Care Bundles to Improve Hemoperfusion Performance in Patients with Severe COVID-19: A Retrospective Study.

Background/Objectives: Hemoperfusion (HP) is employed to modulate cytokine storms in severe coronavirus disease 2019 (COVID-19) patients, requiring careful attention for success and safety. Therefore, we investigated whether our care bundles could enhance HP performance. Methods: We conducted a retrospective cohort study on adult patients (≥20 years old) with severe COVID-19 pneumonia. In the first wave (Phase I), we identified HP-related issues and addressed them with care bundles in the second wave (Phase II). The care bundles included early temperature control, precise hemodynamic monitoring, and clot prevention measures for the HP membrane. The HP success rate and associated adverse events (AEs) were assessed between the two phases. Results: The study included 60 HP (HA330) sessions from 27 cases (Phase I: 21 sessions from 9 cases; Phase II: 39 sessions from 18 cases). Patient characteristics and treatments for COVID-19 were similar, except for baseline body temperature (BT) and heart rate (HR). Phase II showed a higher success rate (67% vs. 89%, p = 0.19), although it did not reach statistical significance. Phase I recorded a significantly higher frequency of AEs (3 [IQR 1, 4] events/case vs. 1 [IQR 0, 2] events/case, p = 0.014). After implementing the care bundles, hypothermia significantly decreased (78% vs. 33%, p = 0.037), with an adjusted odds ratio of 0.15; 95% CI 0.02-0.95, p = 0.044 for baseline BT. Conclusions: Further exploration with a larger sample size is required to establish the advantages of care bundles. However, the bundles' implementation has significantly improved hypothermia prevention.

The National Early Warning Score 2 with Age and Body Mass Index (NEWS2 Plus) to Determine Patients with Severe COVID-19 Pneumonia.

(1) Background: Early identification of severe coronavirus disease 2019 (COVID-19) pneumonia at the initial phase of hospitalization is very crucial. To address this, we validated and updated the National Early Warning Score 2 (NEWS2) for this purpose. (2) Methods: We conducted a study on adult patients with COVID-19 infection in Chiang Mai, Thailand, between May 2021 and October 2021. (3) Results: From a total of 725 COVID-19 adult patients, 350 (48.3%) patients suffered severe COVID-19 pneumonia. In determining severe COVID-19 pneumonia, NEWS2 and NEWS2 + Age + BMI (NEWS2 Plus) showed the C-statistic values of 0.798 (95% CI, 0.767-0.830) and 0.821 (95% CI, 0.791-0.850), respectively. The C-statistic values of NEWS2 Plus were significantly improved compared to those of NEWS2 alone (p = 0.012). Utilizing a cut-off point of five, NEWS2 Plus exhibited better sensitivity and negative predictive value than the traditional NEWS2, with values of 99.7% vs. 83.7% and 98.9% vs. 80.7%, respectively. (4) Conclusions: The incorporation of age and BMI into the traditional NEWS2 score enhanced the efficacy of determining severe COVID-19 pneumonia. Physicians can rely on NEWS2 Plus (NEWS2 + Age + BMI) as a more effective decision-making tool for triaging COVID-19 patients during early hospitalization.

