Critical Coronavirus Disease 2019 Research Articles

[COVID-19 in patients with Good syndrome: report of 4 cases and literature review].

Objective: To summarize the clinical characteristics of coronavirus disease 2019 (COVID-19) in patients with Good's syndrome. Methods: We included all cases of COVID-19 in patients with Good's syndrome in the Second Xiangya Hospital of Central South University from January 1, 2023 to August 31, 2023. In addition to our cases, we searched the published literature in Wanfang database and PubMed database using the keywords "Good's syndrome" and "COVID-19". The clinical characteristics, treatment and outcome of the patients were summarized and analyzed. Results: A total of four patients with Good's syndrome complicated by COVID-19 were identified in our hospital, all of them were male, and the days of hospitalization were 17, 23, 7, and 13 days, respectively. Databases were searched for a total of six patients with Good's syndrome complicated by COVID-19, including three females and three males, all foreign patients, with hospitalization days of 12, 22, 13, 25, 21, and 34 days respectively. All ten patients met the diagnostic criteria for severe or critical COVID-19, and three(all middle-aged males) of them died, two from sepsis and one from respiratory failure. They were. Conclusion: COVID-19 in patients with Good's syndrome are prone to develop severe or critical disease and are more likely to be infected with multiple pathogens. Timely immunoglobulin supplementation is the key to treatment.

Prediction of COVID-19 Severity at Delivery after Asymptomatic or Mild COVID-19 during Pregnancy.

This study aimed to develop a prediction model that estimates the probability that a pregnant person who has had asymptomatic or mild coronavirus disease 2019 (COVID-19) prior to delivery admission will progress in severity to moderate, severe, or critical COVID-19. This was a secondary analysis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive patients who delivered from March through December 2020 at hospitals across the United States. Those eligible for this analysis presented for delivery with a current or previous asymptomatic or mild SARS-CoV-2 infection. The primary outcome was moderate, severe, or critical COVID-19 during the delivery admission through 42 days postpartum. The prediction model was developed and internally validated using stratified cross-validation with stepwise backward elimination, incorporating only variables that were known on the day of hospital admission. Of the 2,818 patients included, 26 (0.9%; 95% confidence interval [CI], 0.6-1.3%) developed moderate-severe-critical COVID-19 during the study period. Variables in the prediction model were gestational age at delivery admission (adjusted odds ratio [aOR], 1.15; 95% CI, 1.08-1.22 per 1-week decrease), a hypertensive disorder in a prior pregnancy (aOR 3.05; 95% CI, 1.25-7.46), and systolic blood pressure at admission (aOR, 1.04; 95% CI, 1.02-1.05 per mm Hg increase). This model yielded an area under the receiver operating characteristic curve of 0.82 (95% CI, 0.72-0.91). Among individuals presenting for delivery who had asymptomatic-mild COVID-19, gestational age at delivery admission, a hypertensive disorder in a prior pregnancy, and systolic blood pressure at admission were predictive of delivering with moderate, severe, or critical COVID-19. This prediction model may be a useful tool to optimize resources for SARS-CoV-2-infected pregnant individuals admitted for delivery. · Three factors were associated with delivery with more severe COVID-19.. · The developed model yielded an area under the receiver operating characteristic curve of 0.82 and model fit was good.. · The model may be useful tool for SARS-CoV-2 infected pregnancies admitted for delivery..

Suppression of Type I Interferon Signaling in Myeloid Cells by Autoantibodies in Severe COVID-19 Patients.

Auto-antibodies (auto-abs) to type I interferons (IFNs) have been identified in patients with life-threatening coronavirus disease 2019 (COVID-19), suggesting that the presence of auto-abs may be a risk factor for disease severity. We therefore investigated the mechanism underlying COVID-19 exacerbation induced by auto-abs to type I IFNs. We evaluated plasma from 123 patients with COVID-19 to measure auto-abs to type I IFNs. We performed single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells from the patients with auto-abs and conducted epitope mapping of the auto-abs. Three of 19 severe and 4 of 42 critical COVID-19 patients had neutralizing auto-abs to type I IFNs. Patients with auto-abs to type I IFNs showed no characteristic clinical features. scRNA-seq from 38 patients with COVID-19 revealed that IFN signaling in conventional dendritic cells and canonical monocytes was attenuated, and SARS-CoV-2-specific BCR repertoires were decreased in patients with auto-abs. Furthermore, auto-abs to IFN-α2 from COVID-19 patients with auto-abs recognized characteristic epitopes of IFN-α2, which binds to the receptor. Auto-abs to type I IFN found in COVID-19 patients inhibited IFN signaling in dendritic cells and monocytes by blocking the binding of type I IFN to its receptor. The failure to properly induce production of an antibody to SARS-CoV-2 may be a causative factor of COVID-19 severity.

