Impact of the COVID-19 pandemic on cardiac implantable electronic device implantation in China: Insights from 2 years of changing pandemic conditions.

Background: A substantial reduction in the number of cardiac implantable electronic device (CIED) implantation was reported in the early stages of the COVID-19 pandemic. None of the studies have yet explored changes in CIED implantation during the following pandemic. Objective: To explore changes in CIED implantation during the COVID-19 pandemic from 2020 to 2021. Methods: From 2019 to 2021, 177,263 patients undergone CIED implantation from 1,227 hospitals in China were included in the analysis. Generalized linear models measured the differences in CIED implantation in different periods. The relationship between changes in CIED implantation and COVID-19 cases was assessed by simple linear regression models. Results: Compared with the pre-COVID-19 period, the monthly CIED implantation decreased by 17.67% (95% CI: 16.62-18.72%, p < 0.001) in 2020. In 2021, the monthly number of CIED implantation increased by 15.60% (95% CI: 14.34-16.85%, p < 0.001) compared with 2020. For every 10-fold increase in the number of COVID-19 cases, the monthly number of pacemaker implantation decreased by 429 in 2021, while it decreased by 676 in 2020. The proportion of CIED implantation in secondary medical centers increased from 52.84% in 2019 to 56.77% in 2021 (p < 0.001). For every 10-fold increase in regional accumulated COVID-19 cases, the proportion of CIED implantation in secondary centers increased by 6.43% (95% CI: 0.47-12.39%, p = 0.036). Conclusion: The impact of the COVID-19 pandemic on the number of CIED implantation is diminishing in China. Improving the ability of secondary medical centers to undertake more operations may be a critical way to relieve the strain on healthcare resources during the epidemic.

Meplazumab in hospitalized adults with severe COVID-19 (DEFLECT): a multicenter, seamless phase 2/3, randomized, third-party double-blind clinical trial.

Meplazumab, a humanized CD147 antibody, has shown favourable safety and efficacy in our previous clinical studies. In DEFLECT (NCT04586153), 167 patients with severe COVID-19 were enroled and randomized to receive three dosages of meplazumab and a placebo. Meplazumab at 0.12 mg/kg, compared to the placebo group, showed clinical benefits in significantly reducing mortality by 83.6% (2.4% vs. 14.6%, p = 0.0150), increasing the proportion of patients alive and discharged without supplemental oxygen (82.9% vs. 70.7%, p = 0.0337) and increasing the proportion of patients who achieved sustained clinical improvement (41.5% vs. 31.7%). The response rate in the 0.2 mg/kg group was relatively increased by 16.0% compared with the placebo group (53.7% vs. 46.3%). Meplazumab also reduced the viral loads and multiple cytokine levels. Compare with the placebo group, the 0.3 mg/kg significantly increased the virus negative rate by 40.6% (p = 0.0363) and reduced IL-8 level (p = 0.0460); the 0.2 mg/kg increased the negative conversion rate by 36.9%, and reduced IL-4 (p = 0.0365) and IL-8 levels (p = 0.0484). In this study, the adverse events occurred at a comparable rate across the four groups, with no unexpected safety findings observed. In conclusion, meplazumab promoted COVID-19 convalescence and reduced mortality, viral load, and cytokine levels in severe COVID-19 population with good safety profile.

Impact of COVID-19 pandemic on catheter ablation in China: A spatiotemporal analysis.

Background: The COVID-19 pandemic has significantly impacted routine cardiovascular health assessments and services. We aim to depict the temporal trend of catheter ablation (CA) and provide experience in dealing with the negative impact of the COVID-19 pandemic. Methods: Data on CA between January 2019, and December 2021, were extracted from the National Center for Cardiovascular Quality Improvement platform. CA alterations from 2019 to 2021 were assessed with a generalized estimation equation. Results: A total of 347,924 patients undergoing CA were included in the final analysis. The CA decreased remarkably from 122,839 in 2019 to 100,019 (-18.58%, 95% CI: -33.40% to -3.75%, p = 0.02) in 2020, and increased slightly to 125,006 (1.81%, 95% CI: -7.01% to 3.38%, p = 0.49) in 2021. The CA experienced the maximal reduction in February 2020 (-88.78%) corresponding with the peak of monthly new COVID-19 cases and decreased by 54.32% (95%CI: -71.27% to -37.37%, p < 0.001) during the 3-month lockdown and increased firstly in June 2020 relative to 2019. Since then, the CA in 2020 remained unchanged relative to 2019 (-0.06%, 95% CI: -7.01% to 3.38%, p = 0.98). Notably, the recovery of CA in 2021 to pre-COVID-19 levels was mainly driven by the growth of CA in secondary hospitals. Although there is a slight increase (2167) in CA in 2021 relative to 2019, both the absolute number and proportion of CA in the top 50 hospitals nationwide [53,887 (43.09%) vs. 63,811 (51.95%), p < 0.001] and top three hospitals in each province [66,152 (52.73%) vs. 72,392 (59.28%), p < 0.001] still declined significantly. Conclusions: The CA experienced a substantial decline during the early phase of the COVID-19 pandemic, and then gradually returned to pre-COVID-19 levels. Notably, the growth of CA in secondary hospitals plays an important role in the overall resumption, which implies that systematic guidance of secondary hospitals with CA experience may aid in mitigating the negative impact of the COVID-19 pandemic.

