Efficacy and safety of awake prone positioning in the treatment of non-intubated spontaneously breathing patients with COVID-19-related acute respiratory failure: A systematic review and meta-analysis.

Background: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, prone positioning has been widely applied for non-intubated, spontaneously breathing patients. However, the efficacy and safety of prone positioning in non-intubated patients with COVID-19-related acute hypoxemic respiratory failure remain unclear. We aimed to systematically analyze the outcomes associated with awake prone positioning (APP). Methods: We conducted a systematic literature search of PubMed/MEDLINE, Cochrane Library, Embase, and Web of Science from January 1, 2020, to June 3, 2022. This study included adult patients with acute respiratory failure caused by COVID-19. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and the study quality was assessed using the Cochrane risk-of-bias tool. The primary outcome was the reported cumulative intubation risk across randomized controlled trials (RCTs), and the effect estimates were calculated as risk ratios (RRs; 95% confidence interval [CI]). Results: A total of 495 studies were identified, of which 10 fulfilled the selection criteria, and 2294 patients were included. In comparison to supine positioning, APP significantly reduced the need for intubation in the overall population (RR=0.84, 95% CI: 0.74-0.95). The two groups showed no significant differences in the incidence of adverse events (RR=1.16, 95% CI: 0.48-2.76). The meta-analysis revealed no difference in mortality between the groups (RR=0.93, 95% CI: 0.77-1.11). Conclusions: APP was safe and reduced the need for intubation in patients with respiratory failure associated with COVID-19. However, it did not significantly reduce mortality in comparison to usual care without prone positioning.

Association of gut microbiota with COVID-19 susceptibility and severity: A two-sample Mendelian randomization study.

Evidence supports the observational associations of gut microbiota with the risk of COVID-19; however, it is unclear whether these associations reflect a causal relationship. This study investigated the association of gut microbiota with COVID-19 susceptibility and severity. Data were obtained from a large-scale gut microbiota data set (n = 18 340) and the COVID-19 Host Genetics Initiative (n = 2 942 817). Causal effects were estimated with inverse variance weighted (IVW), MR-Egger, and weighted median, and sensitivity analyses were implemented with Cochran's Q test, MR-Egger intercept test, MR-PRESSO, leave-one-out analysis, and funnel plots. For COVID-19 susceptibility, IVW estimates suggested that Gammaproteobacteria (odds ratio [OR] = 0.94, 95% confidence interval [CI], 0.89-0.99, p = 0.0295] and Streptococcaceae (OR = 0.95, 95% CI, 0.92-1.00, p = 0.0287) had a reduced risk, while Negativicutes (OR = 1.05, 95% CI, 1.01-1.10, p = 0.0302), Selenomonadales (OR = 1.05, 95% CI, 1.01-1.10, p = 0.0302), Bacteroides (OR = 1.06, 95% CI, 1.01-1.12, p = 0.0283), and Bacteroidaceae (OR = 1.06, 95% CI, 1.01-1.12, p = 0.0283) were associated with an increased risk (all p < 0.05, nominally significant). For COVID-19 severity, Subdoligranulum (OR = 0.80, 95% CI, 0.69-0.92, p = 0.0018), Cyanobacteria (OR = 0.85, 95% CI, 0.76-0.96, p = 0.0062), Lactobacillales (OR = 0.87, 95% CI, 0.76-0.98, p = 0.0260), Christensenellaceae (OR = 0.87, 95% CI, 0.77-0.99, p = 0.0384), Tyzzerella3 (OR = 0.89, 95% CI, 0.81-0.97, p = 0.0070), and RuminococcaceaeUCG011 (OR = 0.91, 95% CI, 0.83-0.99, p = 0.0247) exhibited negative correlations, while RikenellaceaeRC9 (OR = 1.09, 95% CI, 1.01-1.17, p = 0.0277), LachnospiraceaeUCG008 (OR = 1.12, 95% CI, 1.00-1.26, p = 0.0432), and MollicutesRF9 (OR = 1.14, 95% CI, 1.01-1.29, p = 0.0354) exhibited positive correlations (all p < 0.05, nominally significant). Sensitivity analyses validated the robustness of the above associations. These findings suggest that gut microbiota might influence the susceptibility and severity of COVID-19 in a causal way, thus providing novel insights into the gut microbiota-mediated development mechanism of COVID-19.

