Mitochondrial disturbance related to increased caspase-1 of CD4+T cells in HIV-1 infection.

BACKGROUND: In HIV-1 infection, more than 95% of CD4+T cells die of caspase-1 mediated pyroptosis. What governs the increased susceptibility of CD4+T cells to pyroptosis is poorly understood. METHODS: Blood samples were obtained from 31 untreated HIV-infected patients (UNT), 29 antiretroviral therapy treated HIV-infected patients (ART), and 21 healthy control donors (HD). Plasma levels of IL-18 and IL-1ß, caspase-1 expression, mitochondrial mass (MM) and mitochondrial fusion/fisson genes of CD4+T subsets were measured. RESULTS: A significantly higher IL-18 level in plasma and MM level of CD4+T cells were found in HIV-infected patients (UNT and ART) compared to HD, and the MMhigh phenotype was manifested, related to increased caspase-1 expression. Moreover, the increased MM was more pronounced in the early differentiated and inactivated CD4+T cells. However, higher MM was not intrinsically linked to T cell differentiation disorder or excessive activation of the CD4+T cells. Mechanistically, the increased MM was significantly correlated with an elevated level of expression of the mitochondrial fusion gene mitofusin1. CONCLUSION: An increase in MM was associated with heightened sensitivity of CD4+T cells to pyroptosis, even in early differentiated and inactivated CD4+T cells, in patients with HIV-1 infection, regardless of whether patients were on antiretroviral therapy or not. These new revelations have uncovered a previously unappreciated challenge to immune reconstitution with antiretroviral therapy.

Ultrahigh Piezocatalytic Performance of Perovskite Ferroelectric Powder via Oxygen Vacancy Engineering.

Piezocatalysis has increasingly gained prominence due to its enormous potential for addressing energy shortages and environmental pollution issues. Nonetheless, the low piezocatalytic activity of state-of-the-art materials seriously inhibits the practical applications of piezocatalysis. Here, it is proposed to greatly enhance the piezocatalytic activity for a perovskite ferroelectric, i.e., Sm-doped 0.68Pb(Mg1/3 Nb2/3 )-0.32PbTiO3 (Sm-PMN-PT, a solid solution with ultrahigh piezoelectricity), by introducing oxygen vacancies (OVs). The results show that the presence of OVs promotes the production of reactive oxygen species while enhancing the adsorption and activation of organic pollutants to improve piezocatalytic performance. The OV-Sm-PMN-PT is found to possess a superior piezocatalytic degradation rate constant of 0.073 min-1 under ultrasonic vibration, which is ≈4.9 times higher than that of pristine Sm-PMN-PT. Furthermore, the OV-Sm-PMN-PT can efficiently remove RhB under 400 rpm stirring, making it a promising candidate for water purification using low-frequency mechanical energy from nature. This research sheds light on the design of piezocatalytic materials via defect engineering.

The impact of HBV infection on clinical outcomes of COVID-19 patients: a systematic review and meta-analysis.

The impact of hepatitis B virus (HBV) infection on clinical outcomes of coronavirus disease 2019 (COVID-19) remains unclear. The aim of this study is to explore this impact. For this systematic review and meta-analysis, we searched PubMed, Web of Science, Embase, Cochrane library, China National Knowledge Infrastructure (CKNI), China Science and Technology Journal Database (VIP), and Wan Fang database for articles between 1 January 2020 and 1 February 2023. We used the Newcastle-Ottawa Quality Assessment to evaluate the study's quality. A random-effects meta-analysis was performed utilising the rates of severe/critical illness and death in COVID-19 patients with and without HBV infection. Eighteen studies with a total of 40,502 participants met the inclusion criteria. The meta-analysis showed that compared to those without HBV infection, COVID-19 patients with HBV were at increased risk of mortality (OR = 1.65, I2 = 58%, and 95% CI 1.08-2.53) and severity (OR = 1.90, I2 = 44%, and 95% CI 1.62-2.24). The region and gender may influence the outcomes of COVID-19 patients with HBV infection, but it requires more global data to confirm. In conclusion, HBV infection is significantly linked to an increased risk of severity and mortality in COVID-19.