Accuracy of Cytologic vs Histologic Specimens for Assessment of Programmed Cell Death Ligand-1 Expression in Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Programmed cell death ligand-1 (PD-L1) expression on tumor cells, evaluated by immunohistochemistry, guides the use of immunotherapy in advanced non-small cell lung cancer (NSCLC). RESEARCH QUESTION: What is the sensitivity and specificity of PD-L1 testing performed in cytologic vs paired histologic specimens in patients with NSCLC? STUDY DESIGN AND METHODS: The MEDLINE, Embase, Web of Science, and Cochrane Library databases were searched through June 1, 2021. The primary outcome was pooled sensitivity and specificity of PD-L1 testing performed on cytologic specimens compared with the reference standard of histologic specimens, analyzed at the PD-L1 expression cutoffs (tumor proportion score) ≥ 1% and ≥ 50%. Pooled sensitivity and specificity, and associated 95% CIs, were estimated using bivariate generalized linear mixed models. RESULTS: Twenty-six articles were included, encompassing a total of 1,064 pairs of histology specimens and cytology cell blocks, and 267 pairs of histology specimens and direct smears. Among these, 946 paired specimens were acquired without interval treatment between the collection of histology and cytology samples. The pooled sensitivity and specificity of cytology specimens compared with paired histology specimens at the PD-L1 expression cutoff ≥ 1% were 0.84 (95% CI, 0.77-0.89) and 0.88 (95% CI, 0.82-0.93), respectively, whereas the pooled sensitivity and specificity at cutoff ≥ 50% were 0.78 (95% CI, 0.69-0.86) and 0.94 (95% CI, 0.91-0.96), respectively. When only paired specimens acquired without interval treatment were considered, the pooled sensitivity and specificity of cytology specimens at PD-L1 expression cutoff ≥ 1% were 0.84 (95% CI, 0.76-0.90) and 0.89 (95% CI, 0.82-0.94), respectively, whereas the pooled sensitivity and specificity at cutoff ≥ 50% were 0.80 (95% CI, 0.71-0.89) and 0.94 (95% CI, 0.91-0.96), respectively. INTERPRETATION: Cytologic specimens provide an accurate assessment of PD-L1 expression in most patients with NSCLC, at both ≥ 1% and ≥ 50% cutoffs, when compared with histologic specimens. TRIAL REGISTRATION: PROSPERO; No.: CRD42020153279; URL: https://www.crd.york.ac.uk/prospero/.

The long-term impact of COVID-19 pneumonia on pulmonary function and exercise capacity.

Background: The sequelae of post-coronavirus disease 2019 (COVID-19) have been widely reported. However, the time point of the follow-up time in the previous studies varied ranging from 3-24 months and the interval time of the follow-up time was too long (6 or 12 months). Thus, a shorter interval time during recovery for assessment of the sequelae of post COVID-19 on lung function and exercise capacity is still required. Therefore, this study aims to explore the long-term impact of COVID-19 pneumonia on pulmonary function and exercise capacity. Methods: A prospective observational study was conducted on post COVID-19 pneumonia at the Lung Health Center, Division of Pulmonary, Critical Care and Allergy, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand between May 2021 and April 2022. Spirometry, impulse oscillometry (IOS), and fractional exhaled nitric oxide (FeNO) were assessed at 1-, 6-, 9-, and 12-month post-hospital discharge when compared to healthy controls. The six-minute walk test (6-MWT) was also assessed. Results: Thirty-eight post COVID-19 pneumonia with ages 41.1±14.8 years (52.6% male) and twenty-five healthy controls were enrolled. The %predicted of forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1) were significantly lower in post COVID-19 pneumonia compared to healthy controls at month 1 and month 9. The improvement of %predicted FVC and FEV1 was observed in post COVID-19 pneumonia. The six-minute walk distance (6-MWD) was significantly lower in post COVID-19 pneumonia compared to healthy controls in all visits, while the 6-MWD improved overtime in post COVID-19 pneumonia. Conclusions: The long term sequelae of post COVID-19 pneumonia on lung function and exercise capacity were observed. Pulmonary function tests and six-minutes walk test are useful tools for detection of long term sequelae of post COVID-19 pneumonia.

Neutralizing antibody and T-cell responses against SARS-CoV-2 variants by heterologous CoronaVac/ChAdOx-1 vaccination in elderly subjects with chronic obstructive pulmonary disease.