Impact of the COVID-19 pandemic on cardiac implantable electronic device implantation in China: Insights from 2 years of changing pandemic conditions

Background A substantial reduction in the number of cardiac implantable electronic device (CIED) implantation was reported in the early stages of the COVID-19 pandemic. None of the studies have yet explored changes in CIED implantation during the following pandemic. Objective To explore changes in CIED implantation during the COVID-19 pandemic from 2020 to 2021. Methods From 2019 to 2021, 177,263 patients undergone CIED implantation from 1,227 hospitals in China were included in the analysis. Generalized linear models measured the differences in CIED implantation in different periods. The relationship between changes in CIED implantation and COVID-19 cases was assessed by simple linear regression models. Results Compared with the pre-COVID-19 period, the monthly CIED implantation decreased by 17.67% (95% CI: 16.62–18.72%, p < 0.001) in 2020. In 2021, the monthly number of CIED implantation increased by 15.60% (95% CI: 14.34–16.85%, p < 0.001) compared with 2020. For every 10-fold increase in the number of COVID-19 cases, the monthly number of pacemaker implantation decreased by 429 in 2021, while it decreased by 676 in 2020. The proportion of CIED implantation in secondary medical centers increased from 52.84% in 2019 to 56.77% in 2021 (p < 0.001). For every 10-fold increase in regional accumulated COVID-19 cases, the proportion of CIED implantation in secondary centers increased by 6.43% (95% CI: 0.47–12.39%, p = 0.036). Conclusion The impact of the COVID-19 pandemic on the number of CIED implantation is diminishing in China. Improving the ability of secondary medical centers to undertake more operations may be a critical way to relieve the strain on healthcare resources during the epidemic.

General recommendation for assessment and management on the risk of glucocorticoid-induced osteonecrosis in patients with COVID-19.

BACKGROUND/OBJECTIVE: Coronavirus disease 2019 (COVID-19) is a disaster in human medical history and glucocorticoids remain the most promising therapy. Osteonecrosis is a disease caused by reduced intraosseous blood flow to bones in the joints, which will rapidly induce joint destruction. Approximately one-third patients with severe acute respiratory syndrome (SARS) who received high cumulative doses and long treatment durations of glucocorticoids occurred osteonecrosis. Considering the similarity of SARS and COVID-19 on their pathogen, clinical characteristics, and therapeutic strategies, it is particularly desirable to investigate whether osteonecrosis will become a common sequela among convalescent COVID-19 patients. METHODS: This multi-strategy study was designed by integrating different research methods, such as meta-analysis, systematic review, and cross-sectional investigations to address above study objectives. At first, two meta-analyses were performed on the osteonecrosis incidence among SARS patients and the clinical data of glucocorticoid exposure among COVID-19 patients. Then, a systematic review of low-dosage glucocorticoid associated osteonecrosis and a cross-sectional investigation of glucocorticoid exposure of COVID-19 patients in Wuhan city of China were also conducted. Moreover, the pathogenesis, diagnosis, prevention, and treatment options for osteonecrosis patients with COVID-19 infection were further presented and discussed. RESULTS: Our meta-analysis showed that 32% of SARS patients had developed osteonecrosis after receiving glucocorticoid treatment with high dose, and our system review supported that low level glucocorticoid exposure might also lead to the occurrence of osteonecrosis. Similarly, 40% of COVID-19 patients had undergone glucocorticoid treatment according to our meta-analysis. The cross-sectional investigation in Wuhan city of China found that the average of cumulative glucocorticoid exposure level was 504 â€‹mg calculated by the dosage of methylprednisolone. Notably, a confirmed osteonecrosis case was identified from 1406 patients with COVID-19 during our cross-sectional investigation, implying that preventive management of osteonecrosis should be better started with regular clinical follow-up observation. CONCLUSION: Growing evidence of the glucocorticoid therapy for COVID-19 patients prompts us to establish risk-classification-based early screening and to introduce early prevention protocol of its associated osteonecrosis that will be of clinical significance in favor of improved prognosis of this disease. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: To establish risk-classification-based early screening and to introduce early prevention protocol of glucocorticoid-induced osteonecrosis will be of clinical significance in favor of improved prognosis of COVID-19.

