CCQM-P199b: Interlaboratory comparability study of SARS-CoV-2 RNA copy number quantification (preprint)

Nucleic acid amplification tests including reverse transcription-quantitative PCR (RT-qPCR) are used to detect RNA from Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of the Coronavirus disease 2019 (COVID-19) pandemic. Standardized measurements of RNA can facilitate comparable performance of laboratory tests in the absence of existing reference measurement systems early on in a pandemic. Interlaboratory study CCQM-P199b 'SARS-CoV-2 RNA copy number quantification' was designed to test the fitness-for-purpose of developed candidate reference measurement procedures (RMPs) for SARS-CoV-2 genomic targets in purified RNA materials, and was conducted under the auspices of the Consultative Committee for Amount of Substance: Metrology in Chemistry and Biology (CCQM) to evaluate the measurement comparability of national metrology institutes (NMIs) and designated institutes (DIs), thereby supporting international standardization. Twenty-one laboratories participated in CCQM-P199b and were requested to report the RNA copy number concentration, expressed in number of copies per microliter, of the SARS-CoV-2 nucleocapsid (N) gene partial region (NC_045512.2: 28274-29239) and envelope (E) gene (NC_045512.2: 26245-26472) (optional measurement) in samples consisting of in vitro transcribed RNA or purified RNA from lentiviral constructs. Materials were provided in two categories: lower concentration (approximately 10 x 1 - 10 x 4/uL in aqueous solution containing human RNA background) and high concentration (approximately 10 x 9/uL in aqueous solution without any other RNA background). For the measurement of N gene concentration in the lower concentration study materials, the majority of laboratories (n = 17) used one-step reverse transcription-digital PCR (RT-dPCR), with three laboratories applying two-step RT-dPCR and one laboratory RT-qPCR. Sixteen laboratories submitted results for E gene concentration. Reproducibility (% CV or equivalent) for RT-dPCR ranged from 19 % to 31 %. Measurements of the high concentration study material by orthogonal methods (isotope dilution-mass spectrometry and single molecule flow cytometry) and a gravimetrically linked lower concentration material were in a good agreement, suggesting a lack of overall bias in RT-dPCR measurements. However methodological factors such as primer and probe (assay) sequences, RT-dPCR reagents and dPCR partition volume were found to be potential sources of interlaboratory variation which need to be controlled when applying this technique. This study demonstrates that the accuracy of RT-dPCR is fit-for-purpose as a RMP for viral RNA target quantification in purified RNA materials and highlights where metrological approaches such as the use of in vitro transcribed controls, orthogonal methods and measurement uncertainty evaluation can support standardization of molecular methods.

The impact of vaccination on patients with COVID-19 during the wave of Omicron in Shanghai

Background The global health has been affected by the COVID-19 pandemic persistently, of which Omicron is currently the predominant variant. However, the impact of vaccination on Omicron remained uncertain. Objective This study sought to explore the effect of vaccination on patients infected with Omicron. Methods A retrospective observational cohort was conducted in the largest Fangcang shelter hospital in Shanghai from April 1 to May 30, 2022. The demographics, length of hospital stay, clinical symptoms, the comorbidities and vaccination status were recorded. Clinical outcomes of the vaccinated and non-vaccinated groups were compared and analyzed. Results Of the 3,119 patients who fulfilled the eligibility criteria and were enrolled in the study, 2,226 (71.4%) patients had received nCoV-19 vaccine while 893 (28.6%) patients had not received it before admission. Patients in the vaccinated group had significantly shorter length of hospital stay than those in the unvaccinated group (15.48 ± 2.708 vs. 15.85 ± 3.102, p < 0.001). More asymptomatic patients were observed in the vaccinated group than the non-vaccinated (70.4 vs. 64.5%, p < 0.001). Further subgroup analysis demonstrated that the older the age, the more significant the difference was (p < 0.005). Conclusions Vaccination was associated with a significant reduction in the severity of Omicron infection compared with no vaccination. Vaccination appears to make Omicron-infected people with milder symptoms than unvaccinated people. This suggests the potential effectiveness of current vaccines against Omicron.