BACKGROUND: Data on humoral and cellular immune responses against SARS-CoV-2 after receiving heterologous CoronaVac/ChAdOx-1 (CoVac/ChAd) vaccination in subjects with chronic obstructive pulmonary disease (COPD) are still limited. Therefore, we determined the neutralizing antibody (NAb) and T-cell responses against SARS-CoV-2 wild type (WT) and variants of concern (VOCs) in COPD patients. METHODS: The levels of NAb as well as specific CD4 and CD8 T-cell responses against SARS-CoV-2 WT and VOCs were determined in COPD patients before and after vaccination. RESULTS: Four weeks after vaccinations, the median levels of % inhibition of NAb against SARS-CoV-2 WT, Alpha, Beta, and Delta variants were significantly higher compared to pre-vaccination. The induction of NAb against Omicron was very low compared to other variants. At four weeks after vaccination, in comparison to pre-vaccination, the increasing trend of TNF-α-, IFN-γ-, IL-4-, IL-17-, IL-10-, and FasL-producing CD4 T-cells upon stimulation with WT spike peptides were demonstrated. No difference in T-cell responses to spike peptides of Alpha, Beta, and Delta variants and their WT homologs was observed. CONCLUSION: Heterologous CoVac/ChAd vaccine induced the production of NAb against SARS-CoV-2 WT, Alpha, Beta, and Delta variants, but low for Omicron in COPD patients. Induction of CD4 T-cell subset responses was slightly observed by this vaccine regimen. CLINICAL TRIALS REGISTRY: This study was approved by the Clinical Trials Registry (Study ID: TCTR20210822002).

Reduction of Chest Drain Overuse Through Implementation of a Pleural Drainage Order Set.

BACKGROUND AND OBJECTIVES: Small chest drains are used in many centers as the default drainage strategy for various pleural effusions. This can lead to drain overuse, which may be harmful. This study aimed to reduce chest drain overuse. METHODS: We studied consecutive pleural procedures performed in the radiology department before (August 1, 2015, to July 31, 2016) and after intervention (September 1, 2019, to January 31, 2020). Chest drains were deemed indicated or not based on criteria established by a local interdisciplinary work group. The intervention consisted of a pleural drainage order set embedded in electronic medical records. It included indications for chest drain insertion, prespecified drain sizes for each indication, fluid analyses, and postprocedure radiography orders. Overall chest drain use and proportion of nonindicated drains were the outcomes of interest. RESULTS: We reviewed a total of 288 procedures (pre-intervention) and 155 procedures (post-intervention) (thoracentesis and drains). Order-set implementation led to a reduction in drain use (86.5% vs 54.8% of all procedures, P < .001) and reduction in drain insertions in the absence of an indication (from 45.4% to 29.4% of drains, P = .01). The need for repeat procedures did not increase after order-set implementation (22.0% pre vs 17.7% post, P = .40). Complication rates and length of hospital stay did not differ significantly after the intervention. More pleural infections were treated with drain sizes of 12Fr and greater (31 vs 70%, P < .001) after order-set deployment, and direct procedural costs were reduced by 27 CAN$ per procedure. CONCLUSION: Implementation of a pleural drainage order-set reduced chest drain use, improved procedure selection according to clinical needs, and reduced direct procedural costs. In institutions where small chest drains are used as the default drainage strategy for pleural effusions, this order set can reduce chest drain overuse.

Long-Term Impacts of COVID-19 Pneumonia on Quality of Life: A Single Institutional Pilot Study.

Many studies have demonstrated poor quality of life (QoL) at 3, 6, 12, and 24 months after coronavirus disease 2019 (COVID-19). However, these studies were limited due to cross-sectional design, a longer gap between visits, and lack of controls for comparison. Therefore, the aim of our prospective study was to assess the impact of COVID-19 pneumonia on QoL in both physical and mental health. A prospective study was conducted on adult patients with COVID-19 pneumonia. We used the 36-Item Short Form Health Survey (SF-36) and Euro Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L), EQ visual analogue scale (EQ-VAS), and Hospital Anxiety and Depression Scale to collect data at months, 1, 3, 6, 9, and 12. Thirty-eight patients with COVID-19 pneumonia and twenty-five healthy subjects were completely followed up on all visits. All domains of SF-36, except bodily pain and EQ-5D-5L of the patients, were lower than controls. There was an improvement of EQ-VAS and SF-36 including physical functioning, social functioning, and role limitation (physical problems) domains throughout study period in the COVID-19 pneumonia group. Adult patients who recovered from COVID-19 pneumonia had lower QoL which improved over the one-year follow-up period.