Nano-elemental selenium particle developed via supramolecular self-assembly of chondroitin sulfate A and Na2SeO3 to repair cartilage lesions.

Cartilage repair is a significant clinical issue due to its restricted ability to regenerate and self-heal after cartilage lesions or degenerative disease. Herein, a nano-elemental selenium particle (chondroitin sulfate A­selenium nanoparticle, CSA-SeNP) is developed by the supramolecular self-assembly of Na2SeO3 and negatively charged chondroitin sulfate A (CSA) via electrostatic interactions or hydrogen bonds followed by in-situ reducing of l-ascorbic acid for cartilage lesions repair. The constructed micelle exhibits a hydrodynamic particle size of 171.50 ± 2.40 nm and an exceptionally high selenium loading capacity (9.05 ± 0.03 %) and can promote chondrocyte proliferation, increase cartilage thickness, and improve the ultrastructure of chondrocytes and organelles. It mainly enhances the sulfation modification of chondroitin sulfate by up-regulating the expression of chondroitin sulfate 4-O sulfotransferase-1, -2, -3, which in turn promotes the expression of aggrecan to repair articular and epiphyseal-plate cartilage lesions. The micelles combine the bio-activity of CSA with selenium nanoparticles (SeNPs), which are less toxic than Na2SeO3, and low doses of CSA-SeNP are even superior to inorganic selenium in repairing cartilage lesions in rats. Thus, the developed CSA-SeNP is anticipated to be a promising selenium supplementation preparation in clinical application to address the difficulty of healing cartilage lesions with outstanding repair effects.

Dynamic Changes of ORF1ab and N Gene Ct Values in COVID-19 Omicron Inpatients of Different Age Groups - Beijing Municipality, China, November-December 2022.

Introduction: In November 2021, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant was identified as the variant of concern and has since spread globally, replacing other cocirculating variants. To better understand the dynamic changes in viral load over time and the natural history of the virus infection, we analyzed the expression of the open reading frames 1ab (ORF1ab) and nucleocapsid (N) genes in patients infected with Omicron. Methods: We included patients initially admitted to the hospital for SARS-CoV-2 infection between November 5 and December 25, 2022. We collected daily oropharyngeal swabs for quantitative reverse transcriptase-polymerase chain reaction tests using commercial kits. We depicted the cycle threshold (Ct) values for amplification of ORF1ab and N genes from individual patients in age-specific groups in a time series. Results: A total of 480 inpatients were included in the study, with a median age of 59 years (interquartile range, 42 to 78; range, 16 to 106). In the <45-year-old age group, the Ct values for ORF1ab and N gene amplification remained below 35 for 9.0 and 11.5 days, respectively. In the ≥80-year-old age group, the Ct values for ORF1ab and N genes stayed below 35 for 11.5 and 15.0 days, respectively, which was the longest among all age groups. The Ct values for N gene amplification took longer to rise above 35 than those for ORF1ab gene amplification. Conclusion: The time to test negative varied among different age groups, with viral nucleic acid shedding taking longer in older age groups compared to younger age groups. As a result, the time to resolution of Omicron infection increased with increasing age.

Drug Resistance to HIV-1 Integrase Inhibitors Among Treatment-Naive Patients in Beijing, China.

Introduction: Integrase strand transfer inhibitors (INSTIs) are important drugs that are currently used as the first line treatment for HIV-1 patients. The aim of this study was to characterize HIV-1 INSTI mutations among ART-naive patients in Beijing from 2019-2021. Methods: 865 ART-naive patients were enrolled in this study between January 2019 and June 2021 in Beijing. The amplification of the entire pol gene containing the reverse transcriptase, protease and integrase regions was performed using a validated In-house SBS method. HIV-1 subtypes and circulating recombinant forms (CRFs) were determined using the COMET online tool (http://comet.retrovirology.lu). Stanford HIV-1 drug resistance database (HIVdb version 8.9) was used to analyze the mutations. Results: 865 HIV-1 pol sequences were successfully amplified and sequenced. Among them, no major INSTI-related mutations were identified, but 12 polymorphic accessory mutations were found. Two patients have E138A and G163R mutations respectively and both could cause low-level resistance to RAL and EVG. Furthermore, one patient having S230R mutation resulted in low-level resistance to RAL, EVG, DTG and BIC. Conclusion: The prevalence of INSTIs mutations remains low, which demonstrated that INSTIs have good applicability currently in our city. Nevertheless, it is very important to monitor the INSTI-related mutations in Beijing.