Compassion satisfaction and compassion fatigue in frontline nurses during the COVID-19 pandemic in Wuhan, China.

AIM: The aim of this study is to investigate the compassion satisfaction and compassion fatigue among Chinese frontline nurses during the COVID-19 pandemic in Wuhan, China and to explore the related factors. BACKGROUND: Frontline nurses undertake a huge nursing workload with a risk of infection, causing great pressure on them and making them face a risk of compassion fatigue during the pandemic. METHODS: A cross-sectional online survey was conducted from 9 March to 15 March 2020. A total of 1582 nurses caring for critical patients with COVID-19 participated. Compassion satisfaction and compassion fatigue (comprising burnout and secondary traumatic stress) were assessed with the Professional Quality of Life Scale, and resilience was measured with the Chinese 10-item Connor-Davidson Resilience Scale. RESULTS: Moderate levels of compassion satisfaction (36.99 ± 6.71), burnout (24.14 ± 5.33) and secondary traumatic stress (24.53 ± 5.24) were experienced by frontline nurses. Resilience and perceived work pressure were the main predictors. CONCLUSIONS: Frontline nurses demonstrated a moderate level of compassion satisfaction and compassion fatigue. IMPLICATIONS FOR NURSING MANAGEMENT: The compassion fatigue of frontline nurses should be considered. Strategies aiming to reduce stress and enhance resilience, such as training about psychological adjustment, developing professional skills and creating a supportive workplace environment, are several options. The trial is not registered. This study is a cross-sectional study, and according to China's clinical trial registration standards, such studies are not required to be registered. So the trial is not registered. However, oral consent was obtained from the ethics committee of the hospital before this study was conducted.

COVID-19 Information Overload, Negative Emotions and Posttraumatic Stress Disorder: A Cross-Sectional Study

Background Under the context of the COVID-19 pandemic, a large amount of COVID-19-related information can cause an individual's perceived information overload, further halting the individual's psychological health. As a minor psychological discomfort could develop severe mental disorders such as posttraumatic stress disorder, it is necessary to understand the chain linkage of COVID-19 information overload turn to posttraumatic stress disorder to ensure timely intervention can be offered at each point of mental state transformation. Hence, we examined the negative outcomes of COVID-19 information overload and investigated the direct and indirect effects of COVID-19 on posttraumatic stress disorder. Methods A convenient sample of Chinese adults (n = 1150) was investigated by an online survey from July 2020 to March 2021. The extent of COVID-19 information overload was measured by the information overload severity scale on the text of the COVID-19 pandemic. Psychological distress symptoms were measured using a 7-item anxiety scale (GAD-7), the 9-item Patient Health Questionnaire depression module (PHQ-9), and the psychometric properties of the PTSD Checklist (PCL-C). Structural equation modeling and bootstrap methods were utilized to analyze the relationships between variables. Results COVID-19 information overload is positively related to an individual's anxiety, depression, and posttraumatic stress disorder. Furthermore, COVID-19 information overload can indirectly affect an individual's PTSD symptoms by increasing the feeling of depression. R2 values of anxiety, depression, and PTSD were 0.471, 0.324, and 0.795, respectively. Conclusion COVID-19 information overload, anxiety, depression, and PTSD are negative psychological states, and each variable is closely linked with the others, suggesting the need for potential psychological interventions at specific times. Practical public training, such as crisis coping and information filtering, is essential. Regulation of technology companies is also essential.

