Corrigendum to "Comprehensive Humoral and Cellular Immune Responses to SARS-CoV-2 Variants in Diverse Chinese Population".

[This corrects the article DOI: 10.34133/2022/9873831.].

Mining adverse events in large frequency tables with ontology, with an application to the vaccine adverse event reporting system.

Many statistical methods have been applied to VAERS (vaccine adverse event reporting system) database to study the safety of COVID-19 vaccines. However, none of these methods considered the adverse event (AE) ontology. The AE ontology contains important information about biological similarities between AEs. In this paper, we develop a model to estimate vaccine-AE associations while incorporating the AE ontology. We model a group of AEs using the zero-inflated negative binomial model and then estimate the vaccine-AE association using the empirical Bayes approach. This model handles the AE count data with excess zeros and allows borrowing information from related AEs. The proposed approach was evaluated by simulation studies and was further illustrated by an application to the Vaccine Adverse Event Reporting System (VAERS) dataset. The proposed method is implemented in an R package available at https://github.com/umich-biostatistics/zGPS.AO.

Prevalence and genetic diversity of canine coronavirus in northeastern China during 2019-2021.

Canine coronavirus (CCoV) is associated with diarrhea in dogs, with a high incidence and sometimes even death. However, there is currently limited information about its prevalence and molecular characterization in northeastern China. Therefore, in this study, we examined 325 canine fecal specimens in four provinces in northeastern China from 2019 to 2021. PCR results revealed that 57 out of 325 (17.5%) samples were found to be positive for CCoV, and the positive rate varies obviously with city, season, age and so on. High incidence (65%) of viral co-infection was detected in the diarrhea samples and mixed infection of distinct CCoV genotypes occurs extensively. More importantly, sequence analysis showed that the S gene has a strong mutation. Phylogenetic analysis demonstrated that CCoV-I and CCoV-II strains has different origins. In particular, we found the CCoV-IIa strains of S gene sequenced and the reference strain B906_ZJ_2019 were highly clustered, and the reference strain was a recombinant strain of CCoV-I and CCoV-II. Our findings provide useful orienting clues for evaluating the pathogenic potential of CCoV in canines, and point out more details on characterization in northeastern China. Further work is required to determine the significance and continuous genetic evolution of CCoV.

Evolution of Care and Outcomes Across Surges in Hospitalized Patients with Coronavirus Disease 2019.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has unfolded in distinct surges. Understanding how surges differ may reveal important insights into the evolution of the pandemic and improve patient care. METHODS: We leveraged the Michigan Medicine COVID-19 Cohort, a prospective observational study at an academic tertiary medical center that systematically enrolled 2309 consecutive patients hospitalized for COVID-19, comprising 5 distinct surges. RESULTS: As the pandemic evolved, patients hospitalized for COVID-19 tended to have a lower burden of comorbidities and a lower inflammatory burden as measured by admission levels of C-reactive protein, ferritin, lactate dehydrogenase, and D-dimer. Use of hydroxychloroquine and azithromycin decreased substantially after Surge 1, while use of corticosteroids and remdesivir markedly increased (P < .001 for all). In-hospital mortality significantly decreased from 18.3% in Surge 1 to 5.3% in Surge 5 (P < .001). The need for mechanical ventilation significantly decreased from 42.5% in Surge 1 to 7.0% in Surge 5 (P < .001), while the need for renal replacement therapy decreased from 14.4% in Surge 1 to 2.3% in Surge 5 (P < .001). Differences in patient characteristics, treatments, and inflammatory markers accounted only partially for the differences in outcomes between surges. CONCLUSIONS: The COVID-19 pandemic has evolved significantly with respect to hospitalized patient populations and therapeutic approaches, and clinical outcomes have substantially improved. Hospitalization after the first surge was independently associated with improved outcomes, even after controlling for relevant clinical covariates.

COVID-19 vaccine effectiveness against omicron (B.1.1.529) variant infection and hospitalisation in patients taking immunosuppressive medications: a retrospective cohort study.

