Clinical presentation, viral shedding, and neutralizing antibody responses of mpox cases in South Korea: Single center experience.

BACKGROUND: A global mpox outbreak occurred in 2022, and a domestic outbreak started in South Korea in April 2023. This study aimed to evaluate the clinical characteristics, viral shedding, and immune response of mpox in South Korea. METHODS: Patients hospitalized with mpox in the National Medical Center between September 2022 and June 2023 were included in this study. Oropharyngeal (OP), anogenital lesion (AL), and skin lesion (SL) swabs and blood samples were collected, and monkeypox virus (MPXV) DNA using real-time polymerase chain reaction (RT-PCR) and culture assays were performed. Neutralizing antibodies (NAbs) against MPXV A.2.1, B.1.1, and B.1.3 were detected using plaque reduction neutralization tests. RESULTS: Eighteen patients were enrolled, of whom 17 (94.4 %) were male, with a median (IQR) age of 32.5 (24-51) years. While nine (50 %) were HIV-infected individuals, none of them revealed CD4+ counts less than 200 cells/µL. MPXV DNA was detected in 87.3 % and 82.7 % of patient's ALs and SLs, respectively, until 2 weeks after symptom onset. While MPXV was isolated for up to 15 days in all three sample types, the culture positivity decreased to 53.8 % and 42.9 % in ALs and SLs after 10 days, respectively, and 28.6 % and 22.2 %, respectively, after 2 weeks from symptom onset. The NAb titers against MPXV A.2.1 were significantly lower than those against B.1.1 and B.1.3. CONCLUSIONS: Infectious MPXV was isolated from various anatomical sites up to 15 days after symptom onset. The MPXV NAb response was varied among different lineages, and this implies limited cross-lineage protection.

Severe mpox requiring colostomy in a patient with advanced HIV disease: A case report and literature review.

This severe monkeypox case described a 23-year-old male with advanced HIV-1 disease presenting perirectal abscess, extensive anal ulcerative lesions requiring colostomy, and tecovirimat resistance. Radiologically non-liquefied perirectal abscess presented diagnostic challenges highlighting the complexity of aggressive monkeypox manifestations in immunocompromised individuals.

Expert Consensus on the Structure, Role, and Procedures of the Korea Expert Committee on Immunization Practices.

BACKGROUND: The Korea Expert Committee on Immunization Practices (KECIP) is a key advisory body the government to develop guidelines and provide technical advisory activities on immunization policies in Korea. A recent policy study, inspired by global best practices, aims to enhance KECIP's functionality for providing timely and transparent recommendations in the face of evolving vaccine science and emerging infectious diseases like COVID-19. METHODS: This study reviewed the current status of KECIP and collected expert opinions through surveys and consultations. Among the 40 panel members who were surveyed, 19 responded to a questionnaire specifically designed to assess the potential areas of improvement within KECIP. RESULTS: The majority of respondents favored maintaining the current member count and emphasized the need for a subcommittee. Opinions varied on issues such as the length of KECIP's term, the representation of vaccine manufacturers' perspectives, and the chairperson's role. However, there was a consensus on the importance of expertise, transparency, and fair proceedings within the committee. CONCLUSION: This study underscores the pivotal role of KECIP in shaping national immunization policies, emphasizing the necessity for informed guidance amidst evolving vaccine science and emerging infectious diseases. Furthermore, it stressed the importance of enhancing KECIP's capacity to effectively address evolving public health challenges and maintain successful immunization programs in South Korea.

Genomic Analysis of Monkeypox Virus During the 2023 Epidemic in Korea.