Efficacy and safety of awake prone positioning in the treatment of non-intubated spontaneously breathing patients with COVID-19-related acute respiratory failure: A systematic review and meta-analysis

Background Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, prone positioning has been widely applied for non-intubated, spontaneously breathing patients. However, the efficacy and safety of prone positioning in non-intubated patients with COVID-19-related acute hypoxemic respiratory failure remain unclear. We aimed to systematically analyze the outcomes associated with awake prone positioning (APP). Methods We conducted a systematic literature search of PubMed/MEDLINE, Cochrane Library, Embase, and Web of Science from January 1, 2020, to June 3, 2022. This study included adult patients with acute respiratory failure caused by COVID-19. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and the study quality was assessed using the Cochrane risk-of-bias tool. The primary outcome was the reported cumulative intubation risk across randomized controlled trials (RCTs), and the effect estimates were calculated as risk ratios (RRs;95% confidence interval [CI]). Results A total of 495 studies were identified, of which 10 fulfilled the selection criteria, and 2294 patients were included. In comparison to supine positioning, APP significantly reduced the need for intubation in the overall population (RR=0.84, 95% CI: 0.74–0.95). The two groups showed no significant differences in the incidence of adverse events (RR=1.16, 95% CI: 0.48–2.76). The meta-analysis revealed no difference in mortality between the groups (RR=0.93, 95% CI: 0.77–1.11). Conclusions APP was safe and reduced the need for intubation in patients with respiratory failure associated with COVID-19. However, it did not significantly reduce mortality in comparison to usual care without prone positioning.

Therapeutic strategies for critically ill patients with COVID-19.

Since the 2019 novel coronavirus disease (COVID-19) outbreak originated from Wuhan, Hubei Province, China, at the end of 2019, it has become a clinical threat to the general population worldwide. Among people infected with the novel coronavirus (2019-nCoV), the intensive management of the critically ill patients in intensive care unit (ICU) needs substantial medical resource. In the present article, we have summarized the promising drugs, adjunctive agents, respiratory supportive strategies, as well as circulation management, multiple organ function monitoring and appropriate nutritional strategies for the treatment of COVID-19 in the ICU based on the previous experience of treating other viral infections and influenza. These treatments are referable before the vaccine and specific drugs are available for COVID-19.

Efficacy and safety of Paxlovid in severe adult patients with SARS-Cov-2 infection: a multicenter randomized controlled study.

Background: Nirmatrelvir plus ritonavir (Paxlovid) reduced the risk of hospitalization or death by 89% in high-risk, ambulatory adults with COVID-19. We aimed at studying the efficacy and safety of Paxlovid in hospitalized adult patients with SARS-Cov-2 (Omicron BA.2.2 variant) infection and severe comorbidities. Methods: We conducted an open-label, multicenter, randomized controlled trial in which hospitalized adult patients with severe comorbidities were eligible and assigned in a 1:1 ratio to receive either 300 mg of nirmatrelvir plus 100 mg of ritonavir every 12 h for 5 days with standard treatment or only standard treatment. All-cause mortality on day 28, the duration of SARS-CoV-2 RNA clearance, and safety were evaluated. Findings: 264 patients (mean age, 70.35 years; 122 [46.21%] female) who met the criteria were enrolled at 5 sites in Shanghai from April 10 to May 19 in 2022. After randomization, a total of 132 patients were assigned to receive Paxlovid treatment plus standard treatment, and 132 patients were assigned to receive only standard treatment. The overall 28-day mortality was 4.92%, 8 patients died in the standard treatment group and 5 died in the Paxlovid plus standard treatment group. There was no significant difference in mortality from any cause at 28 days between the Paxlovid plus standard treatment group and the standard treatment group (absolute risk difference [ARD], 2.27; 95% CI -2.94 to 7.49, P = 0.39). There was no significant difference in the duration of SARS-CoV-2 RNA clearance among the two groups (mean days, 10 in Paxlovid plus standard treatment group and 10.50 in the standard treatment group; ARD, -0.62; 95% CI -2.29 to 1.05, P = 0.42). The incidence of adverse events that occurred during the treatment period was similar in the two groups (any adverse event, 10.61% with Paxlovid plus standard treatment vs. 7.58% with the standard, P = 0.39; serious adverse events, 4.55% vs. 3.788%, P = 0.76). Interpretation: Paxlovid showed no significant reduction in the risk of all-cause mortality on day 28 and the duration of SARS-CoV-2 RNA clearance in hospitalized adult COVID-19 patients with severe comorbidities. Funding: National Natural Science Foundation of China (grant number: 82172152, 81873944).