Levels and durability of neutralizing antibodies against SARS-CoV-2 Omicron and other variants after ChAdOx-1 or BNT162b2 booster in CoronaVac-primed elderly individuals.

The outbreak of the SARS-CoV-2 Omicron variant raised the need for vaccine boosting. We evaluated the efficiency of the third booster vaccine, ChAdOx-1 or BNT162b2, in causing a neutralizing antibody (NAb) response and its durability against the Omicron and other variants in elderly individuals previously vaccinated with 2-dose CoronaVac inactivated vaccine. After receiving 2-dose CoronaVac, only 2.2% of subjects had NAbs against the Omicron variant above the cut-off value. Four weeks after boosting, the number of subjects who had NAb levels above the cut-off values in the ChAdOx-1 and BNT162b2 vaccine boosting groups increased to 41.7% and 54.5%, respectively. However, after 12 and 24 weeks of boosting with any vaccines, NAb levels against the Omicron variant dramatically waned. Twenty-four weeks after boosting, only 2% had high levels of NAbs against the Omicron variant. Compared to other variants, the Omicron variant was less responsive to boosting vaccines. The waning rate of NAb levels for the Omicron variant was much faster than that observed in the Alpha, Beta and Delta variants. To combat the Omicron variant, the fourth booster dose is, therefore, recommended for elderly individuals.

Validation of the Pulmonary Embolism Severity Index Risk Classification and the 2019 European Society of Cardiology Risk Stratification in the Southeast Asian Population with Acute Pulmonary Embolism.

AIM: To date, no studies representing the Southeast Asian population have validated the Pulmonary Embolism Severity Index (PESI) and 2019 European Society of Cardiology (ESC) risk stratification. Therefore, this study aimed to validate the PESI score, simplified PESI (sPESI), PESI risk classification, and 2019 ESC risk stratification in Southeast Asian patients with acute pulmonary embolism (APE). METHODS: The present study is a 10-year cross-sectional study. Here, risk regressions were conducted to identify the PESI risk classification, sPESI, and 2019 ESC risk stratification as predictors for 30-day all-cause and PE-related mortalities. Receiver operating characteristic (ROC) curves were constructed to determine the diagnostic ability of the PESI score, sPESI score, PESI risk classification, and 2019 ESC risk stratification to predict 30-day mortality. RESULTS: A total of 696 patients (male, 286; female, 410; mean age, 57.7±15.7 years) were included in this study from 2011 to 2020. The risk of 30-day all-cause mortality progressively increased with the 2019 ESC risk stratification, being approximately 6-fold higher in the high-risk than in the low-risk class [risk ratio: 6.24 (95% confidence interval (CI), 3.12, 12.47), P＜0.001]. The risk of 30-day all-cause mortality with the PESI risk classification also increased with the risk classes, being approximately 6-fold higher in class V than in class I [adjusted risk ratio: 5.91 (95% CI, 2.25, 15.51), P＜0.001]. The highest area under the receiver operating characteristic curve (AuROC) of the predictive model was the PESI score [AuROC=0.733 (95% CI, 0.685, 0.782)]. CONCLUSION: Our study represents a good validation of the PESI and 2019 ESC risk stratification to predict 30-day mortality after APE diagnosis in the Southeast Asian population.

Predictive Ability of the National Early Warning Score in Mortality Prediction of Acute Pulmonary Embolism in the Southeast Asian Population.