Factors Associated with SARS-CoV-2 Repeat Positivity - Beijing, China, June-September 2020.

INTRODUCTION: Repeat positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) following COVID-19 initial viral clearance (re-positivity) poses a public health management challenge. The objective was to determine factors associated with neutralizing antibody (Nab) level and re-positivity among patients infected with a single strain SARS-CoV-2. METHODS: During a single strain SARS-CoV-2 cluster in Beijing, China, longitudinal individual clinical, virological, and immunological data were collected from 368 infections from June 13 to September 22, 2020. Factors associated with Nab level and re-positivity were analyzed using generalized estimating equations. RESULTS: A total of 353 (96%) SARS-CoV-2 infections had demographic, clinical, and laboratory data available. Among the 353 infections, 55 (15.5%) were re-positive, and blood draws were taken from 346 individuals (98.0%) during hospitalization and/or during the follow-up period. Symptoms were milder for the second-time admission for the re-positives, although 36.4% of re-positives presented with radiographic appearance of pneumonia manifestation. Compared to non-re-positive patients, NAb titers were lower among re-positives; NAb was positively associated with clinical severity. Samples from the lower respiratory tract manifested higher viral load than that from the upper respiratory tract. Multivariable analysis showed re-positivity was positively associated with being female [odd ratio (OR)=1.7, 95% confidence interval (CI) 1.1-2.8] and being aged <18 years (OR=5.2, 95% CI 1.5-18.1); having initially asymptomatic infection (OR=13.7, 95% CI 1.6-116.3); and negatively associated with a higher NAb level (OR=0.9, 95% CI 0.5-1.7). CONCLUSIONS: NAb may be important for sustained viral clearance. Lower respiratory tract infection was associated with higher viral load among all infections when compared to upper respiratory tract infection. Continuous lower respiratory and intermittent upper respiratory viral shedding among COVID-19 infections may occur.

Accelerated Aging of T-Cell Subsets Among ART-Naïve HIV-Infected Chinese Men Who have Sex with Men: A Case-Control Study.

BACKGROUND: Evidence of lymphopoiesis, exhaustion, and premature aging in Chinese patients with human immunodeficiency virus (HIV) is very limited. OBJECTIVE: To assess biological aging and immune senescence in Chinese healthy controls (HC) and ART-naïve HIV-infected men who have sex with men (MSM). METHODS: This case-control study was conducted in Beijing Ditan Hospital from March 2018 to June 2019. The percentages of naïve (TN), central memory (TCM), effector memory (TEM), and terminally differentiated memory (TemRA) subsets of CD4 and CD8 T cells were studied, along with markers of senescence (CD28-CD57+) and activation (HLA-DR+). Telomere length of naïve (CD45RA+) and memory (CD45RO+) CD8 T cells were quantified by real-time PCR. RESULTS: A total of 26 HIV-infected and 20 age-matched HC MSM were included. Compared to the HC group, the CD4/CD8 ratio of the HIV-infected group was significantly reduced (0.30 vs. 1.70, P<0.001); significant differences emerged among all CD8 but not CD4 T cell subsets (all P<0.05). In the HIV-infected group, the percentages of senescent cells (CD28-CD57+) in TN, TCM, TEM, and TemRA subsets of CD8 T cells were higher (all P<0.05); while a significant difference was only found in naïve CD4 T cells (P<0.05). HLA-DR expression was increased significantly in all CD4 and CD8 T cell subsets. Both naïve (CD45RA+) and memory (CD45RO+) CD8 T cells in this population had significantly shorter telomere lengths (P<0.01) compared to the HC group. CONCLUSION: HIV-infected MSM exhibit signs of accelerated immune senescence and biological aging, which particularly affects the CD8 T-cell subsets.

