Temporal changes in biomarkers of neutrophil extracellular traps and NET-promoting autoantibodies following adenovirus-vectored, mRNA, and recombinant protein COVID-19 vaccination.

Neutrophil extracellular traps (NETs) play a role in innate pathogen defense and also trigger B-cell response by providing antigens. NETs have been linked to vaccine-induced thrombotic thrombocytopenia. We postulated a potential link between NET biomarkers, NET-promoting autoantibodies, and adverse events (AEs) after COVID-19 vaccine boosters. Healthy donors (HDs) who received ChAdOx1-S (A), mRNA-1273 (M), or recombinant protein (MVC-COV1901) vaccines at the National Taiwan University Hospital between 2021 and 2022 were recruited. We measured serial NET-associated biomarkers, citrullinated-histone3 (citH3), and myeloperoxidase (MPO)-DNA. Serum citH3 and MPO-DNA were significantly or numerically higher in HDs who reported AEs (n = 100, booster Day 0/Day 30, p = 0.01/p = 0.03 and p = 0.30/p = 0.35, respectively). We also observed a positive correlation between rash occurrence in online diaries and elevated citH3. A linear mixed model also revealed significantly higher citH3 levels in mRNA-1273/ChAdOx1-S recipients than MVC-COV1901 recipients. Significant positive correlations were observed between the ratios of anti-heparin platelet factor 4 and citH3 levels on Booster Day 0 and naïve and between the ratios of anti-NET IgM and citH3 on Booster Day 30/Day 0 in the AA-M and MM-M group, respectively. The increased levels of citH3/MPO-DNA accompanied by NET-promoting autoantibodies suggest a potential connection between mRNA-1273/ChAdOx1-S vaccines and cardiovascular complications. These findings provide insights for risk assessments of future vaccines.

Monitoring the performance of a dedicated weaning unit using risk-adjusted control charts for the weaning rate in prolonged mechanical ventilation.

BACKGROUND: Weaning rate is an important quality indicator of care for patients with prolonged mechanical ventilation (PMV). However, diverse clinical characteristics often affect the measured rate. A risk-adjusted control chart may be beneficial for assessing the quality of care. METHODS: We analyzed patients with PMV who were discharged between 2018 and 2020 from a dedicated weaning unit at a medical center. We generated a formula to estimate monthly weaning rates using multivariate logistic regression for the clinical, laboratory, and physiologic characteristics upon weaning unit admission in the first two years (Phase I). We then applied both multiplicative and additive models for adjusted p-charts, displayed in both non-segmented and segmented formats, to assess whether special cause variation existed. RESULTS: A total of 737 patients were analyzed, including 503 in Phase I and 234 in Phase II, with average weaning rates of 59.4% and 60.3%, respectively. The p-chart of crude weaning rates did not show special cause variation. Ten variables from the regression analysis were selected for the formula to predict individual weaning probability and generate estimated weaning rates in Phases I and II. For risk-adjusted p-charts, both multiplicative and additive models showed similar findings and no special cause variation. CONCLUSION: Risk-adjusted control charts generated using a combination of multivariate logistic regression and control chart-adjustment models may provide a feasible method to assess the quality of care in the setting of PMV with standard care protocols.

Immunogenicity and safety of homologous and heterologous ChAdOx1-S and mRNA-1273 vaccinations in healthy adults in Taiwan.