Efficacy and safety of Paxlovid in severe adult patients with SARS-Cov-2 infection: a multicenter randomized controlled study

Background Nirmatrelvir plus ritonavir (Paxlovid) reduced the risk of hospitalization or death by 89% in high-risk, ambulatory adults with COVID-19. We aimed at studying the efficacy and safety of Paxlovid in hospitalized adult patients with SARS-Cov-2 (Omicron BA.2.2 variant) infection and severe comorbidities. Methods We conducted an open-label, multicenter, randomized controlled trial in which hospitalized adult patients with severe comorbidities were eligible and assigned in a 1:1 ratio to receive either 300 mg of nirmatrelvir plus 100 mg of ritonavir every 12 h for 5 days with standard treatment or only standard treatment. All-cause mortality on day 28, the duration of SARS-CoV-2 RNA clearance, and safety were evaluated. Findings 264 patients (mean age, 70.35 years;122 [46.21%] female) who met the criteria were enrolled at 5 sites in Shanghai from April 10 to May 19 in 2022. After randomization, a total of 132 patients were assigned to receive Paxlovid treatment plus standard treatment, and 132 patients were assigned to receive only standard treatment. The overall 28-day mortality was 4.92%, 8 patients died in the standard treatment group and 5 died in the Paxlovid plus standard treatment group. There was no significant difference in mortality from any cause at 28 days between the Paxlovid plus standard treatment group and the standard treatment group (absolute risk difference [ARD], 2.27;95% CI −2.94 to 7.49, P = 0.39). There was no significant difference in the duration of SARS-CoV-2 RNA clearance among the two groups (mean days, 10 in Paxlovid plus standard treatment group and 10.50 in the standard treatment group;ARD, −0.62;95% CI −2.29 to 1.05, P = 0.42). The incidence of adverse events that occurred during the treatment period was similar in the two groups (any adverse event, 10.61% with Paxlovid plus standard treatment vs. 7.58% with the standard, P = 0.39;serious adverse events, 4.55% vs. 3.788%, P = 0.76). Interpretation Paxlovid showed no significant reduction in the risk of all-cause mortality on day 28 and the duration of SARS–CoV-2 RNA clearance in hospitalized adult COVID-19 patients with severe comorbidities. Funding 10.13039/501100001809National Natural Science Foundation of China (grant number: 82172152, 81873944).

Corticosteroid treatment in severe patients with SARS-CoV-2 and chronic HBV co-infection: a retrospective multicenter study.

BACKGROUND: The impact of corticosteroids on patients with severe coronavirus disease 2019 (COVID-19)/chronic hepatitis B virus (HBV) co-infection is currently unknown. We aimed to investigate the association of corticosteroids on these patients. METHODS: This retrospective multicenter study screened 5447 confirmed COVID-19 patients hospitalized between Jan 1, 2020 to Apr 18, 2020 in seven centers in China, where the prevalence of chronic HBV infection is moderate to high. Severe patients who had chronic HBV and acute SARS-cov-2 infection were potentially eligible. The diagnosis of chronic HBV infection was based on positive testing for hepatitis B surface antigen (HBsAg) or HBV DNA during hospitalization and a medical history of chronic HBV infection. Severe patients (meeting one of following criteria: respiratory rate > 30 breaths/min; severe respiratory distress; or SpO2 ≤ 93% on room air; or oxygen index < 300 mmHg) with COVID-19/HBV co-infection were identified. The bias of confounding variables on corticosteroids effects was minimized using multivariable logistic regression model and inverse probability of treatment weighting (IPTW) based on propensity score. RESULTS: The prevalence of HBV co-infection in COVID-19 patients was 4.1%. There were 105 patients with severe COVID-19/HBV co-infections (median age 62 years, 57.1% male). Fifty-five patients received corticosteroid treatment and 50 patients did not. In the multivariable analysis, corticosteroid therapy (OR, 6.32, 95% CI 1.17-34.24, P = 0.033) was identified as an independent risk factor for 28-day mortality. With IPTW analysis, corticosteroid treatment was associated with delayed SARS-CoV-2 viral RNA clearance (OR, 2.95, 95% CI 1.63-5.32, P < 0.001), increased risk of 28-day and in-hospital mortality (OR, 4.90, 95% CI 1.68-14.28, P = 0.004; OR, 5.64, 95% CI 1.95-16.30, P = 0.001, respectively), and acute liver injury (OR, 4.50, 95% CI 2.57-7.85, P < 0.001). Methylprednisolone dose per day and cumulative dose in non-survivors were significantly higher than in survivors. CONCLUSIONS: In patients with severe COVID-19/HBV co-infection, corticosteroid treatment may be associated with increased risk of 28-day and in-hospital mortality.

