Computed tomography–based COVID–19 triage through a deep neural network using mask–weighted global average pooling

Background There is an urgent need to find an effective and accurate method for triaging coronavirus disease 2019 (COVID-19) patients from millions or billions of people. Therefore, this study aimed to develop a novel deep-learning approach for COVID-19 triage based on chest computed tomography (CT) images, including normal, pneumonia, and COVID-19 cases. Methods A total of 2,809 chest CT scans (1,105 COVID-19, 854 normal, and 850 non-3COVID-19 pneumonia cases) were acquired for this study and classified into the training set (n = 2,329) and test set (n = 480). A U-net-based convolutional neural network was used for lung segmentation, and a mask-weighted global average pooling (GAP) method was proposed for the deep neural network to improve the performance of COVID-19 classification between COVID-19 and normal or common pneumonia cases. Results The results for lung segmentation reached a dice value of 96.5% on 30 independent CT scans. The performance of the mask-weighted GAP method achieved the COVID-19 triage with a sensitivity of 96.5% and specificity of 87.8% using the testing dataset. The mask-weighted GAP method demonstrated 0.9% and 2% improvements in sensitivity and specificity, respectively, compared with the normal GAP. In addition, fusion images between the CT images and the highlighted area from the deep learning model using the Grad-CAM method, indicating the lesion region detected using the deep learning method, were drawn and could also be confirmed by radiologists. Conclusions This study proposed a mask-weighted GAP-based deep learning method and obtained promising results for COVID-19 triage based on chest CT images. Furthermore, it can be considered a convenient tool to assist doctors in diagnosing COVID-19.

Computed tomography-based COVID-19 triage through a deep neural network using mask-weighted global average pooling.

Background: There is an urgent need to find an effective and accurate method for triaging coronavirus disease 2019 (COVID-19) patients from millions or billions of people. Therefore, this study aimed to develop a novel deep-learning approach for COVID-19 triage based on chest computed tomography (CT) images, including normal, pneumonia, and COVID-19 cases. Methods: A total of 2,809 chest CT scans (1,105 COVID-19, 854 normal, and 850 non-3COVID-19 pneumonia cases) were acquired for this study and classified into the training set (n = 2,329) and test set (n = 480). A U-net-based convolutional neural network was used for lung segmentation, and a mask-weighted global average pooling (GAP) method was proposed for the deep neural network to improve the performance of COVID-19 classification between COVID-19 and normal or common pneumonia cases. Results: The results for lung segmentation reached a dice value of 96.5% on 30 independent CT scans. The performance of the mask-weighted GAP method achieved the COVID-19 triage with a sensitivity of 96.5% and specificity of 87.8% using the testing dataset. The mask-weighted GAP method demonstrated 0.9% and 2% improvements in sensitivity and specificity, respectively, compared with the normal GAP. In addition, fusion images between the CT images and the highlighted area from the deep learning model using the Grad-CAM method, indicating the lesion region detected using the deep learning method, were drawn and could also be confirmed by radiologists. Conclusions: This study proposed a mask-weighted GAP-based deep learning method and obtained promising results for COVID-19 triage based on chest CT images. Furthermore, it can be considered a convenient tool to assist doctors in diagnosing COVID-19.

Telemedicine is associated with reduced socioeconomic disparities in outpatient clinic no-show rates.

INTRODUCTION: The global pandemic caused by coronavirus (COVID-19) sped up the adoption of telemedicine. We aimed to assess whether factors associated with no-show differed between in-person and telemedicine visits. The focus is on understanding how social economic factors affect patient no-show for the two modalities of visits. METHODS: We utilized electronic health records data for outpatient internal medicine visits at a large urban academic medical center, from February 1, 2020 to December 31, 2020. A mixed-effect logistic regression was used. We performed stratified analysis for each modality of visit and a combined analysis with interaction terms between exposure variables and visit modality. RESULTS: A total of 111,725 visits for 72,603 patients were identified. Patient demographics (age, gender, race, income, partner), lead days, and primary insurance were significantly different between the two visit modalities. Our multivariable regression analyses showed that the impact of sociodemographic factors, such as Medicaid insurance (OR 1.23, p < 0.01 for in-person; OR 1.03, p = 0.57 for telemedicine; p < 0.01 for interaction), Medicare insurance (OR 1.11, p = 0.04 for in-person; OR 0.95, p = 0.32 for telemedicine; p = 0.03 for interaction) and Black race (OR 1.36, p < 0.01 for in-person; OR 1.20, p < 0.01 for telemedicine; p = 0.03 for interaction), on increased odds of no-show was less for telemedicine visits than for in-person visits. In addition, inclement weather and younger age had less impact on no-show for telemedicine visits. DISCUSSION: Our findings indicated that if adopted successfully, telemedicine had the potential to reduce no-show rate for vulnerable patient groups and reduce the disparity between patients from different socioeconomic backgrounds.