BACKGROUND: In Taiwan, the vaccination program started in March 2021, with ChAdOx1-S being the first available WHO-approved COVID-19 vaccine, followed by Moderna vaccine. This study aimed to investigate the immunogenicity and safety of homologous and heterologous prime-boost regimens with ChAdOx1-S and mRNA-1273. METHODS: From March to November 2021, homologous or heterologous regimens with ChAdOx1-S and mRNA-1273 vaccination (ChAdOx1-S/ChAdOx1-S, mRNA-1273/mRNA-1273, ChAdOx1-S/mRNA-1273) were given to 945 healthy participants. Serum samples were collected at designated time points. The anti-RBD/S1 antibody titers and neutralizing ability were measured by three different immunoassays: Elecsys® Anti-SARS-CoV-2 S (Roche Diagnostics, Mannheim, Germany), AdviseDx SARS-CoV-2 IgG II (Abbott Diagnostics Division, Sligo, Ireland), and cPass™ SARS-CoV-2 Neutralization Antibody Detection Kit (GenScript, New Jersey, USA). RESULTS: We found that heterologous vaccination with ChAdOx1-S/mRNA-1273 had an acceptable safety profile and induced higher total anti-RBD/S1 antibody production (p < 0.0001), yet lower anti-RBD/S1 IgG titer (p < 0.0001) and neutralizing ability (p = 0.0101) than mRNA-1273/mRNA-1273 group. Both regimens showed higher antibody titers and superior neutralizing abilities than ChAdOx1-S/ChAdOx1-S. An age-dependent antibody response to ChAdOx1-S/mRNA-1273 was shown after both the priming and the booster doses. Younger age was associated with higher antibody production and neutralizing ability. CONCLUSIONS: Heterologous ChAdOx1-S/mRNA-1273 vaccination regimen is generally safe and induces a robust humoral immune response that is non-inferior to that of mRNA-1273/mRNA-1273.

Improving the Process of Shared Decision-Making by Integrating Online Structured Information and Self-Assessment Tools.

The integration of face-to-face communication and online processes to provide access to information and self-assessment tools may improve shared decision-making (SDM) processes. We aimed to assess the effectiveness of implementing an online SDM process with topics and content developed through a participatory design approach. We analyzed the triggered and completed SDM cases with responses from participants at a medical center in Taiwan. Data were retrieved from the Research Electronic Data Capture (REDCap) database of the hospital for analysis. Each team developed web-based patient decision aids (PDA) with empirical evidence in a multi-digitized manner, allowing patients to scan QR codes on a leaflet using their mobile phones and then read the PDA content online. From July 2019 to December 2020, 48 web-based SDM topics were implemented in the 24 clinical departments of this hospital. The results showed that using the REDCap system improved SDM efficiency and quality. Implementing an online SDM process integrated with face-to-face communication enhanced the practice and effectiveness of SDM, possibly through the flexibility of accessing information, self-assessment, and feedback evaluation.

Effect of implementing decision support to activate a rapid response system by automated screening of verified vital sign data: A retrospective database study.

AIM: Activating a rapid response system (RRS) at general wards requires memorizing trigger criteria, identifying deterioration, and timely notification of abnormalities. We aimed to assess the effect of decision support (DS)-linked RRS activation on management and outcomes. METHODS: We retrospectively analyzed general ward RRS activation cases from 2013 to 2017 and the incidence of cardiopulmonary resuscitations (CPR) from 2013 to 2020. A DS-alerting mechanism was added to the conventional RRS activation process in 2017, with an alert window appearing whenever the system automatically detected any verified abnormal vital sign entry, alerting the nurse to take further action. Logistic and linear regression analyses were used to compare outcomes. RESULTS: We analyzed 27,747 activations and 64,592 DS alerts. RRS activations increased from 3.5 to 30.3 per 1,000 patient-days (P < 0.001) after DS implementation. The first DS activations occurred earlier than conventional ones (-2.9 days, 95% confidence interval = -3.6 to -2.1 days). After adjustment with inverse probability of treatment weighting, main (conventional vs DS-linked activations after implementation) and sensitivity analyses showed that DS activation cases had a lower risk of CPR and in-hospital mortality. Cases with more DS alerts before RRS activation had a higher risk of CPR (P trend = 0.017) and in-hospital mortality (P trend < 0.001). The incidence of CPR at the general ward decreased. CONCLUSION: Implementing a DS mechanism with an automated screening of verified abnormal vital signs linked to RRS activations at general wards was associated with improved practice and timeliness of hospital-wide RRS activations and reduced in-hospital resuscitations and mortality.

Machine learning for emerging infectious disease field responses.

