentre, and the majority open-label vs standard treatment. IL-6 inhibitors were associated with reduced all-cause mortality at the longest follow-up (1315/5,380 [24.4%] in the IL-6 inhibitors group versus 1080/3,814 [28.3%] in the control group, RR = 0.90; 95% CI 0.84 to 0.96; p for effect = 0.003, I2 = 0%, with 13 studies included), with reduction in 28/30-day mortality and intubation rates, and with no increase in adverse events and secondary infections. CONCLUSION: IL-6 inhibitors reduced longest follow-up mortality and intubation in COVID-19 patients. Findings need to be confirmed in high-quality RCTs.

Methylprednisolone as Adjunctive Therapy for Patients Hospitalized With Coronavirus Disease 2019 (COVID-19; Metcovid): A Randomized, Double-blind, Phase IIb, Placebo-controlled Trial.

BACKGROUND: Steroid use for coronavirus disease 2019 (COVID-19) is based on the possible role of these drugs in mitigating the inflammatory response, mainly in the lungs, triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study aimed to evaluate the efficacy of methylprednisolone (MP) among hospitalized patients with suspected COVID-19. METHODS: A parallel, double-blind, placebo-controlled, randomized, Phase IIb clinical trial was performed with hospitalized patients aged ≥18 years with clinical, epidemiological, and/or radiological suspected COVID-19 at a tertiary care facility in Manaus, Brazil. Patients were randomly allocated (1:1 ratio) to receive either intravenous MP (0.5 mg/kg) or placebo (saline solution) twice daily for 5 days. A modified intention-to-treat (mITT) analysis was conducted. The primary outcome was 28-day mortality. RESULTS: From 18 April to 16 June 2020, 647 patients were screened, 416 were randomized, and 393 were analyzed as mITT, with 194 individuals assigned to MP and 199 to placebo. SARS-CoV-2 infection was confirmed by reverse transcriptase polymerase chain reaction in 81.3%. The mortality rates at Day 28 were not different between groups. A subgroup analysis showed that patients over 60 years old in the MP group had a lower mortality rate at Day 28. Patients in the MP arm tended to need more insulin therapy, and no difference was seen in virus clearance in respiratory secretion until Day 7. CONCLUSIONS: The findings of this study suggest that a short course of MP in hospitalized patients with COVID-19 did not reduce mortality in the overall population. CLINICAL TRIALS REGISTRATION: NCT04343729.

Intensive care management of patients with COVID-19: a practical approach.

SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19), is responsible for the largest pandemic facing humanity since the Spanish flu pandemic in the early twentieth century. Since there is no specific antiviral treatment, optimized support is the most relevant factor in the patient's prognosis. In the hospital setting, the identification of high-risk patients for clinical deterioration is essential to ensure access to intensive treatment of severe conditions in a timely manner. The initial management of hypoxemia includes conventional oxygen therapy, high-flow nasal canula oxygen, and non-invasive ventilation. For patients requiring invasive mechanical ventilation, lung-protective ventilation with low tidal volumes and plateau pressure is recommended. Cardiovascular complications are frequent and include myocardial injury, thrombotic events, myocarditis, and cardiogenic shock. Acute renal failure is a common complication and is a marker of poor prognosis, with significant impact in costs and resources allocation. Regarding promising therapies for COVID-19, the most promising drugs until now are remdesivir and corticosteroids although further studies may be needed to confirm their effectiveness. Other therapies such as, tocilizumab, anakinra, other anti-cytokine drugs, and heparin are being tested in clinical trials. Thousands of physicians are living a scenario that none of us have ever seen: demand for hospital exceed capacity in most countries. Until now, the certainty we have is that we should try to decrease the number of infected patients and that an optimized critical care support is the best strategy to improve patient's survival.

Worsening of heart failure by coronavirus disease 2019 is associated with high mortality.

