Administration Timing and Efficacy of Tocilizumab in Patients With COVID-19 and Elevated IL-6.

BACKGROUND: Tocilizumab (TCZ), an interleukin-6 receptor antibody, has previously been used for treating patients with the coronavirus disease 2019 (COVID-19), but there is a lack of data regarding the administration timing of TCZ. OBJECTIVES: This study aimed to evaluate the timing and efficacy of TCZ in the treatment of patients with COVID-19. METHODS: Laboratory-confirmed patients with COVID-19 with an elevated interleukin-6 (IL-6) level (>10 pg/ml) were offered TCZ intravenously for compassionate use. Clinical characteristics, laboratory tests, and chest imaging before and after the administration of TCZ were retrospectively analyzed. RESULTS: A total of 58 consecutive patients who met the inclusion criteria and with no compliance to the exclusion criteria were included. Of these 58 patients, 39 patients received TCZ treatment, and 19 patients who declined TCZ treatment were used as the control cohort. In the TCZ-treatment group, 6 patients (15.4%) were in mild condition, 16 (41.0%) were in severe condition, and 17 (43.6%) were in critical condition. After TCZ treatment, the condition of 27 patients (69.2%) improved and 12 (30.8%) died. Compared with the improvement group, patients in the death group had higher baseline levels of IL-6 (P = 0.0191) and procalcitonin (PCT) (P = 0.0003) and lower lymphocyte percentage (LYM) (P = 0.0059). Patients receiving TCZ treatment had better prognoses than those without TCZ treatment (P = 0.0273). Furthermore, patients with a baseline IL-6 level of ≥100 pg/ml in the TCZ-treatment group had poorer clinical outcomes than those with an IL-6 level of <100 pg/ml (P = 0.0051). CONCLUSION: The administration of TCZ in an early stage of cytokine storm (IL-6 level < 100 pg/ml) may effectively improve the clinical prognosis of patients with COVID-19 by blocking the IL-6 signal pathway.

New onset neurologic events in people with COVID-19 in 3 regions in China.

OBJECTIVE: To investigate new-onset neurologic impairments associated with coronavirus disease 2019 (COVID-19). METHODS: A retrospective multicenter cohort study was conducted between January 18 and March 20, 2020, including people with confirmed COVID-19 from 56 hospitals officially designated in 3 Chinese regions; data were extracted from medical records. New-onset neurologic events as assessed by neurology consultants based on manifestations, clinical examination, and investigations were noted, in which critical events included disorders of consciousness, stroke, CNS infection, seizures, and status epilepticus. RESULTS: We enrolled 917 people with average age 48.7 years and 55% were male. The frequency of new-onset critical neurologic events was 3.5% (32/917) overall and 9.4% (30/319) among those with severe or critical COVID-19. These were impaired consciousness (n = 25) or stroke (n = 10). The risk of critical neurologic events was highly associated with age above 60 years and previous history of neurologic conditions. Noncritical events were seen in fewer than 1% (7/917), including muscle cramp, unexplained headache, occipital neuralgia, tic, and tremor. Brain CT in 28 people led to new findings in 9. Findings from lumbar puncture in 3 with suspected CNS infection, unexplained headache, or severe occipital neuralgia were unremarkable. CONCLUSIONS: People with COVID-19 aged over 60 and with neurologic comorbidities were at higher risk of developing critical neurologic impairment, mainly impaired consciousness and cerebrovascular accidents. Brain CT should be considered when new-onset brain injury is suspected, especially in people under sedation or showing an unexplained decline in consciousness. Evidence of direct acute insult of severe acute respiratory syndrome coronavirus 2 to the CNS is lacking.

Combining initial chest CT with clinical variables in differentiating coronavirus disease 2019 (COVID-19) pneumonia from influenza pneumonia.

Coronavirus disease 2019 (COVID-19) has spread in more than 100 countries and regions around the world, raising grave global concerns. COVID-19 has a similar pattern of infection, clinical symptoms, and chest imaging findings to influenza pneumonia. In this retrospective study, we analysed clinical and chest CT data of 24 patients with COVID-19 and 79 patients with influenza pneumonia. Univariate analysis demonstrated that the temperature, systolic pressure, cough and sputum production could distinguish COVID-19 from influenza pneumonia. The diagnostic sensitivity and specificity for the clinical features are 0.783 and 0.747, and the AUC value is 0.819. Univariate analysis demonstrates that nine CT features, central-peripheral distribution, superior-inferior distribution, anterior-posterior distribution, patches of GGO, GGO nodule, vascular enlargement in GGO, air bronchogram, bronchiectasis within focus, interlobular septal thickening, could distinguish COVID-19 from influenza pneumonia. The diagnostic sensitivity and specificity for the CT features are 0.750 and 0.962, and the AUC value is 0.927. Finally, a multivariate logistic regression model combined the variables from the clinical variables and CT features models was made. The combined model contained six features: systolic blood pressure, sputum production, vascular enlargement in the GGO, GGO nodule, central-peripheral distribution and bronchiectasis within focus. The diagnostic sensitivity and specificity for the combined features are 0.87 and 0.96, and the AUC value is 0.961. In conclusion, some CT features or clinical variables can differentiate COVID-19 from influenza pneumonia. Moreover, CT features combined with clinical variables had higher diagnostic performance.

