Assessment of respiratory support decision and the outcome of invasive mechanical ventilation in severe COVID-19 with ARDS.

Background: The coronavirus disease 2019 (COVID-19) is an ongoing pandemic. Invasive mechanical ventilation (IMV) is essential for the management of COVID-19 with acute respiratory distress syndrome (ARDS). We aimed to assess the impact of compliance with a respiratory decision support system on the outcomes of patients with COVID-19-associated ARDS who required IMV. Methods: In this retrospective, single-center, case series study, patients with COVID-19-associated ARDS who required IMV at Zhongnan Hospital of Wuhan University, China, from January 8th, 2020, to March 24th, 2020, with the final follow-up date of April 20th, 2020, were included. Demographic, clinical, laboratory, imaging, and management information were collected and analyzed. Compliance with the respiratory support decision system was documented, and its relationship with 28-day mortality was evaluated. Results: The study included 46 COVID-19-associated ARDS patients who required IMV. The median age of the 46 patients was 68.5 years, and 31 were men. The partial pressure of arterial oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio at intensive care unit (ICU) admission was 104 mmHg. The median total length of IMV was 12.0 (interquartile range [IQR]: 6.0-27.3) days, and the median respiratory support decision score was 11.0 (IQR: 7.8-16.0). To 28 days after ICU admission, 18 (39.1%) patients died. Survivors had a significantly higher respiratory support decision score than non-survivors (15.0 [10.3-17.0] vs. 8.5 (6.0-10.3), P = 0.001). Using receiver operating characteristic (ROC) curve to assess the discrimination of respiratory support decision score to 28-day mortality, the area under the curve (AUC) was 0.796 (95% confidence interval [CI]: 0.657-0.934, P = 0.001) and the cut-off was 11.5 (sensitivity = 0.679, specificity = 0.889). Patients with a higher score (>11.5) were more likely to survive at 28 days after ICU admission (log-rank test, P < 0.001). Conclusions: For severe COVID-19-associated ARDS with IMV, following the respiratory support decision and assessing completion would improve the progress of ventilation. With a decision score of >11.5, the mortality at 28 days after ICU admission showed an obvious decrease.

Decreased Heart Rate Variability in COVID-19.

Purpose: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which primarily infects the lower airways and binds to angiotensin-converting enzyme 2 (ACE2) on alveolar epithelial cells. ACE2 is widely expressed not only in the lungs but also in the cardiovascular system. Therefore, SARS-CoV-2 can also damage the myocardium. This report aimed to highlight decreased heart rate variability (HRV) and cardiac injury caused by SARS-CoV-2. Materials and Methods: We evaluated three COVID-19 patients who died. Patients' data were collected from electronic medical records. We collected patient's information, including baseline information, lab results, body temperature, heart rate (HR), clinical outcome and other related data. We calculated the HRV and the difference between the expected and actual heart rate changes as the body temperature increased. Results: As of March 14, 2020, 3 (2.2%) of 136 patients with COVID-19 in Tianjin died in the early stage of the COVID-19 epidemic. The immediate cause of death for Case 1, Case 2, and Case 3 was cardiogenic shock, cardiac arrest and cardiac arrest, respectively. The HRV were substantially decreased in the whole course of all three cases. The actual increases in heart rate were 5 beats/min, 13 beats/min, and 4 beats/min, respectively, less than expected as their temperature increased. Troponin I and Creatine Kinase MB isoenzyme (CK-MB) were substantially increased only in Case 3, for whom the diagnosis of virus-related cardiac injury could not be made until day 7. In all three cases, decreased in HRV and HR changes occurred earlier than increases in cardiac biomarkers (e.g., troponin I and CK-MB). Conclusions: In conclusion, COVID-19 could affect HRV and counteract tachycardia in response to increases in body temperature. The decreases of HRV and HR changes happened earlier than the increases of myocardial markers (troponin I and CK-MB). It suggested the decreases of HRV and HR changes might help predict cardiac injury earlier than myocardial markers in COVID-19, thus its early identification might help improve patient prognosis. Supplementary Information: The online version contains supplementary material available at 10.1007/s44231-022-00024-1.