[Expert statement on the construction criteria of critical care department in municipal and district designated hospitals under the pandemic prevention and control].

The global coronavirus disease 2019 epidemic is still in a pandemic state. Aging population with underlying diseases is prone to become severe, and have a higher mortality. The treatment capacity of the critical care department directly determines the treatment success rate of critical illness. At present, there is still a certain gap between domestic and foreign countries in intensive care unit (ICU), which is not only in the allocation of medical staff, but also in the beds and settings. The current medical model cannot fully meet the needs of development. The experience and lessons of many major public health emergencies suggested that "dual track of peace and war" approach in discipline construction of critical care is the best medical model. Following the concept of "combination of peace and war", strengthening the discipline construction of critical care department in municipal and district designated hospitals, allocating reasonable standard ICU, step-down ICU and combat readiness ICU, establishing rapid response team, and strengthening regular training and scientific management may be the key measures to deal with the epidemic.

Baseline eHealth Behaviors of Service Members: A Retrospective, Cross-Sectional Analysis of Patient Portal Use Before the Pandemic.

INTRODUCTION: The use of electronic health (eHealth) tools has the potential to support the overall health, wellness, fitness status, and ability to deploy worldwide of active duty service members (SMs). Additionally, the Coronavirus Disease 2019 pandemic forced healthcare organizations to quickly convert to virtual care settings to decrease face-to-face interactions and increase access to healthcare using technology. The shift to virtual care and the push to increase use of eHealth tools heightened the need to understand how military members interact with eHealth tools. Little is known about the factors that influence SMs use of eHealth tools and if having a health condition increases or decreases use. To evaluate these factors, we completed a cross-sectional, retrospective analysis on a sample of 198,388 active duty SMs aged 18 to 68 years. MATERIALS AND METHODS: We used two Military Health System (MHS) data sources-Tricare Online (TOL) Patient Portal 2018 audit logs and outpatient electronic health record data. Using eHealth behaviors identified in the audit logs, we evaluated and compared individual characteristics (i.e., "gender", "age", "race", and "marital status"), environmental factors (i.e., "rank", "military branch", and "geographic location"), and six available health conditions (i.e., congenital health defects, amputation, anxiety, sleep, traumatic brain injury, and depression). Since moderate usage of eHealth tools is linked to improved health outcomes, adherence, communication, and increased consumer satisfaction, a logistic regression model was developed to find the factors most associated with moderate (3-11 logins per year) use of the portal. RESULTS: Electronic health use increased by SMs with underlying health conditions or if they were managing family member health. Most SMs who used the TOL Patient Portal were of ages 25-34 years, White, and married. The mean age is 32.53 for males and 29.98 for females. Over half of the TOL Patient Portal SM users utilized the portal one to two times. Most SMs used the TOL Patient Portal in Virginia, Texas, California, Florida, North Carolina, Georgia, and Maryland. The highest use was during the months of March to May. Frequent patient portal actions include searching for appointments, viewing health information, viewing medical encounters, and refilling medications. Although SMs with congenital health defects, anxiety, sleep issues, and depression have higher patient portal use rates, SMs with depression have a negative association with using the patient portal at a "moderate" rate. Viewing family member health information and searching for appointments were strongly associated with patient portal moderate use. CONCLUSIONS: Our findings support top military initiatives to improve the overall health, wellness, and readiness of SMs while decreasing the MHS's overall cost of care while providing a foundation to compare "pre" and "post" pandemic eHealth behaviors. It is essential to note that SMs are more likely to use a patient portal to seek information or manage family member health. This key factor identifies the significance of family health promotion and readiness in the active duty SM's life. The long-term goal of our study is to build the foundation for delivering tailored health information and eHealth tools to promote health and readiness-centric patient engagement.