Clinical Study of Human Coronavirus NL63, OC43, 229E, HKU1 Infentions in Hospitalized Children from 2015 to 2020

Objective This study aims to analyze the clinical characteristics of hospitalized children infected with HCoV-NL63, OC43, 229E, HKU1 and provide the basis for disease diagnosis and treatment. Methods A retrospective analysis was conducted on clinical manifestations, imaging data, and treatment measures of hospitalized children with positive HCoV-NL63, OC43, 229E, HKU1 from 2015 to 2020. Results A total of 1062 children aged 33 days to 12 years were analyzed, including 879 (82.77%) between 33 days to three years. Lower respiratory tract infections were the most common in 698 children positive for HCoVs (65.72%). The incidences of runny nose, cough, pharyngeal hyperemia, and fine crackles in the mild case group (n = 894, 84.18%) were significantly higher than in the severe case group, and the differences were statistically significant (P < 0.01). The incidences of gasp, stridor, and convulsions, the proportion of underlying diseases, such as congenital heart disease, laryngomalacia, and general developmental disorders, anemia, and abnormal liver function, and mixed infections in the severe group (n = 168, 15.82%) were significantly higher than in the mild group, and the differences were statistically significant (P < 0.01 or P < 0.05). Imaging manifestations differed. Pleural effusion and atelectasis occurred in the severe cases. After treatment, patients fully recovered or improved and were discharged from the hospital. There were no deaths. Conclusion HCoV-NL63, OC43, 229E, HKU1 infection is most common in children under three years old, and the infection site is mainly the lower respiratory tract. The main clinical manifestations include fever, cough, and runny nose. Inspiratory three concave signs, respiratory failure, and heart failure occurred in the severe cases, with pleural effusion and atelectasis possibly occurring at the same time. Severe cases should be identified early so that they may be given comprehensive treatment in time to improve the prognosis.

Risk assessment and control of nosocomial infection in fever clinic of general hospital

OBJECTIVE: To establish the risk assessment system of nosocomial infection in fever outpatient department of general hospital, and to realize the accurate risk control to reduce the occurrence of nosocomial infection in doctors and patients. METHODS: Based on the healthcare failure mode and effect analysis(HFMEA), the quantitative risk assessment was carried out in the fever clinic in a general hospital to establish the risk system. Regular evaluation was performed to find out the key risks that should be controlled. Accurate measures were implemented and re-evaluated were performed and then adjusted. The cycle of the process will be conducted in a row to get the improvement. RESULTS: The risk assessment system of fever clinic included the building layout and facilities whether meet the requirements of the infectious diseases prevention and control, whether the system of prevention and control of hospital infection was complete, whether the personnel management and protection was proper, whether the item management, environment cleaning and disinfection were legal compliance and whether the medical process can meet the demands of the hospital infection prevention and control, etc. At the beginning of COVID-19 epidemic, the first round of risk assessment was carried out on fever clinics, and 44 risk points were identified, among which 8 risk points needed to be controlled by key intervention measures. Targeted improvement measures were performed, then the second round of risk assessment was conducted to evaluate the control effect, which showed good risk control effect. CONCLUSION: The quantitative risk assessment system established based on HFMEA was used to regularly evaluate the risk to find out the potential nosocomial infection, to timely detect the potential nosocomial infection risk in fever outpatient clinics, to achieve accurate prevention and control of nosocomial infection in fever outpatient clinics, which can greatly reduce the risk of cross-infection of infectious diseases in hospitals and nip it in the bud.

Clinicopathological and Immunological Features of Patients With New Onset Kidney Disease After Inactivated SARS-CoV-2 Vaccination: An Observational Cohort Study (preprint)