The safety and efficacy of mesenchymal stromal cells in ARDS: a meta-analysis of randomized controlled trials.

Mesenchymal stromal cells (MSC) have shown potential efficacy in both animal and human trials of acute respiratory distress syndrome (ARDS). Especially during the COVID-19 pandemic, MSC was intensely studied for treating COVID-19-induced ARDS. The purpose of this study is to evaluate the safety and efficacy of MSC in ARDS via a meta-analysis of randomized controlled trials (RCTs). Therefore, a meta-analysis of RCTs of MSC as a therapy for ARDS was conducted. The protocol of this review was registered on Open Science Framework. With no language restriction and according to the "PICOs" principle, searches were conducted on Pubmed and Embase to retrieve any clinical literature on MSC for ARDS. Any RCT, which compared MSC to controls for ARDS, where MSC and controls were intravenously infused, of any dosage, was eligible for inclusion. A total of 13 RCTs, which evaluated MSC versus control for treating ARDS, enrolling a total of 655 cases, met the inclusion criteria and appeared in this meta-analysis. A heterogeneity assessment was carried out using the χ2 test, where a P value less than 0.05 was considered significant. The choice of a fixed-effect or a random-effect model was decided by the I2 value in each of the analyses. This meta-analysis indicated that there was no significant difference in terms of adverse events between MSC and control for ARDS (OR = 0.64, 95% CI [0.34, 1.20], P = 0.17, and I2 = 0%). In comparison with control, MSC could reduce the mortality of ARDS (OR = 0.66, 95% CI [0.46, 0.96], P = 0.03, and I2 = 10%). Based on the results of our meta-analysis, the safety of MSC was demonstrated to be non-inferior to that of standard treatment, and MSC may reduce the mortality rate of ARDS. Though the heterogeneity in the main results was low (I2 < 25%), more high-quality and large-scale clinical trials are needed to further confirm our findings.

Decreased Heart Rate Variability in COVID-19

Purpose Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which primarily infects the lower airways and binds to angiotensin-converting enzyme 2 (ACE2) on alveolar epithelial cells. ACE2 is widely expressed not only in the lungs but also in the cardiovascular system. Therefore, SARS-CoV-2 can also damage the myocardium. This report aimed to highlight decreased heart rate variability (HRV) and cardiac injury caused by SARS-CoV-2. Materials and Methods We evaluated three COVID-19 patients who died. Patients’ data were collected from electronic medical records. We collected patient’s information, including baseline information, lab results, body temperature, heart rate (HR), clinical outcome and other related data. We calculated the HRV and the difference between the expected and actual heart rate changes as the body temperature increased. Results As of March 14, 2020, 3 (2.2%) of 136 patients with COVID-19 in Tianjin died in the early stage of the COVID-19 epidemic. The immediate cause of death for Case 1, Case 2, and Case 3 was cardiogenic shock, cardiac arrest and cardiac arrest, respectively. The HRV were substantially decreased in the whole course of all three cases. The actual increases in heart rate were 5 beats/min, 13 beats/min, and 4 beats/min, respectively, less than expected as their temperature increased. Troponin I and Creatine Kinase MB isoenzyme (CK-MB) were substantially increased only in Case 3, for whom the diagnosis of virus-related cardiac injury could not be made until day 7. In all three cases, decreased in HRV and HR changes occurred earlier than increases in cardiac biomarkers (e.g., troponin I and CK-MB). Conclusions In conclusion, COVID-19 could affect HRV and counteract tachycardia in response to increases in body temperature. The decreases of HRV and HR changes happened earlier than the increases of myocardial markers (troponin I and CK-MB). It suggested the decreases of HRV and HR changes might help predict cardiac injury earlier than myocardial markers in COVID-19, thus its early identification might help improve patient prognosis. Supplementary Information The online version contains supplementary material available at 10.1007/s44231-022-00024-1.