BACKGROUND: The National Early Warning Scores (NEWS) easily and objectively measures acute clinical deterioration. However, the performance of NEWS to predict mortality in patients with acute pulmonary embolism (APE) is still required. Therefore, the objective of this study was to evaluate the performance of the NEWS in predicting the mortality of patients with APE. METHODS: NEWS and Pulmonary Embolism Severity Index (PESI) at diagnosis time were calculated. Risk regression analysis was performed to identify the NEWS and PESI risk classification as a predictor for 30 days all-cause mortality and PE-related mortality. RESULTS: NEWS was significantly higher in non-survivors compared to survivors (median (IQR) was 10 (7, 11) vs. 7 (2, 9), respectively, p < 0.001). The best cut-off point of NEWS in discriminating APE patients who non-survived from those who survived at 30 days was ≥9, with a sensitivity and specificity of 66.9% and 66.3%, respectively. The adjusted risk ratio of 30-day all-cause mortality in patients with initial NEWS ≥ 9 was 2.96 (95% CI; 2.13, 4.12, p < 0.001). CONCLUSIONS: The NEWS can be used for mortality prediction in patients with APE. APE patients with NEWS ≥ 9 are associated with a high risk of mortality and should be closely monitored.

The National Early Warning Score 2(NEWS2) to Predict Early Progression to Severe Community-Acquired Pneumonia.

This study aimed to assess the predictive performance of the National Early Warning Score 2 (NEWS2) to identify the early progression to severe disease in patients with community-acquired pneumonia (CAP). A prospective-cohort study was conducted among patients with CAP admitted to a university hospital between October 2020 and December 2021. The endpoint of interest was the progression to severe CAP, defined as the requirement for a mechanical ventilator, a vasopressor, or death within 72 h after hospital admission. Among 260 patients, 53 (25.6%) had early progression to severe CAP. The median NEWS2 of the early progression group was higher than that of the non-progression group [8 (6-9) vs. 7 (5-8), p = 0.015, respectively]. The AUROC of NEWS2 to predict early progression to severe CAP was 0.61 (95% CI: 0.52-0.70), while IDSA/ATS minor criteria ≥ 3 had AUROC 0.56 (95% CI 0.48-0.65). The combination of NEWS2 ≥ 8, albumin level < 3 g/dL and BUN ≥ 30 mg/dL improved AUROC from 0.61 to 0.71 (p = 0.015). NEWS2 and IDSA/ATS minor criteria showed fair predictive-accuracy in predicting progression to severe CAP. The NEWS2 cut-off ≥ 8 in combination with low albumin and uremia improved predictive-accuracy, and could be easily used in general practice.

Humoral and cellular immune responses against SARS-CoV-2 variants of concern induced by heterologous CoronaVac/ChAdOx-1 versus homologous ChAdOx-1 vaccination in the elderly.

BACKGROUND: The concept of heterologous vaccination against SARS-CoV-2 infection has been adopted in Thailand with limited data on the induction of humoral and cellular immunity, particularly the CoronaVac/ChAdOx-1 (CoVac/ChAd) regimen in the elderly. OBJECTIVE: In this study, the immune responses of the elderly induced by heterologous CoVac/ChAd and homologous ChAdOx-1 (ChAd/ChAd) vaccinations were demonstrated. METHODS: A prospective observational study involving healthy participants aged ≥ 60 years who received heterologous CoVac/ChAd or homologous ChAd/ChAd vaccination was conducted. Surrogate neutralizing antibody (NAb) and T-cell responses against the SARS-CoV-2 wild type (WT) and variants of concern were determined at pre and post vaccinations. RESULTS: At 4 and 12 weeks after heterologous or homologous vaccination, the NAb levels against WT, Alpha, Beta, and Delta variants between each group were not significantly different, except for significant lower NAb against the Beta variant in heterologous group at 12 weeks after vaccination. The NAb against the Omicron at 4 weeks post-vaccination were below the cutoff level for antibody detection in both groups. However, higher spike-specific CD4 T cell producing IFN-γ and TNF-α in the heterologous than the homologous vaccination were observed. Insignificant difference of cellular immune responses to spike-peptides of Alpha, Beta, and Delta variants and their WT homologues was demonstrated. CONCLUSIONS: In the elderly, heterologous CoVac/ChAd vaccination could induce NAb response against the WT and non-Omicron variants not different from the homologous ChAd/ChAd vaccination. Both regimens could not give adequate NAb of the Omicron strain. The heterologous vaccination, however, induced higher spike-specific Th1 cell response.

Clinical Characteristics, Risk Factors, and Outcomes of Acute Pulmonary Embolism in Asian Population.