Background: The onset of various kidney diseases have been reported after COVID-19 vaccination. However, detailed clinical and pathological examination of kidney injury in patients receiving inactivated vaccines are lacking.Methods: We screened and analyzed patients with newly diagnosed kidney diseases after inactivated SARS-CoV-2 vaccination in Peking University First Hospital from January 2021 to August 2021. We obtained samples of blood, urine, and renal biopsy tissues. Clinical and laboratory information, as well as light microscopy, immunostaining and ultrastructural observation were described. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike protein and Nucleoprotein were stained using immune-fluorescence technique in the kidney biopsy samples. SARS-CoV-2 specific antibodies were tested using magnetic particle chemiluminescence immunoassay.Findings: The study group included 17 patients, including immune complex mediated kidney diseases (IgA nephropathy, membranous nephropathy and lupus nephritis), podocytopathy (minimal change disease and focal segmental glomerulosclerosis) and others (antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, anti-GBM nephritis, acute tubulointerstitial nephritis, and thrombotic microangiopathy). Seven patients (41.18%) developed renal disease after the first dose and 10 (58.82%) after the second dose. We found no definitive evidence of SARS-CoV-2 Spike protein or Nucleoprotein deposition in the kidney biopsy samples. Serological markers implicated abnormal immune responses in predisposed individuals. Treatment and follow-up (median = 86 days) showed that biopsy diagnosis informed treatment and prognosis in all patients.Interpretation: We observed various kidney diseases following inactivated SARS-CoV-2 vaccine administration. Our findings provide an evidence against direct vaccine protein deposition as the major pathomechanism, but implicate abnormal immune responses in predisposed individuals. These findings expand our understanding of inactivated SARS-CoV-2 vaccine renal safety.Funding: This study was funded by National Natural Science Foundation of China (91742205, 82170711, 81800636, 82070733, 81625004), Clinical Medicine Plus X—Young Scholars Project of Peking University (PKU2021LCXQ017), the Fundamental Research Funds for the Central Universities, CAMS Innovation Fund for Medical Sciences (2019-I2M-5-046), Yunnan Provincial Science and Technology Department (202102AA100051 and 202003AC100010, China), and Beijing Young Scientist Program (BJJWZYJH01201910001006).Declaration of Interest: The authors declare no competing interests.Ethical Approval: This study was approved by the institutional review board of Peking University First Hospital (2021-352) and the Committee on Human Subject Research and Ethics of Yunnan University (CHSRE2021020). Written Informed Consent Form was obtained from each participant.

Laboratory parameters between multisystem inflammatory syndrome in children and Kawasaki disease (preprint)

Multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19) has been described to partially overlap with Kawasaki disease (KD) with regard to clinical symptoms, but they are unlikely to share the same disease entity. We conducted a systematic review and meta-analysis to characterize the laboratory parameters of MIS-C compared with those of KD and Kawasaki disease shock syndrome (KDSS). Databases were searched for studies on laboratory parameters of MIS-C (hematology, inflammatory markers, cardiac markers and biochemistry) through May 31, 2021. Twelve studies with 3073 participants yielded 969 MIS-C patients. In terms of hematology, MIS-C patients had lower levels of leukocytes, absolute lymphocyte count and platelet count (PLT) than KD patients and had similar absolute neutrophil count (ANC) and hemoglobin (Hb) levels. In terms of inflammatory markers, MIS-C patients had higher levels of C-reactive protein, D-dimer and ferritin than KD patients and had similar levels of procalcitonin and ESR. In terms of cardiac markers, MIS-C patients had higher CPK levels than KD patients. The levels of NT-proBNP, troponin and AST were not significantly different between MIS-C and KD patients. In terms of biochemistry, MIS-C patients had lower levels of albumin, sodium and ALT and higher levels of creatinine than KD patients. In addition, MIS-C patients had lower levels of PLT, Hb and ESR and higher levels of ANC than KDSS patients. Measurement of laboratory parameters might assist clinicians with accurate evaluation of MIS-C and further mechanistic research.

Controlling multiple COVID-19 epidemic waves: an insight from a multi-scale model linking the behavior change dynamics to the disease transmission dynamics (preprint)