Prevalence of Diabetes, Ketosis, and Ketoacidosis and Their Correlation With Mortality in Critical COVID-19 Patients: A Single-Center Retrospective Study.

Aim We aimed to find out the prevalence of diabetes, ketosis, and ketoacidosis in coronavirus disease 2019 (COVID-19) critically ill patients and to explore the clinical impact of the development of ketosis and ketoacidosis on the outcome of COVID-19 critically ill patients and identify them as potential risk factors for these patients. Methods We collected data on COVID-19 patients admitted to the intensive care unit (ICU) retrospectively. The study population will be classified into two groups based on the presence of diabetes or ketosis. Results The study comprises data on 253 ICU patients admitted with COVID-19 pneumonia. Two hundred patients (79.05%) had diabetes or prediabetes on admission. Seventy-six patients (30%) presented with ketosis. Nine patients had progressed to diabetic ketoacidosis during their ICU stay. Concerning the outcome, among 150 patients who died (59.3%), there was significantly higher mortality among the ketotic patients (69.7%) compared to nonketotic patients (54.8%) with a P-value < 0.027. We noted that the peak blood glucose level during ICU stay was statistically significantly higher in nonsurvivors (mean 345 mg/dl) compared to survivors (mean 298 mg/dl) with a P-value of 0.006. Our data showed that peak serum levels of lactate, procalcitonin (PCT), C-reactive protein, white blood cells (WBC), D dimer, and lactate dehydrogenase strongly positively correlated to the length of ICU stay. We used the ROC curve (receiver operating characteristic curve) to assess the relation between many laboratories and mortality. We noted that uncontrolled hyperglycemia and other laboratory variables are significant predictors of mortality of COVID-19 patients (e.g., peak blood glucose (P = 0.004), PCT (P = 0.047), and P < 0.001 of other laboratories (e.g. lactate, PH, WBC, D dimer, ferritin). Conclusion We reported a high prevalence of diabetes and ketosis among COVID-19 patients admitted to the ICU. Ketosis is associated with an increased mortality risk. Uncontrolled hyperglycemia is a significant predictor of mortality in critically ill COVID-19 patients.

[Analysis of the factors influencing the severity of coronavirus disease 2019 in patients with myeloproliferative neoplasms based on an online questionnaire].

Objective: To explore the variables associated with the severity of coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 omicron variant during the epidemic in patients with myeloproliferative neoplasms (MPN). Methods: A cross-sectional study. During the SARS-CoV-2 omicron variant pandemic from December 15, 2022, to March 15, 2023, COVID-19 related data for patients with MPN who were treated at Peking University People's Hospital were collected through an online questionnaire-based survey. All questionnaires and clinical data were checked by medical assistants. Logistic multivariate analysis was used to explore the prevalence and variables associated with the severity of COVID-19 in patients with MPN. Results: A total of 239 patients with MPN, including 90 (37.7%) presenting with essential thrombocythemia (ET), 50 (20.9%) with polycythemia vera (PV), and 99 (41.4%) with myelofibrosis (MF), were enrolled in the study. The 99 patients with MF included 87 (87.9%) with primary MF, 5 (5.1%) with post-PV MF, and 7 (7.1%) with post-ET MF. Overall, 239 (100%) patients reported that they experienced COVID-19 during the pandemic. Of these, 226 (94.6%) had mild disease, 4 (1.7%) had moderate disease, 7 (2.9%) had severe disease, and 2 (0.8%) had critical disease. Two (0.8%) patients with severe COVID-19 died, one of which suffered from MT and the other from PV. Multivariate analysis showed that older age (OR=2.36, 95%CI 1.24-4.49), MF (OR=10.22, 95%CI 1.13-92.80), or comorbidity (OR=5.25, 95%CI 1.25-22.03) were associated with a significantly higher risk of developing moderate, severe, or critical COVID-19. Among patients with MF, higher risk stratification reflected an increased risk of developing moderate, severe, or critical COVID-19 (P=0.034). Conclusion: During the omicron pandemic, older age, MF (especially higher-risk categories), and comorbidity were associated with a higher risk of developing moderate, severe, or critical COVID-19.

Delayed Antibody Response in the Acute Phase of Infection Is Associated with a Lower Mental Component of Quality of Life in Survivors of Severe and Critical COVID-19.