Clinical and Pulmonary CT Characteristics of Patients Infected With the SARS-CoV-2 Omicron Variant Compared With Those of Patients Infected With the Alpha Viral Strain.

Background: Omicron has become the dominant variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) globally. We aimed to compare the clinical and pulmonary computed tomography (CT) characteristics of the patients infected with SARS-CoV-2 Omicron with those of patients infected with the Alpha viral strain. Methods: Clinical profiles and pulmonary CT images of 420 patients diagnosed with coronavirus disease-2019 (COVID-19) at Ningbo First Hospital between January 2020 and April 2022 were collected. Demographic characteristics, symptoms, and imaging manifestations of patients infected with the SARS-CoV-2 Omicron variant were compared with those of patients infected with the Alpha strain. Results: A total of 38 patients were diagnosed to be infected with the Alpha strain of SARS-CoV-2, whereas 382 patients were thought to be infected with the Omicron variant. Compared with patients infected with the Alpha strain, those infected with the Omicron variant were younger, and a higher proportion of men were infected (P < 0.001). Notably, 93 (24.3%) of the patients infected with Omicron were asymptomatic, whereas only two (5.3%) of the patients infected with the Alpha strain were asymptomatic. Fever (65.8%), cough (63.2%), shortness of breath (21.1%), and diarrhea (21.1%) were more common in patients infected with the SARS-CoV-2 Alpha strain, while runny nose (24.1%), sore throat (31.9%), body aches (13.6%), and headache (12.3%) were more common in patients with the Omicron variant. Compared with 33 (86.84%) of 38 patients infected with the Alpha strain, who had viral pneumonia on pulmonary CT images, only 5 (1.3%) of 382 patients infected with the Omicron variant had mild foci. In addition, the distribution of opacities in the five patients was unilateral and centrilobular, whereas most patients infected with the Alpha strain had bilateral involvement and multiple lesions in the peripheral zones of the lung. Conclusion: The SARS-CoV-2 Alpha strain mainly affects the lungs, while Omicron is confined to the upper respiratory tract in patients with COVID-19.

Case Report: The Experience of Managing a Moderate ARDS Caused by SARS-CoV-2 Omicron BA.2 Variant in Chongqing, China: Can We Do Better?

Background: The severe coronavirus disease 2019 (COVID-19) pandemic is still raging worldwide, and the Omicron BA.2 variant has become the new circulating epidemic strain. However, our understanding of the Omicron BA.2 variant is still scarce. This report aims to present a case of a moderate acute respiratory distress syndrome (ARDS) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Omicron BA.2 variant and to discuss some management strategies that may benefit this type of case. Case Presentation: A 78-year-old man, who had four negative nucleic acid tests and a fifth positive, was admitted to our hospital. This patient was generally good upon admission and tested negative for anti-SARS-CoV-2 antibodies even after receiving two doses of the COVID-19 vaccine. On the 7th day of hospitalization, he developed a moderate ARDS. Improved inflammatory index and decreased oxygen index were primarily found in this patient, and a series of treatments, including anti-inflammation and oxygen therapies, were used. Then this patient's condition improved soon and reached two negative results of nucleic acid tests on the 18th day of hospitalization. Conclusion: At-home COVID-19 rapid antigen test could be complementary to existing detection methods, and the third booster dose of COVID-19 vaccine may be advocated in the face of the omicron BA.2 variant. Anti-inflammatory and oxygen therapies are still essential treatments for ARDS patients infected with SARS-CoV-2 Omicron BA.2 variant.

Changes in molecular characteristics and antimicrobial resistance of invasive Staphylococcus aureus infection strains isolated from children in Kunming, China during the COVID-19 epidemic.