COVID-19 epidemics exhibited multiple waves regionally and globally since 2020. It is important to understand the insight and underlying mechanisms of the multiple waves of COVID-19 epidemics in order to design more efficient non-pharmaceutical interventions (NPIs) and vaccination strategies to prevent future waves. We propose a multi-scale model by linking the behavior change dynamics to the disease transmission dynamics to investigate the effect of behavior dynamics on COVID-19 epidemics using the game theory. The proposed multi-scale model was calibrated and key parameters related to disease transmission dynamics and behavioral dynamics with/without vaccination were estimated based on COVID-19 epidemic data and vaccination data. Our modeling results demonstrate that the feedback loop between behavior changes and COVID-19 transmission dynamics plays an essential role in inducing multiple epidemic waves. We find that the long period of high-prevalence or persistent deterioration of COVID-19 epidemics could drive almost all population to change their behaviors and maintain the altered behaviors, however, the effect of behavior changes faded out gradually along the progress of epidemics. This suggests that it is essential not only to have persistent, but also effective behavior changes in order to avoid subsequent epidemic waves. In addition, our model also suggests the importance to maintain the effective altered behaviors during the initial stage of vaccination, and to counteract relaxation of NPIs, it requires quick and massive vaccination to avoid future epidemic waves.

Group IIA Secreted Phospholipase A2 Plays a Central Role in the Pathobiology of COVID-19 (preprint)

There is an urgent need to identify cellular and molecular mechanisms responsible for severe COVID-19 disease accompanied by multiple organ failure and high mortality rates. Here, we performed untargeted/targeted lipidomics and focused biochemistry on 127 patient plasma samples, and showed high levels of circulating, enzymatically active secreted phospholipase A2 Group IIA (sPLA2-IIA) in severe and fatal COVID-19 disease compared with uninfected patients or mild illness. Machine learning demonstrated that sPLA2-IIA effectively stratifies severe from fatal COVID-19 disease. We further introduce a PLA-BUN index that combines sPLA2-IIA and blood urea nitrogen (BUN) threshold levels as a critical risk factor for mitochondrial dysfunction, sustained inflammatory injury and lethal COVID-19. With the availability of clinically tested inhibitors of sPLA2-IIA, our study opens the door to a precision intervention using indices discovered here to reduce COVID-19 mortality.

Assessing Age-Specific Vaccination Strategies and Post-Vaccination Reopening Policies for COVID-19 Control Using SEIR Modeling Approach (preprint)

Background As the availability of COVID-19 vaccines, it is badly needed to develop vaccination guidelines to prioritize the vaccination delivery in order to effectively stop COVID-19 epidemic and minimize the loss. Methods We evaluated the effect of age-specific vaccination strategies on the number of infections and deaths using an SEIR model, considering the age structure and social contact patterns for different age groups for each of different countries. Results In general, the vaccination priority should be given to those younger people who are active in social contacts to minimize the number of infections; while the vaccination priority should be given to the elderly to minimize the number of deaths. But this principle may not always apply when the interaction of age structure and age-specific social contact patterns is complicated. Partially reopening schools, workplaces or households, the vaccination priority may need to be adjusted accordingly. Conclusions Prematurely reopening social contacts could initiate a new outbreak or even a new pandemic out of control if the vaccination rate and the detection rate are not high enough. Our result suggests that it requires at least nine months of vaccination before fully reopening social contacts in order to avoid a new pandemic.

Clinical Characteristics of Severe COVID-19 in China: A Case Series and Meta-analysis (preprint)

Background: There have been inconsistent reports regarding the unique manifestations of severe coronavirus disease 2019 (COVID-19) occurring in China. This study analyzed the clinical manifestation of 13 severe COVID-19 cases at a single institution and compared the data to previously reported characteristics of severe COVID-19 in China. Methods: This retrospective case study included patients with severe COVID-19 who were admitted to the isolation ward of the Shandong Chest Hospital from January 2020 to February 2020. The clinical signs and symptoms, laboratory examination results, imaging features, treatment strategies, and patient prognoses were summarized. A database search was then conducted for studies published through December 2020 documenting characteristics of severe COVID-19 cases in China. The pooled results for severe COVID-19 patients in China were calculated by using the random-effects model.Results: A total of 4 severe and 9 critical patients were included from Shandong Chest Hospital. The average patient age was 55.3 (range 23-88) years, and 61.5% of patients were male. Chest computed tomography for all patients showed multiple lesions as ground-glass shadows in both lungs. All patients presented bacterial infection and various degrees of liver and myocardial injury. The treatment strategies for patients included antibiotics, immunoglobulin, and glucocorticoids, and mechanical ventilation was used in all patients for respiratory failure. Two patients died, and 11 recovered. In the pooled data for severe COVID-19 patients, the most common comorbidities were hypertension, diabetes mellitus, and coronary heart disease. The common signs in these patients were fever, cough, fatigue, chest tightness, and a leukocyte count > 10. Conclusions: Older males with hypertension, diabetes mellitus, and coronary heart disease may be at higher risk of developing severe COVID-19. Patients should be assessed for concomitant bacterial infections. Cardiac and liver enzymes, fever, cough, fatigue, chest tightness, and leukocytosis should be monitored for signs of disease progression. 

