Efficacy and safety of three passive immunotherapies for Corona Virus Disease 2019：a system review and network meta-analysis (preprint)

Background Passive immunotherapies to augment the humoral immunity against virus have been associated with prevention of severe illnesses and reduction of mortality of patients with coronavirus disease 2019 (COVID-19). However, less is known about the comparative effectiveness of different types of passive immunotherapies. The aim of this study is to compare efficacy and safety of passive immunotherapy in patients with COVID-19. Methods This is a two-part network meta-analysis which evaluate the efficacy of passive immunotherapy in outpatients and hospitalized patients separately. Electronic databases, including PubMed, EMBASE, and Cochrane CENTRAL were systematically searched for articles published before 26th April 2022. Randomized clinical trials that compared COVID-19 specific antiviral antibodies, convalescence plasma and hyperimmune anti-COVID-19 Intravenous Immunoglobulin with placebo, or control plasma, or standard of care in patients with COVID-19 were included. Two authors screened the studies independently. We extracted data and assessed the risk of bias of studies using the revised Cochrane risk of bias tool (RoB 2 tool) at study level. The primary outcome for outpatients is hospitalization within 30 days from randomization and are mortality, need of invasive mechanical ventilation, and severe advent events for hospitalized patients. Results In this systematic review and network meta-analysis, data were pooled from 41 eligible randomized control trials involving 42298 participants. In the first part of network meta-analysis which is consist of 9 eligible trials with 10093 participants, compared with control, specific antiviral antibodies (odds ratio [OR]: 0.22, 95% CI: 0.16, 0.28) rather than CP (OR: 0.75, 95%CI: 0.56, 1.01) reduced the risk of hospitalization; treatment with antibody reduced a greater risk of hospitalization (OR: 0.29, 95%CI: 0.19, 0.43) when compared with CP. For the analysis of secondary outcome in outpatients, antibody (OR: 0.10, 95%CI: 0.01, 0.37) rather than CP (OR: 0.81, 95%CI: 0.23, 2.78) reduced the risk of mortality. In the second party of meta-analysis, none of the passive immunotherapy was associated with the reduction of mortality, need of invasive mechanical ventilation and severe adverse events. Furthermore, none of passive immunotherapy was associated with improvement in 6 secondary outcomes. However, in subgroup analysis, the administration of antibody was associated with improvement of mortality, need of invasive mechanical ventilation, rate of discharge, duration of hospital stay, time to death and with less adverse events. Conclusions In this network meta-analysis of clinical trials of patients with COVID-19, we found that treatment with antiviral antibodies reduced the risk of hospitalization in outpatients. Among hospitalized adult patients, all three passive immunotherapies compared with control did not result in a statistically significant improvement of the primary outcomes, but use of neutralizing antibodies may lead to improvement of primary outcomes and key secondary outcomes in seronegative patients. Further development of broader-spectrum antibodies targeting to highly conserved domain of spike protein which avoids immune escape of new variants are needed.

Long-term chest CT follow-up in COVID-19 Survivors: 102-361 days after onset.

BACKGROUND: The aim of this study was to evaluate long-term longitudinal changes in chest computed tomography (CT) findings in coronavirus disease 2019 (COVID-19) survivors and their correlations with dyspnea after discharge. METHODS: A total of 337 COVID-19 survivors who underwent CT scan during hospitalization and between 102 and 361 days after onset were retrospectively included. Subjective CT findings, lesion volume, therapeutic measures and laboratory parameters were collected. The severity of the survivors' dyspnea was determined by follow-up questionnaire. The evolution of the CT findings from the peak period to discharge and throughout follow-up and the abilities of CT findings and clinical parameters to predict survival with and without dyspnea were analyzed. RESULTS: Ninety-one COVID-19 survivors still had dyspnea at follow-up. The age, comorbidity score, duration of hospital stays, receipt of hormone administration, receipt of immunoglobulin injections, intensive care unit (ICU) admission, receipt of mechanical ventilation, laboratory parameters, clinical classifications and parameters associated with lesion volume of the survivors with dyspnea were significantly different from those of survivors without dyspnea. Among the clinical parameters and CT parameters used to identify dyspnea, parameters associated with lesion volume showed the largest area under the curve (AUC) values, with lesion volume at discharge showing the largest AUC (0.820). Lesion volume decreased gradually from the peak period to discharge and through follow-up, with a notable decrease observed after discharge. Absorption of lesions continued 6 months after discharge. CONCLUSIONS: Among the clinical parameters and subjective CT findings, CT findings associated with lesion volume were the best predictors of post-discharge dyspnea in COVID-19 survivors.

Demographic, signs and symptoms, imaging characteristics of 2126 patients with COVID-19 pneumonia in the whole quarantine of Wuhan, China.

OBJECTIVE: The accurate knowledge of demographic, signs and symptoms, imaging characteristics of coronavirus disease 2019 (COVID-19) is essential for the accurate management of these patients. However, the claims between the previous papers are not always consistent and may even contradict each other, for example, some claims the virus infects more men than women in Wuhan. In this large-scale cohort study, we aimed to update the demographic, signs and symptoms, imaging characteristics of patients with COVID-19 in the whole quarantine of Wuhan, China. METHODS: A cohort of 2126 patients with a diagnosis of COVID-19 pneumonia (confirmed by real-time reverse transcriptase-polymerase chain reaction, RT-PCR) who were admitted to one hospital in Wuhan were retrospectively enrolled. Data were collected between January 13, 2020, and April 8, 2020, the end of Wuhan quarantine. Demographic, signs and symptoms, imaging characteristics were analyzed. CT imaging characteristics associated with respiratory failure or death were identified. RESULTS: Of the 2126 patients with COVID-19, 1051 (49.44%) were men and 1075 (50.56%) were women, 1933 (90.92%) have fever and 1328 (62.46%) have dry cough. The mean age was 57.43 years of age (range 1-95). The CT imaging findings were bilateral pneumonia (1883[88.57%]), unilateral pneumonia (243[11.43%]), ground-glass opacity (GGO) or consolidation (1175[55.27%]), pleural effusion (69[3.25%]). Patients with respiratory failure or death were more likely to have pleural effusion on CT than patients without respiratory failure or death (p < 0.05). CONCLUSION: Men and women have been infected by SARS-CoV-2 in roughly equal numbers. Fever and cough are the most prevalent symptoms at disease onset in patients. Other prevalent symptoms include fatigue, and sputum production. COVID-19 patients with bilateral pneumonia and pleural effusion are more likely to develop respiratory failure or death.