Invasive Staphylococcus aureus (S. aureus) infection is associated with high rates of mortality in children. No studies have been reported on invasive S. aureus infection among children in Kunming, China, and it remains unknown whether the COVID-19 epidemic has affected S. aureus prevalence in this region. Thus, this study investigated the changes in molecular characteristics and antimicrobial resistance of invasive S. aureus strains isolated from children in Kunming during 2019-2021. In total, 66 invasive S. aureus strains isolated from children were typed by multilocus sequence typing (MLST), spa, and Staphylococcal cassette chromosome mec (SCCmec), and antimicrobial resistance and virulence genes were analyzed. A total of 19 ST types, 31 spa types and 3 SCCmec types were identified. Thirty nine (59.09%) strains were methicillin-sensitive S. aureus (MSSA) and 27 (40.91%) strains were methicillin-resistant S. aureus (MRSA). The most common molecular type was ST22-t309 (22.73%, 15/66), followed by ST59-t437 (13.64%, 9/66). In 2019 and 2021, the dominant molecular type was ST22-t309, while in 2020, it was ST59-t437. After 2019, the dominant molecular type of MRSA changed from ST338-t437 to ST59-t437. All strains were susceptible to tigecycline, ciprofloxacin, moxifloxacin, vancomycin, quinopudine-dafoputin, linezolid, levofloxacin, and rifampicin. From 2019 to 2021, the resistance to penicillin and sulfamethoxazole initially decreased and then increased, a trend that contrasted with the observed resistance to oxacillin, cefoxitin, erythromycin, clindamycin, and tetracycline. Sixteen antimicrobial resistance profiles were identified, with penicillin-tetracycline-erythromycin-clindamycin-oxacillin-cefoxitin being the most common, and the antimicrobial resistance profiles varied by year. The carrier rates of virulence genes, icaA, icaD, hla, fnbA, fnbB, clfA, clfB, and cna were 100.00%. Furthermore, sak, pvl, icaC, icaR, fib, lip, hlb, hysA, sea, seb, and tsst-1 had carrier rates of 96.97, 92.42, 87.88, 69.70, 84.85, 62.12, 56.06, 50, 37.87, 30.30, and 7.58%, respectively. Since COVID-19 epidemic, the annual number of invasive S. aureus strains isolated from children in Kunming remained stable, but the molecular characteristics and antimicrobial resistance profiles of prevalent S. aureus strains have changed significantly. Thus, COVID-19 prevention and control should be supplemented by surveillance of common clinical pathogens, particularly vigilance against the prevalence of multidrug-resistant and high-virulence strains.

Corticosteroids showed more efficacy in treating hospitalized patients with COVID-19 than standard care but the effect is minimal: A systematic review and meta-analysis.

Background: During the ongoing coronavirus disease 2019 (COVID-19) pandemic, the use of corticosteroids for COVID-19 has ignited worldwide debate. Previous systematic reviews, including randomized controlled trials (RCTs) and retrospective observational studies, found that corticosteroids have beneficial effects in treating COVID-19. Aim: This systematic review and meta-analysis only included RCTs to assess the effectiveness and safety of corticosteroids in hospitalized patients with COVID-19. Methods: Comprehensive research strategies (PubMed, Embase, MEDLINE, and Coherence Library) were used to search for RCTs from December 2019 to January 2021. Results: Five RCTs were included with 7,235 patients, of which 2,508 patients were receiving corticosteroid treatments (dexamethasone or methylprednisolone), and 4,727 received standard care. The primary outcome was mortality within 28 days. The use of corticosteroids decreased the 28-day mortality of patients with COVID-19, but the findings were not statistically significant (RR, 0.91; 95% CI, 0.78-1.06, p = 0.24). The secondary outcome was the duration of hospitalization; no differences were found between the corticosteroid and standard care groups. However, corticosteroids were associated with a higher hospital discharge rate than standard treatment, but the result was not statistically significant (RR, 1.36; 95% CI, 0.95-1.96, p = 0.09). Conclusions: The results suggest that corticosteroids are comparable to standard care in terms of safety in treating COVID-19. Corticosteroids showed greater efficacy than standard care; however, the effect was minimal.