We aimed to characterize the genomes of monkeypox virus isolates from the Far East, providing insights into viral transmission and evolution. Genomic analysis was conducted on 8 isolates obtained from patients with monkeypox virus disease in the Republic of Korea between May 2022 and early 2023. These isolates were classified into Clade IIb. Distinct lineages, including B.1.1, A.2.1, and B.1.3, were observed in 2022 and 2023 isolates, with only the B.1.3 lineage detected in six isolates of 2023. These genetic features were specific to Far East isolates (the Republic of Korea, Japan, and Taiwan), distinguishing them from the diverse lineages found in the Americas, Europe, Africa, and Oceania. In early 2023, the prevalence of the B.1.3 lineage of monkeypox virus identified in six patients with no overseas travel history is considered as an indicator of the potential initiation of local transmission in the Republic of Korea.

Adverse Reactions After Intradermal Vaccination With JYNNEOS for Mpox in Korea.

In response to the Mpox domestic epidemic, South Korea initiated a nationwide vaccination program in May 2023, administering a 0.1 mL intradermal dose of JYNNEOS (Modified Vaccinia Ankara vaccine, Bavarian Nordic) to a high-risk group. To investigate the adverse reactions after intradermal JYNNEOS vaccination, an anonymous online survey was conducted at the National Medical Center from May 22 to July 31, 2023. Overall, 142 individuals responded. Over 80% of the respondents reported local reactions of predominantly mild severity. The predominant local reactions were pruritus, redness, and swelling; their incidence rates after the first dose were 66.2%, 48.1%, and 49.4%, respectively; the corresponding rates after the second dose were 69.2%, 60.6%, and 53.8%. Fewer respondents reported systemic symptoms. The most common systemic symptom was fatigue, the incidence rates of which after the first and second doses were 37.7% and 24.6%, respectively. Overall, the intradermally administered JYNNEOS vaccine appeared well tolerated.

Double Primary Cancers of Earlobe Merkel Cell Carcinoma and Lung Adenocarcinoma.

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine carcinoma with a high rate of metastasis. MCC is rarely suspected during clinical examination, thus requiring biopsy to establish a pathologic diagnosis. In addition, MCC sometimes occurs in double primary cancers. Although there have been reviews on double primary cancers, only a few cases involving MCC have been described. Herein, we report a case of a 54-year-old female patient who presented to our clinic with a diagnosis of earlobe MCC following an excisional biopsy performed by another clinic. Further evaluation, including chest imaging, revealed a mass in the lung. The patient underwent a wide excision of the right earlobe, and video-assisted thoracic surgery on the lung. Pathology confirmed MCC in the right earlobe and adenocarcinoma in the lung. The patient underwent postoperative adjuvant chemotherapy followed by radiotherapy. Up to this point, 3 years after the surgery, there has been no evidence of recurrence.

Clinical Features of Mpox Patients in Korea: A Multicenter Retrospective Study.

BACKGROUND: Mpox is a viral illness with a characteristic skin rash caused by the monkeypox virus. In 2022, Mpox spread throughout the world, and an epidemic through domestic transmission started in South Korea in early 2023. This study aimed to summarize the clinical features of Mpox patients in South Korea. METHODS: This is a multicenter retrospective study conducted at four hospitals in South Korea. All adult patients diagnosed with Mpox who were admitted to the study hospitals between June 1, 2022 and May 26, 2023 and were discharged by June 30, 2023 were reviewed. RESULTS: Sixty patients were included, accounting for 65.9% of Mpox cases reported in South Korea during the study period. Median age was 32 years and 97% (58/60) of patients were male. In total, 85% (51/60) of patients reported their sexual orientation as homosexual or bisexual. The most common route of transmission was sexual or close contact (55/60). Every patient had a skin rash and 88% (53/60) had constitutional symptoms. In total, 42% (25/60) of patients had human immunodeficiency virus and 25% (15/60) had concomitant sexually transmitted infections. Severe manifestations of Mpox were identified in only two patients. CONCLUSION: Mpox patients in South Korea were mainly young adult males and were infected through sexual contact. The clinical outcomes were favorable.

The Association Between Antibody Responses and Prolonged Viable Severe Acute Respiratory Syndrome Coronavirus 2 Shedding in Immunocompromised Patients: A Prospective Cohort Study.