Safety and efficacy of meplazumab in healthy volunteers and COVID-19 patients: a randomized phase 1 and an exploratory phase 2 trial.

Recent evidence suggests that CD147 serves as a novel receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Blocking CD147 via anti-CD147 antibody could suppress the in vitro SARS-CoV-2 replication. Meplazumab is a humanized anti-CD147 IgG2 monoclonal antibody, which may effectively prevent SARS-CoV-2 infection in coronavirus disease 2019 (COVID-19) patients. Here, we conducted a randomized, double-blinded, placebo-controlled phase 1 trial to evaluate the safety, tolerability, and pharmacokinetics of meplazumab in healthy subjects, and an open-labeled, concurrent controlled add-on exploratory phase 2 study to determine the efficacy in COVID-19 patients. In phase 1 study, 59 subjects were enrolled and assigned to eight cohorts, and no serious treatment-emergent adverse event (TEAE) or TEAE grade ≥3 was observed. The serum and peripheral blood Cmax and area under the curve showed non-linear pharmacokinetic characteristics. No obvious relation between the incidence or titer of positive anti-drug antibody and dosage was observed in each cohort. The biodistribution study indicated that meplazumab reached lung tissue and maintained >14 days stable with the lung tissue/cardiac blood-pool ratio ranging from 0.41 to 0.32. In the exploratory phase 2 study, 17 COVID-19 patients were enrolled, and 11 hospitalized patients were involved as concurrent control. The meplazumab treatment significantly improved the discharged (P = 0.005) and case severity (P = 0.021), and reduced the time to virus negative (P = 0.045) in comparison to the control group. These results show a sound safety and tolerance of meplazumab in healthy volunteers and suggest that meplazumab could accelerate the recovery of patients from COVID-19 pneumonia with a favorable safety profile.

Chinese herbal Huo-Gu formula for the treatment of steroid-associated osteonecrosis of femoral head: A 14-year follow-up of convalescent SARS patients.

PURPOSE: The coronavirus disease 2019 (COVID-19) reminds us of the severe acute respiratory syndrome (SARS) outbreak in 2003, and up to date, corticosteroid is commonly administrated to severe patients with COVID-19. Osteonecrosis of the femoral head (ONFH) is a common disabling complication among convalescent SARS patients who received corticosteroid therapy. In China, a considerable number of convalescent SARS patients with steroid-associated ONFH had undergone conservative treatment by traditional Chinese medicine, and this study aims to evaluate the long-term results of a spleen-invigorating Huo-Gu formula (HGF) therapy in these patients. PARTICIPANTS AND METHODS: A total of 33 convalescent SARS patients (9 males and 24 females) with bilateral steroid-associated ONFH (66 hips) were enrolled in this study. All patients received oral HGF therapy for 6 months when they were confirmed the diagnosis of steroid-associated ONFH. They had been regularly followed up at an interval of 1 year. Harris hip score and medical imaging modalities, including plain radiography, computed tomography and magnetic resonance imaging, were performed to evaluate the outcomes. RESULTS: Based on average 14 years of follow-up of HGF therapy (ranging from 6 to 16 years), 38 hips (57%) among the 66 hips developed definite osteoarthritis, and 14 hips (26%) in 53 precollapse hips (Association Research Circulation Osseous [ARCO] Stage I or II) progressed to femoral head collapse (ARCO Stage III or IV). Only five patients (also 5 hips) underwent total hip arthroplasty, and the mean hip survival time was over 15 years by the Kaplan-Meier analysis. We observed a mean Harris hip score of 63 points, which represented the reserve of 55% in pain score and 70% in physical function score. The severity of groin pain was not correlated to the severity of osteoarthritis. CONCLUSION: Chinese herbal HGF therapy demonstrates beneficial effects on preventing femoral head collapse, delaying total hip arthroplasty, and maintaining physical function in the treatment of steroid-associated ONFH. HGF therapy might be therefore a good alternative for the treatment of steroid-associated ONFH secondary to rheumatologic and infection diseases. TRANSLATIONAL POTENTIAL OF THE ARTICLE: HGF therapy might be a good alternative for the treatment of steroid-associated ONFH secondary to rheumatologic and infectious diseases.

CRISPR-Assisted DNA Detection: A Novel dCas9-Based DNA Detection Technique.