Nebulized exosomes derived from allogenic adipose tissue mesenchymal stromal cells in patients with severe COVID-19: a pilot study.

BACKGROUND: Existing clinical studies supported the potential efficacy of mesenchymal stromal cells as well as derived exosomes in the treatment of COVID-19. We aimed to explore the safety and efficiency of aerosol inhalation of the exosomes derived from human adipose-derived MSCs (haMSC-Exos) in patients with COVID-19. METHODS: The MEXCOVID trial is a phase 2a single-arm, open-labelled, interventional trial and patients were enrolled in Jinyintan Hospital, Wuhan, China. Eligible 7 patients were assigned to receive the daily dose of haMSCs-Exos (2.0 × 108 nano vesicles) for consecutively 5 days. The primary outcomes included the incidence of prespecified inhalation-associated events and serious adverse events. We also observed the demographic data, clinical characteristics, laboratory results including lymphocyte count, levels of D-dimer and IL-6 as well as chest imaging. RESULTS: Seven severe COVID-19 related pneumonia patients (4 males and 3 females) were enrolled and received nebulized haMSC-Exos. The median age was 57 year (interquartile range (IQR), 43 year to 70 year). The median time from onset of symptoms to hospital admission and administration of nebulized haMSC-Exos was 30 days (IQR, 15 days to 40 days) and 54 d (IQR, 34 d to 69 d), respectively. All COVID-19 patients tolerated the haMSC-Exos nebulization well, with no evidence of prespecified adverse events or clinical instability during the nebulization or during the immediate post-nebulization period. All patients presented a slight increase of serum lymphocyte counts (median as 1.61 × 109/L vs. 1.78 × 109/L). Different degrees of resolution of pulmonary lesions after aerosol inhalation of haMSC-Exos were observed among all patients, more obviously in 4 of 7 patients. CONCLUSIONS: Our trial shows that a consecutive 5 days inhalation dose of clinical grade haMSC-Exos up to a total amount of 2.0 × 109 nano vesicles was feasible and well tolerated in seven COVID-19 patients, with no evidence of prespecified adverse events, immediate clinical instability, or dose-relevant toxicity at any of the doses tested. This safety profile is seemingly followed by CT imaging improvement within 7 days. Further trials will have to confirm the long-term safety or efficacy in larger population. TRIAL REGISTRATION: MEXCOVID, NCT04276987.

COVID-19 associated EBV reactivation and effects of ganciclovir treatment.

BACKGROUND: Systemic reactivation of Epstein-Barr virus (EBV) may occur in novel coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). However, the clinical consequences of EBV reactivation remain uncertain. METHODS: In this retrospective study, we screened 1314 patients with confirmed COVID-19 who died or were discharged between January 1, 2020 and March 12, 2020, in Wuhan Infectious Disease Hospital, Wuhan, China. Patients who had complete data for EBV serology and cytomegalovirus (CMV) serology were eligible. Serum levels of viral capsid antigen (VCA)-immunoglobulin G (IgG), Epstein-Barr nuclear antigen-IgG, VCA-IgM, early antigen (EA)-IgG, CMV-IgG, and CMV-IgM were compared between survivors and nonsurvivors. Dynamic changes of laboratory tests and outcomes were compared in patients with and without ganciclovir treatment. We used 1:1 matching based on age, gender, and illness severity to balance baseline characteristics. RESULTS: EBV reactivation was present in 55 of 217 patients. EBV reactivation was associated with age (57.91 [13.19] vs. 50.28 [12.66] years, p < .001), female gender (31 [56%] vs. 60 [37%], p = .02). Patients with EBV reactivation have statistically nonsignificant higher mortality rate (12 [22%] vs. 18 [11%], p = .08). EA-IgG levels were significantly higher in nonsurvivors than in survivors (median difference: -0.00005, 95% confidence interval, CI [-3.10, 0.00], p = .05). As compared to patients with COVID-19 who did not receive ganciclovir therapy, ganciclovir-treated patients had improved survival rate (0.98, 95% CI [0.95, 1.00] vs. 0.88, 95% CI [0.81, 0.95], p = .01). Hemoglobin (p < .001) and prealbumin (p = .02) levels were significantly higher in ganciclovir-treated patients. CONCLUSION: A high proportion of COVID-19 patients had EBV reactivation that may be associated with an increased risk of death. Whether treatment with ganciclovir may decrease the mortality of COVID-19 patients complicated with EBV reactivation warrants to be addressed in a placebo-controlled randomized trial in the future.

