Human mesenchymal stem cell therapy in severe COVID-19 patients: 2-year follow-up results of a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Long-term effects of human mesenchymal stem cell (MSC) treatment on COVID-19 patients have not been fully characterized. The aim of this study was to evaluate the safety and efficacy of a MSC treatment administered to severe COVID-19 patients enrolled in our previous randomized, double-blind, placebo-controlled clinical trial (NCT04288102). METHODS: A total of 100 patients experiencing severe COVID-19 received either MSC treatment (n = 65, 4 × 107 cells per infusion) or a placebo (n = 35) combined with standard of care on days 0, 3, and 6. Patients were subsequently evaluated 18 and 24 months after treatment to evaluate the long-term safety and efficacy of the MSC treatment. Outcomes measured included: 6-min walking distance (6-MWD), lung imaging, quality of life according to the Short Form 36 questionnaire (SF-36), COVID-19-related symptoms, titers of SARS-CoV-2 neutralizing antibodies, tumor markers, and MSC-related adverse events (AEs). FINDINGS: Two years after treatment, a marginally smaller proportion of patients had a 6-MWD below the lower limit of the normal range in the MSC group than in the placebo group (OR = 0.19, 95% CI: 0.04-0.80, Fisher's exact test, p = 0.015). At month 18, the general health score from the SF-36 was higher in the MSC group than in the placebo group (50.00 vs. 35.00, 95% CI: 0.00-20.00, Wilcoxon rank sum test, p = 0.018). Total severity score of lung imaging and the titer of neutralizing antibodies were similar between the two groups at months 18 and 24. There was no difference in AEs or tumor markers at the 2-year follow-up between the two groups. INTERPRETATION: Long-term safety was observed for the COVID-19 patients who received MSC treatment. However, efficacy of MSC treatment was not significantly sustained through the end of the 2-year follow-up period. FUNDING: The National Key Research and Development Program of China (2022YFA1105604, 2020YFC0860900, 2022YFC2304401), the specific research fund of The Innovation Platform for Academicians of Hainan Province (YSPTZX202216) and the Fund of National Clinical Center for Infectious Diseases, PLA General Hospital (NCRC-ID202105,413FZT6).

Dynamics of SARS-CoV-2 Antibody Responses up to 9 Months Post-Vaccination in Individuals with Previous SARS-CoV-2 Infection Receiving Inactivated Vaccines.

Humoral immunity confers protection against COVID-19. The longevity of antibody responses after receiving an inactivated vaccine in individuals with previous SARS-CoV-2 infection is unclear. Plasma samples were collected from 58 individuals with previous SARS-CoV-2 infection and 25 healthy donors (HDs) who had been vaccinated with an inactivated vaccine. The neutralizing antibodies (NAbs) and S1 domain-specific antibodies against the SARS-CoV-2 wild-type and Omicron strains and nucleoside protein (NP)-specific antibodies were measured using a chemiluminescent immunoassay. Statistical analysis was performed using clinical variables and antibodies at different timepoints after SARS-CoV-2 vaccination. NAbs targeting the wild-type or Omicron strain were detected in individuals with previous SARS-CoV-2 infection at 12 months after infection (wild-type: 81%, geometric mean (GM): 20.3 AU/mL; Omicron: 44%, GM: 9.4 AU/mL), and vaccination provided further enhancement of these antibody levels (wild-type: 98%, GM: 53.3 AU/mL; Omicron: 75%, GM: 27.8 AU/mL, at 3 months after vaccination), which were significantly higher than those in HDs receiving a third dose of inactivated vaccine (wild-type: 85%, GM: 33.6 AU/mL; Omicron: 45%, GM: 11.5 AU/mL). The level of NAbs in individuals with previous infection plateaued 6 months after vaccination, but the NAb levels in HDs declined continuously. NAb levels in individuals with previous infection at 3 months post-vaccination were strongly correlated with those at 6 months post-vaccination, and weakly correlated with those before vaccination. NAb levels declined substantially in most individuals, and the rate of antibody decay was negatively correlated with the neutrophil-to-lymphocyte ratio in the blood at discharge. These results suggest that the inactivated vaccine induced robust and durable NAb responses in individuals with previous infection up to 9 months after vaccination.