Background: There is a scarcity of research regarding the effectiveness of the mRNA-1273 (Moderna) and BNT162b2 (Pfizer-BioNTech) COVID-19 vaccines in patients taking immunosuppressant medications, and no data are published to date pertaining to their effectiveness against omicron (B.1.1.529) variant SARS-CoV-2 infection and hospitalisation. We aimed to assess the relationship between immunosuppressive medications, mRNA vaccination, omicron infection, and severe COVID-19 outcomes (ie, hospitalisation, ICU admission, death). Methods: We did a retrospective cohort study and included vaccinated and unvaccinated people aged 18 years or older in the Michigan Medicine health-care system, USA, during the omicron-dominant period of the pandemic (Dec 16, 2021-March 4, 2022). We collected data from electronic health records (demographics, diagnoses, medications) combined with immunisation data from the Michigan State Registry to determine vaccination status, and we collected COVID-19-related hospitalisation data by chart review. We used a Cox proportional hazards model based on calendar time to assess the effectiveness of the mRNA-1273 and BNT162b2 vaccines in people taking immunosuppressive medications (conventional synthetic disease-modifying antirheumatic drugs [DMARDs], biologic DMARDs, or glucocorticoids within the past 3 months), while controlling for participant characteristics. Using the same model, we assessed the effect of different classes of medication such as immunosuppressive DMARDs, immunomodulatory DMARDs, and glucocorticoids on SARS-CoV-2 infection and hospitalisation due to COVID-19. All analyses were done using complete cases after removing participants with missing covariates. Findings: 209 492 people were identified in Michigan Medicine, including 165 913 who were vaccinated and 43 579 who were unvaccinated. 41 078 people were excluded because they were younger than 18 years, partially vaccinated, had received a vaccine other than the two vaccines studied, or had incomplete covariate data. 168 414 people were included in the analysis; 97 935 (58%) were women, 70 479 (42%) were men, and 129 816 (77%) were White. 5609 (3%) people were taking immunosuppressive medications. In patients receiving immunosuppressants, three doses of BNT162b2 had a vaccine effectiveness of 50% (95% CI 31-64; p<0·0001) and three doses of mRNA-1273 had a vaccine effectiveness of 60% (42-73; p<0·0001) against SARS-CoV-2 infection. Three doses of either vaccine had an effectiveness of 87% (95% CI 73-93; p<0·0001) against hospitalisation due to COVID-19. Receipt of immunosuppressive DMARDs (hazard ratio 2·32, 95% CI 1·23-4·38; p=0·0097) or glucocorticoids (2·93, 1·77-4·86; p<0·0001) and a history of organ or bone marrow transplantation (3·52, 2·01-6·16; p<0·0001) were associated with increased risk of hospitalisation due to COVID-19 compared with those who had not received immunosuppressive medications or transplant. Interpretation: People taking immunosuppressive DMARDs or glucocorticoids are at substantially higher risk of hospitalisation due to COVID-19 than the general population. However, the mRNA-1273 and BNT162b2 vaccines remain effective within this group, and it is important that patients taking these medications remain up to date with vaccinations to mitigate their risk. Funding: National Institute of Allergy and Infectious Diseases, National Institutes of Health.

Relationship Between Preexisting Cardiovascular Disease and Death and Cardiovascular Outcomes in Critically Ill Patients With COVID-19.