Retrospective Study of Critically Ill COVID-19 Patients With and Without Extracorporeal Membrane Oxygenation Support in Wuhan, China.

Background: Extracorporeal membrane oxygenation (ECMO) might benefit critically ill COVID-19 patients. But the considerations besides indications guiding ECMO initiation under extreme pressure during the COVID-19 epidemic was not clear. We aimed to analyze the clinical characteristics and in-hospital mortality of severe critically ill COVID-19 patients supported with ECMO and without ECMO, exploring potential parameters for guiding the initiation during the COVID-19 epidemic. Methods: Observational cohort study of all the critically ill patients indicated for ECMO support from January 1 to May 1, 2020, in all 62 authorized hospitals in Wuhan, China. Results: Among the 168 patients enrolled, 74 patients actually received ECMO support and 94 not were analyzed. The in-hospital mortality of the ECMO supported patients was significantly lower than non-ECMO ones (71.6 vs. 85.1%, P = 0.033), but the role of ECMO was affected by patients' age (Logistic regression OR 0.62, P = 0.24). As for the ECMO patients, the median age was 58 (47-66) years old and 62.2% (46/74) were male. The 28-day, 60-day, and 90-day mortality of these ECMO supported patients were 32.4, 68.9, and 74.3% respectively. Patients survived to discharge were younger (49 vs. 62 years, P = 0.042), demonstrated higher lymphocyte count (886 vs. 638 cells/uL, P = 0.022), and better CO2 removal (PaCO2 immediately after ECMO initiation 39.7 vs. 46.9 mmHg, P = 0.041). Age was an independent risk factor for in-hospital mortality of the ECMO supported patients, and a cutoff age of 51 years enabled prediction of in-hospital mortality with a sensitivity of 84.3% and specificity of 55%. The surviving ECMO supported patients had longer ICU and hospital stays (26 vs. 18 days, P = 0.018; 49 vs. 29 days, P = 0.001 respectively), and ECMO procedure was widely carried out after the supplement of medical resources after February 15 (67.6%, 50/74). Conclusions: ECMO might be a benefit for severe critically ill COVID-19 patients at the early stage of epidemic, although the in-hospital mortality was still high. To initiate ECMO therapy under tremendous pressure, patients' age, lymphocyte count, and adequacy of medical resources should be fully considered.

Efficacy of Thymosin Alpha 1 in the Treatment of COVID-19: A Multicenter Cohort Study.

Background: Thymosin alpha 1 (Tα1) is widely used to treat patients with COVID-19 in China; however, its efficacy remains unclear. This study aimed to explore the efficacy of Tα1 as a COVID-19 therapy. Methods: We performed a multicenter cohort study in five tertiary hospitals in the Hubei province of China between December 2019 and March 2020. The patient non-recovery rate was used as the primary outcome. Results: All crude outcomes, including non-recovery rate (65/306 vs. 290/1,976, p = 0.003), in-hospital mortality rate (62/306 vs. 271/1,976, p = 0.003), intubation rate (31/306 vs. 106/1,976, p = 0.001), acute respiratory distress syndrome (ARDS) incidence (104/306 vs. 499/1,976, p = 0.001), acute kidney injury (AKI) incidence (26/306 vs. 66/1,976, p < 0.001), and length of intensive care unit (ICU) stay (14.9 ± 12.7 vs. 8.7 ± 8.2 days, p < 0.001), were significantly higher in the Tα1 treatment group. After adjusting for confounding factors, Tα1 use was found to be significantly associated with a higher non-recovery rate than non-Tα1 use (OR 1.5, 95% CI 1.1-2.1, p = 0.028). An increased risk of non-recovery rate associated with Tα1 use was observed in the patient subgroups with maximum sequential organ failure assessment (SOFA) scores ≥2 (OR 2.0, 95%CI 1.4-2.9, p = 0.024), a record of ICU admission (OR 5.4, 95%CI 2.1-14.0, p < 0.001), and lower PaO2/FiO2 values (OR 1.9, 95%CI 1.1-3.4, p = 0.046). Furthermore, later initiation of Tα1 use was associated with a higher non-recovery rate. Conclusion: Tα1 use in COVID-19 patients was associated with an increased non-recovery rate, especially in those with greater disease severity.

