Effectiveness and safety of tocilizumab for COVID-19: a systematic review and meta-analysis of randomized clinical trials

ABSTRACT BACKGROUND: Tocilizumab is an anti-human interleukin 6 receptor monoclonal antibody that has been used to treat coronavirus disease 2019 (COVID-19). However, there is no consensus on its efficacy for the treatment of COVID-19. OBJECTIVE: To evaluate the effectiveness and safety of tocilizumab for treating COVID-19. DESIGN AND SETTING: Systematic Review of randomized controlled trials (RCTs), Universidade Federal de São Paulo (UNIFESP), São Paulo (SP), Brazil. METHODS: We searched MEDLINE via PubMed, EMBASE, CENTRAL, and IBECS for RCTs published up to March 2021. Two authors selected studies and assessed the risk of bias and the certainty of the evidence following Cochrane Recommendations. RESULTS: Eight RCTs with 6,139 participants were included. We were not able to find differences between using tocilizumab compared to standard care on mortality in hospitalized patients with COVID-19 (risk ratio (RR) 0.97, 95% confidence interval (CI) 0.84 to 1.13; 8 trials; 5,950 participants; low-certainty evidence). However, hospitalized patients under tocilizumab plus standard care treatment seemed to present a significantly lower risk of needing mechanical ventilation (risk ratio = 0.78; 95% CI 0.64−0.94 moderate-certainty of evidence). CONCLUSIONS: To date, the best evidence available shows no difference between using tocilizumab plus standard care compared to standard care alone for reducing mortality in patients with COVID-19. However, as a finding with a practical implication, the use of tocilizumab in association to standard care probably reduces the risk of progressing to mechanical ventilation in those patients. REGISTRATION: osf.io/qe4fs.

Exploring the experience of the physicians regarding COVID-19, its complications and management

Background: COVID-19 infection is a disease that remains the main concern globally due to high admissions and fatality rates among patients. Clinical manifestation and choice of treatment are various. Therefore, this study was developed to explore the physicians’ perceptions in this regard in a semi-governmental hospital in Sharjah. Aims and Objectives: The objective of this research is to (1) to outline physicians’ descriptions of the clinical presentation of COVID-19, (2) to explore the physicians’ perceptions regarding the different aspects of COVID-19 and its complications, and (3) explore the physicians’ experiences regarding the treatment of COVID-19 cases. Materials and Methods: A descriptive qualitative design was approached. A semi-structured interview guide was developed, validated and used for data collection. Ten in-depth individual interviews with physicians were conducted. Interviews were recorded, transcribed, and thematically analyzed. Results: After analysis, three main themes with their sub-themes emerged to describe physicians’ experience regarding COVID-19’s clinical presentation, complications, and management. Sub-themes cleared-up COVID-19’s signs, symptoms, and risk factors along with admission’s requirements. Furthermore, it showed COVID-19’s complication in main organs. Moreover, COVID-19’s treatment was clarified for both home-quarantine and admitted patients along with instructions for discharged patients. Conclusion: Cases varied in severity and classified from asymptomatic to severe. It showed the requirements for hospitalization and risk factors associated with severity. The management of COVID-19 disease followed by MOHAP protocol and provided adequate outcomes from physicians. Vaccination was one of physicians’ recommendations.

Marcadores de oxigenación para la predicción de mortalidad por neumonía causada por la COVID-19

Introducción: En el Hospital General Docente "Dr. Agostinho Neto" no se ha evaluado el valor de los marcadores de oxígeno para la predicción de mortalidad por neumonía causada por la COVID-19. Objetivo: Determinar el valor de los marcadores de oxigenación para la predicción de mortalidad por neumonía causada por la COVID-19 en el Hospital General Docente "Dr. Agostinho Neto" de Guantánamo, Cuba, en el bienio 2020-2021. Método: Se realizó un estudio de una cohorte de 276 pacientes con neumonía causada por la COVID-19. Se estudiaron la saturación periférica de oxígeno (SpO2), saturación arterial de oxígeno (SaO2), diferencia alveolo-arterial de oxígeno (DA-aO2), relación presión arterial de oxígeno (PaO2) y fracción inspirada de oxígeno (FiO2) [PaO2/FiO2]. Se determinó la asociación entre variables y el egreso fallecido mediante la técnica de Ji cuadrado de independencia y el cálculo de Odds Ratio (OR). Resultados: La variable con mayor valor predictivo positivo fue la SpO2 (87,3 %) menor de 90 mmHg al momento del ingreso. El mayor valor predictivo negativo se registró para la variable DA-aO2 menor de 20 mmHg a las 48 h del ingreso (95,6 %). El riesgo atribuible fue superior para la relación PaO2/FiO2 menor de 300 mmHg (0,59) al momento del ingreso (0,52). El riesgo atribuible porcentual fue mayor para la variable DA-aO2 mayor o igual a 20 mmHg al momento del ingreso (95,8 %) y a las 48 h del ingreso (95,3 %). Conclusiones: La anormalidad de la DA-aO2, la relación PaO2/FiO2, la SaO2 y la SpO2, al momento del ingreso y a las 48 horas de este, son predictores de mortalidad en pacientes con COVID-19.