The characteristics of overseas imported COVID-19 cases and the effectiveness of screening strategies in Beijing, China.

BACKGROUND: In March 2020, the WHO declared the novel coronavirus outbreak a global pandemic. While great success in coronavirus disease 2019 (COVID-19) control has been achieved in China, imported cases have become a major challenge. This study aimed to describe the epidemiological and clinical characteristics of imported COVID-19 cases and to assess the effectiveness of screening strategies in Beijing, China. METHODS: This retrospective study included all imported cases transferred to Beijing Ditan Hospital from 29 February to 20 March 2020 who were screened by both chest computed tomography (CT) and reverse-transcriptase-polymerase chain reaction (RT-PCR) at the initial presentation. Demographic, clinical and laboratory data, in addition to chest CT imaging, were collected and analysed. RESULTS: In total, 2545 cases were included, among which 71 (2.8%) were finally diagnosed with laboratory-confirmed COVID-19. The majority 63 (88.7%) were from Europe. The most common initial symptoms were cough and fever, which accounted for 49.3% and 42.3%, respectively. Only four cases (5.6%) had lymphocytopenia, and thirteen cases (18.3%) demonstrated elevated levels of C-reactive protein (CRP). All cases had normal serum levels of procalcitonin (PCT). At initial presentation, among the 71 confirmed cases, 59 (83.1%) had a positive RT-PCR assay, and 35 (49.3%) had a positive chest CT. Twelve (16.9%) had a negative RT-PCR assay but a positive chest CT. CONCLUSIONS: A combination of RT-PCR and chest CT is an effective strategy for the screening of imported COVID-19 cases. Our findings provide important information and clinical evidence about the infection control of imported COVID-19 cases.

Serum Levels of Seven General Cytokines in Acute Brucellosis Before and After Treatment.

PURPOSE: Human brucellosis is the most common bacterial zoonosis globally that poses a severe health threat. Despite the availability of antibiotic therapy for human brucellosis, its tendencies of chronicity and persistence may lead to severe debilitating and disabling conditions in patients. Comprehensive understanding of the immune response in brucellosis will be helpful in improving the treatment strategies. In this study, we measured serum levels of T helper cell type 1 (Th1), Th2, and Th17 cytokines in patients with acute brucellosis before and after treatment. PATIENTS AND METHODS: Overall, 30 patients with acute brucellosis from the Beijing Di Tan Hospital and 26 healthy controls were enrolled in this study. All the patients received a 6-week therapy regimen comprising ceftriaxone, doxycycline, and rifampicin. Serum samples were collected from patients with acute Brucella infection and healthy controls before and after treatment. Serum seven cytokine levels of Th1 (IL-2, IFN-γ, and TNF-α), Th2 (IL-4, IL-6, IL-10), and Th17 (IL-17A) were measured using cytometric bead array. RESULTS: In patients with acute infection, the IL-2, IFN-γ, and IL-10 levels were significantly increased compared with those in healthy controls (P < 0.001). After treatment, IL-2, IFN-γ, and IL-10 levels significantly decreased (P < 0.05) and the TNF-α level significantly increased compared with the corresponding baseline levels and those in healthy controls (P < 0.05). Furthermore, the IFN-γ, IL-4, and IL-10 levels were higher in patients after treatment than in healthy controls (P < 0.05). IL-2 and IL-6 levels exhibited a positive correlation with the C-reactive protein (CRP) level in acute brucellosis (P < 0.05). CONCLUSION: Levels of most serum Th1 and Th2 cytokines were simultaneously increased in acute infection, followed by reduction in the corresponding cytokine levels and residual cytokine response during treatment. This residual immune response could represent a therapeutic opportunity that may improve the long-term clinical outcomes in patients with acute brucellosis after treatment.