Background: The long-term sequelae of coronavirus disease 2019 (COVID-19) significantly affects quality of life (QoL) in disease survivors. Delayed development of the adaptive immune response is associated with more severe disease and a worse prognosis in COVID-19. The effects of delayed immune response on COVID-19 sequelae and QoL are unknown. Methods: We conducted a prospective study to assess the relationship between the delayed antibody response in the acute phase of infection in naïve unvaccinated patients suffering from severe or critical COVID-19 and their QoL 12 months after hospital discharge. The 12-item Short Form Survey (SF-12) questionnaire was used for assessment of QoL. The SF-12 evaluates both mental and physical components of QoL, incorporating a mental component score (MCS-12) and a physical component score (PCS-12). A delayed antibody response was defined as testing negative for anti-spike SARS-CoV-2 antibodies at the time of hospital admission. Results: The study included 274 patients (154 men and 120 women). Of the enrolled patients, 144 had a delayed immune response. These patients had a significantly lower MCS-12 (p = 0.002), but PCS-12 (p = 0.397) was not significantly different at the 12-month follow-up compared to patients with positive anti-spike SARS-CoV-2 antibodies. The MCS-12 at the time of follow-up was negatively associated with delayed antibody response irrespective of possible confounders (p = 0.006; B = 3.609; ηp2 = 0.035; 95% CI = 1.069-6.150). An MSC-12 below 50 points at the time of follow-up was positively associated with delayed antibody response (p = 0.001; B = 1.092; OR = 2.979; 95% CI = 1.554-5.711). Conclusions: This study confirmed that, in patients with severe and critical COVID-19, a negative result for anti-spike SARS-CoV-2 antibodies at the time of hospital admission is associated with a lower mental component of QoL in unvaccinated patients naïve to COVID-19 one year after hospital discharge.

A generalizable and easy-to-use COVID-19 stratification model for the next pandemic via immune-phenotyping and machine learning.

The coronavirus disease 2019 (COVID-19) pandemic has affected billions of people worldwide, and the lessons learned need to be concluded to get better prepared for the next pandemic. Early identification of high-risk patients is important for appropriate treatment and distribution of medical resources. A generalizable and easy-to-use COVID-19 severity stratification model is vital and may provide references for clinicians. Three COVID-19 cohorts (one discovery cohort and two validation cohorts) were included. Longitudinal peripheral blood mononuclear cells were collected from the discovery cohort (n = 39, mild = 15, critical = 24). The immune characteristics of COVID-19 and critical COVID-19 were analyzed by comparison with those of healthy volunteers (n = 16) and patients with mild COVID-19 using mass cytometry by time of flight (CyTOF). Subsequently, machine learning models were developed based on immune signatures and the most valuable laboratory parameters that performed well in distinguishing mild from critical cases. Finally, single-cell RNA sequencing data from a published study (n = 43) and electronic health records from a prospective cohort study (n = 840) were used to verify the role of crucial clinical laboratory and immune signature parameters in the stratification of COVID-19 severity. Patients with COVID-19 were determined with disturbed glucose and tryptophan metabolism in two major innate immune clusters. Critical patients were further characterized by significant depletion of classical dendritic cells (cDCs), regulatory T cells (Tregs), and CD4+ central memory T cells (Tcm), along with increased systemic interleukin-6 (IL-6), interleukin-12 (IL-12), and lactate dehydrogenase (LDH). The machine learning models based on the level of cDCs and LDH showed great potential for predicting critical cases. The model performances in severity stratification were validated in two cohorts (AUC = 0.77 and 0.88, respectively) infected with different strains in different periods. The reference limits of cDCs and LDH as biomarkers for predicting critical COVID-19 were 1.2% and 270.5 U/L, respectively. Overall, we developed and validated a generalizable and easy-to-use COVID-19 severity stratification model using machine learning algorithms. The level of cDCs and LDH will assist clinicians in making quick decisions during future pandemics.

Inflammasome-Related Genetic Polymorphisms as Severity Biomarkers of COVID-19.