Mediating role of resilience in relationship between occupational stress and depression of staff of centers for disease control and prevention

[Background] Since the outbreak of the COVID-19 epidemic, staff of the centers for disease control and prevention (CDC) have been burdened with heavy epidemic prevention control, and excessive occupational stress can cause depression and other psychological problems. [Objective] To explore the status of occupational stress, resilience, and depression of CDC staff and potential relationships between them. [Methods] From December 2020 to April 2021, a survey was conducted at provincial and municipal levels, and the stratified cluster sampling method was used at county (district) level to select a total of 3514 samples. Their occupational stress, resilience, and depression status were evaluated using the Chinese Effort-Reward Imbalance Scale (ERI), the Chinese Connor-Davidson Resilience Scale (CD-RISC), and the Patient Health Questionnaire (PHQ-9). Independent samplet test, analysis of variance, χ2 test, Pearson correlation analysis, and mediation test (structural equation model) were conducted. [Results] The positive rate of occupational stress was 34.29% in the CDC staff, the resilience score was 66.28±15.32, and the positive rate of depression was 48.58%. Significant differences were found in the positive rates of occupational stress among different groups of gender, age, education background, marital status, administrative duty, weekly exercise frequency, chronic disease prevalence, and participation in epidemic control (P<0.05);in the resilience scores among different groups of gender, age, administrative duty, weekly exercise frequency, chronic disease prevalence, and participation in epidemic control (P<0.05);in the positive rates of depression among different groups of gender, age, educational background, personal monthly income, weekly exercise frequency, chronic disease prevalence, and participation in epidemic control (P<0.05). Occupational stress was negatively correlated with resilience (r=−0.165,P<0.01). Resilience was negatively correlated with depression (r=−0.383,P<0.01). Occupational stress was positively correlated with depression (r=0.343, P<0.01). The structural equation embracing a partial mediating effect of resilience on the relationship occupational stress and depression was established, and the partial mediating effect was 0.039, accounting for 10.46% of the total effect. [Conclusion] High positive rates of occupational stress, reduced resilience, and depression are shown among CDC staff in the context of the COVID-19 epidemic, and resilience partially mediates the effect of occupational stress on depression. The study findings suggest that improving resilience may reduce occupational stress and depression in CDC staff.

Development of a panel of three multiplex allele-specific qRT-PCR assays for quick differentiation of recombinant variants and Omicron subvariants of SARS-CoV-2.

Quick differentiation of the circulating variants and the emerging recombinant variants of SARS-CoV-2 is essential to monitor their transmission. However, the widely used gene sequencing method is time-consuming and costly when facing the viral recombinant variants, because partial or whole genome sequencing is required. Allele-specific real time RT-PCR (qRT-PCR) represents a quick and cost-effective method in SNP genotyping and has been successfully applied for SARS-CoV-2 variant screening. In the present study, we developed a panel of 3 multiplex allele-specific qRT-PCR assays targeting 12 key differential mutations for quick differentiation of SARS-CoV-2 recombinant variants (XD and XE) and Omicron subvariants (BA.1 and BA.2). Two parallel multiplex qRT-PCR reactions were designed to separately target the protype allele and the mutated allele of the four mutations in each allele-specific qRT-PCR assay. The variation of Cp values (ΔCp) between the two multiplex qRT-PCR reactions was applied for mutation determination. The developed multiplex allele-specific qRT-PCR assays exhibited outstanding analytical sensitivities (with limits of detection [LoDs] of 2.97-27.43 copies per reaction), wide linear detection ranges (107-100 copies per reaction), good amplification efficiencies (82% to 95%), good reproducibility (Coefficient of Variations (CVs) < 5% in both intra-assay and inter-assay tests) and clinical performances (99.5%-100% consistency with Sanger sequencing). The developed multiplex allele-specific qRT-PCR assays in this study provide an alternative tool for quick differentiation of SARS-CoV-2 recombinant variants (XD and XE) and Omicron subvariants (BA.1 and BA.2).

Findings and Prognostic Value of Lung Ultrasonography in Coronal Virus Disease 2019 (COVID-19) Pneumonia.