Impact of immune checkpoint molecules on FoxP3+ Treg cells and related cytokines in patients with acute and chronic brucellosis.

BACKGROUND: The immunoregulatory functions of regulatory T cells (Tregs) in the development and progression of some chronic infectious diseases are mediated by immune checkpoint molecules and immunosuppressive cytokines. However, little is known about the immunosuppressive functions of Tregs in human brucellosis, which is a major burden in low-income countries. In this study, expressions of immune checkpoint molecules and Treg-related cytokines in patients with acute and chronic Brucella infection were evaluated to explore their impact at different stages of infection. METHODS: Forty patients with acute brucellosis and 19 patients with chronic brucellosis admitted to the Third People's Hospital of Linfen in Shanxi Province between August 2016 and November 2017 were enrolled. Serum and peripheral blood mononuclear cells were isolated from patients before antibiotic treatment and from 30 healthy subjects. The frequency of Tregs (CD4+ CD25+ FoxP3+ T cells) and expression of CTLA-4, GITR, and PD-1 on Treg cells were detected by flow cytometry. Levels of Treg-related cytokines, including IL-35, TGF-ß1, and IL-10, were measured by customised multiplex cytokine assays using the Luminex platform. RESULTS: The frequency of Tregs was higher in chronic patients than in healthy controls (P = 0.026) and acute patients (P = 0.042); The frequency of CTLA-4+ Tregs in chronic patients was significantly higher than that in healthy controls (P = 0.011). The frequencies of GITR+ and PD-1+ Tregs were significantly higher in acute and chronic patients than in healthy controls (P < 0.05), with no significant difference between the acute and chronic groups (all P > 0.05). Serum TGF-ß1 levels were higher in chronic patients (P = 0.029) and serum IL-10 levels were higher in acute patients (P = 0.033) than in healthy controls. We detected weak correlations between serum TGF-ß1 levels and the frequencies of Tregs (R = 0.309, P = 0.031) and CTLA-4+ Tregs (R = 0.302, P = 0.035). CONCLUSIONS: Treg cell immunity is involved in the chronicity of Brucella infection and indicates the implication of Tregs in the prognosis of brucellosis. CTLA-4 and TGF-ß1 may contribute to Tregs-mediated immunosuppression in the chronic infection stage of a Brucella infection.

Microbiome Profiling Using Shotgun Metagenomic Sequencing Identified Unique Microorganisms in COVID-19 Patients With Altered Gut Microbiota.

COVID-19 is mainly associated with respiratory distress syndrome, but a subset of patients often present gastrointestinal (GI) symptoms. Imbalances of gut microbiota have been previously linked to respiratory virus infection. Understanding how the gut-lung axis affects the progression of COVID-19 can provide a novel framework for therapies and management. In this study, we examined the gut microbiota of patients with COVID-19 (n = 47) and compared it to healthy controls (n = 19). Using shotgun metagenomic sequencing, we have identified four microorganisms unique in COVID-19 patients, namely Streptococcus thermophilus, Bacteroides oleiciplenus, Fusobacterium ulcerans, and Prevotella bivia. The abundances of Bacteroides stercoris, B. vulgatus, B. massiliensis, Bifidobacterium longum, Streptococcus thermophilus, Lachnospiraceae bacterium 5163FAA, Prevotella bivia, Erysipelotrichaceae bacterium 6145, and Erysipelotrichaceae bacterium 2244A were enriched in COVID-19 patients, whereas the abundances of Clostridium nexile, Streptococcus salivarius, Coprococcus catus, Eubacterium hallii, Enterobacter aerogenes, and Adlercreutzia equolifaciens were decreased (p < 0.05). The relative abundance of butyrate-producing Roseburia inulinivorans is evidently depleted in COVID-19 patients, while the relative abundances of Paraprevotella sp. and the probiotic Streptococcus thermophilus were increased. We further identified 30 KEGG orthology (KO) modules overrepresented, with 7 increasing and 23 decreasing modules. Notably, 15 optimal microbial markers were identified using the random forest model to have strong diagnostic potential in distinguishing COVID-19. Based on Spearman's correlation, eight species were associated with eight clinical indices. Moreover, the increased abundance of Bacteroidetes and decreased abundance of Firmicutes were also found across clinical types of COVID-19. Our findings suggest that the alterations of gut microbiota in patients with COVID-19 may influence disease severity. Our COVID-19 classifier, which was cross-regionally verified, provides a proof of concept that a set of microbial species markers can distinguish the presence of COVID-19.