Emerging infectious diseases (EIDs), including the latest COVID-19 pandemic, have emerged and raised global public health crises in recent decades. Without existing protective immunity, an EID may spread rapidly and cause mass casualties in a very short time. Therefore, it is imperative to identify cases with risk of disease progression for the optimized allocation of medical resources in case medical facilities are overwhelmed with a flood of patients. This study has aimed to cope with this challenge from the aspect of preventive medicine by exploiting machine learning technologies. The study has been based on 83,227 hospital admissions with influenza-like illness and we analysed the risk effects of 19 comorbidities along with age and gender for severe illness or mortality risk. The experimental results revealed that the decision rules derived from the machine learning based prediction models can provide valuable guidelines for the healthcare policy makers to develop an effective vaccination strategy. Furthermore, in case the healthcare facilities are overwhelmed by patients with EID, which frequently occurred in the recent COVID-19 pandemic, the frontline physicians can incorporate the proposed prediction models to triage patients suffering minor symptoms without laboratory tests, which may become scarce during an EID disaster. In conclusion, our study has demonstrated an effective approach to exploit machine learning technologies to cope with the challenges faced during the outbreak of an EID.

Seroprevalence Surveys for Anti-SARS-CoV-2 Antibody in Different Populations in Taiwan With Low Incidence of COVID-19 in 2020 and Severe Outbreaks of SARS in 2003.

Accurate detection of anti-SARS-CoV-2 antibodies provides a more accurate estimation of incident cases, epidemic dynamics, and risk of community transmission. We conducted a cross-sectional seroprevalence study specifically targeting different populations to examine the performance of pandemic control in Taiwan: symptomatic patients with epidemiological risk and negative qRT-PCR test (Group P), frontline healthcare workers (Group H), healthy adult citizens (Group C), and participants with prior virologically-confirmed severe acute respiratory syndrome (SARS) infection in 2003 (Group S). The presence of anti-SARS-CoV-2 total and IgG antibodies in all participants were determined by Roche Elecsys® Anti-SARS-CoV-2 test and Abbott SARS-CoV-2 IgG assay, respectively. Sera that showed positive results by the two chemiluminescent immunoassays were further tested by three anti-SARS-CoV-2 lateral flow immunoassays and line immunoassay (MIKROGEN recomLine SARS-CoV-2 IgG). Between June 29 and July 25, 2020, sera of 2,115 participates, including 499 Group P participants, 464 Group H participants, 1,142 Group C participants, and 10 Group S participants, were tested. After excluding six false-positive samples, SARS-CoV-2 seroprevalence were 0.4, 0, and 0% in Groups P, H, and C, respectively. Cross-reactivity with SARS-CoV-2 antibodies was observed in 80.0% of recovered SARS participants. Our study showed that rigorous exclusion of false-positive testing results is imperative for an accurate estimate of seroprevalence in countries with previous SARS outbreak and low COVID-19 prevalence. The overall SARS-CoV-2 seroprevalence was extremely low among populations of different exposure risk of contracting SARS-CoV-2 in Taiwan, supporting the importance of integrated countermeasures in containing the spread of SARS-CoV-2 before effective COVID-19 vaccines available.

Learning from the past: Taiwan's responses to COVID-19 versus SARS.

OBJECTIVES: To evaluate the prevalence of infection prevention behaviors in Taiwan-wearing facemasks and alcohol-based hand hygiene (AHH)-and compare their practice rates during SARS and COVID-19. METHODS: We surveyed 2328 Taiwanese from July 29 to August 6, 2020, assessing demographics, information sources, and preventive behaviors during the 2003 SARS outbreaks, 2009 pandemic influenza H1N1, COVID-19, and with post-survey intentions. Characteristics associated with the practice of preventive behaviors in 2020 were identified through logistic regression. RESULTS: Preventive behaviors were conscientiously practiced by 70.2% of participants. Compared with 2003 SARS/2009 H1N1, the percentages of facemask use (66.6% vs 99.2% [indoors], P < 0.001) and on-person AHH (44.2% vs 65.4% [hand sanitizers], P < 0.001) significantly increasedduring 2020 COVID-19. Highest adherence to preventive behaviors in 2020 was among females (adjusted odds ratio [aOR], 1.72), those receiving government COVID-19 information (aOR, 1.52), participants recruited from primary-care clinics (aOR, 1.43), and those who practiced AHH during 2003 SARS/2009 H1N1 (aOR, 1.37). CONCLUSIONS: Government leadership, healthcare providers risk communication, and public cooperation rapidly mitigated the spread of COVID-19 in Taiwan even before vaccination. Future global efforts must implement such population-based preventive behaviors at a level above the viral-transmission-threshold, particularly in areas with fast-spreading SARS-CoV-2 variants.