Immunocompromised patients with coronavirus disease 2019 were prospectively enrolled from March to November 2022 to understand the association between antibody responses and severe acute respiratory syndrome coronavirus 2 shedding. A total of 62 patients were analyzed, and the results indicated a faster decline in genomic and subgenomic viral RNA in patients with higher neutralizing and S1-specific immunoglobulin G (IgG) antibodies (both P < .001). Notably, high neutralizing antibody levels were associated with a significantly faster decrease in viable virus cultures (P = .04). Our observations suggest the role of neutralizing antibodies in prolonged virus shedding in immunocompromised patients, highlighting the potential benefits of enhancing their humoral immune response through vaccination or monoclonal antibody treatments.

Virological characteristics and the rapid antigen test as deisolation criteria in immunocompromised patients with COVID-19: A prospective cohort study.

There are limited data supporting current Centers for Disease Control and Prevention guidelines for the isolation period in moderate to severely immunocompromised patients with coronavirus disease 2019 (COVID-19). Adult COVID-19 patients who underwent solid organ transplantation (SOT) or received active chemotherapy against hematologic malignancy were enrolled and weekly respiratory samples were collected. Samples with positive genomic real-time polymerase chain reaction results underwent virus culture and rapid antigen testing (RAT). A total of 65 patients (40 with hematologic malignancy and 25 SOT) were enrolled. The median duration of viable virus shedding was 4 weeks (interquartile range: 3-7). Multivariable analysis revealed that B-cell depletion (hazard ratio [HR]: 4.76) was associated with prolonged viral shedding, and COVID-19 vaccination (≥3 doses) was negatively associated with prolonged viral shedding (HR: 0.22). The sensitivity, specificity, positive predictive value, and negative predictive value of RAT for viable virus shedding were 79%, 76%, 74%, and 81%, respectively. The negative predictive value of RAT was only 48% (95% confidence interval [CI]: 33-65) in the samples from those with symptom onset ≤20 days, but it was as high as 92% (95% CI: 85-96) in the samples from those with symptom onset >20 days. About half of immunocompromised COVID-19 patients shed viable virus for ≥4 weeks from the diagnosis, and virus shedding was prolonged especially in unvaccinated patients with B-cell-depleting therapy treatment. RAT beyond 20 days in immunocompromised patients had a relatively high negative predictive value for viable virus shedding.

Routine ophthalmologic examination in Klebsiella pneumoniae bacteremia is not necessary: incidence of and risk factors for ocular involvement.

Klebsiella pneumoniae bacteremia is known to present a virulent clinical course, including multiple metastatic infections, which is not uncommon in Asia. However, there are limited data on the incidence and risk factors for ocular involvement in K. pneumoniae bacteremia. We retrospectively reviewed the medical records of all patients with K. pneumoniae bacteremia who underwent ophthalmologic examination in a tertiary center in Seoul, Korea, from February 2012 to December 2020. Two retinal specialists reviewed the findings of the ophthalmologic examinations and classified them as endophthalmitis, chorioretinitis, and no ocular involvement. Of 689 patients, 56 [8.1%; 95% confidence interval (CI) 6.2-10.4] had ocular involvement, and 9 (1.3%; 95% CI 0.6-2.5) were diagnosed with endophthalmitis. Of 47 patients with chorioretinitis, 45 (95.7%) improved with systemic antibiotic therapy alone. Community-onset bacteremia (100% vs 62.1% vs 57.4%, P = 0.04), cryptogenic liver abscess (55.6% vs 11.8% vs 8.5%, P = 0.003), and metastatic infection (66.7% vs 5.8% vs 10.6%, P < 0.001) were more common in endophthalmitis than in no ocular involvement or chorioretinitis. In the multivariable analysis, cryptogenic liver abscess [adjusted odds ratio (aOR), 6.63; 95% CI 1.44-35.20] and metastatic infection (aOR, 17.52; 95% CI 3.69-96.93) were independent risk factors for endophthalmitis. Endophthalmitis was not associated with 30-day mortality. Endophthalmitis is rare in Asian patients with K. pneumoniae bacteremia. Targeted ophthalmologic examination in those with cryptogenic liver abscess, metastatic infection, or ocular symptoms may be more appropriate than routine examination of all patients.