Immunopharmacological Activities of Luteolin in Chronic Diseases.

Flavonoids have been shown to have anti-oxidative effects, as well as other health benefits (e.g., anti-inflammatory and anti-tumor functions). Luteolin (3', 4', 5,7-tetrahydroxyflavone) is a flavonoid found in vegetables, fruits, flowers, and herbs, including celery, broccoli, green pepper, navel oranges, dandelion, peppermint, and rosemary. Luteolin has multiple useful effects, especially in regulating inflammation-related symptoms and diseases. In this paper, we summarize the studies about the immunopharmacological activity of luteolin on anti-inflammatory, anti-cardiovascular, anti-cancerous, and anti-neurodegenerative diseases published since 2018 and available in PubMed or Google Scholar. In this review, we also introduce some additional formulations of luteolin to improve its solubility and bioavailability.

A full genome tiling array enhanced the inspection and quarantine of SARS-CoV-2.

As the worldwide spreading epidemic of SARS-CoV-2, quick inspection and quarantine of passengers for SARS-CoV-2 infection are essential for controlling the spread of SARS-CoV-2, especially the cross-border transmission. This study reports a SARS-CoV-2 genome sequencing method based on a re-sequencing tiling array successfully used in border inspection and quarantine. The tiling array chip has four cores, with one core of 240,000 probes dedicated to the whole genome sequencing of the SAR-CoV-2 genome. The assay protocol has been improved to reduce the detection time to within one day and can detect 96 samples in parallel. The detection accuracy has been validated. This fast and simple procedure is also of low cost and high accuracy, and it is particularly suitable for the rapid tracking of viral genetic variants in custom inspection applications. Combining these properties means this method has significant application potential in the clinical investigation and quarantine of SARS-CoV-2. We used this SARS-CoV-2 genome re-sequencing tiling array to inspect and quarantine China's entry and exit ports in the Zhejiang Province. From November 2020 to January 2022, we observed the gradual shift of SARS-CoV-2 variants from the D614G type to the Delta Variant, and then to the dominance of the Omicron variant recently, consistently with the global emergency pattern of the new SARS-CoV-2 variant.

New observation of perceptive mechanism behind the long-lasting change of people's community mobility: evidence from COVID-19 in China.

COVID-19 pandemic provides an opportunity to investigate how a new and long-lasting threat affects public risk perception and social distancing behavior, which is important for pandemic risk management and recovery of the tertiary industry. We have found that the mechanism that perception decides behavior changes over time. At the beginning of the pandemic, risk directly shapes people's willingness of going out. But under a persistent threat, perception no longer plays the direct role of shape people's willingness. Instead, perception indirectly influences the willingness by shaping people's judgment about the necessity of traveling. Switching from direct to indirect influence, perception's effect is enlarged, which partially prevents people from returning to normal life even if the governmental ban is removed in a zero-COVID community.

#COVIDisAirborne: AI-enabled multiscale computational microscopy of delta SARS-CoV-2 in a respiratory aerosol.

We seek to completely revise current models of airborne transmission of respiratory viruses by providing never-before-seen atomic-level views of the SARS-CoV-2 virus within a respiratory aerosol. Our work dramatically extends the capabilities of multiscale computational microscopy to address the significant gaps that exist in current experimental methods, which are limited in their ability to interrogate aerosols at the atomic/molecular level and thus obscure our understanding of airborne transmission. We demonstrate how our integrated data-driven platform provides a new way of exploring the composition, structure, and dynamics of aerosols and aerosolized viruses, while driving simulation method development along several important axes. We present a series of initial scientific discoveries for the SARS-CoV-2 Delta variant, noting that the full scientific impact of this work has yet to be realized.

Effect of Methylprednisolone on Mortality and Clinical Courses in Patients with Severe COVID-19: A Propensity Score Matching Analysis.