Effect of a genetically engineered interferon-alpha versus traditional interferon-alpha in the treatment of moderate-to-severe COVID-19: a randomised clinical trial.

BACKGROUND: There are few effective therapies for coronavirus disease 2019 (COVID-19) upon the outbreak of the pandemic. To compare the effectiveness of a novel genetically engineered recombinant super-compound interferon (rSIFN-co) with traditional interferon-alpha added to baseline antiviral agents (lopinavir-ritonavir or umifenovir) for the treatment of moderate-to-severe COVID-19. METHOD: In this multicenter randomized (1:1) trial, patients hospitalized with moderate-to-severe COVID-19 received either rSIFN-co nebulization or interferon-alpha nebulization added to baseline antiviral agents for no more than 28 days. The primary endpoint was the time to clinical improvement. Secondary endpoints included the overall rate of clinical improvement assessed on day 28, the time to radiological improvement and virus nucleic acid negative conversion. RESULTS: A total of 94 patients were included in the safety set (46 patients assigned to rSIFN-co group, 48 to interferon-alpha group). The time to clinical improvement was 11.5 days versus 14.0 days (95% CI 1.10 to 2.81, p = .019); the overall rate of clinical improvement on day 28 was 93.5% versus 77.1% (difference, 16.4%; 95% CI 3% to 30%); the time to radiological improvement was 8.0 days versus 10.0 days (p = .002), the time to virus nucleic acid negative conversion was 7.0 days versus 10.0 days (p = .018) in the rSIFN-co and interferon alpha arms, respectively. Adverse events were balanced with no deaths among groups. CONCLUSIONS AND RELEVANCE: rSIFN-co was associated with a shorter time of clinical improvement than traditional interferon-alpha in the treatment of moderate-to-severe COVID-19 when combined with baseline antiviral agents. rSIFN-co therapy alone or combined with other antiviral therapy is worth to be further studied.Key messagesThere are few effective therapies for coronavirus disease 2019 (COVID-19) upon the outbreak of the pandemic. Interferon alphas, by inducing both innate and adaptive immune responses, have shown clinical efficacy in treating severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus.In this multicenter, head-to-head, randomized, clinical trial which included 94 participants with moderate-to-severe COVID-19, the rSIFN-co plus antiviral agents (lopinavir-ritonavir or umifenovir) was associated with a shorter time of clinical improvement than interferon-alpha plus antiviral agents.

Efficacy of early prone or lateral positioning in patients with severe COVID-19: a single-center prospective cohort.

Background: Position intervention has been shown to improve oxygenation, but its role in non-invasively ventilated patients with severe COVID-19 has not been assessed. The objective of this study was to investigate the efficacy of early position intervention on non-invasively ventilated patients with severe COVID-19. Methods: This was a single-center, prospective observational study in consecutive patients with severe COVID-19 managed in a provisional ICU at Renmin Hospital of Wuhan University from 31 January to 15 February 2020. Patients with chest CT showing exudation or consolidation in bilateral peripheral and posterior parts of the lungs were included. Early position intervention (prone or lateral) was commenced for > 4 hours daily for 10 days in these patients, while others received standard care. Results: The baseline parameters were comparable between the position intervention group (n = 17) and the standard care group (n = 35). Position intervention was well-tolerated and increased cumulative adjusted mean difference of SpO2/FiO2 (409, 95% CI 86 to 733) and ROX index (26, 95% CI 9 to 43) with decreased Borg scale (-9, 95% CI -15 to -3) during the first 7 days. It also facilitated absorption of lung lesions and reduced the proportion of patients with high National Early Warning Score 2 (≥ 7) on days 7 and 14, with a trend toward faster clinical improvement. Virus shedding and length of hospital stay were comparable between the two groups. Conclusions: This study provides the first evidence for improved oxygenation and lung lesion absorption using early position intervention in non-invasively ventilated patients with severe COVID-19, and warrants further randomized trials.

Characteristics of Pulmonary Auscultation in Patients with 2019 Novel Coronavirus in China.