Different antibody responses between liver and kidney transplant recipients elicited by third doses of COVID-19 mRNA vaccines.

Background: Solid organ transplant recipients exhibit decreased antibody responses, mainly due to their weakened immune systems. However, data are limited on antibody responses after the primary series of coronavirus disease 2019 (COVID-19) vaccines among recipients of various solid organ transplant types. Thus, we compared the antibody responses after three COVID-19 vaccine doses between liver transplant (LT) and kidney transplant (KT) recipients. Methods: We prospectively enrolled solid organ transplant recipients who received three COVID-19 vaccine doses from June 2021 to February 2022 and measured S1-specific immunoglobulin G antibodies using an enzyme-linked immunosorbent assay. Results: Seventy-six LT and 17 KT recipients were included in the final analysis. KT recipients showed consistently lower antibody responses even after the third vaccine dose (86.2% vs. 52.9%, P=0.008) and lower antibody titers (median, 423.0 IU/mL [interquartile range, 99.6-2,057 IU/mL] vs. 19.7 IU/mL [interquartile range, 6.9-339.4 IU/mL]; P=0.006) than were observed in LT recipients. Mycophenolic acid was a significant risk factor for a seropositive antibody response after the third vaccine dose in the multivariable analysis (odds ratio, 0.06; 95% confidence interval, 0.00-0.39; P=0.02). Conclusions: We found a weaker antibody response despite the completion of the primary series of COVID-19 vaccines in KT recipients than in LT recipients. Mycophenolic acid use in KT recipients might be the main contributor to this observation.

Triple immune modulator therapy for aberrant hyperinflammatory responses in severe COVID-19.

A dysregulated hyperinflammatory response is a key pathogenesis of severe COVID-19, but optimal immune modulator treatment has not been established. To evaluate the clinical effectiveness of double (glucocorticoids and tocilizumab) and triple (plus baricitinib) immune modulator therapy for severe COVID-19, a retrospective cohort study was conducted. For the immunologic investigation, a single-cell RNA sequencing analysis was performed in serially collected PBMCs and neutrophil specimens. Triple immune modulator therapy was a significant factor in a multivariable analysis for 30-day recovery. In the scRNA-seq analysis, type I and II IFN response-related pathways were suppressed by GC, and the IL-6-associated signature was additionally downregulated by TOC. Adding BAR to GC and TOC distinctly downregulated the ISGF3 cluster. Adding BAR also regulated the pathologically activated monocyte and neutrophil subpopulation induced by aberrant IFN signals. Triple immune modulator therapy in severe COVID-19 improved 30-day recovery through additional regulation of the aberrant hyperinflammatory immune response.

Clinical Sensitivity of the (1-3)-ß-D-glucan Test for Predicting Candidemia.

The sensitivity of the (1-3)-ß-D-glucan (BDG) diagnostic test for candidemia varies in different clinical settings, and its usefulness in early diagnosis of candidemia is suboptimal. We evaluated the sensitivity of the test for early candidemia prediction. All adult patients with culture-proven candidemia who underwent a serum Goldstream Fungus (1-3)-ß-D-Glucan Test within seven days prior to candidemia onset at a tertiary referral hospital between January 2017 and May 2021 were included. Any-positive BDG results within seven days prior to candidemia onset were obtained in 38 out of 93 (40.9%) patients. The positive rate increased when the test was performed near the day of candidemia onset (P=0.04) but reached only 52% on the day of candidemia onset. We observed no significant differences between BDG-positive and -negative groups in terms of underlying disease, risk factors for candidemia, clinical presentation, origin of candidemia, and 30-day mortality. Candida albicans was significantly associated with positive BDG results than with all-negative BDG results (P=0.04). The Goldstream BDG test is unreliable for candidemia prediction because of its low sensitivity. Negative BDG results in patients with a high risk of invasive candidiasis should be interpreted with caution.

