Nirmatrelvir/ritonavir use in patients with COVID-19 on hemodialysis: a case series

Patients undergoing hemodialysis (HD) are particularly vulnerable to coronavirus disease 2019 (COVID-19) and are at increased risk of developing severe infection. However, given the exclusion of such patients from clinical trials, there are limited data regarding the effectiveness of the antiviral drug nirmatrelvir/ritonavir (N/R) in patients on HD. We prescribed N/R to four patients on HD with COVID-19 after obtaining informed consent. Their clinical symptoms were improved at approximately 3 days after N/R administration. The viral load was reduced after approximately 10 days. The main adverse effects were nausea and vomiting. Rational dosage adjustment obtained good tolerance but did not influence the efficacy. These results suggest that N/R may be a promising agent for patients on HD with COVID-19.

The Value of Peripheral Blood Cell Ratios in Primary Membranous Nephropathy: A Single Center Retrospective Study.

Background: Primary membranous nephropathy (PMN) is a common cause of nephrotic syndrome in adults. Forty percent of the patients continue to progress and eventually develop into chronic renal failure. Although phospholipase A2 receptor (PLA2R) is the major antigen of PMN, the clinical features do not often parallel with the antibody titers. Therefore, it is significant to find relative credible markers to predict the treatment response. Methods: One hundred and eighteen PMN patients were recruited. The response to treatment was defined as ALB≥30g/L at 6 months and complete remission (CR) or not at the end of the follow-up. Renal outcome endpoint was defined as 50% or more Cr increase at the end. Results: The patients with poor treatment effects had numerically higher platelet-lymphocytes ratio (PLR). For patients with CR or not, the difference was near to statistic significant (P=0.095). When analyzing CR or not, the fitting of the binary logistic regression model including both PLA2R Ab titer and PLR (Hosmer-Lemeshow test: χ 2=8.328, P = 0.402; OR (PLA2R Ab titer) = 1.002 (95% CI 1.000-1.004, P = 0.042); OR (PLR) = 1.006 (95% CI 0.999-1.013, P = 0.098)) was markedly better than that with only PLA2R Ab titer (Hosmer-Lemeshow test: χ 2=13.885, P = 0.016). The patients with renal function deterioration showed significantly higher monocyte-lymphocyte ratio (MLR) (0.26 (0.22-0.31) vs 0.18 (0.13-0.22), P = 0.012). Conclusion: PMN patients with poor treatment response tended to have higher PLR at the time of renal biopsy, and a higher MLR was associated with poor renal outcomes. Our findings suggested that PLR and MLR might be used to predict treatment efficacy and prognosis for PMN patients, respectively.

The salivary and nasopharyngeal microbiomes are associated with SARS-CoV-2 infection and disease severity.

Emerging evidence suggests the oral and upper respiratory microbiota may play important roles in modulating host immune responses to viral infection. As the host microbiome may be involved in the pathophysiology of coronavirus disease 2019 (COVID-19), we investigated associations between the oral and nasopharyngeal microbiome and COVID-19 severity. We collected saliva (n = 78) and nasopharyngeal swab (n = 66) samples from a COVID-19 cohort and characterized the microbiomes using 16S ribosomal RNA gene sequencing. We also examined associations between the salivary and nasopharyngeal microbiome and age, COVID-19 symptoms, and blood cytokines. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection status, but not COVID-19 severity, was associated with community-level differences in the oral and nasopharyngeal microbiomes. Salivary and nasopharyngeal microbiome alpha diversity negatively correlated with age and were associated with fever and diarrhea. Oral Bifidobacterium, Lactobacillus, and Solobacterium were depleted in patients with severe COVID-19. Nasopharyngeal Paracoccus was depleted while nasopharyngeal Proteus, Cupravidus, and Lactobacillus were increased in patients with severe COVID-19. Further analysis revealed that the abundance of oral Bifidobacterium was negatively associated with plasma concentrations of known COVID-19 biomarkers interleukin 17F and monocyte chemoattractant protein-1. Our results suggest COVID-19 disease severity is associated with the relative abundance of certain bacterial taxa.

Changes in physical activity and sedentary time among children with asthma during the COVID-19 pandemic and influencing factors.