Complex Systems Analysis Informs on the Spread of COVID-19 (preprint)

The non-linear progression of new infection numbers in a pandemic poses challenges to the evaluation of its management. The tools of complex systems research may aid in attaining information that would be difficult to extract with other means. To study the COVID-19 pandemic, we utilize the reported new cases per day for the globe, nine countries and six US states through October 2020. Fourier and univariate wavelet analyses inform on periodicity and extent of change. Evaluating time-lagged data sets of various lag lengths, we find that the autocorrelation function, average mutual information and box counting dimension represent good quantitative readouts for the progression of new infections. Bivariate wavelet analysis and return plots give indications of containment versus exacerbation. Homogeneity or heterogeneity in the population response, uptick versus suppression, and worsening or improving trends are discernible, in part by plotting various time lags in three dimensions. The analysis of epidemic or pandemic progression with the techniques available for observed (noisy) complex data can aid decision making in the public health response.

Clinical Outcomes of COVID-19 Cases and Influencing Factors of Severe Cases in Qingdao City: A Retrospective Cohort Study (preprint)

BackgroundTo analyze the clinical outcomes of COVID-2019 cases and the influencing factors of severe cases in Qingdao City and provide theoretical reference basis for optimizing medical treatment and the strategies of epidemic prevention and control. MethodsThe demographical, epidemiological, clinical data of 81 confirmed COVID-2019 cases in Qingdao City were collected via epidemiological investigation and clinical process tracking. The status of cure, discharge, clinical outcome and influencing factors were analyzed in our study. ResultsAmong the 81 cases，12(14.81%) and 55(67.90%) were mild and ordinary, 9(11.11%) and 4(4.94%) were severe and critical, and 1 critical cases (1.23%) developed into fatal, with the fatality rate 1.23%. The median time from onset of symptoms to hospital admission were 3.67 days (IQR, 1.75 to 6.71). The median duration of illness were 21.00 days (IQR, 16.00 to 26.00) and the median length of hospitalization were 15.63 days (IQR, 11.60 to 20.50). The median time for progression to severe cases was 6.00 days after onset (IQR, 5.00-10.00). The median duration of severe cases was 8.00 days (IQR, 6.25-14.00). Age older than 40 years old (OR=5.797, 95%CI: 1.064~31.568) and first chest CT abnormal (OR=0.1140, 95%CI: 0.014~0.923) were the influencing factors of COVID-2019 severe cases. ConclusionsOlder age and first chest CT normal would be more prone to develop to severe cases of COVID-2019. During the epidemic period, it was necessary to classify and manage cases according to the needs of prevention and control in order to ensure the rational allocation of medical resources.

Mothers infected with SARS-CoV-2 reveals a mild impact on newborns (preprint)

Could pregnant women infected with COVID-19 cause adverse consequences for their newborns?2. Mothers infected with COVID-19 did not cause serious adverse reactions during term labor, but premature infants were prone to gastrointestinal complications.3. It is necessary to strengthen the protective measures of nosocomial infection in NICU. Although the outbreak of SARS-CoV-2 has a serious impact on human health, the impact on newborns seems to be relatively moderate