Successful management of persistent COVID-19 using combination antiviral therapy (nirmatrelvir/ritonavir and remdesivir) and intravenous immunoglobulin transfusion in an immunocompromised host who had received CD20 depleting therapy for follicular lymphoma.

The management of persistent symptomatic coronavirus disease 2019 (COVID-19) infections in immunocompromised patients remains unclear. Here, we present the first case of successful antiviral therapy (nirmatrelvir/ritonavir and remdesivir) in combination with intravenous immunoglobulin (IVIg) in a patient who had received CD20 depleting therapy for follicular lymphoma and experienced recurrent COVID-19 relapses. After the patient received IVIg treatment, the viral load decreased without recurrence. Subsequently, it was found that the anti-spike antibody titer in the administered immunoglobulin was high at 9528.0 binding antibody units/mL. Our case highlights the potential of combination therapy with selective IVIg and antiviral drugs for relapsed immunocompromised COVID-19 patients who have received CD20 depleting therapy.

Large-scale resurgence of herpangina in Japan, following the easing of COVID-19 measures.

Objectives: This study examined the rise in herpangina cases and its demographic trends in Japan post-easing of COVID-19 restrictions in the summer of 2023, assessing its potential strain on pediatric healthcare. Methods: Weekly herpangina cases data from the National Institute of Infectious Diseases from 2017 to 2023 were analyzed using difference-in-differences methodology and Poisson regression models, incorporating variables such as time, the COVID-19 pandemic, and the easing of measures. Statistical significance was set at a two-sided P-value of 0.05. Results: A significant increase in herpangina cases was observed from the 19th to the 27th week of 2023, with a notable shift in age distribution compared to that of pre-pandemic years. Poisson regression analysis revealed a positive correlation between the number of herpangina cases and the easing of infection control measures. There was an increase in other respiratory illnesses, including respiratory syncytial virus, particularly in children aged 3 and above. Conclusion: We found a surge in herpangina cases in Japan after the easing of the COVID-19 restrictions during the summer of 2023, along with a noticeable increase in other respiratory illnesses, emphasizing the potential strain on pediatric healthcare and reinforcing the ongoing significance of implementing general infection prevention strategies.

High diagnostic accuracy of quantitative SARS-CoV-2 spike-binding-IgG assay and correlation with in vitro viral neutralizing activity.

Background: Antibody testing can easily evaluate the clinical status of patients, aid in the diagnosis of multisystem inflammatory syndrome, and monitor the immunity level in the population. However, the applicability of serological tests in detecting antibodies against the severe acute respiratory syndrome 2 (SARS-CoV-2) spike-binding protein remains limited. This study aimed to quantify both serum-derived neutralizing immunoglobulin-G (IgG) antibody activity and the amount of anti-SARS-CoV-2 Spike-IgG (S-IgG) in convalescent sera/plasmas and evaluate the direct correlation between the in vitro IgG-EC50 values and S-IgG values. Methods: We evaluated the neutralizing activity of purified IgG (IgG-EC50), quantified S-IgG in the serum/plasma of consecutive COVID-19 convalescent individuals using a cell-based virus-neutralizing assay, and determined the correlation between IgG-EC50 and S-IgG. In addition, we evaluated rational cut-off values using the receiver operating characteristic (ROC) curve and calculated the sensitivity and specificity of the quantitative S-IgG assay for moderate and high IgG-EC50. Results: A high correlation was observed between S-IgG and IgG-EC50 with a Spearman's ρ value of -0.748 (95 % confidence interval [CI]: -0.804-0.678). Using an IgG-EC50 of 50 µg/mL and 20 µg/mL as the cut-off values for moderate and high in vitro neutralizing activity, respectively, the Youden's index values of 287.5 binding antibody units (BAU)/mL and 454.1 BAU/mL determined from the ROC curve showed the highest diagnostic accuracy, with Kappa values of 0.884 (95 % CI: 0.823-0.946) and 0.920 (95 % CI: 0.681-0.979), respectively. Conclusions: Quantitative S-IgG tests are a useful and convenient tool for estimating in vitro virus-neutralizing activity, with a high correlation with IgG-EC50 when the rational cut-off value is carefully determined.