BACKGROUND: Preexisting cardiovascular disease (CVD) is perceived as a risk factor for poor outcomes in patients with COVID-19. We sought to determine whether CVD is associated with in-hospital death and cardiovascular events in critically ill patients with COVID-19. METHODS: This study used data from a multicenter cohort of adults with laboratory-confirmed COVID-19 admitted to intensive care units at 68 centers across the United States from March 1 to July 1, 2020. The primary exposure was CVD, defined as preexisting coronary artery disease, congestive heart failure, or atrial fibrillation/flutter. Myocardial injury on intensive care unit admission defined as a troponin I or T level above the 99th percentile upper reference limit of normal was a secondary exposure. The primary outcome was 28-day in-hospital mortality. Secondary outcomes included cardiovascular events (cardiac arrest, new-onset arrhythmias, new-onset heart failure, myocarditis, pericarditis, or stroke) within 14 days. RESULTS: Among 5133 patients (3231 male [62.9%]; mean age 61 years [SD, 15]), 1174 (22.9%) had preexisting CVD. A total of 1178 (34.6%) died, and 920 (17.9%) had a cardiovascular event. After adjusting for age, sex, race, body mass index, history of smoking, and comorbidities, preexisting CVD was associated with a 1.15 (95% CI, 0.98-1.34) higher odds of death. No independent association was observed between preexisting CVD and cardiovascular events. Myocardial injury on intensive care unit admission was associated with higher odds of death (adjusted odds ratio, 1.93 [95% CI, 1.61-2.31]) and cardiovascular events (adjusted odds ratio, 1.82 [95% CI, 1.47-2.24]), regardless of the presence of CVD. CONCLUSIONS: CVD risk factors, rather than CVD itself, were the major contributors to outcomes in critically ill patients with COVID-19. The occurrence of myocardial injury, regardless of CVD, and its association with outcomes suggests it is likely due to multiorgan injury related to acute inflammation rather than exacerbation of preexisting CVD. REGISTRATION: NCT04343898; https://clinicaltrials.gov/ct2/show/NCT04343898.

Comprehensive Humoral and Cellular Immune Responses to SARS-CoV-2 Variants in Diverse Chinese Population.

The SARS-CoV-2 variants have been emerging and have made great challenges to current vaccine and pandemic control strategies. It is urgent to understand the current immune status of various Chinese populations given that the preexisting immunity has been established by national vaccination or exposure to past variants. Using sera from 85 individuals (including 21 convalescents of natural infection, 15 cases which suffered a breakthrough infection after being fully vaccinated, and 49 healthy vaccinees), we showed significantly enhanced neutralizing activities against SRAS-CoV-2 variants in convalescent sera, especially those who had been fully vaccinated. The neutralizing antibodies against Omicron were detectable in 75% of convalescents and 44.9% of healthy vaccinees (p = 0.006), with a GMT of 289.5, 180.9-463.3, and 42.6, 31.3-59, respectively. However, the neutralizing activities were weaker in young convalescents (aged < 18 y), with a detectable rate of 50% and a GMT of 46.4 against Omicron. We also examined and found no pan-sarbecovirus neutralizing activities in vaccinated SARS-CoV-1 survivors. A booster dose could further increase the breadth and magnitude of neutralization against WT and variants of concern (VOCs) to different degrees. In addition, we showed that COVID-19-inactivated vaccines can elicit Omicron-specific T-cell responses. The positive rates of ELISpot reactions were 26.7% (4/15) and 43.8% (7/16) in the full vaccination group and the booster vaccination group, respectively, although without statistically significant difference. The neutralizing antibody titers declined while T-cell responses remain consistent over 6 months. These findings will inform the optimization of public health vaccination and intervention strategies to protect diverse populations against SARS-CoV-2 variants. Advances. Breakthrough infection significantly boosted neutralizing activities against SARS-CoV-2 variants as compared to booster immunization with inactivated vaccine. Vaccine-induced virus-specific T-cell immunity, on the other hand, may compensate for the shortfall. Furthermore, the public health system should target the most vulnerable group due to a poorer protective serological response in both infected and vaccinated adolescents.

Clinical Research Progress of Small Molecule Compounds Targeting Nrf2 for Treating Inflammation-Related Diseases.