Intravenous immunoglobulin treatment for patients with severe COVID-19: a retrospective multicentre study.

OBJECTIVES: Intravenous immunoglobulin (IVIG) is commonly used to treat severe COVID-19, although the clinical outcome of such treatment remains unclear. This study evaluated the effectiveness of IVIG treatment in severe COVID-19 patients. METHODS: This retrospective multicentre study evaluated 28-day mortality in severe COVID-19 patients with or without IVIG treatment. Each patient treated with IVIG was matched with one untreated patient. Logistic regression and inverse probability weighting (IPW) were used to control confounding factors. RESULTS: The study included 850 patients (421 IVIG-treated patients and 429 non-IVIG-treated patients). After matching, 406 patients per group remained. No significant difference in 28-day mortality was observed after IPW analysis (average treatment effect (ATE) = 0.008, 95% CI -0.081 to 0.097, p 0.863). There were no significant differences between the IVIG group and non-IVIG group for acute respiratory distress syndrome, diffuse intravascular coagulation, myocardial injury, acute hepatic injury, shock, acute kidney injury, non-invasive mechanical ventilation, invasive mechanical ventilation, continuous renal replacement therapy and extracorporeal membrane oxygenation except for prone position ventilation (ATE = -0.022, 95% CI -0.041 to -0.002, p 0.028). DISCUSSION: IVIG treatment was not associated with significant changes in 28-day mortality in severe COVID-19 patients. The effectiveness of IVIG in treating patients with severe COVID-19 needs to be further investigated through future studies.

Novel phenotypes of coronavirus disease: a temperature-based trajectory model.

BACKGROUND: Coronavirus disease has heterogeneous clinical features; however, the reasons for the heterogeneity are poorly understood. This study aimed to identify clinical phenotypes according to patients' temperature trajectory. METHOD: A retrospective review was conducted in five tertiary hospitals in Hubei Province from November 2019 to March 2020. We explored potential temperature-based trajectory phenotypes and assessed patients' clinical outcomes, inflammatory response, and response to immunotherapy according to phenotypes. RESULTS: A total of 1580 patients were included. Four temperature-based trajectory phenotypes were identified: normothermic (Phenotype 1); fever, rapid defervescence (Phenotype 2); gradual fever onset (Phenotype 3); and fever, slow defervescence (Phenotype 4). Compared with Phenotypes 1 and 2, Phenotypes 3 and 4 had a significantly higher C-reactive protein level and neutrophil count and a significantly lower lymphocyte count. After adjusting for confounders, Phenotypes 3 and 4 had higher in-hospital mortality (adjusted odds ratio and 95% confidence interval 2.1, 1.1-4.0; and 3.3, 1.4-8.2, respectively), while Phenotype 2 had similar mortality, compared with Phenotype 1. Corticosteroid use was associated with significantly higher in-hospital mortality in Phenotypes 1 and 2, but not in Phenotypes 3 or 4 (p for interaction < 0.01). A similar trend was observed for gamma-globulin. CONCLUSIONS: Patients with different temperature-trajectory phenotypes had different inflammatory responses, clinical outcomes, and responses to corticosteroid therapy.

Risk factors for secondary hemophagocytic lymphohistiocytosis in severe coronavirus disease 2019 adult patients.