BACKGROUND: Acute pulmonary embolism (APE) is a common condition with increasing worldwide incidence. However, the clinical characteristics, risk factors, and clinical outcomes of APE in the Asian population especially in the Thai population are still limited. Therefore, the objective of this study was to identify the clinical characteristics, risk factors, and clinical outcomes of APE in the Asian population. METHODS: A cross-sectional study was conducted on patients diagnosed with APE at Chiang Mai University Hospital, Thailand during 2011-2020. RESULTS: During the study period, 696 patients confirmed the diagnosis of APE with a mean age of 57.7 ± 15.7 years and 41.1% males. APE was suspected in 468 of 696 patients (67.2%), while 228 patients (32.8%) had incidental PE. Active malignancy during treatment was found in 388 (55.7%). Dyspnea, cough, and chest pain were the most common presenting symptoms. Respiratory failure was found in 129 patients (18.6%). The thirty-day all-cause mortality rate was 19.1%. PE-related mortality was 5.6%. Most PE-related mortality was high-risk PE. CONCLUSION: APE was not uncommon in the Asian population. Active cancer, especially lung cancer was the most common risk factors. High-risk and intermediate-high-risk PE were associated with high mortality. Risk stratification and prompt management are warranted to improve outcomes.

Neutralizing Antibody and T-Cell Responses against SARS-CoV-2 Wild-Type and Variants of Concern in Chronic Obstructive Pulmonary Disease Subjects after ChAdOx-1/ChAdOx-1 Homologous Vaccination: A Preliminary Study.

Data on immunogenicity of adenovirus-vectored vaccine in chronic obstructive pulmonary disease (COPD) patients is limited. Therefore, we aimed to determine the humoral and cellular immune responses after homologous ChAdOx-1 vaccination in subjects with COPD. COPD subjects and age- and sex-matched healthy elderly receiving ChAdOx-1 homologous vaccination were included. The levels of neutralizing antibodies (NAb) and specific CD4 and CD8 T-cell responses against SARS-CoV-2 wild-type (WT) and variants of concern (VOCs: Alpha, Beta, Delta, and Omicron) were measured. Eight COPD patients were matched with eight control participants. After vaccination for 4 and 12 weeks, % inhibition of NAb against Alpha, Beta, and Delta in both groups were comparable and significantly higher than baseline. The percentage inhibition of NAb at the 12th week was significantly dropped from the 4th week in each group. The NAb against the Omicron variant, however, were much lower than Alpha, Beta, Delta variants. The increasing trend in the number of CD4 T-cells producing TNF-α, IFN-γ, IL-10, and FasL upon stimulation with spike peptides of WT and VOCs was observed in COPD patients compared to the healthy group. These responses were not observed in CD8 T-cells. Homologous ChAdOx-1 vaccination could induce comparable NAb against the SARS-CoV-2 WT, Alpha, Beta, Delta, and Omicron variants between COPD and healthy elderly. The CD4 T-cell responses did not differ between COPD patients and healthy control.

Correlation of Air Pollution and Prevalence of Acute Pulmonary Embolism in Northern Thailand.

BACKGROUND: The relationship between the level of air pollution and acute pulmonary embolism (APE) has had inconsistent results. OBJECTIVE: This study aimed to analyze the relationship between the high level of air pollution exposure and APE. METHODS: A ten-year retrospective cohort, single-center study was performed on patients diagnosed with APE from October 2010 to December 2020. The association between air pollution and monthly APE case diagnosis was analyzed. RESULTS: A total number of 696 patients was included. The effect of every 10 µg/m3 increment of particulate matters with an aerodynamic diameter < 10 µm (PM10) on total monthly APE cases (unprovoked PE and provoked PE) was increased significantly at lag 4, 5 and 6 months with adjusted RR (95% CI) of 1.06 (1.01, 1.12), p = 0.011, 1.07 (1.01, 1.13), p = 0.021 and 1.06 (1.01, 1.12), p = 0.030, respectively. Adjusted RR for APE was significantly increased for PM10 in the second tertile ((adjusted RR (95% CI) 1.76 (1.12, 2.77)), p = 0.014. CONCLUSIONS: We conclude that PM10 is associated with an increased prevalence of APE cases. The policy for tighter control of air pollution in our country is needed to reduce the impact of air pollutants on people's health.