PURPOSE: We used lung ultrasonography to identify features of COVID-19 pneumonia and to evaluate the prognostic value. PATIENTS AND METHODS: We performed lung ultrasonography on 48 COVID-19 patients in an intensive care unit (ICU) (Wuhan, China) using a 12-zone method. The associations between lung ultrasonography score, PaO2/FiO2, APACHE II, SOFA, and PaCO2 with 28-day mortality were analyzed and the receiver operator characteristic curve was plotted. RESULTS: 25.9% areas in all scanning zones presented with B7 lines and 23.5% with B3 lines (B-pattern) on lung ultrasonography; 13% areas with confluent B lines (B-pattern), 24.9% in areas with consolidations, and 9.9% in areas with A lines. Pleural effusion was observed in 2.8% of areas. Lung ultrasonography score was negatively correlated with PaO2/FiO2 (n = 48, r = -0.498, P < 0.05) and positively correlated with APACHE II (n = 48, r = 0.435, P < 0.05). Lung ultrasonography score was independently associated with 28-day mortality. The areas under receiver operator characteristic curves of lung ultrasonography score were 0.735 (95% CI: 0.586-0.844). The sensitivity, specificity, and cutoff values were 0.833, 0.722, and 22.5, respectively. CONCLUSIONS: Lung ultrasonography could be used to assess the severity of COVID-19 pneumonia, and it could also reveal the pathological signs of the disease. The lung ultrasonography score on ICU admission was independently related to the ICU 28-day mortality.

A COVID-19 Outbreak - Nangong City, Hebei Province, China, January 2021.

WHAT IS KNOWN ABOUT THIS TOPIC?: Coronavirus disease 2019 (COVID-19) is widespread globally. In China, COVID-19 has been well controlled and has appeared only in importation-related cases. Local epidemics occur sporadically in China and have been contained relatively quickly. WHAT IS ADDED BY THIS REPORT?: Epidemiological investigation with genome sequence traceability analysis showed that the first case of COVID-19 in Nangong City acquired infection from a confirmed case from Shijiazhuang City; infection subsequently led to 76 local cases. All cases were associated with the index case, and most were located in Fenggong Street and did not spread outside of Nangong City. The main routes of transmission were family clusters, intra-unit transmission, and nosocomial transmission. WHAT ARE THE IMPLICATIONS FOR PUBLIC HEALTH PRACTICE?: This study highlights new techniques for rapidly tracing cases and identifying COVID-19 transmission chains. The different epidemiological characteristics in Nangong City, from the earliest stages of the outbreak, suggest that allocation of health sources for prevention and treatment were reasonable. Preventing transmission within medical institutions and isolation facilities and strengthening management in the community should be priorities for COVID-19 control during a city lockdown.

Analysis of risk factors for subsequent infection in patients with COVID-19

Objective: To explore the risk factors of subsequent bacterial infection in patients with novel coronavirus disease 2019 (COVID-19).

Comparison of three TaqMan real-time reverse transcription-PCR assays in detecting SARS-CoV-2.

Quick and accurate detection of SARS-CoV-2 is critical for COVID-19 control. Dozens of real-time reverse transcription PCR (qRT-PCR) assays have been developed to meet the urgent need of COVID-19 control. However, methodological comparisons among the developed qRT-PCR assays are limited. In the present study, we evaluated the sensitivity, specificity, amplification efficiency, and linear detection ranges of three qRT-PCR assays, including the assays developed by our group (IPBCAMS), and the assays recommended by WHO and China CDC (CCDC). The three qRT-PCR assays exhibited similar sensitivities, with the limit of detection (LoD) at about 10 copies per reaction (except the ORF 1b gene assay in CCDC assays with a LoD at about 100 copies per reaction). No cross reaction with other respiratory viruses were observed in all of the three qRT-PCR assays. Wide linear detection ranges from 106 to 101 copies per reaction and acceptable reproducibility were obtained. By using 25 clinical specimens, the N gene assay of IPBCAMS assays and CCDC assays performed better (with detection rates of 92 % and 100 %, respectively) than that of the WHO assays (with a detection rate of 60 %), and the ORF 1b gene assay in IPBCAMS assays performed better (with a detection rate of 64 %) than those of the WHO assays and the CCDC assays (with detection rates of 48 % and 20 %, respectively). In conclusion, the N gene assays of CCDC assays and IPBCAMS assays and the ORF 1b gene assay of IPBCAMS assays were recommended for qRT-PCR screening of SARS-CoV-2.