BACKGROUND: Secondary hemophagocytic lymphohistiocytosis (sHLH) is a life-threatening hyperinflammatory event and a fatal complication of viral infections. Whether sHLH may also be observed in patients with a cytokine storm induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is still uncertain. We aimed to determine the incidence of sHLH in severe COVID-19 patients and evaluate the underlying risk factors. METHOD: Four hundred fifteen severe COVID-19 adult patients were retrospectively assessed for hemophagocytosis score (HScore). A subset of 7 patients were unable to be conclusively scored due to insufficient patient data. RESULTS: In 408 patients, 41 (10.04%) had an HScore ≥169 and were characterized as "suspected sHLH positive". Compared with patients below a HScore threshold of 98, the suspected sHLH positive group had higher D-dimer, total bilirubin, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, serum creatinine, triglycerides, ferritin, interleukin-6, C-reactive protein, procalcitonin, lactate dehydrogenase, creatine kinase isoenzyme, troponin, Sequential Organ Failure Assessment (SOFA) score, while leukocyte, hemoglobin, platelets, lymphocyte, fibrinogen, pre-albumin, albumin levels were significantly lower (all P < 0.05). Multivariable logistic regression revealed that high ferritin (>1922.58 ng/mL), low platelets (<101 × 109/L) and high triglycerides (>2.28 mmol/L) were independent risk factors for suspected sHLH in COVID-19 patients. Importantly, COVID-19 patients that were suspected sHLH positive had significantly more multi-organ failure. Additionally, a high HScore (>98) was an independent predictor for mortality in COVID-19. CONCLUSIONS: HScore should be measured as a prognostic biomarker in COVID-19 patients. In particular, it is important that HScore is assessed in patients with high ferritin, triglycerides and low platelets to improve the detection of suspected sHLH.

[Practical procedure of prone position ventilation in critical coronavirus disease 2019 patients].

Prone position ventilation has become an important part of lung protective ventilation in acute respiratory distress syndrome (ARDS) patients. Timely and appropriate implementation can improve the mortality of such patients. The same is true for patients with critical coronavirus disease 2019 (COVID-19) patients, but safety assessment, control of implementation details and prevention of complications still need to be further standardized during the practical procedure of prone position ventilation. The purpose of this paper is to explain the specific requirements and key points of prone position ventilation in critical COVID-19 patients, in order to promote the application of prone position ventilation in the treatment of patients with critical COVID-19 and reduce the occurrence of related complications.

Identification and validation of prognostic factors in patients with COVID-19: A retrospective study based on artificial intelligence algorithms.

Background: Novel coronavirus disease 2019 (COVID-19) is an ongoing global pandemic with high mortality. Although several studies have reported different risk factors for mortality in patients based on traditional analytics, few studies have used artificial intelligence (AI) algorithms. This study investigated prognostic factors for COVID-19 patients using AI methods. Methods: COVID-19 patients who were admitted in Wuhan Infectious Diseases Hospital from December 29, 2019 to March 2, 2020 were included. The whole cohort was randomly divided into training and testing sets at a 6:4 ratio. Demographic and clinical data were analyzed to identify predictors of mortality using least absolute shrinkage and selection operator (LASSO) regression and LASSO-based artificial neural network (ANN) models. The predictive performance of the models was evaluated using receiver operating characteristic (ROC) curve analysis. Results: A total of 1145 patients (610 male, 53.3%) were included in the study. Of the 1145 patients, 704 were assigned to the training set and 441 were assigned to the testing set. The median age of the patients was 57 years (range: 47-66 years). Severity of illness, age, platelet count, leukocyte count, prealbumin, C-reactive protein (CRP), total bilirubin, Acute Physiology and Chronic Health Evaluation (APACHE) II score, and Sequential Organ Failure Assessment (SOFA) score were identified as independent prognostic factors for mortality. Incorporating these nine factors into the LASSO regression model yielded a correct classification rate of 0.98, with area under the ROC curve (AUC) values of 0.980 and 0.990 in the training and testing cohorts, respectively. Incorporating the same factors into the LASSO-based ANN model yielded a correct classification rate of 0.990, with an AUC of 0.980 in both the training and testing cohorts. Conclusions: Both the LASSO regression and LASSO-based ANN model accurately predicted the clinical outcome of patients with COVID-19. Severity of illness, age, platelet count, leukocyte count, prealbumin, CRP, total bilirubin, APACHE II score, and SOFA score were identified as prognostic factors for mortality in patients with COVID-19.