AIMS: Patients with advanced heart failure (HF) with reduced left ventricular ejection fraction (HFrEF) and concurrent coronavirus disease 2019 (COVID-19) might have a higher risk of severe events. METHODS AND RESULTS: We retrospectively studied 16 patients with advanced HFrEF who developed COVID-19 between 1 March and 29 May 2020. Follow-up lasted until 30 September. Ten patients previously hospitalized with decompensated HFrEF were infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during hospitalization. Six patients undergoing ambulatory care at initiation of COVID-19 symptoms were hospitalized because of advanced HFrEF. All patients who experienced worsening of HFrEF due to COVID-19 required higher doses or introduction of additional inotropic drugs or intra-aortic balloon pump in the intensive care unit. The mean intravenous dobutamine dose before SARS-CoV-2 infection in previously hospitalized patients (n = 10) and the median (inter-quartile range) peak intravenous dobutamine dose during SARS-CoV-2 infection in all patients (n = 16) were 2 (0-7) µg/kg/min and 20 (14-20) (P < 0.001), respectively. During follow-up, 56% underwent heart transplantation (n = 2) or died (n = 7). Four patients died during hospitalization from mixed shock consequent to severe acute respiratory syndrome with inflammatory storm syndrome associated with septic and cardiogenic shock during COVID-19. After COVID-19 recovery, two patients died from mixed septic and cardiogenic shock and one from sustained ventricular tachycardia and cardiogenic shock. Five patients were discharged from hospital to ambulatory care. Four were awaiting heart transplantation. CONCLUSION: Worsening of advanced HF by COVID-19 is associated with high mortality. This report highlights the importance of preventing COVID-19 in patients with advanced HF.

Confirmed Invasive Pulmonary Aspergillosis and COVID-19: the value of postmortem findings to support antemortem management

We present postmortem evidence of invasive pulmonary aspergillosis (IPA) in a patient with severe COVID-19. Autopsies of COVID-19 confirmed cases were performed. The patient died despite antimicrobials, mechanical ventilation, and vasopressor support. Histopathology and peripheral blood galactomannan antigen testing confirmed IPA. Aspergillus penicillioides infection was confirmed by nucleotide sequencing and BLAST analysis. Further reports are needed to assess the occurrence and frequency of IPA in SARS-CoV-2 infections, and how they interact clinically.

Corticosteroids for Patients With Coronavirus Disease 2019 (COVID-19) With Different Disease Severity: A Meta-Analysis of Randomized Clinical Trials.

OBJECTIVES: Efficacy and safety of corticosteroids in patients with 2019-nCoV (novel coronavirus 2019) infection still are debated. Because large randomized clinical trials (RCTs) and a well-conducted meta-analysis on the use of corticosteroids, focused on patients with coronavirus disease (COVID-19) in intensive care units, recently were published, a meta-analysis of RCTs on corticosteroids therapy in patients with different disease severity was performed to evaluate the effect on survival. DESIGN: A meta-analyses of RCTs was performed. SETTING: Patients admitted to hospital. PARTICIPANTS: Patients with coronavirus disease. INTERVENTIONS: Administration of corticosteroids. MEASUREMENTS AND MAIN RESULTS: A search was performed for RCTs of adult patients with acute hypoxemic failure related to 2019-nCoV infection who received corticosteroids versus any comparator. The primary endpoint was mortality rate. Five RCTs involving 7,692 patients were included. Overall mortality of patients treated with corticosteroids was slightly but significantly lower than mortality of controls (26% v 28%, relative risk {RR} = 0.89 [95% confidence interval {CI} 0.82-0.96], p = 0.003). The same beneficial effect was found in the subgroup of patients requiring mechanical ventilation (RR = 0.85 [95% CI 0.72-1.00], p = 0.05 number needed to treat {NNT} = 19). Remarkably, corticosteroids increased mortality in the subgroup of patients not requiring oxygen (17% v 13%, RR = 1.23 [95% CI 1.00-1.62], p = 0.05 number needed to harm {NNH} = 29). Tests for comparison between mechanically ventilated subgroups and those not requiring oxygen confirmed that treatment with corticosteroids had a statistically significant different effect on survival. Patients treated with corticosteroids had a significantly lower risk of need for mechanical ventilation. CONCLUSIONS: Corticosteroids may be considered in severe critically ill patients with COVID-19 but must be discouraged in patients not requiring oxygen therapy. Urgently, further trials are warranted before implementing this treatment worldwide.

Case Report: Adrenal Pathology Findings in Severe COVID-19: An Autopsy Study.

Although high mortality has been reported in many COVID-19 studies, very limited postmortem information from complete autopsies is available. We report the findings in the adrenal glands in 28 autopsies with confirmed SARS-CoV-2 infection. Microscopic lesions were identified in the adrenal glands in 12/28 patients (46%). Seven cases showed necrosis, generally ischemic; four showed cortical lipid degeneration; two showed hemorrhage; and one unspecific focal adrenalitis. Vascular thrombosis in one patient and focal inflammation in association with other findings in three patients were observed. No case presented adrenal insufficiency. In conclusion, adrenal lesions are frequent in patients with severe COVID-19. The lesions are mild but could contribute to the lethal outcome.

Cancer and Cardiovascular Diseases during the COVID-19 Pandemic. / Câncer e Doenças Cardiovasculares na Pandemia de COVID-19.