OBJECTIVE: Regular physical activity is essential for asthma control in children, but it remains understudied within the context of COVID-19. Physical activity and sedentary time levels before and during the COVID-19 pandemic among children with asthma were documented and differences by characteristics were explored. METHODS: This was a cross-sectional self-administered online survey study of 5- to 17-year-old children with asthma from the United States between December 2020 and April 2021. RESULTS: This study included 68 children with asthma. Although only 4.6% of the children were fully inactive before the pandemic, this number increased to 24.6% during the survey period (p < 0.001). Children spent significantly less time outdoors and more time in front of screens during the pandemic versus before (p < 0.001). The variety of activities in which children with asthma engaged in during the pandemic was lower than what they used to do prior to the COVID-19 crisis. Boys, Hispanic children, those of low-income households, and those not attending school in-person were significantly associated with less participation in physical activity during the pandemic. Ethnicity remained significantly associated after adjusting for multiple comparisons. CONCLUSIONS: During the COVID-19 pandemic, children with asthma were less active and spent more time in front of screens and less time outdoors. Subgroup analyses revealed individual, parental, and organizational characteristics being associated with differential participation in physical activity, highlighting disparities in opportunities for children with asthma of different circumstances to remain active and healthy during the pandemic. Additional, more robust longitudinal studies are needed to confirm these results.

Recent developments in the immunopathology of COVID-19.

There has been an important change in the clinical characteristics and immune profile of Coronavirus disease 2019 (COVID-19) patients during the pandemic thanks to the extensive vaccination programs. Here, we highlight recent studies on COVID-19, from the clinical and immunological characteristics to the protective and risk factors for severity and mortality of COVID-19. The efficacy of the COVID-19 vaccines and potential allergic reactions after administration are also discussed. The occurrence of new variants of concerns such as Omicron BA.2, BA.4, and BA.5 and the global administration of COVID-19 vaccines have changed the clinical scenario of COVID-19. Multisystem inflammatory syndrome in children (MIS-C) may cause severe and heterogeneous disease but with a lower mortality rate. Perturbations in immunity of T cells, B cells, and mast cells, as well as autoantibodies and metabolic reprogramming may contribute to the long-term symptoms of COVID-19. There is conflicting evidence about whether atopic diseases, such as allergic asthma and rhinitis, are associated with a lower susceptibility and better outcomes of COVID-19. At the beginning of pandemic, the European Academy of Allergy and Clinical Immunology (EAACI) developed guidelines that provided timely information for the management of allergic diseases and preventive measures to reduce transmission in the allergic clinics. The global distribution of COVID-19 vaccines and emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with reduced pathogenic potential dramatically decreased the morbidity, severity, and mortality of COVID-19. Nevertheless, breakthrough infection remains a challenge for disease control. Hypersensitivity reactions (HSR) to COVID-19 vaccines are low compared to other vaccines, and these were addressed in EAACI statements that provided indications for the management of allergic reactions, including anaphylaxis to COVID-19 vaccines. We have gained a depth knowledge and experience in the over 2 years since the start of the pandemic, and yet a full eradication of SARS-CoV-2 is not on the horizon. Novel strategies are warranted to prevent severe disease in high-risk groups, the development of MIS-C and long COVID-19.

Adsorption kinetics of 20 glucocorticoids at environmentally relevant concentrations in wastewater by powdered activated carbons and development of surrogate models.

Glucocorticoids (GCs) are widely used in the treatment of the coronavirus disease of 2019 (COVID-19), and the toxicity of GCs to aquatic organisms has aroused widespread concern. Powdered activated carbon (PAC) has proven effective in removing various trace organic pollutants. In this study, the adsorption behaviors of 20 typical GCs onto PACs were investigated at environmentally relevant concentrations (ng/L) in real wastewater, using four commercially available PACs (HDB, WPH, 20BF, PWA). The results showed that PAC adsorption was feasible for GC removal at ng/L concentrations. After adsorption for 60 min, the GC removal efficiencies obtained by HDB, WPH, 20BF, and PWA were 90-98 %, 89-97 %, 84-96 %, and 71-90 %, respectively. The adsorption processes of 20 GCs on PACs were well fitted by the pseudo-second-order kinetics model (with R 2 >0.98). Among the four PACs, HDB achieved the highest rates because of the electrostatic attraction between HDB (positively charged) and the complex of GCs and natural organic matter (GC-NOM, negatively charged). Among the 20 GCs, compounds with substitutions of halogen atoms or five-membered rings at C-17 achieved higher adsorption rates because of the enhanced formation of hydrogen bonds and a resulting increase in electron density. In addition, surrogate models with total fluorescence (TF) and ultraviolet absorbance at 254 nm (UV254) were developed to monitor the attenuation trend of GCs during adsorption processes. Compared with the UV254 model, the TF model showed better sensitivity to GC monitoring, which could greatly simplify the water quality monitoring process and facilitate online monitoring of GCs in water.