Introduction: The value of oxygen as a prognostic maker of mortality due to COVID-19 pneumonia has not been evaluated at the Hospital General Docente "Dr. Agostinho Neto". Objective: To identify the values of oxygenation markers for prognosing mortality caused by COVID-19 pneumonia at the Hospital General Docente "Dr. Agostinho Neto" de Guantánamo, Cuba, throughout period 2020-2021. Method: A cohort of 276 patients with COVID-19 pneumonia was studied. Peripheral oxygen saturation (SpO2), arterial oxygen saturation (SaO2), the difference between the oxygen concentration in the alveoli and arterial system (DA-aO2), arterial oxygen pressure ratio (PaO2) and inspired oxygen fraction (FiO2) [PaO2/FiO2] were studied. The association between variables and deceased discharge was determined using the Chi-square technique and the Odds Ratio (OR) calculation. Results: The variable with the highest positive predictive value was SpO2 (87.3 %) with a value lower than 90 mmHg at admission. The highest negative predictive value was recorded for the DA-aO2 variable (95.6%), less than 20 mmHg at 48 hours after admission. Attributable risk was higher for PaO2/FiO2 ratio, less than 300 mmHg (0.59), at admission (0.52). Attributable risk percent was higher for the variable DA-aO2 ≥ 20 mmHg at admission (95.8 %) and at 48 hours after admission (95.3 %). Conclusions: Abnormal DA-aO2, PaO2/FiO2 ratio, SaO2 and SpO2, at admission and 48 hours after admission, are predictive markers of mortality in patients with COVID-19.

Introdução: No Hospital General Docente "Dr. Agostinho Neto" não avaliou o valor dos marcadores de oxigênio para a previsão de mortalidade por pneumonia causada pelo COVID-19. Objetivo: Determinar o valor dos marcadores de oxigenação para a predição de mortalidade por pneumonia causada por COVID-19 no Hospital General Docente "Dr. Agostinho Neto" de Guantánamo, Cuba, no biênio 2020-2021. Método: Foi realizado um estudo de coorte de 276 pacientes com pneumonia causada por COVID-19. Saturação periférica de oxigênio (SpO2), saturação arterial de oxigênio (SaO2), diferença alvéolo-arterial de oxigênio (DA-aO2), relação pressão arterial de oxigênio (PaO2) e fração inspirada de oxigênio (FiO2) [PaO2/FiO2]. A associação entre variáveis e alta por óbito foi determinada por meio da técnica Qui-quadrado de independência e cálculo de Odds Ratio (OR). Resultados: A variável com maior valor preditivo positivo foi SpO2 (87,3%) inferior a 90 mmHg no momento da admissão. O maior valor preditivo negativo foi registrado para a variável DA-aO2 inferior a 20 mmHg 48 h após a admissão (95,6%). O risco atribuível foi maior para relação PaO2/FiO2 inferior a 300 mmHg (0,59) no momento da admissão (0,52). O percentual de risco atribuível foi maior para a variável AD-aO2 maior ou igual a 20 mmHg no momento da admissão (95,8%) e 48 horas após a admissão (95,3%). Conclusões: A anormalidade da AD-aO2, da relação PaO2/FiO2, SaO2 e SpO2, no momento da admissão e 48 horas após a admissão, são preditores de mortalidade em pacientes com COVID-19.