Studies have found that inflammation is a symptom of various diseases, such as coronavirus disease 2019 (COVID-19) and rheumatoid arthritis (RA); it is also the source of other diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), lupus erythematosus (LE), and liver damage. Nrf2 (nuclear factor erythroid 2-related factor 2) is an important multifunctional transcription factor in cells and plays a central regulatory role in cellular defense mechanisms. In recent years, several studies have found a strong association between the activation of Nrf2 and the fight against inflammation-related diseases. A number of small molecule compounds targeting Nrf2 have entered clinical research. This article reviews the research status of small molecule compounds that are in clinical trials for the treatment of COVID-19, rheumatoid arthritis, Alzheimer's disease, Parkinson's disease, lupus erythematosus, and liver injury.

Profiling COVID-19 Vaccine Adverse Events by Statistical and Ontological Analysis of VAERS Case Reports.

Since the beginning of the COVID-19 pandemic, vaccines have been developed to mitigate the spread of SARS-CoV-2, the virus that causes COVID-19. These vaccines have been effective in reducing the rate and severity of COVID-19 infection but also have been associated with various adverse events (AEs). In this study, data from the Vaccine Adverse Event Reporting System (VAERS) was queried and analyzed via the Cov19VaxKB vaccine safety statistical analysis tool to identify statistically significant (i.e., enriched) AEs for the three currently FDA-authorized or approved COVID-19 vaccines. An ontology-based classification and literature review were conducted for these enriched AEs. Using VAERS data as of 31 December 2021, 96 AEs were found to be statistically significantly associated with the Pfizer-BioNTech, Moderna, and/or Janssen COVID-19 vaccines. The Janssen COVID-19 vaccine had a higher crude reporting rate of AEs compared to the Moderna and Pfizer COVID-19 vaccines. Females appeared to have a higher case report frequency for top adverse events compared to males. Using the Ontology of Adverse Event (OAE), these 96 adverse events were classified to different categories such as behavioral and neurological AEs, cardiovascular AEs, female reproductive system AEs, and immune system AEs. Further statistical comparison between different ages, doses, and sexes was also performed for three notable AEs: myocarditis, GBS, and thrombosis. The Pfizer vaccine was found to have a closer association with myocarditis than the other two COVID-19 vaccines in VAERS, while the Janssen vaccine was more likely to be associated with thrombosis and GBS AEs. To support standard AE representation and study, we have also modeled and classified the newly identified thrombosis with thrombocytopenia syndrome (TTS) AE and its subclasses in the OAE by incorporating the Brighton Collaboration definition. Notably, severe COVID-19 vaccine AEs (including myocarditis, GBS, and TTS) rarely occur in comparison to the large number of COVID-19 vaccinations administered in the United States, affirming the overall safety of these COVID-19 vaccines.

Comparative Effectiveness of Coronavirus Disease 2019 (COVID-19) Vaccines Against the Delta Variant.

BACKGROUND: There is a lack of data regarding how the Delta variant of coronavirus disease 2019 (COVID-19) has impacted the effectiveness of the BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), and Ad26.COV2.S (Johnson & Johnson-Janssen) vaccines at preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 hospitalization. METHODS: We compared the effectiveness of the three vaccines during the pre- and post-Delta variant period (before and after 1 July 2021) in a large cohort of vaccinated and unvaccinated patients in the Michigan Medicine healthcare system. We assessed vaccine effectiveness (VE) using 2 analyses: an inverse propensity weighted (IPW) Kaplan-Meier (KM) analysis based on time from vaccination, and a Cox model based on calendar time with vaccination as a time-varying covariate. RESULTS: Compared to Ad26.COV2.S recipients, the risk of hospitalization for COVID-19 in the post-Delta variant period was lower for BNT162b2 recipients (hazard ratio [HR] = 0.37; 95% confidence interval [CI]: [.14-.98]; P = .05) and mRNA-1273 recipients (HR = 0.21; 95% CI: [.07-.64]; P = .006). Recipients of the mRNA-1273 vaccine had a lower risk of SARS-CoV-2 infection than Ad26.COV2.S recipients (HR = 0.6; 95% CI: [.43-.83]; P = .003) and BNT162b2 recipients (HR = 0.64; 95% CI: [.54-.76]; P < .001). After 1 July, efficacy against SARS-CoV-2 infection declined for Ad26.COV2.S recipients (VE = 76% before; VE = 49% after; P = .02), BNT162b2 recipients (VE = 87% before; VE = 52% after; P < .001), and mRNA-1273 recipients (VE = 92% before; VE = 70% after; P < .001). Waning immunity and the Delta variant contributed independently and significantly to this decline. CONCLUSIONS: Although there is a substantial decline in effectiveness, the approved COVID-19 vaccines remain effective against infection and hospitalization due to the Delta variant. The mRNA-based vaccines are more effective than the Ad26.COV2.S vaccine.

