Low humoral and cellular immune responses early after breakthrough infection may contribute to severe COVID-19.

Background: Little is known about the immune determinants for severe coronavirus disease 2019 (COVID-19) in individuals vaccinated against severe acute respiratory syndrome coronavirus 2. We therefore attempted to identify differences in humoral and cellular immune responses between patients with non-severe and severe breakthrough COVID-19. Methods: We prospectively enrolled hospitalized patients with breakthrough COVID-19 (severe and non-severe groups) and uninfected individuals who were vaccinated at a similar time (control group). Severe cases were defined as those who required oxygen therapy while hospitalized. Enzyme-linked immunosorbent assays and flow cytometry were used to evaluate humoral and cellular immune responses, respectively. Results: Anti-S1 IgG titers were significantly lower in the severe group than in the non-severe group within 1 week of symptom onset and higher in the non-severe group than in the control group. Compared with the control group, the cellular immune response tended to be diminished in breakthrough cases, particularly in the severe group. In multivariate analysis, advanced age and low anti-S1 IgG titer were associated with severe breakthrough COVID-19. Conclusions: Severe breakthrough COVID-19 might be attributed by low humoral and cellular immune responses early after infection. In the vaccinated population, delayed humoral and cellular immune responses may contribute to severe breakthrough COVID-19.

Clinical and economic burden of bacteremia due to multidrug-resistant organisms in Korea: a prospective case control study.

OBJECTIVES: The socioeconomic and clinical burden of multidrug-resistant organisms (MDRO), including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), multidrug-resistant Acinetobacter baumannii (MRAB), multidrug-resistant Pseudomonas aeruginosa (MRPA), and carbapenem-resistant Enterobacteriaceae (CRE) have not yet been adequately addressed. METHODS: We prospectively searched for MDRO bacteremia cases with matched controls from 10 hospitals across Korea during a 6-month period in 2017. Patients were classified into the MDRO, susceptible organism, and no-infection groups. The corresponding susceptible or no-infection controls had been selected according to predefined criteria. We collected clinical information and estimated the total additional medical cost due to MDRO infections using the multistate model. RESULTS: During the 6-month period, a total of 486 MDRO bacteremia cases (260, 87, 18, 20, and 101 cases of MRSA, MRAB, MRPA, CRE, and VRE, respectively) were identified. The 90-d mortality rates were 30.4%, 63.2%, 16.7%, 55.0%, and 47.5%, respectively. The additional costs caused by bacteremia were $15 768, $35 682, $39 908, $72 051, and $33 662 per MDRO type, respectively. Based on these 6-month data, the estimated annual number of bacteremia cases due to these five MDRO in Korea were 7979 (4070, 1396, 218, 461, and 1834 cases, respectively). Overall, this caused an estimated 3280 (1237, 882, 36, 254, and 871, respectively) deaths and cost $294 505 002 ($84 707 359, $74 387 364, $10 344 370, $45 850 215, and $79 215 694, respectively) (range $170,627,020-$416,094,679) in socioeconomic loss. CONCLUSIONS: A tremendous clinical and economic burden is caused by MDRO bacteremia compared with antibiotic-susceptible and no-infection groups. Substantial investment and efforts by related government agencies and medical staffs are needed.

Socioeconomic burden of pneumonia due to multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa in Korea.

We aimed to estimate the socioeconomic burden of pneumonia due to multidrug-resistant Acinetobacter baumannii (MRAB) and Pseudomonas aeruginosa (MRPA). We prospectively searched for MRAB and MRPA pneumonia cases and matched them with susceptible-organism pneumonia and non-infected patients from 10 hospitals. The matching criteria were: same principal diagnosis, same surgery or intervention during hospitalisation, age, sex, and admission date within 60 days. We calculated the economic burden by using the difference in hospital costs, the difference in caregiver costs, and the sum of productivity loss from an unexpected death. We identified 108 MRAB pneumonia [MRAB-P] and 28 MRPA pneumonia [MRPA-P] cases. The estimated number of annual MRAB-P and MRPA-P cases in South Korea were 1309-2483 and 339-644, with 485-920 and 133-253 deaths, respectively. The annual socioeconomic burden of MRAB-P and MRPA-P in South Korea was $64,549,723-122,533,585 and $15,241,883-28,994,008, respectively. The results revealed that MRAB-P and MRPA-P occurred in 1648-3127 patients, resulted in 618-1173 deaths, and caused a nationwide socioeconomic burden of $79,791,606-151,527,593. Multidrug-resistant organisms (MDRO) impose a great clinical and economic burden at a national level. Therefore, controlling the spread of MDRO will be an effective measure to reduce this burden.

Risk factors for early mortality in patients with carbapenem-resistant Acinetobacter baumannii bacteraemia.