Waning of humoral immunity depending on the types of COVID-19 vaccine.

BACKGROUND: There are limited data on the rates of the waning of antibody levels after two-dose and booster vaccination according to the different platforms of COVID-19 vaccines. METHODS: We enrolled healthcare workers (HCWs) in a tertiary care hospital who received homologous two-dose vaccination, followed by a homologous or heterologous booster mRNA vaccine. SARS-CoV-2 S1-specific IgG was measured using ELISA. A linear mixed regression model was used to compare the slope from the peak antibody titre to the lowest antibody titres 3 months after vaccination. RESULTS: A total of 113 HCWs (BNT162b2 (n = 48 [42%]), ChAdOx1 nCoV-19 (n = 52 [46%]) or mRNA-1273 (n = 13 [12%])) were enrolled in this prospective cohort study. More gradual antibody waning was observed over 3 months with the two-dose ChAdOx1 nCoV-19 (ChAdOx1) than with the two-dose BNT162b2 or mRNA-1273 (p < 0.001 and p = 0.001, respectively). In addition, homologous mRNA-1273 booster induced a more durable antibody response than homologous BNT162b2 booster (p < 0.001) or heterologous ChAdOx1-BNT162b2 booster (p < 0.001). CONCLUSIONS: Two-dose homologous ChAdOx1 vaccination or homologous mRNA-1273 booster appears to induce more-durable antibody responses than 2-dose homologous mRNA vaccination, homologous BNT162b2 booster, or 2-dose ChAdOx1 followed by BNT62b2 booster, although our findings are based on the relatively short term (3-month) follow-up after the vaccinations and the evaluation of the slopes from different antibody peak levels. Further studies on long-term durability depending on the types of vaccines are needed.

Comparison of secondary attack rate and viable virus shedding between patients with SARS-CoV-2 Delta and Omicron variants: A prospective cohort study.

There are limited data comparing the transmission rates and kinetics of viable virus shedding of the Omicron variant to those of the Delta variant. We compared these rates in hospitalized patients infected with Delta and Omicron variants. We prospectively enrolled adult patients with COVID-19 admitted to a tertiary care hospital in South Korea between September 2021 and May 2022. Secondary attack rates were calculated by epidemiologic investigation, and daily saliva samples were collected to evaluate viral shedding kinetics. Genomic and subgenomic SARS-CoV-2 RNA was measured by PCR, and virus culture was performed from daily saliva samples. A total of 88 patients with COVID-19 who agreed to daily sampling and were interviewed, were included. Of the 88 patients, 48 (59%) were infected with Delta, and 34 (41%) with Omicron; a further 5 patients gave undetectable or inconclusive RNA PCR results and 1 was suspected of being coinfected with both variants. Omicron group had a higher secondary attack rate (31% [38/124] vs. 7% [34/456], p < 0.001). Survival analysis revealed that shorter viable virus shedding period was observed in Omicron variant compared with Delta variant (median 4, IQR [1-7], vs. 8.5 days, IQR [5-12 days], p < 0.001). Multivariable analysis revealed that moderate-to-critical disease severity (HR: 1.96), and immunocompromised status (HR: 2.17) were independent predictors of prolonged viral shedding, whereas completion of initial vaccine series or first booster-vaccinated status (HR: 0.49), and Omicron infection (HR: 0.44) were independently associated with shorter viable virus shedding. Patients with Omicron infections had higher transmission rates but shorter periods of transmissible virus shedding than those with Delta infections.