A case of endogenous candida endophthalmitis with incidental cytomegalovirus infection and optic neuropathy in a patient recovered from severe COVID-19

A 62-year-old female diabetic recovered from COVID-19 pneumonia after receiving a prolonged course of steroids. She presented with a clinical picture of left-eye panuveitis with white cotton ball chorioretinal lesions and RAPD suggesting an optic neuropathy (VA HM). Diagnostic vitrectomy was performed to take samples for infective screen and to give intravitreal voriconazole empirically. Smear, culture, and PCR for viral DNA confirmed mixed infection of endogenous Candida endophthalmitis and incidental CMV infection. With further treatment, her corrected vision improved to 6/18 with regressing fungal lesions in serial fundus photographs. Prompt diagnosis and intervention preserved her vision and prevented potential life-threatening complications

Pattern of chest computerized tomography scan findings in symptomatic RT-PCR positive COVID-19 patients at the Korle Bu Teaching Hospital, Ghana

Background: Chest Computerized Tomography (CT) features of Corona Virus Disease 2019 (COVID-19) pneumonia are nonspecific, variable and sensitive in detecting early lung disease. Hence its usefulness in triaging in resource-limited regions. Objectives: To assess the pattern of chest CT scan findings of symptomatic COVID-19 patients confirmed by a positive RTPCR in Ghana. Methods: This study retrospectively reviewed chest CT images of 145 symptomatic RT-PCR positive COVID-19 patients examined at the Radiology Department of the Korle Bu Teaching Hospital (KBTH) from 8th April to 30th November 2020. Chi-Squared test was used to determine associations among variables. Statistical significance was specified at p≤0.05. Results: Males represent 73(50.3%). The mean age was 54.15±18.09 years. The age range was 5 months-90 years. Consolidation 88(60.7%), ground glass opacities (GGO) 78(53.8%) and crazy paving 43(29.7%) were the most predominant features. These features were most frequent in the elderly (≥65years). Posterobasal, peripheral and multilobe disease were found bilaterally. The most common comorbidities were hypertension 72(49.7%) and diabetes mellitus 42(29.2%) which had significant association with lobar involvement above 50%. Conclusion: The most predominant Chest CT scan features of COVID-19 pneumonia were GGO, consolidation with air bronchograms, crazy paving, and bilateral multilobe lung disease in peripheral and posterior basal distribution

Diagnostic performance of the RSNA-proposed classification for COVID-19 pneumonia versus pre-pandemic controls

Abstract Objective To evaluate the diagnostic accuracy of the Radiological Society of North America (RSNA) classification system for coronavirus disease 2019 (COVID-19) pneumonia compared to pre-pandemic chest computed tomography (CT) scan images to mitigate the risk of bias regarding the reference standard. Materials and methods This was a retrospective, cross-sectional, diagnostic test accuracy study. Chest CT scans, carried out from May 1 to June 30, 2020, and from May 1 to July 17, 2017, were consecutively selected for the COVID-19 (positive reverse transcription-polymerase chain reaction [RT-PCR] for severe acute respiratory syndrome coronavirus 2 result) and control (pre-pandemic) groups, respectively. Four expert thoracic radiologists blindly interpreted each CT scan image. Sensitivity and specificity were calculated. Results A total of 160 chest CT scan images were included: 79 in the COVID-19 group (56 [43.5-67] years old, 41 men) and 81 in the control group (62 [52-72] years old, 44 men). Typically, an estimated specificity of 98.5% (95% confidence interval [CI] 98.1%-98.4%) was obtained. For the indeterminate classification as a diagnostic threshold, an estimated sensitivity of 88.3% (95% CI 84.7%-91.7%) and a specificity of 79.0% (95% CI 74.5%-83.4%), with an area under the curve of 0.865 (95% CI 0.838-0.895), were obtained. Conclusion The RSNA classification system shows strong diagnostic accuracy for COVID-19 pneumonia, even against pre-pandemic controls. It can be an important aid in clinical decision-making, especially when a typical or indeterminate pattern is found, possibly advising retesting following an initial negative RT-PCR result and streamlining early management and isolation.

Systemic corticosteroid therapy in the post-acute period of COVID-19 pneumonia with torpid clinical and radiological evolution

Abstract COVID-19 pneumonia generates both immediate damage due to the viral effects and distant damage due to inflammatory immune deregulation. Systemic corticosteroid therapy has proven to be beneficial in the first part of the process, but its usefulness in post-acute damage is still unclear. The number of affected patients makes it imperative to find a treatment that reduces potential pulmonary sequelae. This series of cases included 18 patients admitted to polyvalent private medical institutions of Buenos Aires City: 15 were male and 3 were female; age 58.4 ± 13.6 years. History of most common comorbidities: AHT (4 patients), obesity (6 patients) and smoking (4 patients). Five patients had no medical history. All patients showed dyspnea, oxygen desaturation, and persistent or progressive tomo graphic abnormalities 14 days after their infection. All of them received dexamethasone according to current regulations. Subsequently, given the poor evolution, they were administered oral and/or intravenous corticosteroids with the same treatment used for secondary organizing pneumonia (OP). A transbronchial biopsy was performed in 6 of the patients, showing an OP pattern in 3 of them. Four weeks after the beginning of the treatment, all of the patients showed clinical improvement expressed by decreased dyspnea and the fact that they didn't require oxygen anymore and that all chest tomographies showed clearly reduced pulmonary parenchymal involve ment. Systemic corticosteroids administered in the post-acute period of COVID-19 have a clinical and radiological beneficial effect.