Clinical and Pulmonary CT Characteristics of Patients Infected With the SARS-CoV-2 Omicron Variant Compared With Those of Patients Infected With the Alpha Viral Strain

Background Omicron has become the dominant variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) globally. We aimed to compare the clinical and pulmonary computed tomography (CT) characteristics of the patients infected with SARS-CoV-2 Omicron with those of patients infected with the Alpha viral strain. Methods Clinical profiles and pulmonary CT images of 420 patients diagnosed with coronavirus disease-2019 (COVID-19) at Ningbo First Hospital between January 2020 and April 2022 were collected. Demographic characteristics, symptoms, and imaging manifestations of patients infected with the SARS-CoV-2 Omicron variant were compared with those of patients infected with the Alpha strain. Results A total of 38 patients were diagnosed to be infected with the Alpha strain of SARS-CoV-2, whereas 382 patients were thought to be infected with the Omicron variant. Compared with patients infected with the Alpha strain, those infected with the Omicron variant were younger, and a higher proportion of men were infected (P < 0.001). Notably, 93 (24.3%) of the patients infected with Omicron were asymptomatic, whereas only two (5.3%) of the patients infected with the Alpha strain were asymptomatic. Fever (65.8%), cough (63.2%), shortness of breath (21.1%), and diarrhea (21.1%) were more common in patients infected with the SARS-CoV-2 Alpha strain, while runny nose (24.1%), sore throat (31.9%), body aches (13.6%), and headache (12.3%) were more common in patients with the Omicron variant. Compared with 33 (86.84%) of 38 patients infected with the Alpha strain, who had viral pneumonia on pulmonary CT images, only 5 (1.3%) of 382 patients infected with the Omicron variant had mild foci. In addition, the distribution of opacities in the five patients was unilateral and centrilobular, whereas most patients infected with the Alpha strain had bilateral involvement and multiple lesions in the peripheral zones of the lung. Conclusion The SARS-CoV-2 Alpha strain mainly affects the lungs, while Omicron is confined to the upper respiratory tract in patients with COVID-19.

Biomarkers of thromboinflammation correlate to COVID-19 infection and admission status in emergency department patients

Background COVID-19-associated coagulopathy is incompletely understood. Objectives To characterize thrombin generation, Von Willebrand Factor (VWF), neutrophil extracellular traps (NETs), and their role in COVID-19 risk stratification in the emergency department (ED). Patients/methods Plasma samples from 67 ED COVID-19 patients were compared to 38 healthy volunteers (HVs). Thrombin generation (calibrated automated thrombogram, CAT) was expressed as lag time (LT, min), peak height (PH, min), and time to peak (ttPeak, min). Citrullinated nucleosomes and histones were quantified with ELISA, VWF antigen and activity (IU/dL) through latex immunoassay, Factor VIII (IU/dL) through one-stage optical clot detection, and VWF multimers with western blot densitometry. Wilcoxon testing and multivariable logistic regression were performed. Results presented as median [Q1, Q3];p < 0.05 significant. Results COVID-19 patients had longer LT (4.00 [3.26, 4.67];2.95 [2.67, 3.10], p < 0.001) and ttPeak (7.33 [6.33, 8.04];6.45 [6.00, 7.50], p = 0.004), greater VWF antigen (212 [158, 275];110 [91, 128], p < 0.001) and Factor VIII levels (148 [106, 190];106 [86, 129], p < 0.001), with decreased high molecular weight multimers (Normalized multimer ratio 0.807 [0.759, 0.869];0.891 [0.858, 0.966], p < 0.001), than HVs. COVID-19 patients requiring admission from the ED had longer LT and ttPeak with greater VWF antigen and Factor VIII levels than those not admitted. Two and three variable models of CAT parameters and VWF correlated with COVID-19 and admission status (C-statistics 0.677 to 0.922). Conclusions Thrombin generation kinetics and VWF levels, independent of NETs, may have a role in predicting admission need for COVID-19 patients.

Comparative study on ct features of COVID-19 patients of imported and local in Gansu

Objective: To investigate the CT features and clinical features of coronavirus disease 2019(COVID-19) patients imported from abroad, China and infected locally.

Outbreak of Mycoplasma pneumoniae at a military academy.

In 2019, an outbreak of Mycoplasma pneumoniae occurred at a military academy in China. The attack rate (10.08%,60/595) was significantly different among the units. High-intensity training and crowded environments to which cadets are exposed are the high risk factors for the outbreak of M. pneumoniae. In-time prevention and control measures effectively controlled the spread of the epidemic.