Unfractionated Heparin Safety in COVID-19: Incidence and Risks of Bleeding Complications in Japan.

AIM: Several studies have shown the efficacy and safety of low-molecular-weight heparin use in coronavirus disease 2019 (COVID-19), but that of unfractionated heparin (UFH) has not been investigated. We investigated the prevalence of bleeding complications during UFH administration, its impact on mortality, and the risk factors of bleeding outcomes associated with UFH. METHODS: This retrospective cohort study was conducted at a single-center tertiary care hospital, including hospitalized patients with COVID-19. The primary outcomes were measured as the prevalence of bleeding complications during hospitalization, and the secondary outcomes were thromboembolic events and 60-day mortality rates. Logistic regression analysis and propensity score matching were used to assess risk factors for bleeding complications and their impact on mortality. RESULTS: Among 1035 included patients, 516 patients were treated with UFH. Twelve (2.3%) patients in the UFH group experienced major bleeding. The prevalence of major bleeding in patients treated with therapeutic-dose UFH was 9.2%. Logistic regression analysis showed that age ≥ 60 years (adjusted odds ratio [aOR], 3.89; 95% confidence interval [CI], 1.01-15.0; P＜.05) and COVID-19 severity (aOR, 35.9; 95% CI, 4.57-282; P＜.05) were associated with major bleeding complications. After propensity score matching, 11 major and 11 non-major bleeding cases (including minor bleeding) were matched. The 60-day cumulative mortality rate between the two groups did not differ significantly (P=.13, log-rank test). CONCLUSIONS: The incidence of major bleeding in COVID-19 patients using therapeutic-dose UFH was relatively high. Critical COVID-19 and older age were risk factors for bleeding complications.

A novel protocol for de-isolating moderately and severely immunocompromised COVID-19 patients.

Immunocompromised coronavirus disease 2019 patients are at a higher risk of prolonged viral shedding than immunocompetent patients. However, as of August 2023, there is no clear international standard for de-isolating vulnerable patients. A comprehensive assessment is advisable based on various information, such as the increase in immune escape of specific mutant strains as well as the patient's innate immunity and vaccination status; therefore, consultation with an infectious disease specialist is recommended. The patient population defined as moderately or severely immunocompromised by the Centers for Disease Control and Prevention and the European Centre for Disease Prevention and Control is significantly broad. A boundary between the two remains to be delineated, and the existing protocols allow the release of patients based on their symptoms alone. This may lead to an unnecessary extension or premature termination of isolation. In this study, we searched for studies, particularly those that used real-world data, discussed the results with experts in our hospital, and proposed new isolation criteria based on both testing and clinical symptoms. We classified patients into three groups namely severely, moderately, and mildly immunocompromised, defined by their background and the administration of immunosuppressive drugs. A separate flowchart for ending isolation is indicated for each group. This standard may be a useful support material, especially for non-specialists. Nevertheless, our criteria must be revised and added continuously; accumulating real-world data to support revision of and addition to the list is becoming increasingly important.

Characterization of a SARS-CoV-2 EG.5.1 clinical isolate in vitro and in vivo.

EG.5.1 is a subvariant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron XBB variant that is rapidly increasing in prevalence worldwide. However, the pathogenicity, transmissibility, and immune evasion properties of isolates of EG.5.1 are largely unknown. Here, we show that there are no obvious differences in growth ability and pathogenicity between EG.5.1 and XBB.1.5 in hamsters. We also demonstrate that, like XBB.1.5, EG.5.1 is transmitted more efficiently between hamsters compared to its predecessor, BA.2. In contrast, unlike XBB.1.5, we detect EG.5.1 in the lungs of four of six exposed hamsters, suggesting that the virus properties of EG.5.1 are different from those of XBB.1.5. Finally, we find that the neutralizing activity of plasma from convalescent individuals against EG.5.1 was slightly, but significantly, lower than that against XBB.1.5 or XBB.1.9.2. Our data suggest that the different virus properties after transmission and the altered antigenicity of EG.5.1 may be driving its increasing prevalence over XBB.1.5 in humans.