Nucleic acid detection techniques are always critical to diagnosis, especially in the background of the present coronavirus disease 2019 pandemic. Simple and rapid detection techniques with high sensitivity and specificity are always urgently needed. However, current nucleic acid detection techniques are still limited by traditional amplification and hybridization. To overcome this limitation, here we developed CRISPR-Cas9-assisted DNA detection (CADD). In this detection, a DNA sample is incubated with a pair of capture single guide RNAs (sgRNAs; sgRNAa and sgRNAb) specific to a target DNA, dCas9, a signal readout-related probe, and an oligo-coated solid support beads or microplate at room temperature (RT) for 15 min. During this incubation, the dCas9-sgRNA-DNA complex is formed and captured on solid support by the capture sequence of sgRNAa, and the signal readout-related probe is captured by the capture sequence of sgRNAb. Finally, the detection result is reported by a fluorescent or colorimetric signal readout. This detection was verified by detecting DNA of bacteria, cancer cells, and viruses. In particular, by designing a set of sgRNAs specific to 15 high-risk human papillomaviruses (HPVs), the HPV infection in 64 clinical cervical samples was successfully detected by the method. All detections can be finished in 30 min at RT. This detection holds promise for rapid on-the-spot detection or point-of-care testing.

Behavioral and Emotional Disorders in Children during the COVID-19 Epidemic

This article has been published in English before [1]. Эта статья была опубликована ранее на английском языке [1].

Prognostic value of NT-proBNP in patients with severe COVID-19.

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China has been declared a public health emergency of international concern. The cardiac injury is a common condition among the hospitalized patients with COVID-19. However, whether N terminal pro B type natriuretic peptide (NT-proBNP) predicted outcome of severe COVID-19 patients was unknown. METHODS: The study initially enrolled 102 patients with severe COVID-19 from a continuous sample. After screening out the ineligible cases, 54 patients were analyzed in this study. The primary outcome was in-hospital death defined as the case fatality rate. Research information and following-up data were obtained from their medical records. RESULTS: The best cut-off value of NT-proBNP for predicting in-hospital death was 88.64 pg/mL with the sensitivity for 100% and the specificity for 66.67%. Patients with high NT-proBNP values (> 88.64 pg/mL) had a significantly increased risk of death during the days of following-up compared with those with low values (≤88.64 pg/mL). After adjustment for potential risk factors, NT-proBNP was independently correlated with in-hospital death. CONCLUSION: NT-proBNP might be an independent risk factor for in-hospital death in patients with severe COVID-19. TRIAL REGISTRATION: ClinicalTrials, NCT04292964. Registered 03 March 2020.

Meplazumab treats COVID-19 pneumonia: an open-labelled, concurrent controlled add-on clinical trial (preprint)

Background: SARS-CoV-2 is a novel human coronavirus, there is no specific antiviral drugs. It has been proved that host-cell-expressed CD147 could bind spike protein of SARS-CoV-2 and involve in host cell invasion. Antibody against CD147 could block the infection of SARS-CoV-2. We aimed to assess the efficacy and safety of meplazumab, a humanized anti-CD147 antibody, as add-on therapy in patients with COVID-19 pneumonia. Methods: All patients received recommended strategy from Diagnosis and Treatment for 2019 Novel Coronavirus Diseases released by National Health Commission of China. Eligible patients were add-on administered 10 mg meplazumab intravenously at days 1, 2, and 5. Patients hospitalized in the same period were observed as concurrent control. The endpoints include virological clearance rate, case severity, chest radiographic, and laboratory test. This trial was approved by the Ethics Committee of Institution at the Tangdu hospital, and registered with ClinicalTrials.gov, NCT 04275245. Findings:17 patients were enrolled and assigned to meplazumab group between Feb 3, 2020 and Feb 10, 2020. 11 hospitalized patients served as concurrent control. Baseline characteristics were generally balanced across two groups. Compared to control group, meplazumab treatment significantly improved the discharged (p=0.006) and case severity (p=0.021) in critical and severe patients. The time to virus negative in meplazumab group was reduced than that in control group (median 3, 95%CI[1.5-4.5] vs. 13, [6.5-19.5]; p=0.014, HR=0.37, 95%CI[0.155-0.833]). The percentages of patients recovered to the normal lymphocyte count and CRP concentration were also increased remarkably and rapidly in meplazumab group. No adverse effect was found in meplazumab-treated patients. Interpretation:Meplazumab efficiently improved the recovery of patients with SARS-CoV-2 pneumonia with a favorable safety profile. Our results support to carry out a large-scale investigation of meplazumab as a treatment for COVID-19 pneumonia. Funding:National Science and Technology Major Project.

Prognostic value of NT-proBNP in patients with severe COVID-19 (preprint)

The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China has been declared a public health emergency of international concern. The cardiac injury was dominate in the process. However, whether N terminal pro B type natriuretic peptide (NT-proBNP) predicted outcome of COVID-19 patients was unknown. The study initially enrolled 102 patients with severe COVID-19 pneumonia from a continuous sample. After screening out the ineligible cases, 54 patients were analyzed in this study. Results found that patients with higher NT-proBNP (above 88.64 pg/mL) level had more risks of in-hospital death. After adjusting for potential cofounders in separate modes, NT-proBNP presented as an independent risk factor of in-hospital death in patients with severe COVID-19.