Background: Whether methylprednisolone therapy can reduce the mortality rate of patients with severe coronavirus disease 2019 (COVID-19) remains controversial, and its effects on the length of hospital stay and virus shedding time are also unknown. This retrospective study investigates the previous issues to provide more evidence for methylprednisolone treatment in severe COVID-19. Methods: This retrospective study included 563 of 4827 patients with confirmed COVID-19 admitted to Wuhan Huoshenshan Hospital or Wuhan Guanggu Hospital between February 3, 2020 and March 30, 2020 who met the screening criteria. The participants' epidemiological and demographic data, comorbidities, laboratory test results, treatments, outcomes, and vital clinical time points were extracted from electronic medical records. The primary outcome was in-hospital death, and the secondary outcomes were 2 clinical courses: length from admission to viral clearance and discharge. Univariate and multivariate logistic or linear regression analyses were used to assess the role of methylprednisolone in different outcomes. Propensity score matching was performed to control for confounding factors. Results: Of the 563 patients who met the screening criteria and were included in the subsequent analysis, 138 were included in the methylprednisolone group and 425 in the nonmethylprednisolone group. The in-hospital death rate between the methylprednisolone and nonmethylprednisolone groups showed a significant difference (23.91% vs. 1.65%, P < 0.001), which was maintained after propensity score matching (13.98% vs. 5.38%, P = 0.048). However, univariate logistic analysis in the matched groups showed that methylprednisolone treatment (odds ratio [OR], 5.242; 95% confidence interval [CI], 0.802 to 34.246; P = 0.084) was not a risk factor for in-hospital death in severe patients. Further multivariate logistic regression analysis found comorbidities (OR, 3.327; 95% CI, 1.702 to 6.501; P < 0.001), lower lymphocyte count (OR, 0.076; 95% CI, 0.012 to 0.461; P = 0.005), higher lactate dehydrogenase (LDH) levels (OR, 1.008; 95% CI, 1.003 to 1.013; P = 0.002), and anticoagulation therapy (OR, 11.187; 95% CI, 2.459 to 50.900; P = 0.002) were associated with in-hospital mortality. Multivariate linear regression analysis in the matched groups showed that methylprednisolone treatment was not a risk factor for a prolonged duration from admission to viral clearance (ß Value 0.081; 95% CI, -1.012 to 3.657; P = 0.265) or discharge (ß Value 0.114; 95% CI, -0.723 to 6.408; P = 0.117). d-dimer (ß Value, 0.144; 95% CI, 0.012 to 0.817; P = 0.044), LDH (ß Value 0.260; 95% CI, 0.010 to 0.034; P < 0.001), and antiviral therapy (ß Value 0.220; 95% CI, 1.373 to 6.263; P = 0.002) were associated with a longer length from admission to viral clearance. The lymphocyte count (ß Value -0.206; 95% CI, -6.248 to -1.197; P = 0.004), LDH (ß Value 0.231; 95% CI, 0.012 to 0.048; P = 0.001), antiviral therapy (ß Value 0.143; 95% CI, 0.058 to 7.497; P = 0.047), and antibacterial therapy (ß Value 0.152; 95% CI, 0.133 to 8.154; P = 0.043) were associated with a longer hospitalization duration from admission to discharge. Further stratified analysis revealed that the low daily dose group (≤60 mg/d) and the low total dose group (≤200 mg) had shorter duration from admission to viral clearance (Z=-2.362, P = 0.018; Z=-2.010, P = 0.044) and a shorter hospital stay (Z=-2.735, P = 0.006; Z=-3.858, P < 0.001). Conclusions: In patients with severe COVID-19, methylprednisolone is safe and does not prolong the duration from admission to viral clearance or discharge. Low-dose, short-term methylprednisolone treatment may be more beneficial in shortening the disease course.

Continuous care needs in patients with cancer receiving chemotherapy during the recent omicron wave of COVID-19 in Shanghai: A qualitative study.