Bradycardia and Heart Rate Fluctuation Are Associated with a Prolonged Intensive Care Unit Stay in Patients with Severe COVID-19.

Background and Objective: Bradycardia has been observed among patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is suspected to be associated with poorer outcomes. Heart rate (HR) fluctuation has been found to be correlated with a greater mortality rate in critically ill patients. The association of bradycardia and HR fluctuation with the outcome of severe coronavirus disease 2019 (COVID-19) patients has not been clarified. Therefore, we aimed to examine whether bradycardia and HR fluctuation correlated with poor outcomes in patients with severe COVID-19. Materials and Methods: We conducted a secondary analysis from a prospective data collection of patients admitted to the intensive care unit, between April and June 2021, at Chiang Mai University Hospital. Results: The results showed that 62 of 86 patients (72.1%) had bradycardia, defined by HR < 60 beats per minute (bpm). The number of patients with high HR fluctuation, defined as the difference in HR during admission ≥ 40 bpm, was greater among the bradycardia group than in the non-bradycardia group (70.9% vs. 14.7%, p = 0.015, respectively). The patients with bradycardia had greater levels of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). In addition, a greater proportion of patients with bradycardia received interleukin-6 inhibitors and hemoperfusion as a rescue therapy than those with non-bradycardia. After adjusting for age, gender, body mass index, CRP, and mechanical ventilator; bradycardia and the high HR fluctuation were significantly associated with a longer length of stay in the intensive care unit (ICU-LOS), with adjusted risk ratios of 2.67, 95% CI; 1.02, 6.94, p = 0.045 and 2.88, 95% CI; 1.22, 6.78, p = 0.016, respectively. Conclusion: We found that bradycardia and a high heart rate fluctuation were associated with a poorer ICU outcome in terms of longer ICU-LOS among the patients with severe COVID-19.

Correlation Analysis of Anti-SARS-CoV-2 RBD IgG and Neutralizing Antibody against SARS-CoV-2 Omicron Variants after Vaccination.

Various vaccines have been developed to control the COVID-19 pandemic, but the available vaccines were developed using ancestral SARS-CoV-2 wild-type (WT) strains. Commercial anti-SARS-CoV-2 receptor binding domain (RBD) antibody assays have been established and employed for validation of vaccine efficacy. However, these assays were developed before the SARS-CoV-2 variants of concern (VOCs) emerged. It is unclear whether anti-RBD IgG levels can predict immunity against VOCs. In this study, we determined the correlations between the levels of anti-RBD IgG and neutralizing antibodies (NAbs) against SARS-CoV-2 variants in vaccinated subjects. After vaccination, 100% of subjects showed an anti-RBD IgG response, whereas 82, 79, 30, 75, and 2% showed NAb responses against WT, Alpha, Beta, Delta, and Omicron variants, respectively. A high correlation was observed between anti-RBD IgG and NAbs against WT, Alpha, Beta, and Delta, but not so for the Omicron NAbs. Among subjects with high levels of anti-RBD IgG, 93, 93, 71, 93, and 0% of them had NAbs against WT, Alpha, Beta, Delta, and Omicron variants, respectively. These results indicate that anti-RBD IgG levels cannot be used as a predictor for the presence of NAbs against the globally dominant SARS-CoV-2 Omicron variant.

Neutralizing antibody and T cell responses against SARS-CoV-2 variants of concern following ChAdOx-1 or BNT162b2 boosting in the elderly previously immunized with CoronaVac vaccine.