The most critical forms of coronavirus disease 2019 (COVID-19) are associated with excessive activation of the inflammasome. Despite the COVID-19 impact on public health, we still do not fully understand the mechanisms by which the inflammatory response influences disease prognosis. Accordingly, we aimed to elucidate the role of polymorphisms in the key genes of the formation and signaling of the inflammasome as biomarkers of COVID-19 severity. For this purpose, a large and well-defined cohort of 377 COVID-19 patients with mild (n = 72), moderate (n = 84), severe (n = 100), and critical (n = 121) infections were included. A total of 24 polymorphisms located in inflammasome-related genes (NLRP3, NLRC4, NLRP1, CARD8, CASP1, IL1B, IL18, NFKB1, ATG16L1, and MIF) were genotyped in all of the patients and in the 192 healthy controls (HCs) (who were without COVID-19 at the time of and before the study) by RT-qPCR. Our results showed that patients with mild, moderate, severe, and critical COVID-19 presented similar allelic and genotypic distribution in all the variants studied. No statistically significant differences in the haplotypic distribution of NLRP3, NLRC4, NLRP1, CARD8, CASP1, IL1B, and ATG16L1 were observed between COVID-19 patients, who were stratified by disease severity. Each stratified group of patients presented a similar genetic distribution to the HCs. In conclusion, our results suggest that the inflammasome polymorphisms studied are not associated with the worsening of COVID-19.

Plasma neutrophil gelatinase-associated lipocalin independently predicts dialysis need and mortality in critical COVID-19

Neutrophil gelatinase-associated lipocalin (NGAL) is a novel kidney injury and inflammation biomarker. We investigated whether NGAL could be used to predict continuous renal replacement therapy (CRRT) and mortality in critical coronavirus disease 2019 (COVID-19). This prospective multicenter cohort study included adult COVID-19 patients in six intensive care units (ICUs) in Sweden between May 11, 2020 and May 10, 2021. Blood was sampled at admission, days two and seven in the ICU. The samples were batch analyzed for NGAL, creatinine, and cystatin c after the end of the study period. Initiation of CRRT and 90-day survival were used as dependent variables in regression models. Of 498 included patients, 494 were analyzed regarding CRRT and 399 were analyzed regarding survival. Seventy patients received CRRT and 154 patients did not survive past 90 days. NGAL, in combination with creatinine and cystatin c, predicted the subsequent initiation of CRRT with an area under the curve (AUC) of 0.95. For mortality, NGAL, in combination with age and sex, had an AUC of 0.83. In conclusion, NGAL is a valuable biomarker for predicting subsequent initiation of CRRT and 90-day mortality in critical COVID-19. NGAL should be considered when developing future clinical scoring systems.

Genetic overlap and causality between COVID-19 and multi-site chronic pain: the importance of immunity.

The existence of chronic pain increases susceptibility to virus and is now widely acknowledged as a prominent feature recognized as a major manifestation of long-term coronavirus disease 2019 (COVID-19) infection. Given the ongoing COVID-19 pandemic, it is imperative to explore the genetic associations between chronic pain and predisposition to COVID-19. We conducted genetic analysis at the single nucleotide polymorphism (SNP), gene, and molecular levels using summary statistics of genome-wide association study (GWAS) and analyzed the drug targets by summary data-based Mendelian randomization analysis (SMR) to alleviate the multi-site chronic pain in COVID-19. Additionally, we performed a latent causal variable (LCV) method to investigate the causal relationship between chronic pain and susceptibility to COVID-19. The cross-trait meta-analysis identified 19 significant SNPs shared between COVID-19 and chronic pain. Coloc analysis indicated that the posterior probability of association (PPH4) for three loci was above 70% in both critical COVID-19 and COVID-19, with the corresponding top three SNPs being rs13135092, rs7588831, and rs13135092. A total of 482 significant overlapped genes were detected from MAGMA and CPASSOC results. Additionally, the gene ANAPC4 was identified as a potential drug target for treating chronic pain (P=7.66E-05) in COVID-19 (P=8.23E-03). Tissue enrichment analysis highlighted that the amygdala (P=7.81E-04) and prefrontal cortex (P=8.19E-05) as pivotal in regulating chronic pain of critical COVID-19. KEGG pathway enrichment further revealed the enrichment of pleiotropic genes in both COVID-19 (P=3.20E-03,Padjust=4.77E-02,hsa05171) and neurotrophic pathways (P=9.03E-04,Padjust =2.55E-02,hsa04621). Finally, the latent causal variable (LCV) model was applied to find the genetic component of critical COVID-19 was causal for multi-site chronic pain (P=0.015), with a genetic causality proportion (GCP) of was 0.60. In this study, we identified several functional genes and underscored the pivotal role of the inflammatory system in the correlation between the paired traits. Notably, heat shock proteins emerged as potential objective biomarkers for chronic pain symptoms in individuals with COVID-19. Additionally, the ubiquitin system might play a role in mediating the impact of COVID-19 on chronic pain. These findings contribute to a more comprehensive understanding of the pleiotropy between COVID-19 and chronic pain, offering insights for therapeutic trials.