Evaluating medical capacity for hospitalization and intensive care unit of COVID-19: A queue model approach.

BACKGROUND: The surge of COVID-19 pandemic has caused severe respiratory conditions and a large number of deaths due to the shortage of intensive care unit (ICU) in many countries. METHODS: We developed a compartment queue model to describe the process from case confirmation, home-based isolation, hospitalization, ICU, recovery, and death. By using public assessed data in Lombardy, Italy, we estimated two congestion indices for isolation wards and ICU. The excess ICU needs were estimated in Lombardy, Italy, and other countries when data were available, including France, Spain, Belgium, New York State in the USA, South Korea, and Japan. RESULTS: In Lombardy, Italy, the congestion of isolation beds had increased from 2.2 to the peak of 6.0 in March and started to decline to 3.9 as of 9th May, whereas the demand for ICU during the same period has not decreased yet with an increasing trend from 2.9 to 8.0. The results showed the unmet ICU need from the second week in March as of 9th May. The same situation was shown in France, Spain, Belgium, and New York State, USA but not for South Korea and Japan. The results with data until December 2020 for Lombardy, Italy were also estimated to reflect the demand for hospitalization and ICU after the occurrence of viral variants. CONCLUSION: Two congestion indices for isolation wards and ICU beds using open assessed tabulated data with a compartment queue model underpinning were developed to monitor the clinical capacity in hospitals in response to the COVID-19 pandemic.

Multicenter evaluation of four immunoassays for the performance of early diagnosis of COVID-19 and assessment of antibody responses of patients with pneumonia in Taiwan.

BACKGROUND/PURPOSE: Our study goals were to evaluate the diagnostic performance of four anti-SARS-CoV-2 antibodies tests and the differences in dynamic immune responses between COVID-19 patients with and without pneumonia. METHODS: We collected 184 serum samples from 70 consecutively qRT-PCR-confirmed COVID-19 patients at four participating hospitals from 23 January 2020 to 30 September 2020. COVID-19 pneumonia was defined as the presence of new pulmonary infiltration. Serum samples were grouped by the duration after symptom onset on a weekly basis for antibody testing and analysis. The four immunoassays: Beckman SARS-CoV-2 IgG/IgM (Beckman Test), Siemens (ADVIA Centaur®) SARS-CoV-2 Total (COV2T) (Siemens Test), SBC COVID-19 IgG ELISA (SBC Test) and EliA SARS-CoV-2-Sp1 IgG/IgM/IgA P2 Research (EliA Test) were used for detecting the SARS-CoV-2 specific antibodies. RESULTS: The sensitivity of all tests reached 100% after 42 days of symptom onset. Siemens Test, the only test detecting total anti-SARS-CoV-2 antibodies, had the best performance in the early diagnosis of COVID-19 infection (day 0-7: 77%; day 8-14: 95%) compared to the other 3 serological tests. All tests showed 100% specificity except SBC Test (98%). COVID-19 patients with pneumonia had significantly higher testing signal values than patients without pneumonia (all p values < 0.05, except EliA IgM Test). However, Siemens Test and SBC Test had highest probability in early prediction of the presence of COVID-19 pneumonia. CONCLUSION: Chronological analysis of immune response among COVID-19 patients with different serological tests provides important information in the early diagnosis of SARS-CoV-2 infection and prediction of the risk of pneumonia after infection.

Increased antimicrobial resistance during the COVID-19 pandemic.

In addition to SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection itself, an increase in the incidence of antimicrobial resistance poses collateral damage to the current status of the COVID-19 (coronavirus disease 2019) pandemic. There has been a rapid increase in multidrug-resistant organisms (MDROs), including extended-spectrum ß-lactamase (ESBL)-producing Klebsiella pneumoniae, carbapenem-resistant New Delhi metallo-ß-lactamase (NDM)-producing Enterobacterales, Acinetobacter baumannii, methicillin-resistant Staphylococcus aureus (MRSA), pan-echinocandin-resistant Candida glabrata and multi-triazole-resistant Aspergillus fumigatus. The cause is multifactorial and is particularly related to high rates of antimicrobial agent utilisation in COVID-19 patients with a relatively low rate of co- or secondary infection. Appropriate prescription and optimised use of antimicrobials according to the principles of antimicrobial stewardship as well as quality diagnosis and aggressive infection control measures may help prevent the occurrence of MDROs during this pandemic.