The challenges that the COVID-19 pandemic cretead to the healthcare system have made it necessary to adapt routines and services, with the objectives of controlling the spread of the virus and preserving health. Safe and correct management of patients in risks groups, such as elderly patients, patients with cardiovascular diseases, and patients with cancer, has become even more important. Thus, cardio-oncology has gained a new dimension, with the aim of adapting to patients' needs during the pandemic by restructuring the system of care in a manner that offers quality and safety in healthcare.

O desafio imposto ao sistema de saúde pela pandemia da COVID-19 faz com que haja uma necessidade de readequações de rotinas e serviços de saúde, com os objetivos de controlar a disseminação do vírus e preservar a saúde. Torna-se ainda mais importante o manejo seguro e correto dos pacientes dos grupos de risco, como os pacientes idosos, os portadores de doenças cardiovasculares e os pacientes com câncer. Dessa forma, a cardio-oncologia ganha novo dimensionamento, no intuito de se adequar às necessidades dos pacientes diante de uma pandemia, reestruturando o sistema de atendimento de forma a oferecer qualidade e segurança na assistência à saúde.

The Heart and COVID-19: What Cardiologists Need to Know. / O Coração e a COVID-19: O que o Cardiologista Precisa Saber.

In face of the pandemic of the novel coronavirus disease 2019 (COVID-19), the management of patients with cardiovascular risk factors and/or disease is challenging. The cardiovascular complications evidenced in patients with COVID-19 derive from several mechanisms, ranging from direct viral injury to complications secondary to the inflammatory and thrombotic responses to the infection. The proper care of patients with COVID-19 requires special attention to the cardiovascular system aimed at better outcomes.

Frente à pandemia da doença causada pelo novo coronavírus (COVID-19), o manejo do paciente com fator de risco e/ou doença cardiovascular é desafiador nos dias de hoje. As complicações cardiovasculares evidenciadas nos pacientes com COVID-19 resultam de vários mecanismos, que vão desde lesão direta pelo vírus até complicações secundárias à resposta inflamatória e trombótica desencadeada pela infecção. O cuidado adequado do paciente com COVID-19 exige atenção ao sistema cardiovascular em busca de melhores desfechos.

Cardiovascular Imaging and Interventional Procedures in Patients with Novel Coronavirus Infection. / Imagem Cardiovascular e Procedimentos Intervencionistas em Pacientes com Infecção pelo Novo Coronavírus.

The coronavirus disease 2019 (COVID-19) pandemic is a huge challenge to the health system because of the exponential increase in the number of individuals affected. The rational use of resources and correct and judicious indication for imaging exams and interventional procedures are necessary, prioritizing patient, healthcare personnel, and environmental safety. This review was aimed at guiding health professionals in safely and effectively performing imaging exams and interventional procedures.

Position Statement: Cardiopulmonary Resuscitation of Patients with Confirmed or Suspected COVID-19 - 2020. / Posicionamento para Ressuscitação Cardiopulmonar de Pacientes com Diagnóstico ou Suspeita de COVID-19 ­ 2020.

Care for patients with cardiac arrest in the context of the coronavirus disease 2019 (COVID-19) pandemic has several unique aspects that warrant particular attention. This joint position statement by the Brazilian Association of Emergency Medicine (ABRAMEDE), Brazilian Society of Cardiology (SBC), Brazilian Association of Intensive Care Medicine (AMIB), and Brazilian Society of Anesthesiology (SBA), all official societies representing the corresponding medical specialties affiliated with the Brazilian Medical Association (AMB), provides recommendations to guide health care workers in the current context of limited robust evidence, aiming to maximize the protection of staff and patients alike. It is essential that full aerosol precautions, which include wearing appropriate personal protective equipment, be followed during resuscitation. It is also imperative that potential causes of cardiac arrest of particular interest in this patient population, especially hypoxia, cardiac arrhythmias associated with QT prolongation, and myocarditis, be considered and addressed. An advanced invasive airway device should be placed early. Use of HEPA filters at the bag-valve interface is mandatory. Management of cardiac arrest occurring during mechanical ventilation or during prone positioning demands particular ventilator settings and rescuer positioning for chest compressions which deviate from standard cardiopulmonary resuscitation techniques. Apart from these logistical issues, care should otherwise follow national and international protocols and guidelines, namely the 2015 International Liaison Committee on Resuscitation (ILCOR) and 2019 American Heart Association (AHA) guidelines and the 2019 Update to the Brazilian Society of Cardiology Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Guideline.