Clinical and Temporal Radiological Findings from Critical Patients with COVID-19 Pneumonia: A Descriptive Study.

In late December 2019, Wuhan, the capital of Hubei Province, China, became the center of an outbreak of pneumonia caused by severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2). The radiological changes in the lungs of critical people with coronavirus disease 2019 (COVID-19) pneumonia at different times have not been fully characterized. We aim to describe the computed tomography findings of patients with critical COVID-19 pneumonia at different disease stages. Clinical and laboratory features of critical patients were assessed. CT scans were assigned to groups 1, 2, 3, or 4 based on the interval from symptom onset (within 2 weeks; ≥ 2-4 weeks; ≥ 4-6 weeks; or ≥ 6 weeks, respectively). Imaging features were analyzed and compared across the four groups. Total CT scores, corresponding periods of laboratory findings, and glucocorticoid dosages during the imaging intervals were longitudinally observed in five patients with complete data. All 11 critical patients (median age: 60 years [42-69]) underwent a total of 40 CT examinations, and the acquisition times ranged from 1-59 days after symptom onset. Median total CT scores were 18 (9-25.25); 44.5 (42.88-47.62); 43.75 (38.62-49.38); and 42 (32.25-53.25) in groups 1, 2, 3, and 4, respectively. The observed lesions were mainly bilateral (37 [92.5%]). The median values of involved lung segments were 10.5 (4.5-13.5); 17 (16-18.5); 18 (18-19.5); and 18 (18-19) in groups 1-4, respectively. The predominant patterns of observed abnormalities were ground-glass opacities (GGO) (9 [90%]); GGO with reticulation and mixed patterns (3 [37.5%] for both); GGO with consolidation (3 [30%]); and GGO with reticulation (8 [66.7%]) in groups 1-4, respectively. Patients developed fibrotic manifestations at later stages. Critical patients with COVID-19 infection generally presented with temporally changing abnormal CT features from focal unilateral to diffuse bilateral GGO and consolidation that progressed to or coexisted with reticulation in the long term after symptom onset. Low-dose glucocorticoids may be effective in patients with interstitial changes on CT findings.

Specific adverse outcomes associated with selective serotonin reuptake inhibitors use in COVID-19 patients might be potentiated by remdesivir use.

Due to non-consistent reports in the literature, there are uncertainties about the potential benefits and harms of selective serotonin reuptake inhibitors (SSRIs) in patients with Coronavirus disease 2019 (COVID-19). To investigate associations of SSRIs with clinical characteristics and unwanted outcomes among real-life severe and critical COVID-19 patients and their relationship with remdesivir (RDV) use. This retrospective cohort study evaluated a total of 1558 COVID-19 patients of the white race treated in a tertiary center institution, among them 779 patients treated with RDV and 779 1:1 case-matched patients. A total of 78 (5%) patients were exposed to SSRIs during hospitalization, similarly distributed among patients treated with RDV and matched patients (5.1 and 4.9%). No significant associations of SSRI use with age, sex, comorbidity burden, and COVID-19 severity were present in either of the two cohorts (p < 0.05 for all analyses). In multivariate analyses adjusted for clinically meaningful variables, SSRI use was significantly associated with higher mortality among RDV (adjusted odds ratio (aOR) 2.0, p = 0.049) and matched patients (aOR 2.22, p = 0.044) and with higher risk for mechanical-ventilation (aOR 2.57, p = 0.006), venous-thromboembolism (aOR 3.69, p = 0.007), and bacteremia (aOR 2.22, p = 0.049) among RDV treated patients. Adverse outcomes associated with SSRI use in COVID-19 patients might be potentiated by RDV use, and clinically significant interactions between these two drug classes might exist. Although our findings raise important considerations for clinical practice, they are limited by retrospective nature of the study, lack of ethnic diversity, and the potential for unmeasured confounding factors. Future studies exploring underlying biological mechanisms are needed.

The relationship between morphological electrocardiographic characteristics and survival in critical COVID-19 patients