Prevalence of pneumonia by chest x-ray, associated demographic characteristics and health risk factors among COVID-19 patients in Ghana

Objective: The study was conducted to determine the prevalence of radiologically diagnosed pneumonia among COVID-19 patients and associated factors. Design, setting, and participants: A retrospective manual data extraction of 275 medical records of COVID-19 patients was conducted at two COVID-19 national treatment centres in Accra from March to May 2020. All patients had a chest x-ray done. Main outcome and analysis: The main outcome was the presence of pneumonia. Descriptive statistics and Chi-square test of independence were employed to determine the associations between independent variables and the presence of pneumonia. All analysis was performed using Stata 16, and a p-value ≤ 0.05 was deemed significant Results: The prevalence of pneumonia was 44%(95%CI) =38.2-50.0). Chi-square independent test indicated that pneumonia in the COVID-19 patients was associated with educational level, history of domestic and international travel, mass gathering in the past 14 days before diagnosis, and discharge plan (p-value< 0.05). Patients classified as secondary cases (61.5%) and those discharged as fully recovered from the health facility (61.2%) had a higher prevalence of pneumonia. In addition, COVID-19 patients with hypertension (32.1%) and asthma (5.2%) had a significantly higher prevalence of pneumonia. Conclusion: Overall, the prevalence of pneumonia was 44% and was associated with the demographic and personal characteristics of the patients. Early detection through contact tracing and community surveillance should be intensified to pick up more asymptomatic cases. The role of the chest x-ray for triaging patients and for clinical management of symptomatic patients remains key

[T1 ESP]Pneumocystis jirovecii y SARS-CoV-2; COVID-19 / [T1 ENG]Pneumocystis jirovecii and SARS-CoV-2; COVID-19

Resumen Pneumocystis jirovecii, es un agente fúngico oportunista causante de neumonía (pneumocistosis) que puede ser mortal en personas con condición de inmunocompromiso, incluyendo pacientes VIH con recuento de linfocitos T CD4+ < 200 céls/mm3 y en pacientes inmunocomprometidos por otras etiologías como trasplantes de órgano sólido y cáncer, entre otras. Muchas personas pueden ser portadoras sanas de este agente etiológico y actuar como reservorio y fuente de infección. Artículos relacionados con coinfección entre SARS-CoV-2 y los de carácter oportunistas como P. jirovecii y Aspergillus fumigatus empiezan a publicarse, donde se argumenta que esta infección viral tiene un alto riesgo de coinfección y se manifiesta la importancia de no excluir los patógenos respiratorios, como P. jirovecii, entre otros. La coinfección con P. jirovecii puede no ser detectada en pacientes con infección grave por SARS-CoV-2, dado que pueden compartir características clínicas comunes como infiltrados multifocales bilaterales e hipoxemia profunda entre otras. Por lo tanto, es necesario realizar pruebas diagnósticas adicionales para P. jirovecii en pacientes con infección por SARS-CoV-2, especialmente cuando se presenten otras características clínicas que pueden apoyar la coinfección, como hallazgos quísticos en la TC torácica y niveles elevados en sangre de 1,3-D-glucano, incluso en ausencia de factores de riesgo clásicos para P. jirovecii, para el diagnóstico de neumonía por Pneumocystis en pacientes con sospecha de infección por SARS-CoV-2.

Abstract Pneumocystis jirovecii, is an opportunistic fungal agent that causes pneumonia (pneumocistosis) that can be fatal in people with immunocomprome status, including HIV patients with CD4+ T lymphocyte count < 200 cels/mm3 and in patients immunocompromised by other aetiologies such as solid organ transplants and cancer, among others. Many people may be healthy carriers of this etiological agent and act as a reservoir and source of infection. Articles related to co-infection between SARS-CoV-2 and opportunistic articles such as P. jirovecii and Aspergillus fumigatus begin publication, where it is argued that this viral infection has a high risk of co-infection, expressing the importance of not excluding respiratory pathogens, such as P. jirovecii, among others. Co-infection with P. jirovecii, may not be detected in patients with severe SARS-CoV-2 infection as they may share common clinical characteristics such as bilateral multifocal infiltrates and deep hypoxemia among others. Therefore, additional diagnostic tests for P. jirovecii, are necessary in patients with SARS-CoV-2 infection, especially when other clinical characteristics that may support co-infection are present such as cystic findings in thoracic CT and elevated blood levels of 1.3-D-glucan, including in the absence of classic risk factors for P. jirovecii, for the diagnosis of Pneumocystis pneumonia in patients with suspected SARS-CoV-2 infection.