Comparative study on the clinical characteristics of local cases of COVID-19 and imported cases from abroad: A retrospective cohort study.

ABSTRACT: It is presently unknown whether imported cases of the 2019 coronavirus disease (COVID-19) have different characteristics when compared with local cases. To compare the clinical characteristics of local cases of COVID-19 in China compared with those imported from abroad.This was a retrospective study of confirmed cases of COVID-19 admitted at the Beijing Ditan Fever Emergency Department between February 29th, 2020, and March 27th, 2020. The clinical characteristics of the patients were compared between local and imported cases.Compared with local cases, the imported cases were younger (27.3 ±â€Š11.7 vs. 43.6 ±â€Š22.2 years, P < .001), had a shorter interval from disease onset to admission (1.0 (0.0-2.0) vs 4.0 (2.0-7.0) days, P < .001), lower frequencies of case contact (17.4% vs 94.1%, P < .001), fever (39.1% vs 82.4%, P < .001), cough (33.3% vs 51.0%, P = .03), dyspnea (1.9% vs 11.8%, P = .01), fatigue (7.5% vs. 27.5%, P = 0.001), muscle ache (4.7% vs. 25.5%, P < 0.001), and comorbidities (P < .05). The imported cases were less severe than the local cases, with 40.4% versus 5.9% mild cases, 2.8% versus 15.7% severe cases, and no critical cases (P < .001). The length of hospital stay was longer in imported cases than in local cases (32.3 ±â€Š14.5 vs 21.7 ±â€Š11.2 days, P < .001). The imported cases showed smaller biochemical perturbations than the local cases. More imported cases had no sign of pneumonia at computed tomography (45.0% vs 14.9%, P = .001), and none had pleural effusion (0% vs 14.9%, P < .001).Compared with local cases, the imported cases of COVID-19 presented with milder disease and less extensive symptoms and signs.

Early and consecutive RT-PCR tests with both oropharyngeal swabs and sputum could improve testing yield for patients with COVID-19: An observation cohort study in China.

OBJECTIVE: The real-time polymerase chain reaction (RT-PCR) test is recommended for the diagnosis of COVID-19 and provides a powerful tool to identify new infections and facilitate contact tracing. In fact, as the prevalence of COVID-19 decreases, this RT-PCR testing remains as the main preventive measure to avoid rebound. However, inconsistent results can lead to misdiagnoses in the clinic. These inconsistencies are due to the variability in (1) the collection times of biological samples post infection, and (2) sampling procedures. METHODS: We applied the Kaplan-Meier method and multivariate logistic regression on RT-PCR results from 258 confirmed patients with COVID-19 to evaluate the factors associated with negative conversion. We also estimated the proportion (%) of negative conversion among patients who had tested twice or more, and compared the proportions arising from oropharyngeal swabs, sputum, and combined double testing, respectively. MAIN RESULTS: The proportion of negative conversion was 6.7% on day 4, 16.4% on day 7, 41.0% at 2 weeks, and 61.0% at 3 weeks post-admission. We also found that 34.1% and 60.3% of subjects had at least one negative RT-PCR result on days 7 and 14 after the onset of symptoms, respectively. The proportion of negative conversions following sputum testing was higher than that from oropharyngeal swabs in the early stages but this declined after the onset of symptoms. CONCLUSION: In the absence of effective treatments or vaccines, efficient testing strategies are critical if we are to control the COVID-19 epidemic. According to this study, early, consecutive and combined double testing, will be the key to identify infected patients, particularly for asymptomatic and mild symptomatic cases. These strategies will minimize misdiagnosis and the ineffective isolation of infected patients.