BACKGROUND: Effective auscultations are often hard to implement in isolation wards. To date, little is known about the characteristics of pulmonary auscultation in novel coronavirus (COVID-19) pneumonia. OBJECTIVES: The aim of this study was to explore the features and clinical significance of pulmonary auscultation in COVID-19 pneumonia using an electronic stethoscope in isolation wards. METHODS: This cross-sectional, observational study was conducted among patients with laboratory-confirmed COVID-19 at Wuhan Red-Cross Hospital during the period from January 27, 2020, to February 12, 2020. Standard auscultation with an electronic stethoscope was performed and electronic recordings of breath sounds were analyzed. RESULTS: Fifty-seven patients with average age of 60.6 years were enrolled. The most common symptoms were cough (73.7%) during auscultation. Most cases had bilateral lesions (96.4%) such as multiple ground-glass opacities (69.1%) and fibrous stripes (21.8%). High-quality auscultation recordings (98.8%) were obtained, and coarse breath sounds, wheezes, coarse crackles, fine crackles, and Velcro crackles were identified. Most cases had normal breath sounds in upper lungs, but the proportions of abnormal breath sounds increased in the basal fields where Velcro crackles were more commonly identified at the posterior chest. The presence of fine and coarse crackles detected 33/39 patients with ground-glass opacities (sensitivity 84.6% and specificity 12.5%) and 8/9 patients with consolidation (sensitivity 88.9% and specificity 15.2%), while the presence of Velcro crackles identified 16/39 patients with ground-glass opacities (sensitivity 41% and specificity 81.3%). CONCLUSIONS: The abnormal breath sounds in COVID-19 pneumonia had some consistent distributive characteristics and to some extent correlated with the radiologic features. Such evidence suggests that electronic auscultation is useful to aid diagnosis and timely management of the disease. Further studies are indicated to validate the accuracy and potential clinical benefit of auscultation in detecting pulmonary abnormalities in COVID-19 infection.

Subcutaneous injection of IFN alpha-2b for COVID-19: an observational study.

BACKGROUND: The global pandemic of coronavirus disease 2019 (COVID-19) infection is ongoing and associated with high mortality. The aim of this study was to investigate the efficacy and safety of subcutaneous injection of interferon alpha-2b (IFN alpha-2b) combined with lopinavir/ritonavir (LPV/r) in the treatment of COVID-19 infection, compared with that of using LPV/r alone. METHODS: Patients diagnosed with laboratory-confirmed COVID-19 infection in Wuhan Red Cross hospital during the period from January 23, 2020 to March 19, 2020 were included. The length of stay, the time to viral clearance and adverse reactions during hospitalization were compared between patients using oral LPV/r and combined therapy of LPV/r and subcutaneous injection of IFN alpha-2b. RESULTS: A total of 22 patients were treated with LPV/r alone and 19 with combined therapy with subcutaneous injection of IFN alpha-2b. The average length of hospitalization in the combination group was shorter than that of LPV/r group (16 ± 9.7 vs 23 ± 10.5 days; P = 0.028). Moreover, the days of hospitalization in early intervention group decreased from 25 ± 8.5 days to 10 ± 2.9 days compared with delayed intervention group (P = 0.001). Combined therapy with IFN alpha-2b also significantly reduced the duration of detectable virus in the upper respiratory tract. No patient in each group was transferred to intensive care unit (ICU) or died during the treatment. There was no significant difference in the adverse effect composition between two groups. CONCLUSIONS: Subcutaneous injection of IFN alpha-2b combined with LPV/r shortened the length of hospitalization and accelerated viral clearance in COVID-19 patients, which deserves further investigation in clinical practice.

Practical strategies to reduce nosocomial transmission to healthcare professionals providing respiratory care to patients with COVID-19.

Coronavirus disease (COVID-19) is an emerging viral infection that is rapidly spreading across the globe. SARS-CoV-2 belongs to the same coronavirus class that caused respiratory illnesses such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). During the SARS and MERS outbreaks, many frontline healthcare workers were infected when performing high-risk aerosol-generating medical procedures as well as when providing basic patient care. Similarly, COVID-19 disease has been reported to infect healthcare workers at a rate of ~ 3% of cases treated in the USA. In this review, we conducted an extensive literature search to develop practical strategies that can be implemented when providing respiratory treatments to COVID-19 patients, with the aim to help prevent nosocomial transmission to the frontline workers.

Prevention and treatment system of novel coronavirus infection in medical and health institutions: experience in West China Hospital of Sichuan University.

The novel coronavirus infection broke out in Wuhan, China, in December 2019, and progressed to a global pandemic. We describe the measures taken by West China Hospital of Sichuan University to address the diagnosis, prevention and treatment of the infection.

Therapeutic response to corticosteroids in a critically ill patient with COVID-19: A case report.