Background: Myocardial damage is a sign of poor prognosis in coronavirus disease 2019 (COVID-19). Electrocardiography (ECG) would be useful to evaluate the effects of ECG findings on survival in severe COVID-19. We studied the relationship of pathological ECG findings in patients of COVID-19 admitted in ICU with other adverse physiological parameters as well as the mortality.&#x0D; Methodology: The study population comprised critical COVID-19 patients in the intensive care unit (ICU). Patients with findings other than normal sinus rhythm, atrial extra beat, and ventricular extra beat were defined as patients with pathological ECG findings. Two groups were formed: patients with pathological ECG findings (n = 109) and patients without pathological ECG findings (n = 84). Data were compared and analysed between the groups.  The relationship among the risk factors, and ECG findings with mortality was investigated.&#x0D; Results: The presence of hypertension (69% vs. 40%, OR 5.49, CI 1.71-17.66, P = 0.004), peripheral oxygen saturation (SpO2) (88 vs. 95, OR 0.8, CI 0.7-0.9, P &lt; 0.001) were found to be related to mortality in multivariable analyses. Patients with pathological ECG finding were older [74 (27-98) vs. 61 (22-89); P &lt; 0.001], and more likely to have hypertension (68% vs. 44%, P = 0.001). Pathological ECG findings (66% vs. 51%, P = 0.02), atrial fibrillation (AF) (37% vs. 20%, P = 0.01), right branch bundle block (RBBB) (10% vs. 3%, P = 0.048) were associated with higher mortality in univariable analyses.&#x0D; Conclusion: Although abnormal findings on ECG, especially AF and RBBB, are associated with a poor prognosis, they are not primary effective in increasing the mortality of critical COVID-19 patients.&#x0D; Abbreviations: AF- Atrial Fibrillation; CRP- C-reactive protein; ICU- intensive care unit; RBBB- Right Bundle-Branch Block; RT-PCR- reverse-transcription polymerase chain reaction; VTE- venous thromboembolism&#x0D; Key words: Atrial Fibrillation; Biomarkers; COVID-19; ECG; Mortality; Right Bundle-Branch Block&#x0D; Citation: Sayan M, Altinisik HB. The relationship between morphological electrocardiographic characteristics and survival in critical COVID-19 patients. Anaesth. pain intensive care 2024;28(1):139−150.&#x0D; DOI: 10.35975/apic.v28i1.2385&#x0D; Received: November 21, 2023; Reviewed: November 30, 2023; Accepted: December 21, 2023

Analysis of related factors of plasma antibody levels in patients with severe and critical COVID-19

Coronavirus disease 2019 (COVID-19) continues to impact global public health. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become less virulent as it mutates, prompting China to ease restrictions at the end of 2022. With the complete reopening, a surge in COVID-19 cases has ensued. Therefore, we conducted a study to explore the correlation between plasma antibody levels and baseline conditions or clinical outcomes in severe and critical patients. We collected the basic information of 79 included patients. Enzyme-linked immunosorbent assay (ELISA) tests were performed on plasma samples. The receptor-binding domain (RBD) IgG antibody level of the mild group was significantly higher than that of the severe/critical group (P = 0.00049). And in the severe/critical group, there existed an association between plasma antibody levels and age (P < 0.001, r = − 0.471), as well as plasma antibody levels and vaccination status (P = 0.00147, eta2 = 0.211). Besides, the level of plasma antibody seemed to be moderately correlated with the age, indicating the need for heightened attention to infections in the elderly. And plasma antibody levels were strongly associated with vaccination status in the severe/critical patients.

COVID-19 in immunocompromised patients after hematopoietic stem cell transplantation: a pilot study.

Data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients at early stage of immune reconstitution after hematopoietic stem cell transplantation (HSCT) are limited. In the present study, we retrospectively investigated the incidence and clinical features of SARS-CoV-2 infection in patients who underwent HSCT in 2022. Patients (allo-HSCT, n = 80; auto-HSCT, n = 37) were consecutively included in the study. The SARS-CoV-2 infection rate was 59.8%, and the median interval of HSCT to coronavirus disease 2019 (COVID-19) was 4.8 (range: 0.5-12) months. Most patients were categorized as mild (41.4%) or moderate (38.6%), and 20% as severe/critical. No deaths were attributable to COVID-19. Further analysis showed that lower circulating CD8+ T-cell counts and calcineurin inhibitor administration increased the risk of SARS-CoV-2 infection. Exposure to rituximab significantly increased the probability of severe or critical COVID-19 compared with that of mild/moderate illness (P < .001). In the multivariate analysis, rituximab use was associated with severe COVID-19. Additionally, COVID-19 had no significant effect on immune reconstitution. Furthermore, it was found that Epstein-Barr virus infection and rituximab administration possibly increase the risk of developing severe illness. Our study provides preliminary insights into the effect of SARS-CoV-2 on immune reconstitution and the outcomes of allo-HSCT recipients.