Phylogenomic tracing of asymptomatic transmission in a COVID-19 outbreak.

SARS-CoV-2 has caused over 100 million deaths and continues to spread rapidly around the world. Asymptomatic transmission of SARS-CoV-2 is the Achilles' heel of COVID-19 public health control measures. Phylogenomic data on SARS-CoV-2 could provide more direct information about asymptomatic transmission. In this study, using a novel MINERVA sequencing technology, we traced asymptomatic transmission of COVID-19 patients in Beijing, China. One hundred and seventy-eight close contacts were quarantined, and 14 COVID-19 patients were laboratory confirmed by RT-PCR. We provide direct phylogenomic evidence of asymptomatic transmission by constructing the median joining network in the cluster. These data could help us to determine whether the current symptom-based screening should cover asymptomatic persons.

Bacterial and fungal co-infections among COVID-19 patients in intensive care unit.

This study aimed to investigate the frequency and characteristics of respiratory co-infections in COVID-19 patients in the intensive care unit (ICU). In this retrospective observational study, pathogens responsible for potential co-infections were detected by the bacterial culture, real-time polymerase chain reaction (RT-PCR), or serological fungal antigen tests. Demographic and clinical characteristics, as well as microbial results, were analyzed. Bacterial culture identified 56 (58.3%) positive samples for respiratory pathogens, with the most common bacteria being Burkholderia cepacia (18, 18.8%). RT-PCR detected 38 (76.0%) and 58 (87.9%) positive results in the severe and critical groups, respectively. Most common pathogens detected were Stenotrophomonas maltophilia (28.0%) and Pseudomonas aeruginosa (28.0%) in the severe group and S. maltophilia (45.5%) in the critical group. P. aeruginosa was detected more during the early stage after ICU admission. Acinetobacter baumannii and Staphylococcus aureus were more frequently identified during late ICU admission. Fungal serum antigens were more frequently positive in the critical group than in the severe group, and the positive rate of fungal serum antigens frequency increased with prolonged ICU stay. A high frequency of respiratory co-infections presented in ICU COVID-19 patients. Careful examinations and necessary tests should be performed to exclude these co-infections.

Cross-reactive antibody against human coronavirus OC43 spike protein correlates with disease severity in COVID-19 patients: a retrospective study.

Seasonal human coronaviruses (HCoVs) including HCoV-229E, -OC43, -NL63, and -HKU1 widely spread in global human populations. However, the relevance of humoral response against seasonal HCoVs to COVID-19 pathogenesis is elusive. In this study, we profiled the temporal changes of IgG antibody against spike proteins (S-IgG) of SARS-CoV-2 and seasonal HCoVs in 838 plasma samples collected from 344 COVID-19 patients. We tested the antigenic cross-reactivities of S protein between SARS-CoV-2 and seasonal HCoVs and evaluated the correlations between the levels of HCoV-OC43 S-IgG and the disease severity in COVID-19 patients. We found that SARS-CoV-2 S-IgG titres mounted until days 22-28, whereas HCoV-OC43 antibody titres increased until days 15-21 and then plateaued until day 46. However, IgG titres against HCoV-NL63, -229E, and -HKU1 showed no significant increase. A two-way cross-reactivity was identified between SARS-CoV-2 and HCoV-OC43. Neutralizing antibodies against SARS-CoV-2 were not detectable in healthy controls who were positive for HCoV-OC43 S-IgG. HCoV-OC43 S-IgG titres were significantly higher in patients with severe disease than those in mild patients at days 1-21 post symptom onset (PSO). Higher levels of HCoV-OC43 S-IgG were also observed in patients requiring mechanical ventilation. At days 1-10 PSO, HCoV-OC43 S-IgG titres correlated to disease severity in the age group over 60. Our data indicate that there is a correlation between cross-reactive antibody against HCoV-OC43 spike protein and disease severity in COVID-19 patients.