Lopinavir/ritonavir: is early administration better in Covid-19?

Background: To share the data of coronavirus 2019 (Covid-19) patients started on lopinavir-ritonavir (lopi/r) in relation to time period from the onset of symptoms.Method: Observational descriptive study of 23 Covid-19 patients admitted in a tertiary care center in India from March 2020 to May 2020. Patients categorized into 2 groups based on the timing of initiation of lopi/r from the onset of symptoms. Group 1 were given the drug early (≤7 days) and group 2 late (>7 days). The clinical events (oxygen requirement days and ICU stay) and outcomes of hospital stay between the two groups were evaluated.Results: Patients were started on lopi/r for a period of 14 days on admission, out of which 12 patients were in group 1 and 11 patients in group 2. Underlying co-morbidities were present in 15 patients (65.21%). The mean duration from onset of symptoms to lopi/r initiation was 4 days and 11.1 days in Group 1 and 2 respectively. Requirement for oxygen support (2.16 versus 6.54 days), mean duration of hospitalization (8.58 versus 11.54 days) and mean duration of obtaining first Covid-19 negative report from the onset of symptoms (10.5 versus 19.57 days) were all significantly lesser in group 1 (p<0.05). All patients belonging to Group 1 and eight patients of group 2 recovered completely and were discharged whereas 3 patients of group 2 expired. Diarrhea was the most commonly observed adverse effect of lopi/r in our patients.Conclusion: With no approved weapon to tackle the Covid-19 pandemic, we should keep lopi/r in our armamentarium of drugs and use it at the earliest. More clinical trials are needed in future to ascertain if lopi/r can reduce hospital stay, prompt faster recovery and result in better clinical outcome.

Cardiovascular involvement in COVID-19: not to be missed

Abstract In December 2019, a striking appearance of new cases of viral pneumonia in Wuhan led to the detection of a novel coronavirus (SARS-CoV2). By analyzing patients with severe manifestations, it became apparent that 20 to 35% of patients who died had preexisting cardiovascular disease. This finding warrants the important need to discuss the influence of SARS-CoV2 infection on the cardiovascular system and hemodynamics in the context of clinical management, particularly during mechanical ventilation. The SARS-CoV2 enters human cells through the spike protein binding to angiotensin-converting enzyme 2 (ACE2), which is important to cardiovascular modulation and endothelial signaling. As ACE2 is highly expressed in lung tissue, patients have been progressing to acute respiratory injury at an alarming frequency during the Coronavirus Disease (COVID-19) pandemic. Moreover, COVID-19 leads to high D-dimer levels and prothrombin time, which indicates a substantial coagulation disorder. It seems that an overwhelming inflammatory and thrombogenic condition is responsible for a mismatching of ventilation and perfusion, with a somewhat near-normal static lung compliance, which describes two types of pulmonary conditions. As such, positive pressure during invasive mechanical ventilation (IMV) must be applied with caution. The authors of this review appeal to the necessity of paying closer attention to assess microhemodynamic repercussion, by monitoring central venous oxygen saturation during strategies of IMV. It is well known that a severe respiratory infection and a scattered inflammatory process can cause non-ischemic myocardial injury, including progression to myocarditis. Early strategies that guide clinical decisions can be lifesaving and prevent extended myocardial damage. Moreover, cardiopulmonary failure refractory to standard treatment may necessitate the use of extreme therapeutic strategies, such as extracorporeal membrane oxygenation.

Discussion of Medical Protective Consumables Management to Fight against COVID-19 Pneumonia / 中国医疗器械杂志

This article researches how to allocate medical protective consumables in hospital and ensure the safety of emergency marketing procurement under the condition that people are easily susceptible to COVID-19. To inform medical staffs about the standard instruction, we establish the corresponding hierarchical control management system and standards of medical protective consumables. To reduce the stress of clinical medical staff and prevent excessive protection, we enhance the training mechanisms and promote the superior normative guidance. The aim is to fully play the effectiveness of the key departments of medical protective consumables, reduce the risk of infection of clinical medical staff and ensure the safety of medical staffs.