Aims: This study aimed to investigate the care needs, to clarify the factors affecting the quality of homecare, and to provide reference for constructing a homecare system for patients with cancer receiving chemotherapy during the recent omicron wave of COVID-19 in Shanghai. Methods: From March to May 2022 when the omicron wave emerged in Shanghai, 50 consecutive patients who received chemotherapy at Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, were enrolled, and underwent face-to-face or telephone-based semi-structured interviews regarding continuous care needs. Some of their homecare-givers, caring nurses, and physicians were also interviewed. The Colaizzi method was used for data analysis. Results: Fifty patients, 4 homecare-givers, 4 nurses, and 4 physicians were interviewed. Three themes and six subthemes emerged from analysis of the interviews: The first theme was "Disease management needs," including needs for knowledge of managing adverse events associated with chemotherapy, and needs for treatment-related information. Patients expressed most concern about not being able to go to the hospital for blood review and disease evaluation in time due to the outbreak. With the COVID-19 pandemic being ongoing, factors such as pandemic panic, inconvenient medical treatment, and worry about hospital cross-infection might reduce disease management for patients with cancer. The second theme was "Medical needs," including needs for mobile healthcare and needs for medical resources. All interviewees emphasized the importance of mobile healthcare during the COVID-19 pandemic, as access to hospitals was difficult. The third theme was "Spiritual needs," including demands for psychological counseling and intervention, and needs for spiritual care. Patients and homecare-givers commonly lacked a feeling of security and needed communication, encouragement, and reassurance that medical care could be delivered to them, and patients reported that they very much wanted psychological advice. Conclusion: For patients with cancer receiving chemotherapy during the COVID-19 pandemic, continuous care is greatly needed. Medical personnel should strengthen the healthcare education for patients and their caregivers during hospitalization, and further improve the patients' information intake rate through Internet-based digital healthcare methods during homecare, to further meet the information needs of patients after discharge from hospital.

Atrial Fibrillation (AFIB) in the ICU: Incidence, Risk Factors, and Outcomes: The International AFIB-ICU Cohort Study.

OBJECTIVES: To assess the incidence, risk factors, and outcomes of atrial fibrillation (AF) in the ICU and to describe current practice in the management of AF. DESIGN: Multicenter, prospective, inception cohort study. SETTING: Forty-four ICUs in 12 countries in four geographical regions. SUBJECTS: Adult, acutely admitted ICU patients without a history of persistent/permanent AF or recent cardiac surgery were enrolled; inception periods were from October 2020 to June 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We included 1,423 ICU patients and analyzed 1,415 (99.4%), among whom 221 patients had 539 episodes of AF. Most (59%) episodes were diagnosed with continuous electrocardiogram monitoring. The incidence of AF was 15.6% (95% CI, 13.8-17.6), of which newly developed AF was 13.3% (11.5-15.1). A history of arterial hypertension, paroxysmal AF, sepsis, or high disease severity at ICU admission was associated with AF. Used interventions to manage AF were fluid bolus 19% (95% CI 16-23), magnesium 16% (13-20), potassium 15% (12-19), amiodarone 51% (47-55), beta-1 selective blockers 34% (30-38), calcium channel blockers 4% (2-6), digoxin 16% (12-19), and direct current cardioversion in 4% (2-6). Patients with AF had more ischemic, thromboembolic (13.6% vs 7.9%), and severe bleeding events (5.9% vs 2.1%), and higher mortality (41.2% vs 25.2%) than those without AF. The adjusted cause-specific hazard ratio for 90-day mortality by AF was 1.38 (95% CI, 0.95-1.99). CONCLUSIONS: In ICU patients, AF occurred in one of six and was associated with different conditions. AF was associated with worse outcomes while not statistically significantly associated with 90-day mortality in the adjusted analyses. We observed variations in the diagnostic and management strategies for AF.

Comparing hybrid and regular COVID-19 vaccine-induced immunity against the Omicron epidemic.

Evidence on the effectiveness of COVID-19 vaccines among people who recovered from a previous SARS-CoV-2 infection is warranted to inform vaccination recommendations. Using the territory-wide public healthcare and vaccination records of over 2.5 million individuals in Hong Kong, we examined the potentially differential risk of SARS-CoV-2 infection, hospitalization, and mortality between those receiving two homologous doses of BNT162b2 or CoronaVac versus those with a previous infection receiving only one dose amid the Omicron epidemic. Results show a single dose after a SARS-CoV-2 infection is associated with a lower risk of infection (BNT162b2: adjusted incidence rate ratio [IRR] = 0.475, 95% CI: 0.410-0.550; CoronaVac: adjusted IRR = 0.397, 95% CI: 0.309-0.511) and no significant difference was detected in the risk of COVID-19-related hospitalization or mortality compared with a two-dose vaccination regimen. Findings support clinical recommendations that those with a previous infection could receive a single dose to gain at least similar protection as those who received two doses without a previous infection.