The impact of the coronavirus disease 2019 epidemic on notifiable infectious diseases in Taiwan: A database analysis.

INTRODUCTION: The impact of the COVID-19 pandemic on the incidence of notifiable infectious diseases (NIDs) in Taiwan remains unclear. MATERIALS AND METHODS: The number of cases of NID (n = 42) between January and September 2019 and 2020 were obtained from the open database from Taiwan Centers for Disease Control. RESULTS: The number of NID cases was 21,895 between January and September 2020, which was lower than the number of cases during the same period in 2019 (n = 24,469), with a decline in incidence from 102.9 to 91.7 per 100,000 people in 2019 and 2020, respectively. Fourteen airborne/droplet, 11 fecal-oral, seven vector-borne, and four direct-contact transmitted NID had an overall reduction of 2700 (-28.1%), 156 (-23.0%), 557 (-54.8%), and 73 (-45.9%) cases, respectively, from 2019 to 2020. Similar trends were observed for the changes in incidence, which were 11.5 (-28.4%), 6.7 (-23.4%), 2.4 (-55.0%), and 0.3 (-46.2%) per 100,000 people for airborne/droplet, fecal-oral, vector-borne, and direct-contact transmitted NID, respectively. In addition, all the 38 imported NID showed a reduction of 632 (-73.5%) cases from 2019 to 2020. In contrast, 4 sexually transmitted diseases (STDs) showed an increase of 903 (+7.2%) cases from 2019 to 2020, which was attributed to the increase in gonorrhea (from 3220 to 5028). The overall incidence of STDs increased from 52.5 to 56.0 per 100,000 people, with a percentage change of +6.7%. CONCLUSION: This study demonstrated a collateral benefit of COVID-19 prevention measures for various infectious diseases, except STDs, in Taiwan, during the COVID-19 epidemic.

Multicenter evaluation of two chemiluminescence and three lateral flow immunoassays for the diagnosis of COVID-19 and assessment of antibody dynamic responses to SARS-CoV-2 in Taiwan.

This multicenter, retrospective study included 346 serum samples from 74 patients with coronavirus disease 2019 (COVID-19) and 194 serum samples from non-COVID-19 patients to evaluate the performance of five anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody tests, i.e. two chemiluminescence immunoassays (CLIAs): Roche Elecsys® Anti-SARS-CoV-2 Test (Roche Test) and Abbott SARS-CoV-2 IgG (Abbott Test), and three lateral flow immunoassays (LFIAs): Wondfo SARS-CoV-2 Antibody Test (Wondfo Test), ASK COVID-19 IgG/IgM Rapid Test (ASK Test), and Dynamiker 2019-nCoV IgG/IgM Rapid Test (Dynamiker Test). We found high diagnostic sensitivities (%, 95% confidence interval [CI]) for the Roche Test (97.4%, 93.4-99.0%), Abbott Test (94.0%, 89.1-96.8%), Wondfo Test (91.4%, 85.8-94.9%), ASK Test (97.4%, 93.4-99.0%), and Dynamiker Test (90.1%, 84.3-94.0%) after >21 days of symptom onset. Meanwhile, the diagnostic specificity was 99.0% (95% CI, 96.3-99.7%) for the Roche Test, 97.9% (95% CI, 94.8-99.2%) for the Abbott Test, and 100.0% (95% CI, 98.1-100.0%) for the three LFIAs. Cross-reactivity was observed in sera containing anti-cytomegalovirus (CMV) IgG/IgM antibodies and autoantibodies. No difference was observed in the time to seroconversion detection of the five serological tests. Specimens from patients with COVID-19 pneumonia demonstrated a shorter seroconversion time and higher chemiluminescent signal than those without pneumonia. Our data suggested that understanding the dynamic antibody response after COVID-19 infection and performance characteristics of different serological test are crucial for the appropriate interpretation of serological test result for the diagnosis and risk assessment of patient with COVID-19 infection.