Assessment of Glucocorticoid Removal by UVA/Chlorination and Ozonation: Performance Comparison in Kinetics, Degradation Pathway, and Toxicity

Glucocorticoids (GCs) have drawn great concern due to widespread contamination in the environment and application in treating COVID-19. This work aimed to compare the performance of UVA/chlorination and ozonation on GC removal in terms of removal efficiency, degradation pathway, and toxicity change, with fluocinolone acetonide (FA), triamcinolone acetonide (TA), and clobetasol propionate (CP) as target compounds. The results showed that both UVA/chlorination and ozonation could degrade GCs. Compared with UVA/chlorination (removal efficiency of 89% for FA, 86% for TA, and 90% for CP at 7 h), ozonation (removal efficiency of 90% for FA, 96% for TA, and 98% for CP at 15 min) was more effective in GC removal. Photodegradation contributed most to GC removal during UVA/chlorination, while O3 molecules were the main functional species during ozonation. H-ion, dechlorination, carbon–carbon bond cleavage, and ester hydrolysis were proposed for both UVA/chlorination and ozonation based on the identification of intermediates. However, ozone tended to attack C=C double bonds, resulting in the cracked benzene ring of GCs, while chlorine was more likely to attack alcohol and ketone groups. Although most GCs were removed during ozonation and UVA/chlorination, their acute toxicities slightly declined. Compared with UVA/chlorination, ozonation was more effective in toxicity reduction.

Simultaneous degradation of glucocorticoids and sterilization using bubbling corona discharge plasma based systems: A promising terminal water treatment facility for hospital wastewater.

Glucocorticoids (GCs) have drawn great concern due to their widespread contamination in the environment and application in treating patients with COVID-19. Due to the lack of data about GC removal using advanced treatment processes, a novel Paralleling and bubbling corona discharge reactor (PBCD) combined with iron-loaded activated-carbon fibre (Fe-ACF) was addressed in this study to degrade GCs represented by Hydrocortisone (HC) and Betamethasone (BT). The results showed that the PBCD-based system can degrade GCs effectively and can achieve effective sterilization. The removal rates of GCs were ranked as PBCD/Fe-ACF > PBCD/ACF > PBCD. The concentration of E. coli was reduced from 109 to 102 CFU/mL after 60 min of PBCD-based system treatment. The abundance of bacteria in actual Hospital wastewater (HWW) was significantly reduced. Plasma changed the physical and chemical properties of ACF and Fe-ACF by etching axial grooves and enhancing stretching vibrations of surface functional groups, thus promoting adsorption and catalytic degradation. For GC degradation, the functional reactive species were identified as •OH, 1O2, and •O2 radicals. Possible degradation pathways for HC and BT were proposed, which mainly included defluorination, keto acid decarboxylation, demethylation, intramolecular cyclization, cleavage and ester hydrolysis, indicating a reduction in GC toxicity. Since GCs are widely used in patients with COVID-19 and their wastewater needs to be sterilized simultaneously, the intensive and electrically driven PBCD-based system is promising in GC pollution control and sterilization in terminal water treatment facilities.

Twin girls infected with SARS-CoV-2

This article reports the diagnosis and treatment of twin girls who were diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Hunan Province, China. The twin girls, aged 1 year and 2 months, were admitted on January 29, 2020 due to fever for one day and cough and sneezing for two days respectively. Both recovered after symptomatic treatment. The two girls had mild symptoms and rapid recovery, suggesting that children with SARS-CoV-2 infection may be mild and have a good prognosis. There were differences in the clinical symptoms and imaging findings between the twin girls, suggesting that SARS-CoV-2 infection has diverse clinical features in children.

Effectiveness of chelating agent-assisted Fenton-like processes on remediation of glucocorticoid-contaminated soil using chemical and biological assessment: performance comparison of CaO2 and H2O2.