Risk Contagion between Global Commodities from the Perspective of Volatility Spillover

Prices of oil and other commodities have fluctuated wildly since the outbreak of the COVID-19 pandemic. It is crucial to explore the causes of price fluctuations and understand the source and path of risk contagion to better mitigate systemic risk and maintain economic stability. The paper adopts the method of network topology to examine the path of risk contagion between China's and foreign commodities, focusing on the dynamic evolution and transmission mechanism of risk contagion during the pandemic. This research found that among China's commodities, energy, grain, and textiles are net recipients of risk contagion, while chemical products and metals are net risk exporters. Among international commodities, industries have positive risk spillover effects on metals and textiles. During the first phase of the pandemic, China's commodities were the main exporters of risk contagion. However, international industries and metals became the main risk exporters and exerted risk spillover on China's commodities in the second phase of the pandemic. Moreover, based on total volatility spillover index of commodities, the risk contagion among the commodities follows three paths: 'interest rate →commodities →money supply';, 'China's economic expectation →commodities →foreign economic expectation';, and 'commodities →consumer confidence';.

Efficacy of COVID-19 vaccines in patients taking immunosuppressants.

OBJECTIVES: We intended to assess the effectiveness of all three US Food and Drug Administration approved COVID-19 vaccines at preventing SARS-CoV-2 infection and COVID-19 hospitalisation in a large cohort of individuals on immunosuppressants for a diverse range of conditions. METHODS: We studied the effectiveness of BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna) and Ad26.COV2.S (Johnson & Johnson-Janssen) vaccines among individuals who take immunosuppressants (including disease-modifying antirheumatic drugs and glucocorticoids) by comparing vaccinated (n=97688) and unvaccinated (n=42094) individuals in the Michigan Medicine healthcare system from 1 January to 7 December 2021, using Cox proportional hazards modelling with time-varying covariates. RESULTS: Among vaccinated and unvaccinated individuals, taking immunosuppressants increased the risk of SARS-CoV-2 infection (adjusted HR (aHR)=2.17, 95% CI 1.69 to 2.79 for fully vaccinated and aHR=1.40, 95% CI 1.07 to 1.83 for unvaccinated). Among individuals taking immunosuppressants, we found: (1) vaccination reduced the risk of SARS-CoV-2 infection (aHR=0.55, 95% CI 0.39 to 0.78); (2) the BNT162b2 and mRNA-1273 vaccines were highly effective at reducing the risk of SARS-CoV-2 infection (n=2046, aHR=0.59, 95% CI 0.38 to 0.91 for BNT162b2; n=2064, aHR=0.52, 95% CI 0.33 to 0.82 for mRNA-1273); (3) with a smaller sample size (n=173), Ad26.COV2.S vaccine protection did not reach statistical significance (aHR=0.34, 95% CI 0.09 to 1.30, p=0.17); and (4) receiving a booster dose reduced the risk of SARS-CoV-2 infection (aHR=0.42, 95% CI 0.24 to 0.76). CONCLUSIONS: The mRNA-1273 and BNT162b2 vaccines are effective in individuals who take immunosuppressants. However, individuals who are vaccinated but on immunosuppressants are still at higher risk of SARS-CoV-2 infection and COVID-19 hospitalisation than the broader vaccinated population. Booster doses are effective and crucially important for individuals on immunosuppressants.