Development of two TaqMan real-time reverse transcription-PCR assays for the detection of severe acute respiratory syndrome coronavirus-2.

The outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, was caused by a novel coronavirus (CoV), named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The rapid detection of viral nucleic acids is critical for the early identification of infected cases. We have developed two TaqMan real-time reverse transcription-PCR assays to detect SARS-CoV-2. The designed primers target the nucleocapsid (N) and open reading frame (ORF) 1b gene regions, where the probes discriminate SARS-CoV-2 from other human and animal CoVs. The sensitivities are one genomic copy per reaction for the N gene assay and ten copies for the ORF 1b gene assay. The overall linear detection ranges are 1-106 and 10-106 copies per reaction for the N gene assay and the ORF 1b gene assay, respectively. Surveillance of 23 suspected COVID-19 patients demonstrated that SARS-CoV-2 could be detected from 100% (23/23) and 62.5% (16/23) of clinical specimens by the N gene assay and the ORF 1b gene assay, respectively. All of the samples not detected by the ORF 1b gene assay were throat swabs, indicating a lower viral load in the upper respiratory tract and the relatively lower sensitivity of the ORF 1b gene assay. The assays developed in the present study offer alternative diagnostic tests for COVID-19.

Analysis of factors affecting the prognosis of COVID-19 patients and viral shedding duration.

The clinical characteristics of patients with COVID-19 were analysed to determine the factors influencing the prognosis and virus shedding time to facilitate early detection of disease progression. Logistic regression analysis was used to explore the relationships among prognosis, clinical characteristics and laboratory indexes. The predictive value of this model was assessed with receiver operating characteristic curve analysis, calibration and internal validation. The viral shedding duration was calculated using the Kaplan-Meier method, and the prognostic factors were analysed by univariate log-rank analysis and the Cox proportional hazards model. A retrospective study was carried out with patients with COVID-19 in Tianjin, China. A total of 185 patients were included, 27 (14.59%) of whom were severely ill at the time of discharge and three (1.6%) of whom died. Our findings demonstrate that patients with an advanced age, diabetes, a low PaO2/FiO2 value and delayed treatment should be carefully monitored for disease progression to reduce the incidence of severe disease. Hypoproteinaemia and the fever duration warrant special attention. Timely interventions in symptomatic patients and a time from symptom onset to treatment <4 days can shorten the duration of viral shedding.

Clinical features and short-term outcomes of 221 patients with COVID-19 in Wuhan, China.

BACKGROUND: In late December 2019, an outbreak of acute respiratory illness, coronavirus disease 2019 (COVID-19), emerged in Wuhan, China. We aimed to study the epidemiology, clinical features and short-term outcomes of patients with COVID-19 in Wuhan, China. METHODS: We performed a single center, retrospective case series study in 221 patients with laboratory confirmed SARS-CoV-2 pneumonia at a university hospital, including 55 severe patients and 166 non-severe patients, from January 2, 2020 to February 10, 2020. RESULTS: Of the 221 patients with COVID-19, the median age was 55.0 years and 48.9% were male and only 8 (3.6%) patients had a history of exposure to the Huanan Seafood Market. Compared to the non-severe pneumonia patients, the median age of the severe patients was significantly older, and they were more likely to have chronic comorbidities. Most common symptoms in severe patients were high fever, anorexia and dyspnea. On admission, 33.0% patients showed leukopenia and 73.8% showed lymphopenia. In addition, the severe patients suffered a higher rate of co-infections with bacteria or fungus and they were more likely to developing complications. As of February 15, 2020, 19.0% patients had been discharged and 5.4% patients died. 80% of severe cases received ICU (intensive care unit) care, and 52.3% of them transferred to the general wards due to relieved symptoms, and the mortality rate of severe patients in ICU was 20.5%. CONCLUSIONS: Patients with elder age, chronic comorbidities, blood leukocyte/lymphocyte count, procalcitonin level, co-infection and severe complications might increase the risk of poor clinical outcomes.