Glucocorticoids (GCs) have drawn great concern due to widespread contamination in the environment and application in treating COVID-19. Most studies on GC removal mainly focused on aquatic environment, while GC behaviors in soil were less mentioned. In this study, degradation of three selected GCs in soil has been investigated using citric acid (CA)-modified Fenton-like processes (H2O2/Fe(III)/CA and CaO2/Fe(III)/CA treatments). The results showed that GCs in soil can be removed by modified Fenton-like processes (removal efficiency gt; 70% for 24 h). CaO2/Fe(III)/CA was more efficient than H2O2/Fe(III)/CA at low oxidant dosage (< 0.28-0.69 mmol/g) for long treatment time (> 4 h). Besides the chemical assessment with GC removal, effects of Fenton-like processes were also evaluated by biological assessments with bacteria and plants. CaO2/Fe(III)/CA was less harmful to the richness and diversity of microorganisms in soil compared to H2O2/Fe(III)/CA. Weaker phytotoxic effects were observed on GC-contaminated soil treated by CaO2/Fe(III)/CA than H2O2/Fe(III)/CA. This study, therefore, recommends CaO2-based treatments to remediate GC-contaminated soils.

Degradation of glucocorticoids in water by a synergistic system of peroxymonosulfate, microbubble and dielectric barrier discharges

Glucocorticoids (GCs) in the environment have been an increasing concern. Most recently, GCs have been shown to be an effective remedy to manage septic shock in patients infected with COVID-19. In this study, a self-made dielectric barrier discharge reactor integrating microbubbles and peroxymonosulfate (DBD/MB/PMS) was used to degrade the GCs in water. At neutral pH and ambient temperature, hydrocortisone (HC), betamethasone (BT) and fluocinolone acetonide (FA) were degraded effectively by the DBD/MB/PMS system with the 90-min degradation efficiencies of 77%, 80% and 82%, respectively (discharge power: 83.5 W;PMS:GC ratio: 20:1). In comparison, the 90-min degradation efficiencies for HC, BT and FA by DBD/MB system (discharge power: 83.5 W, pH unadjusted, flow rate 40 mg/L) were only 49%, 54% and 60% respectively;and the efficiencies by heat activated PMS (90 °C) were only 24%, 12%, and 16%, respectively. Hence, DBD/MB is an efficient approach for PMS activation, which resulted in increased removal efficiencies and energy yields for GCs degradation. The rate constants for GCs degradation also increased with the increase of PMS dosage and initial solution pH. Both SO4− and OH were prominent species for GCs degradation. Based on the results of scavenging experiment, the contributions of SO4− for HC, BT and FA degradation were roughly estimated to be 51%, 59% and 60%, respectively, and the contributions of OH were 30%, 29% and 27%, respectively. This work not only provides a novel approach in dealing with GCs contaminated water, but also highlights the synergistic effect of plasma, MB and PMS.

Enhanced degradation of glucocorticoids, a potential COVID-19 remedy, by co-fermentation of waste activated sludge and animal manure: The role of manure type and degradation mechanism.

Waste activated sludge (WAS) and animal manure are two significant reservoirs of glucocorticoids (GCs) in the environment. However, GC degradation during anaerobic digestion (AD) of WAS or animal manure has rarely been investigated. In this study, co-fermentation of WAS and animal manure was conducted to investigate the performance of AD in controlling GC dissemination. Effects of manure type on GC degradation and sludge acidification were investigated. The results showed that co-fermentation of WAS and chicken manure (CM) significantly enhanced the degradation of hydrocortisone (HC) to 99%, betamethasone (BT) to 99%, fluocinolone acetonide (FA) to 98%, and clobetasol propionate (CP) to 82% in 5 days with a mixing ratio of 1:1 (g TS sludge/g dw manure) at 55 °C and initial pH of 7. Simultaneously, sludge reduction was increased by 30% and value-added volatile fatty acid (VFA) production was improved by 40%. Even a high GC content of biomass (3.6 mg/g TS) did not impact both sludge hydrolysis and acidification. The amendment of WAS with CM increased soluble organic carbon, Ca2+, and relative abundance of anaerobes (Eubacterium) associated with organic compound degradation. Furthermore, 44 transformation products of HC, BT, FA, and CP with lower lipophilicity and toxicity were identified, indicating possible degradation pathways including hydroxylation, ketonization, ring cleavage, defluorination, hydrogenation, methylation, and de-esterification. Overall, this study provides a practical way to control GC pollution and simultaneously promote waste reduction and VFA production. Animal manure type as an overlooked factor for influencing co-fermentation performance and pollutant degradation was also highlighted.