Four point-of-care lateral flow immunoassays for diagnosis of COVID-19 and for assessing dynamics of antibody responses to SARS-CoV-2.

OBJECTIVES: We aimed to evaluate the role of rapid serological tests in the management of coronavirus disease 2019 (COVID-19) patients. METHODS: This retrospective study enrolled 16 real-time reverse transcription polymerase chain reaction-confirmed symptomatic patients with COVID-19 and 58 COVID-19 negative patients at a medical center in Taiwan over a 3-month period. Serial serum samples were collected and tested for antibody response using four point-of-care (POC) lateral flow immunoassays (LFIA) (ALLTEST 2019-nCoV IgG/IgM Rapid Test, Dynamiker 2019-nCoV IgG/IgM Rapid Test, ASK COVID-19 IgG/IgM Rapid Test, and Wondfo SARS-CoV-2 Antibody Test). Time-dependent detection sensitivity and timeliness of seroconversion were determined and compared between the four POC rapid tests. RESULTS: The overall sensitivity and specificity of the four tests for detecting anti-SARS-CoV-2 antibodies after 3 weeks of symptom onset were 100% and 100%, respectively. There was no significant difference between the rapid tests used for detection of IgM and IgG separately and those used for detection of combined total antibody (mainly IgM/IgG). There was no significant difference between the four POC rapid tests in terms of time required for determining seroconversion of COVID-19. Patients with COVID-19 with pneumonia demonstrated shorter seroconversion time than those without pneumonia. CONCLUSION: Though the POC antibody rapid tests based on LFIA showed reliable performance in the detection of SARS-CoV-2-specific antibodies, the results of these tests should be interpreted and applied appropriately in the context of antibody dynamic of COVID-19 infection. COVID-19 patients complicated with pneumonia exhibited earlier anti-SARS-CoV-2 antibody response than COVID-19 patients without pneumonia.

A Double Triage and Telemedicine Protocol to Optimize Infection Control in an Emergency Department in Taiwan During the COVID-19 Pandemic: Retrospective Feasibility Study.

BACKGROUND: Frontline health care workers, including physicians, are at high risk of contracting coronavirus disease (COVID-19) owing to their exposure to patients suspected of having COVID-19. OBJECTIVE: The aim of this study was to evaluate the benefits and feasibility of a double triage and telemedicine protocol in improving infection control in the emergency department (ED). METHODS: In this retrospective study, we recruited patients aged ≥20 years referred to the ED of the National Taiwan University Hospital between March 1 and April 30, 2020. A double triage and telemedicine protocol was developed to triage suggested COVID-19 cases and minimize health workers' exposure to this disease. We categorized patients attending video interviews into a telemedicine group and patients experiencing face-to-face interviews into a conventional group. A questionnaire was used to assess how patients perceived the quality of the interviews and their communication with physicians as well as perceptions of stress, discrimination, and privacy. Each question was evaluated using a 5-point Likert scale. Physicians' total exposure time and total evaluation time were treated as primary outcomes, and the mean scores of the questions were treated as secondary outcomes. RESULTS: The final sample included 198 patients, including 93 cases (47.0%) in the telemedicine group and 105 cases (53.0%) in the conventional group. The total exposure time in the telemedicine group was significantly shorter than that in the conventional group (4.7 minutes vs 8.9 minutes, P<.001), whereas the total evaluation time in the telemedicine group was significantly longer than that in the conventional group (12.2 minutes vs 8.9 minutes, P<.001). After controlling for potential confounders, the total exposure time in the telemedicine group was 4.6 minutes shorter than that in the conventional group (95% CI -5.7 to -3.5, P<.001), whereas the total evaluation time in the telemedicine group was 2.8 minutes longer than that in the conventional group (95% CI -1.6 to -4.0, P<.001). The mean scores of the patient questionnaire were high in both groups (4.5/5 to 4.7/5 points). CONCLUSIONS: The implementation of the double triage and telemedicine protocol in the ED during the COVID-19 pandemic has high potential to improve infection control.