Risk factors, outcomes, and epidemiological and etiological study of hospitalized COVID-19 patients with bacterial co-infection and secondary infections

BackgroundAs a common complication of viral respiratory tract infection, bacterial infection was associated with higher mortality and morbidity. Determining the prevalence, culprit pathogens, outcomes, and risk factors of co-infection and secondary infection occurring in hospitalized patients with coronavirus disease 2019 (COVID-19) will be beneficial for better antibiotic management.MethodsIn this retrospective cohort research, we assessed clinical characteristics, laboratory parameters, microbiologic results, and outcomes of laboratory-confirmed COVID-19 patients with bacterial co-infection and secondary infection in West China Hospital from 2022 December 2nd to 2023 March 15th.ResultsThe incidence of bacterial co-infection and secondary infection, as defined by positive culture results of clinical specimens, was 16.3% (178/1091) and 10.1% (110/1091) respectively among 1091 patients. Acinetobacter, Klebsiella, and Pseudomonas were the most commonly identified bacteria in respiratory tract samples of COVID-19 patients. In-hospital mortality of COVID-19 patients with co-infection (17.4% vs 9.5%, p = 0.003) and secondary infection (28.2% vs 9.5%, p < 0.001) greatly exceeded that of COVID-19 patients without bacterial infection. Cardiovascular disease (1.847 (1.202–2.837), p = 0.005), severe COVID-19 (1.694 (1.033–2.778), p = 0.037), and critical COVID-19 (2.220 (1.196–4.121), p = 0.012) were proved to be risk factors for bacterial co-infection, while only critical COVID-19 (1.847 (1.202–2.837), p = 0.005) was closely related to secondary infection.ConclusionsBacterial co-infection and secondary infection could aggravate the disease severity and worsen clinical outcomes of COVID-19 patients. Notably, only critical COVID-19 subtype was proved to be an independent risk factor for both co-infection and secondary infection. Therefore, standard empirical antibiotics was recommended for critically ill COVID-19 rather than all the inpatients according to our research.

Risk Factors for Severe and Critical Coronavirus Disease 2019 in Children.

Coronavirus disease 2019 (COVID-19) is generally mild in children; however, severe or critical cases may occur. In this nationwide study, we analyzed clinical manifestations in children diagnosed with severe acute respiratory syndrome coronavirus 2 to identify high-risk groups for severe or critical disease and compared the clinical features between the Delta- and Omicron-dominant periods. Data were retrieved from the National Health Insurance Service (NHIS) database and merged with the Korea Disease Control and Prevention Agency-COVID-19-NHIS cohort, which includes information on COVID-19 cases and vaccination records. We included individuals <20 years old diagnosed with COVID-19 during both periods (Delta: July 25, 2021-January 15, 2022; Omicron: January 16, 2022-March 31, 2022). Proportion of severe or critical cases was higher during the Delta period than during the Omicron period. The Omicron period saw increased hospitalization for pneumonia and croup and increased likelihood of hospitalization for neurological manifestations. The risk of severe COVID-19 depended on age group (Delta: highest for 12-19 years; Omicron: 0-4 years). This risk was high in children with multiple complex chronic conditions during both periods and with obesity or asthma during the Delta but not during the Omicron period. Two-dose COVID-19 vaccination provided strong protection against severe disease in the Delta period (adjusted odds ratio: 0.20), with reduced effectiveness in the Omicron period (adjusted odds ratio: 0.91). However, it significantly reduced the risk of critical illness (adjusted odds ratio: 0.14). These findings can facilitate identification of children at high risk of severe or critical COVID-19, who may require intensive medical support, and development of vaccination policies.

Impact of Sedation Practices on Mortality in COVID-19-Associated Adult Respiratory Distress Syndrome Patients: A Multicenter Retrospective Descriptive Study.