Impact of cancer on mortality and severity of corona virus disease 2019: A protocol for systematic review and meta-analysis.

BACKGROUND: Cancer patients are in a state of systemic immunosuppression and are considered a highly vulnerable population in the Corona Virus Disease 2019 (COVID-19) epidemic. However, the relationship between cancer and the severity and mortality of patients with COVID-19 remains unclear. This study aims to evaluate whether cancer patients with COVID-19 may be at an increased risk of severe illness and mortality. METHODS: We will perform comprehensive searches in PubMed, EMBASE.com, Web of Science, and the Cochrane Central Register of Controlled Trials to identify studies providing prevalence of cancer between patients with severe and non-severe illness or between non-survivors and survivors. We will use the Newcastle-Ottawa quality assessment scale to assess the quality of included studies. We will conduct pairwise meta-analyses to compute the odds ratio and 95% confidence interval using the Mantel Haenszel method with the random-effects model. The statistical heterogeneity will be assessed using the I statistic. Subgroup analyses, sensitivity analyses, and meta-regression analyses will be performed to explore the sources of heterogeneity. RESULTS: The results of this study will be published in a peer-reviewed journal. CONCLUSION: Our meta-analysis will systematically evaluate the association between cancer and the severity and mortality of patients with COVID-19. This study will provide evidence to help determine whether cancer patients should be provided with special precautions and advised to use stronger personal protection. INPLASY REGISTRATION NUMBER: INPLASY202090093.

The Impact of High-Flow Nasal Cannula Use on Patient Mortality and the Availability of Mechanical Ventilators in COVID-19.

Rationale: How to provide advanced respiratory support for coronavirus disease (COVID-19) to maximize population-level survival while optimizing mechanical ventilator access is unknown.Objectives: To evaluate the use of high-flow nasal cannula for COVID-19 on population-level mortality and ventilator availability.Methods: We constructed dynamical (deterministic) simulation models of high-flow nasal cannula and mechanical ventilation use for COVID-19 in the United States. Model parameters were estimated through consensus based on published literature, local data, and experience. We had the following two outcomes: 1) cumulative number of deaths and 2) days without any available ventilators. We assessed the impact of various policies for the use of high-flow nasal cannula (with or without "early intubation") versus a scenario in which high-flow nasal cannula was unavailable.Results: The policy associated with the fewest deaths and the least time without available ventilators combined the use of high-flow nasal cannula for patients not urgently needing ventilators with the use of early mechanical ventilation for these patients when at least 10% of ventilator supply was not in use. At the national level, this strategy resulted in 10,000-40,000 fewer deaths than if high-flow nasal cannula were not available. In addition, with moderate national ventilator capacity (30,000-45,000 ventilators), this strategy led to up to 25 (11.8%) fewer days without available ventilators. For a 250-bed hospital with 100 mechanical ventilators, the availability of 13, 20, or 33 high-flow nasal cannulas prevented 81, 102, and 130 deaths, respectively.Conclusions: The use of high-flow nasal cannula coupled with early mechanical ventilation when supply is sufficient results in fewer deaths and greater ventilator availability.

Clinical and computed tomographic imaging features of novel coronavirus pneumonia caused by SARS-CoV-2.

PURPOSE: To investigate the clinical and imaging characteristics of computed tomography (CT) in novel coronavirus pneumonia (NCP) caused by SARS-CoV-2. MATERIALS AND METHODS: A retrospective analysis was performed on the imaging findings of patients confirmed with COVID-19 pneumonia who had chest CT scanning and treatment after disease onset. The clinical and imaging data were analyzed. RESULTS: Fifty patients were enrolled, including mild type in nine, common in 28, severe in 10 and critically severe in the rest three. Mild patients (29 years) were significantly (P<0.03) younger than either common (44.5 years) or severe (54.7) and critically severe (65.7 years) patients, and common patients were also significantly (P<0.03) younger than severe and critically severe patients. Mild patients had low to moderate fever (<39.1 °C), 49 (98%) patients had normal or slightly reduced leukocyte count, 14 (28%) had decreased counts of lymphocytes, and 26 (52%) patients had increased C-reactive protein. Nine mild patients were negative in CT imaging. For all the other types of NCP, the lesion was in the right upper lobe in 30 cases, right middle lobe in 22, right lower lobe in 39, left upper lobe in 33 and left lower lobe in 36. The lesion was primarily located in the peripheral area under the pleura with possible extension towards the pulmonary hilum. Symmetrical lesions were seen in 26 cases and asymmetrical in 15. The density of lesion was mostly uneven with ground glass opacity as the primary presentation accompanied by partial consolidation and fibrosis. CONCLUSION: CT imaging presentations of NCP are mostly patchy ground glass opacities in the peripheral areas under the pleura with partial consolidation which will be absorbed with formation of fibrotic stripes if improved. CT scanning provides important bases for early diagnosis and treatment of NCP.