Management of haemophilia patients in the COVID-19 pandemic: Experience in Wuhan and Tianjin, two differently affected cities in China.

OBJECTIVE: To identify lessons learned from haemophilia care experience in Wuhan (COVID-19 outbreak epicenter in China) and Tianjin (with relatively low COVID-19 incidence) in the pandemic. METHODS: We compared the challenges in haemophilia management attributed to local COVID-19 containment policies, healthcare resource availability, clotting factors supply, daily living restrictions and coping strategies employed. RESULTS: Wuhan was in lockdown with strict traffic controls, enforced quarantine and overwhelmed resources. Tianjin was in relatively relaxed countermeasures to COVID-19. In Wuhan, haemophilia treatment (for bleeding, prophylaxis, multidisciplinary team care, immune tolerance induction) and patient education were severely affected, while the challenges in Tianjin were less. In both cities, patients' fear for COVID-19 infection also affected their management. Coping strategy in Wuhan included channelling of clotting factors supply from hospitals to nine pharmacies; timely transfers of in-need patients to healthcare facilities by a volunteer service network jointly coordinated by the government, hospitals and the community. Although factor concentrate supply in each city was adequate, patients still worried whether there would be enough supply to last through the pandemics. Consequently, many downgraded their treatment regimens resulting in increased bleeding episodes. In both cities, telemedicine was promoted for patient care and education. CONCLUSIONS: The COVID-19 pandemic had varying adverse impacts on haemophilia care depending on the local infection incidence. Our experience suggests that haemophilia management strategies in the pandemic need to be established according to the local virus containment/mitigation policies, daily living restrictions and resource availability.

Prevention of COVID-19 infection in a pediatric oncology ward in Wuhan.

OBJECTIVE: To assess the screening and isolation measures for preventing coronavirus disease 2019 (COVID-19) infection from newly admitted patients into a pediatric oncology ward. METHODS: We retrospectively analyzed 44 patients with established hematologic malignancies admitted for chemotherapy from January 23 to March 27, 2020 in the Department of Pediatric Hematology of Tongji Hospital, Wuhan. Every patient and their caregivers were well educated on personal protection and put it into effect at home and in hospital. Screening for COVID-19 of all the patients and caregivers before admission was performed. Both clinical features and screening results including chest computerized tomography (CT); nucleic acid testing of nasopharyngeal, oropharyngeal or anal swabs; and quantitative antibodies (IgM and IgG) detecting of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) of these patients were described. RESULTS: The results of nucleic acid and antibodies (IgM and IgG) testing of all the 44 inpatients and their caregivers were negative. Abnormal chest CT images were observed in six symptomatic patients, while chest CT images of their caregivers did not show the changes related to viral pneumonia. These symptomatic patients all recovered after antibacterial combined with antifungal treatment, but without any antiviral agents. CONCLUSIONS: COVID-19 infection could be prevented in pediatric patients with malignancies if proper protective measures were implemented. For patients presenting suspicious symptoms, comprehensive examinations should be carried out.

Screening of SARS-CoV-2 in 299 Hospitalized Children with Hemato-oncological Diseases: A Multicenter Survey in Hubei, China.

The SARS-CoV-2 infection status of hospitalized children was surveyed in the department of pediatric hematology and oncology in three different hospitals of epidemic areas in Hubei, China. A cross-sectional study was performed to investigate the clinical characteristics, lung CT scan, SARS-CoV-2 nucleic acid test and serum antibodies of hospitalized children with hemato-oncological diseases from January 23 to April 24, 2020. 299 children were enrolled in this study, including 176 males (58.9%) and 123 females (41.1%), aged from 2 months to 16 years. 255 cases (85.3%) received chemotherapy or other immunosuppressive therapies, and there were 44 cases (14.7%) of other benign diseases. Nucleic acid test was performed on 258 children (86.3%) and one case was positive. 163 cases (54.5%) were tested for serum antibodies, and all of them were negative. Lung CT scan was performed on 247 children (82.6%), and 107 of them showed infectious changes. Only one case (0.33%) of COVID-19 was diagnosed in the group. The prevalence rate of COVID-19 in enrolled children with hemato-oncological diseases in Hubei was 0.33%. Immunosuppressed patients are not prone to produce related antibodies. Comprehensive protective measures and ward management can reduce the risk of SARS-CoV-2 infection in the group patients.