Prognosis of Myocarditis Developing After mRNA COVID-19 Vaccination Compared With Viral Myocarditis.

BACKGROUND: Association between messenger RNA (mRNA) COVID-19 vaccines and myocarditis has aroused public concern over vaccine safety. OBJECTIVES: The goal of this study was to compare the prognosis of this condition with viral infection-related myocarditis over 180 days. METHODS: A territory-wide electronic public health care database in Hong Kong linked with population-based vaccination records was used to conduct a retrospective cohort study. Since the roll-out of BNT162b2 (Pfizer-BioNTech), patients aged ≥12 years hospitalized with myocarditis within 28 days after BNT162b2 vaccination were compared against viral infection-related myocarditis recorded before the pandemic (2000-2019), over a 180-day follow-up period (starting from diagnosis of myocarditis). All-cause mortality, heart failure, dilated cardiomyopathy, heart transplant, and postdischarge health care utilization were examined with Cox proportional hazards models. RESULTS: A total of 866 patients were included for analysis. Over the follow-up period, 1 death (1.0%) of 104 patients with postvaccination myocarditis and 84 deaths (11.0%) of 762 patients with viral infection-related myocarditis were identified. One case (1.0%) of dilated cardiomyopathy and 2 cases (1.9%) of heart failure were identified in the postvaccination group, compared with 28 (3.7%) and 93 (12.2%) in the viral infection-related myocarditis group, respectively. Adjusted analysis showed that the postvaccination myocarditis group had a 92% lower mortality risk (adjusted HR: 0.08; 95% CI: 0.01-0.57). No significant differences in other prognostic outcomes were seen. CONCLUSIONS: This study found a significantly lower rate of mortality among individuals with myocarditis after mRNA vaccination compared with those with viral infection-related myocarditis. Prognosis of this iatrogenic condition may be less severe than naturally acquired viral infection-related myocarditis.

Association between sleep disturbance and mental health of healthcare workers: A systematic review and meta-analysis.

Objectives: Sleep disturbance and mental health are challenges for healthcare workers (HCWs). Especially during the COVID-19 pandemic, they experienced more severe sleep and mental health problems. However, the association between sleep disturbance and the mental health of HCWs is still controversial. This study aimed to systematically review the relationship by conducting a systematic review and meta-analysis. Method: Two researchers retrieved the literature from Web of Science, PubMed, EMBASE, CINAHL, Psyclnfo, and Cochrane Library from the establishment of the databases until November 20, 2021. We used the New Castle-Ottawa Scale (NOS) and Agency for Healthcare Research and Quality (AHRQ) to evaluate the risk of bias in prospective research and cross-sectional research, respectively. The major exposure was HCWs' sleep disturbance, and the major outcome was mental health. The correlation coefficients (r), regression coefficients (ß) and odds ratios (OR) of the included studies were integrated. Result: Fifty-nine studies were included for qualitative analysis, of which 30 studies could be combined and entered into quantitative analysis. There were 23 studies during the COVID-19 pandemic among the 59 included studies. The results of the meta-analysis showed that the correlation coefficient between sleep disturbance and mental health was 0.43 (95% CI: 0.39-0.47). HCWs with sleep disturbance had a 3.74 (95% CI: 2.76-5.07) times higher risk of mental health problems than those without sleep disturbance. The correlation coefficient during the COVID-19 epidemic was 0.45 (95% CI: 0.37-0.53), while it was 0.40 (95% CI: 0.36-0.44) during the non-epidemic period. Subgroup analysis compared the OR results in epidemic and non-epidemic periods of COVID-19, which were 4.48 (95% CI: 2.75-5.07) and 3.74 (95% CI: 2.74-7.32), respectively. Conclusion: Sleep disturbance and mental health problems were positively correlated among HCWs. Particularly in the COVID-19 pandemic, more attention should be given to this issue.