Prognostic Value of Histidine-Rich Glycoprotein for Community-Acquired Pneumonia.

PURPOSE: Histidine-rich glycoprotein (HRG) is abundant in serum and has been implicated in several processes including blood coagulation and immune response. This prospective study is aimed at exploring HRG as a biomarker in patients hospitalized for community-acquired pneumonia (CAP). METHODS: A total of 160 patients (73 severe CAP, 57 nonsevere CAP), and 30 healthy controls were enrolled in 2019. Demographic and clinical data were recorded for all patients. Serum HRG concentration was measured upon admission using ELISA. RESULTS: HRG levels were significantly lower in severe CAP patients compared with other groups, regardless of etiology, and were negatively correlated with serum interleukin-6 and disease severity index scores. Combination of CURB-65, PSI, and APACHE II scores with HRG values significantly improved the accuracy of predicting 30-day mortality in these patients. Cox regression analysis showed that HRG could serve as an independent risk factor for 30-day mortality. Notably, patients with HRG ≤ 16.92 µg/mL had significantly lower cumulative survival than those with HRG > 16.92 µg/mL. CONCLUSION: Serum HRG levels are lower in patients with severe CAP and are negatively correlated with disease severity scores. Measurement of HRG upon admission can provide valuable prognostic information for patients with CAP.

Inflammation, Hyperglycemia, and Adverse Outcomes in Individuals With Diabetes Mellitus Hospitalized for COVID-19.

OBJECTIVE: Diabetes mellitus (DM) is a major risk factor for severe coronavirus disease 2019 (COVID-19) for reasons that are unclear. RESEARCH DESIGN AND METHODS: We leveraged the International Study of Inflammation in COVID-19 (ISIC), a multicenter observational study of 2,044 patients hospitalized with COVID-19, to characterize the impact of DM on in-hospital outcomes and assess the contribution of inflammation and hyperglycemia to the risk attributed to DM. We measured biomarkers of inflammation collected at hospital admission and collected glucose levels and insulin data throughout hospitalization. The primary outcome was the composite of in-hospital death, need for mechanical ventilation, and need for renal replacement therapy. RESULTS: Among participants (mean age 60 years, 58.2% males), those with DM (n = 686, 33.5%) had a significantly higher cumulative incidence of the primary outcome (37.8% vs. 28.6%) and higher levels of inflammatory biomarkers than those without DM. Among biomarkers, DM was only associated with higher soluble urokinase plasminogen activator receptor (suPAR) levels in multivariable analysis. Adjusting for suPAR levels abrogated the association between DM and the primary outcome (adjusted odds ratio 1.23 [95% CI 0.78, 1.37]). In mediation analysis, we estimated the proportion of the effect of DM on the primary outcome mediated by suPAR at 84.2%. Hyperglycemia and higher insulin doses were independent predictors of the primary outcome, with effect sizes unaffected by adjusting for suPAR levels. CONCLUSIONS: Our findings suggest that the association between DM and outcomes in COVID-19 is largely mediated by hyperinflammation as assessed by suPAR levels, while the impact of hyperglycemia is independent of inflammation.

Investigation of the impact of SARS-CoV infection on the immunologic status and lung function after 15 years.