INTRODUCTION: Since the coronavirus disease 2019 (COVID-19) outbreak in Wuhan in late 2019, controversy on the use of corticosteroids for COVID-19 has obtained increasing attention. We present 1 critically ill patient who had a rapid therapeutic response to moderate-dose corticosteroids. PATIENT CONCERNS: A 53-year-old critically ill woman from Wuhan suffered with COVID-19. DIAGNOSIS: The chest computed tomography scan was suggestive of COVID-19. The diagnosis was confirmed by a real-time reverse transcription polymerase chain reaction test for SARS-CoV-2. The critically ill status was characterized by worsening dyspnea, progressing bilateral lung consolidation, and poor oxygenation (SiO2/FiO2:110 mm Hg). INTERVENTIONS: The patient was treated with a moderate dose of intravenous corticosteroids and high-flow nasal cannula oxygen therapy. OUTCOMES: After the initiation of corticosteroids, the patient rapidly improved over the following 6 days. Serial chest computed tomography scans showed good absorption of the consolidations. The patient was discharged on Day 17 of hospitalization without obvious adverse effects. CONCLUSIONS: Early use of moderate-dose corticosteroids over a short period may enhance recovery from COVID-19 in critically ill patients.

The Role of Chest Imaging in Patient Management during the COVID-19 Pandemic: A Multinational Consensus Statement from the Fleischner Society.

With more than 900 000 confirmed cases worldwide and nearly 50 000 deaths during the first 3 months of 2020, the coronavirus disease 2019 (COVID-19) pandemic has emerged as an unprecedented health care crisis. The spread of COVID-19 has been heterogeneous, resulting in some regions having sporadic transmission and relatively few hospitalized patients with COVID-19 and others having community transmission that has led to overwhelming numbers of severe cases. For these regions, health care delivery has been disrupted and compromised by critical resource constraints in diagnostic testing, hospital beds, ventilators, and health care workers who have fallen ill to the virus exacerbated by shortages of personal protective equipment. Although mild cases mimic common upper respiratory viral infections, respiratory dysfunction becomes the principal source of morbidity and mortality as the disease advances. Thoracic imaging with chest radiography and CT are key tools for pulmonary disease diagnosis and management, but their role in the management of COVID-19 has not been considered within the multivariable context of the severity of respiratory disease, pretest probability, risk factors for disease progression, and critical resource constraints. To address this deficit, a multidisciplinary panel comprised principally of radiologists and pulmonologists from 10 countries with experience managing patients with COVID-19 across a spectrum of health care environments evaluated the utility of imaging within three scenarios representing varying risk factors, community conditions, and resource constraints. Fourteen key questions, corresponding to 11 decision points within the three scenarios and three additional clinical situations, were rated by the panel based on the anticipated value of the information that thoracic imaging would be expected to provide. The results were aggregated, resulting in five main and three additional recommendations intended to guide medical practitioners in the use of chest radiography and CT in the management of COVID-19.

The Role of Chest Imaging in Patient Management During the COVID-19 Pandemic: A Multinational Consensus Statement From the Fleischner Society.

With more than 900,000 confirmed cases worldwide and nearly 50,000 deaths during the first 3 months of 2020, the coronavirus disease 2019 (COVID-19) pandemic has emerged as an unprecedented health care crisis. The spread of COVID-19 has been heterogeneous, resulting in some regions having sporadic transmission and relatively few hospitalized patients with COVID-19 and others having community transmission that has led to overwhelming numbers of severe cases. For these regions, health care delivery has been disrupted and compromised by critical resource constraints in diagnostic testing, hospital beds, ventilators, and health care workers who have fallen ill to the virus exacerbated by shortages of personal protective equipment. Although mild cases mimic common upper respiratory viral infections, respiratory dysfunction becomes the principal source of morbidity and mortality as the disease advances. Thoracic imaging with chest radiography and CT are key tools for pulmonary disease diagnosis and management, but their role in the management of COVID-19 has not been considered within the multivariable context of the severity of respiratory disease, pretest probability, risk factors for disease progression, and critical resource constraints. To address this deficit, a multidisciplinary panel comprised principally of radiologists and pulmonologists from 10 countries with experience managing patients with COVID-19 across a spectrum of health care environments evaluated the utility of imaging within three scenarios representing varying risk factors, community conditions, and resource constraints. Fourteen key questions, corresponding to 11 decision points within the three scenarios and three additional clinical situations, were rated by the panel based on the anticipated value of the information that thoracic imaging would be expected to provide. The results were aggregated, resulting in five main and three additional recommendations intended to guide medical practitioners in the use of chest radiography and CT in the management of COVID-19.

Performing Bronchoscopy in Times of the COVID-19 Pandemic: Practice Statement from an International Expert Panel.

These recommendations for physicians who perform bronchoscopy will help to protect those patients (un)-affected by the current COVID-19 pandemic, minimize the risk of transmission, and maintain clinical care for all patients.