BACKGROUND: The existence of SARS-CoV-2 variants of concern (VOCs) in association with evidence of breakthrough infections despite vaccination resulted in the need for vaccine boosting. In elderly individuals, information on the immunogenicity of booster vaccinations is limited. In countries where the CoronaVac inactivated vaccine is the primary vaccine, the appropriate boosting regimen is not clear. Immunologic studies of the effects of booster vaccination against VOCs, particularly Delta and Omicron, following CoronaVac in elderly individuals are helpful for policy makers. In this study, we determined the immune responses against VOCs following ChAdOx-1 or BNT162b2 boosting in elderly individuals previously immunized with CoronaVac. RESULTS: Before boosting, the median % inhibition of neutralizing antibodies (NAbs) against the wild-type (WT), Alpha, Beta, Delta and Omicron variants in the ChAdOx-1 and BNT162b2 groups was 52.8% vs. 53.4, 36.6% vs. 39.9, 5.2% vs. 13.7, 34.3% vs. 44.9, and 20.8% vs. 18.8%, respectively. After boosting with ChAdOx-1 or BNT162b2, the % inhibition of NAbs were increased to 97.3% vs. 97.4, 94.3% vs. 97.3%, 79.9 vs. 93.7, 95.5% vs. 97.5, and 26.9% vs. 31.9% for WT, Alpha, Beta, Delta and Omicron variants, respectively. Boosting with BNT162b2 induced significantly higher NAb levels than boosting with ChAdOx-1 against the Alpha, Beta and Delta variants but not the WT and Omicron variants. NAb levels against Omicron variant were not significantly different before and after boosting with ChAdOx-1 or BNT162b2. To evaluate T-cell responses, S peptides of the WT, Alpha, Beta and Delta variants were used to stimulate T cells. Upon stimulation, the expression of IL-17A in CD8 T cells was higher in the BNT162b2 group than in the ChAdOx-1 boosting group. However, IFN-γ production in CD4 and CD8 T cells did not significantly differ under all vaccination regimens. The expression of FasL in CD4 T cells, but not CD8 T cells, was higher in the BNT162b2-boosted group. CONCLUSION: Boosting with either ChAdOx-1 or BNT162b2 in CoronaVac-primed healthy elderly individuals induced high NAb production against all examined VOCs except Omicron. BNT162b2 stimulated higher NAb and some T-cell responses than ChAdOx-1. Vaccine boosting is, therefore, recommended for elderly individuals previously immunized with CoronaVac.

Comparative Study of Early Impacts of Post-COVID-19 Pneumonia on Clinical Manifestations, Pulmonary Function, and Chest Radiographs.

Background and Objectives: Scant data regarding early post-COVID-19 effects are available, especially in younger people. Therefore, the objective of this study was to explore the early clinical impacts of post-COVID-19 pneumonia, comparing severe and non-severe patients. Materials and Methods: A cross-sectional study was conducted in adult patients admitted with COVID-19 pneumonia from April to May 2021. Demographic data, symptoms and signs, quality of life, Hospital Anxiety and Depression Scale (HADS), chest radiograph (CXR), pulmonary function tests (spirometry, impulse oscillometry), fractional exhaled nitric oxide (FeNO), and exercise capacity were assessed one month after hospital discharge. Twenty-five healthy control subjects that were age- and gender-matched were recruited for comparisons. Results: One hundred and five patients, with a mean age of 35.6 ± 15.8 years and 54 (51.4%) males, participated and were categorized into the non-severe pneumonia (N = 68) and severe pneumonia groups (N = 37). At a one-month follow-up visit (the time from the onset of the disease symptoms = 45.4 ± 5.9 days), the severe group had more cough, fatigue, and skin rash with higher dyspnea scale, more residual CXR lesions, and lower quality of life scores. Forced vital capacity (FVC) was lower in the severe group (88.3% of predicted value) and non-severe group (94.6% of predicted value) than in the healthy controls (p = 0.001). The six-minute walk distance was significantly lower in the non-severe group, at 79.2 m, and in the severe group, at 103.8 m, than in the healthy control subjects (p < 0.001). Conclusions: Adult patients with COVID-19, especially those with clinically severe pneumonia, still had residual symptoms and chest radiographic abnormalities, together with poorer quality of life and lower exercise capacity, one month after hospital discharge.