BACKGROUND: We investigate the long-term effects of SARS-CoV on patients' lung and immune systems 15 years post-infection. SARS-CoV-2 pandemic is ongoing however, another genetically related beta-coronavirus SARS-CoV caused an epidemic in 2003-2004. METHODS: We enrolled 58 healthcare workers from Peking University People's Hospital who were infected with SARS-CoV in 2003. We evaluated lung damage by mMRC score, pulmonary function tests, and chest CT. Immune function was assessed by their serum levels of globin, complete components, and peripheral T cell subsets. ELISA was used to detect SARS-CoV-specific IgG antibodies in sera. RESULTS: After 15 years of disease onset, 19 (36.5%), 8 (34.6%), and 19 (36.5%) subjects had impaired DL (CO), RV, and FEF25-75, respectively. 17 (30.4%) subjects had an mMRC score ≥ 2. Fourteen (25.5%) cases had residual CT abnormalities. T regulatory cells were a bit higher in the SARS survivors. IgG antibodies against SARS S-RBD protein and N protein were detected in 11 (18.97%) and 12 (20.69%) subjects, respectively. Subgroup analysis revealed that small airway dysfunction and CT abnormalities were more common in the severe group than in the non-severe group (57.1% vs 22.6%, 54.5% vs 6.1%, respectively, p < 0.05). CONCLUSIONS: SARS-CoV could cause permanent damage to the lung, which requires early pulmonary rehabilitation. The long-lived immune memory response against coronavirus requires further studies to assess the potential benefit. Trial registration ClinicalTrials.gov, NCT03443102. Registered prospectively on 25 January 2018.

Angiotensin-Converting Enzyme Inhibitors, Angiotensin II Receptor Blockers, and Outcomes in Patients Hospitalized for COVID-19.

Background Use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (ACEi/ARB) is thought to affect COVID-19 through modulating levels of angiotensin-converting enzyme 2, the cell entry receptor for SARS-CoV2. We sought to assess the association between ACEi/ARB, biomarkers of inflammation, and outcomes in patients hospitalized for COVID-19. Methods and Results We leveraged the ISIC (International Study of Inflammation in COVID-19), identified patients admitted for symptomatic COVID-19 between February 1, 2020 and June 1, 2021 for COVID-19, and examined the association between in-hospital ACEi/ARB use and all-cause death, need for ventilation, and need for dialysis. We estimated the causal effect of ACEi/ARB on the composite outcomes using marginal structural models accounting for serial blood pressure and serum creatinine measures. Of 2044 patients in ISIC, 1686 patients met inclusion criteria, of whom 398 (23.6%) patients who were previously on ACEi/ARB received at least 1 dose during their hospitalization for COVID-19. There were 215 deaths, 407 patients requiring mechanical ventilation, and 124 patients who required dialysis during their hospitalization. Prior ACEi/ARB use was associated with lower levels of soluble urokinase plasminogen activator receptor and C-reactive protein. In multivariable analysis, in-hospital ACEi/ARB use was associated with a lower risk of the composite outcome of in-hospital death, mechanical ventilation, or dialysis (adjusted hazard ratio 0.49, 95% CI [0.36-0.65]). Conclusions In patients hospitalized for COVID-19, ACEi/ARB use was associated with lower levels of inflammation and lower risk of in-hospital outcomes. Clinical trials will define the role of ACEi/ARB in the treatment of COVID-19. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04818866.

Detection of Antibodies Against the SARS-CoV-2 Spike Protein and Analysis of the Peripheral Blood Mononuclear Cell Transcriptomic Profile, 15 Years After Recovery From SARS.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shows a high degree of homology with SARS-CoV. They share genes, protein sequences, clinical manifestations, and cellular entry patterns. Thus, SARS research may serve helpful in gaining a better understanding of the current coronavirus disease 2019 (COVID-19) pandemic. Serum antibodies from convalescent patients with SARS collected in 2018 were used to target the recombinant SARS-CoV-2 spike protein via a chemiluminescence microsphere immunoassay. Antibodies of convalescent patients with SARS exhibited serous immune cross-reactivity with the SARS-CoV-2 spike protein. The serous antibodies, excluding S22 of convalescent patients with SARS, did not competitively inhibit the binding of SARS-CoV-2 spike protein to ACE2. T cellular immunity research was conducted in vitro using peripheral blood mononuclear cells (PBMCs) stimulated by pooled peptide epitopes 15 years post-infection. Interferon gamma was detected and the PBMC transcriptomic profile was obtained. The heatmap of the transcriptomic profile showed that mRNAs and circRNAs of the SARS group clustered together after being stimulated by the peptide epitope pool. Differentially expressed mRNAs were most significantly enriched in immunity and signal transduction (P < 0.01). SARS elicits cytokine and chemokine responses, partially consistent with previously published data about COVID-19. Overall, our results indicate that antibodies from convalescent patients with SARS persisted for 15 years and displayed immune cross-reactivity with the SARS-CoV-2 spike protein. The immune status of patients with SARS 15 years post-infection may provide a better understanding of the future immune status of patients with COVID-19.