Secondary Infection in Severe and Critical COVID-19 Patients in China: A Multicenter Retrospective Study (preprint)

Background. Since 2020 COVID-19 pandemic became an emergent public sanitary incident. The epidemiology data and the impact on prognosis of secondary infection in severe and critical COVID-19 patients in China remained largely unclear.Methods. We retrospectively reviewed medical records of all adult patients with laboratory-confirmed COVID-19 who were admitted to ICUs from January 18th 2020 to April 26th 2020 at two hospitals in Wuhan, China and one hospital in Guangzhou, China. We measured the frequency of bacteria and fungi cultured from respiratory tract, blood and other body fluid specimens. The risk factors for and impact of secondary infection on clinical outcomes were also assessed. Results. Secondary infections were very common (86.6%) when patients were admitted to ICU for >72 hours. The majority of infections were respiratory, with the most common organisms being Klebsiella pneumoniae (24.5%), Acinetobacter baumannii (21.8%), Stenotrophomonas maltophilia (9.9%), Candida albicans (6.8%), and Pseudomonas spp. (4.8%). Furthermore, the proportions of multidrug resistant (MDR) bacteria and carbapenem resistant Enterobacteriaceae (CRE) were high. We also found that age ≥60 years and mechanical ventilation ≥13days independently increased the likelihood of secondary infection. Finally, patients with positive cultures had reduced ventilator free days in 28 days and patients with CRE and/or MDR bacteria positivity showed lower 28 day survival rate.Conclusions. In a retrospective cohort of severe and critical COVID-19 patients admitted to ICUs in China, the prevalence of secondary infection was high, especially with CRE and MDR bacteria, resulting in poor clinical outcomes.

Assessment of the Severity of Coronavirus Disease: Quantitative Computed Tomography Parameters versus Semiquantitative Visual Score.

OBJECTIVE: To compare the accuracies of quantitative computed tomography (CT) parameters and semiquantitative visual score in evaluating clinical classification of severity of coronavirus disease (COVID-19). MATERIALS AND METHODS: We retrospectively enrolled 187 patients with COVID-19 treated at Tongji Hospital of Tongji Medical College from February 15, 2020, to February 29, 2020. Demographic data, imaging characteristics, and clinical data were collected, and based on the clinical classification of severity, patients were divided into groups 1 (mild) and 2 (severe/critical). A semiquantitative visual score was used to estimate the lesion extent. A three-dimensional slicer was used to precisely quantify the volume and CT value of the lung and lesions. Correlation coefficients of the quantitative CT parameters, semiquantitative visual score, and clinical classification were calculated using Spearman's correlation. A receiver operating characteristic curve was used to compare the accuracies of quantitative and semi-quantitative methods. RESULTS: There were 59 patients in group 1 and 128 patients in group 2. The mean age and sex distribution of the two groups were not significantly different. The lesions were primarily located in the subpleural area. Compared to group 1, group 2 had larger values for all volume-dependent parameters (p < 0.001). The percentage of lesions had the strongest correlation with disease severity with a correlation coefficient of 0.495. In comparison, the correlation coefficient of semiquantitative score was 0.349. To classify the severity of COVID-19, area under the curve of the percentage of lesions was the highest (0.807; 95% confidence interval, 0.744-0.861: p < 0.001) and that of the quantitative CT parameters was significantly higher than that of the semiquantitative visual score (p = 0.001). CONCLUSION: The classification accuracy of quantitative CT parameters was significantly superior to that of semiquantitative visual score in terms of evaluating the severity of COVID-19.

Vascular Endothelial Growth Factor (VEGF) as a Vital Target for Brain Inflammation during the COVID-19 Outbreak.

The coronavirus disease 19 (COVID-19) pandemic has brought a great threat to global public health. Currently, mounting evidence has shown the occurrence of neurological symptoms in patients with COVID-19. However, the detailed mechanism by which the SARS-CoV-2 attacks the brain is not well characterized. Recent investigations have revealed that a cytokine storm contributes to brain inflammation and subsequently triggers neurological manifestations during the COVID-19 outbreak. Targeting brain inflammation may provide significant clues to the treatment of neurologic complications caused by SARS-CoV-2. Vascular growth factor (VEGF), which is widely distributed in the brain, probably plays a crucial role in brain inflammation via facilitating the recruitment of inflammatory cells and regulating the level of angiopoietins II (Ang II). Also, Ang II is considered as the products of SARS-CoV-2-attacking target, angiotensin-converting enzyme 2 (ACE2). Further investigation of the therapeutic potential and the underlying mechanisms of VEGF-targeted drugs on the neurological signs of COVID-19 are warranted. In any case, VEGF is deemed a promising therapeutic target in suppressing inflammation during SARS-CoV-2 infection with neurological symptoms.