Background: Reduction in sedation exposure is an important metric in intensive care unit (ICU) patients. However, challenges arose during the coronavirus disease-2019 (COVID-19) pandemic in adhering to this practice, driven by concerns on transmission and disease severity issues. Accordingly, diverse sedation approaches emerged, although the effect on mortality has not been studied thoroughly. Methods: Retrospective cohort study in the medical ICU of seven hospitals within a major Health System in Northeast Ohio. We included all adult patients admitted with COVID-19 requiring invasive mechanical ventilation (IMV) from March 2020 to December 2021. Results: Study included 2394 COVID-19 patients requiring IMV. Across waves, sample included 55-63% male subjects, with an average age of 61-68 years (P < 0.001), Acute Physiologic and Chronic Health Evaluation (APACHE)-III score 65.8-68.9 (P = 0.37), median IMV duration 8-10 days (P = 0.14), and median ICU duration 9.8-11.6 days (P = 0.084). Propofol remained the primary sedative (84-92%; P = 0.089). Ketamine use increased from the first (9.7%) to fourth (19%) wave (P = 0.002). Midazolam use decreased from the first (27.4%) to third (9.4%) wave (P = 0.001). Dexmedetomidine use declined from 35% to 27-28% (P = 0.002) after the first wave. A multivariable regression analysis indicated clinical variables explained 34% of the variation in hospital mortality (R2). Factors associated with higher mortality included age [aOR = 1.059 (95% CI 1.049-1.069); P < 0.001], COVID-19 wave, especially fourth wave [aOR = 2.147, (95% CI 1.370-3.365); P = 0.001], and higher number of vasopressors [aOR = 31.636, (95% CI 17.603-56.856); P < 0.001]. Addition of sedative medications to a second model led to an increase in the R2 by only 1.6% to 35.6% [aOR = 1 (95% CI 1-1); P > 0.05] for propofol, ketamine, and midazolam. Dexmedetomidine demonstrated a decrease in the odds of mortality [aOR = 0.96 (95% CI 0.94-0.97); P < 0.001]. Conclusion: Mortality in critical COVID-19 patients was mostly driven by illness severity, and the choice of sedation might have minimal impact when other factors are controlled.

Quantification of hs-Troponin Levels and Global Longitudinal Strain among Critical COVID-19 Patients with Myocardial Involvement.

Background. Myocardial involvement among critically ill patients with coronavirus disease 2019 (COVID-19) often has worse outcomes. An imbalance in the oxygen supply causes the excessive release of pro-inflammatory cytokines, which results in increased ventilation requirements and the risk of death in COVID-19 patients. Purpose. We evaluated the association between the hs-troponin I levels and global longitudinal strain (GLS) as evidence of myocardial involvement among critical COVID-19 patients. Methods. We conducted a prospective cohort study from 1 February to 31 July 2021 at RSUD Dr. Soetomo, Surabaya, as a COVID-19 referral center. Of the 65 critical COVID-19 patients included, 41 (63.1%) were men, with a median age (interquartile range) of 51.0 years (20.0-75.0). Subjects were recruited based on WHO criteria for severe COVID-19, and myocardial involvement in the form of myocarditis was assessed using CDC criteria. Subjects were examined using echocardiography to measure the GLS, and blood samples were taken to measure the hs-troponin. Subjects were then followed for their need for mechanical ventilation and in-hospital mortality. Results. Severe COVID-19 patients with cardiac injury were associated with an increased need for intubation (78.5%) and an increased incidence of myocarditis (50.8%). There was a relationship between the use of intubation and the risk of death in patients (66.7% vs. 33.3%, p-value < 0.001). Decreased GLS and increased hs-troponin were associated with increased myocarditis (p values < 0.001 and 0.004, respectively). Decreased GLS was associated with a higher need for mechanical ventilation (12.17 + 4.79 vs. 15.65 + 4.90, p-value = 0.02) and higher mortality (11.36 + 4.64 vs. 14.74 + 4.82; p-value = 0.005). Elevated hs-troponin was associated with a higher need for mechanical ventilation (25.33% vs. 3.56%, p-value = 0.002) and higher mortality (34.57% vs. 5.76%, p-value = 0.002). Conclusions. Critically ill COVID-19 patients with myocardial involvement and elevated cardiac troponin levels are associated with a higher need for mechanical ventilation and higher mortality.

Reduction of Complements C3 and C4 in Saliva and Serum of Patients Suffering SARS-CoV-2 Infection

Background: The complement system plays a role in chronic immune activation during viral infections. Objectives: This study aimed to evaluate the levels of saliva and serum complements C3 and C4 in coronavirus disease 2019 (COVID-19) patients and healthy individuals. Methods: This cross-sectional study included 36 severe and 22 critical COVID-19 hospitalized patients and 22 healthy individuals. Serum and unstimulated salivary C3 and C4 levels were assessed using the immunoturbidimetric method and analyzed using one-way analysis of variance (ANOVA) with the Student-Newman-Keuls test as a post hoc analysis. Results: Salivary C3 and C4 levels were significantly lower in patients with severe and critical COVID-19 than in healthy individuals. There was no significant difference between the groups infected with severe and critical COVID-19. Serum C3 and C4 levels were lower in critical COVID-19 patients than in healthy individuals; nevertheless, no significant difference was observed between severe COVID-19 patients and healthy individuals. Additionally, serum C4 levels were lower in critical COVID-19 patients than in severe COVID-19 patients. Conclusions: It appears that serum and salivary C3 and C4 levels decrease in patients with COVID-19 infection.