Severity Assessment of COVID-19 Using a CT-Based Radiomics Model.

The coronavirus disease of 2019 (COVID-19) has evolved into a worldwide pandemic. Although CT is sensitive in detecting lesions and assessing their severity, these works mainly depend on radiologists' subjective judgment, which is inefficient in case of a large-scale outbreak. This work focuses on developing a CT-based radiomics model to assess whether COVID-19 patients are in the early, progressive, severe, or absorption stages of the disease. We retrospectively analyzed the CT images of 284 COVID-19 patients. All of the patients were divided into four groups (0-3): early (n = 75), progressive (n = 58), severe (n = 75), and absorption (n = 76) groups, according to the progression of the disease and the CT features. Meanwhile, they were split randomly to training and test datasets with the fixed ratio of 7 : 3 in each category. Thirty-eight radiomic features were nominated from 1688 radiomic features after using select K-best method and the ElasticNet algorithm. On this basis, a support vector machine (SVM) classifier was trained to build this model. Receiver operating characteristic (ROC) curves were generated to determine the diagnostic performance of various models. The precision, recall, and f 1-score of the classification model of macro- and microaverage were 0.82, 0.82, 0.81, 0.81, 0.81, and 0.81 for the training dataset and 0.75, 0.73, 0.73, 0.72, 0.72, and 0.72 for the test dataset. The AUCs for groups 0, 1, 2, and 3 on the training dataset were 0.99, 0.97, 0.96, and 0.93, and the microaverage AUC was 0.97 with a macroaverage AUC of 0.97. On the test dataset, AUCs for each group were 0.97, 0.86, 0.83, and 0.89 and the microaverage AUC was 0.89 with a macroaverage AUC of 0.90. The CT-based radiomics model proved efficacious in assessing the severity of COVID-19.

Soluble Urokinase Receptor (SuPAR) in COVID-19-Related AKI.

BACKGROUND: AKI commonly occurs in patients with coronavirus disease 2019 (COVID-19). Its pathogenesis is poorly understood. The urokinase receptor system is a key regulator of the intersection between inflammation, immunity, and coagulation, and soluble urokinase plasminogen activator receptor (suPAR) has been identified as an immunologic risk factor for AKI. Whether suPAR is associated with COVID-19-related AKI is unknown. METHODS: In a multinational observational study of adult patients hospitalized for COVID-19, we measured suPAR levels in plasma samples from 352 adult patients that had been collected within 48 hours of admission. We examined the association between suPAR levels and incident in-hospital AKI. RESULTS: Of the 352 patients (57.4% were male, 13.9% were black, and mean age was 61 years), 91 (25.9%) developed AKI during their hospitalization, of whom 25 (27.4%) required dialysis. The median suPAR level was 5.61 ng/ml. AKI incidence rose with increasing suPAR tertiles, from a 6.0% incidence in patients with suPAR <4.60 ng/ml (first tertile) to a 45.8% incidence of AKI in patients with suPAR levels >6.86 ng/ml (third tertile). None of the patients with suPAR <4.60 ng/ml required dialysis during their hospitalization. In multivariable analysis, the highest suPAR tertile was associated with a 9.15-fold increase in the odds of AKI (95% confidence interval [95% CI], 3.64 to 22.93) and a 22.86-fold increase in the odds of requiring dialysis (95% CI, 2.77 to 188.75). The association was independent of inflammatory markers and persisted across subgroups. CONCLUSIONS: Admission suPAR levels in patients hospitalized for COVID-19 are predictive of in-hospital AKI and the need for dialysis. SuPAR may be a key component of the pathophysiology of AKI in COVID-19.