Exploring an Integrative Therapy for Treating COVID-19: A Randomized Controlled Trial.

OBJECTIVES: To develop a new Chinese medicine (CM)-based drug and to evaluate its safety and effect for suppressing acute respiratory distress syndrome (ARDS) in COVID-19 patients. METHODS: A putative ARDS-suppressing drug Keguan-1 was first developed and then evaluated by a randomized, controlled two-arm trial. The two arms of the trial consist of a control therapy (alpha interferon inhalation, 50 µg twice daily; and lopinavir/ritonavir, 400 and 100 mg twice daily, respectively) and a testing therapy (control therapy plus Keguan-1 19.4 g twice daily) by random number table at 1:1 ratio with 24 cases each group. After 2-week treatment, adverse events, time to fever resolution, ARDS development, and lung injury on newly diagnosed COVID-19 patients were assessed. RESULTS: An analysis of the data from the first 30 participants showed that the control arm and the testing arm did not exhibit any significant differences in terms of adverse events. Based on this result, the study was expanded to include a total of 48 participants (24 cases each arm). The results show that compared with the control arm, the testing arm exhibited a significant improvement in time to fever resolution (P=0.035), and a significant reduction in the development of ARDS (P=0.048). CONCLUSIONS: Keguan-1-based integrative therapy was safe and superior to the standard therapy in suppressing the development of ARDS in COVID-19 patients. (Trial registration No. NCT04251871 at www.clinicaltrials.gov ).

Persistent Viral Presence Determines the Clinical Course of the Disease in COVID-19.

BACKGROUND: The clinical management of coronavirus disease 2019 (COVID-19) is dependent on understanding the underlying factors that contribute to the disease severity. In the absence of effective antiviral therapies, other host immunomodulatory therapies such as targeting inflammatory response are currently being used without clear evidence of their effectiveness. Because inflammation is an essential component of host antiviral mechanisms, therapies targeting inflammation may adversely affect viral clearance and disease outcome. OBJECTIVE: To understand whether the persistent presence of the virus is a key determinant in the disease severity during COVID-19 and to determine whether the viral reactivation in some patients is associated with infectious viral particles. METHODS: The data for patients were available including the onset of the disease, duration of viral persistence, measurements of inflammatory markers such as IL-6 and C-reactive protein, chest imaging, disease symptoms, and their durations among others. Follow-up tests were performed to determine whether the viral negative status persists after their recovery. RESULTS: Our data show that patients with persistent viral presence (>16 days) have more severe disease outcomes including extensive lung involvement and requirement of respiratory support. Two patients who died of COVID-19 were virus-positive at the time of their death. Four patients demonstrated virus-positive status on the follow-up tests, and these patient samples were sent to viral culture facility where virus culture could not be established. CONCLUSIONS: These data suggest that viral persistence is the key determining factor of the disease severity. Therapies that may impair the viral clearance may impair the host recovery from COVID-19.

Treat 2019 novel coronavirus (COVID-19) with IL-6 inhibitor: Are we already that far?

The world is in the midst of the coronavirus disease 2019 (COVID-19) pandemic. Interleukin 6 (IL-6) inhibitor (tocilizumab) had been suggested for the treatment of acute respiratory distress syndrome (ARDS) patients based on the concept of "cytokine storm" in COVID-19. However, we still lack reliable studies to verify "cytokine storm" in COVID-19 pneumonia. Furthermore, IL-6 inhibitor has potential hazards of inducing infectious diseases. The efficacy of IL-6 monoclonal antibody-directed therapy remains to be fully evaluated.