OBJECTIVES: Although many deaths due to carbapenem-resistant Acinetobacter baumannii (CRAB) bacteraemia occur within a few days after the onset of bacteraemia, risk factors for early mortality (EM) have not been deeply investigated. We aimed to determine the risk factors for EM and the difference between risk factors associated with EM and late mortality (LM) in CRAB bacteraemia. METHODS: Clinical information on all patients with CRAB bacteraemia in 10 hospitals during a 1-year period was collected. Among the cases with mortality within 30 days, EM and LM were defined as death within 3 and more than 5 calendar days from the first positive blood culture, respectively. RESULTS: In total, 212 CRAB bacteraemia cases were included in the analysis. Of 122 (57.5%) patients with 30-day mortality, EM was observed in 75 (61.5%) patients and LM in 39 (32.0%) patients. The proportion of severe sepsis or septic shock, Pitt score, and Sequential Organ Failure Assessment (SOFA) score was significantly higher in patients with EM than those with LM. Although urinary tract infection as the site of infection and the severity of illness were independent predictors of LM, only factors representing the severity of illness were independent risk factors for EM. CONCLUSION: Our results suggest that a large proportion of CRAB bacteraemia with high severity progresses to a rapidly fatal course, regardless of the underlying diseases or source of infection. Further studies might be needed to investigate the microbiological factors associated with CRAB and pathogen-host interaction in patients with EM.

Different levels of humoral and cellular immunity to varicella-zoster virus in seropositive healthcare workers.

BACKGROUND: There have been occasional reports on varicella infection among healthcare workers (HCWs) despite varicella-zoster virus (VZV) seropositivity. We compared the levels of humoral and cellular immunity to VZV in seropositive HCWs who had acquired immunity by natural infection or vaccination. METHODS: Seropositive healthy HCWs with an apparent history of varicella or VZV vaccination once or twice were recruited. Their samples were assessed for anti-VZV IgG levels, the relative avidity index (RAI), and the frequencies of VZV-specific cytokine-producing or polyfunctional CD4+ or CD8+ T cells. RESULTS: A total of 75 seropositive HCWs (29 with a history of varicella, 25 vaccinated once, and 21 vaccinated twice) were assessed for humoral immunity. Cellular responses could be analyzed in 59 (28, 21, and 10 in the respective groups). The anti-VZV IgG level, RAI, and memory CD4+ T cell responses were significantly higher in the past infection group than in the vaccinated once group. The RAI levels were significantly higher in the past infection group than in the vaccinated twice group. CONCLUSION: Seropositive HCWs without a varicella history, especially those who received the vaccine only once, had significantly lower levels of immune responses to VZV. Such HCWs might need to comply with airborne precautions.

Different clinical characteristics and impact of carbapenem-resistance on outcomes between Acinetobacter baumannii and Pseudomonas aeruginosa bacteraemia: a prospective observational study.

This study aimed to evaluate the differences in clinical characteristics and impact of carbapenem resistance (CR) on outcomes between Acinetobacter baumannii (Ab) and Pseudomonas aeruginosa (Pa) bacteraemia. We prospectively identified all patients with Ab and Pa bacteraemia in 10 hospitals over 1 year. Treatment failure was defined as all-cause 30-day mortality, persistent bacteraemia, or recurrent bacteraemia within 30 days. We included 304 Ab and 241 Pa bacteraemia cases. CR was detected in 216 patients (71%) with Ab bacteraemia and 55 patients (23%) with Pa bacteraemia. Treatment failure was significantly higher in CR-Ab than in CR-Pa (60.6% vs. 34.5%, P = 0.001). In Ab, severe sepsis or septic shock and high Pitt bacteraemia score were independent risk factors for treatment failure in the inappropriate empirical antibiotics group. In Pa, hospital-acquired infection and high Pitt bacteraemia score were independent risk factors for treatment failure in both groups. CR was an independent risk factor in Ab for treatment failure in both groups, but not in Pa bacteraemia. We demonstrated significant differences in clinical characteristics and impact of CR on clinical outcomes between Ab and Pa bacteraemia, suggesting that different treatment approaches may be needed.

Changes in Anxiety Level and Personal Protective Equipment Use Among Healthcare Workers Exposed to COVID-19.

BACKGROUND: The relationship between changes in anxiety levels and personal protective equipment (PPE) use is yet to be evaluated. The present study assessed this relationship among healthcare workers (HCWs) involved in the care of patients with coronavirus disease 2019 (COVID-19). METHODS: An online survey was conducted in a municipal hospital with 195 nationally designated negative pressure isolation units in Korea. Anxiety level was measured using the self-rating anxiety scale (SAS), and changes in anxiety levels were assessed based on the time when COVID-19 vaccine was introduced in March 2021 in Korea. Monthly PPE usage between June 2020 and May 2021 was investigated. RESULTS: The mean SAS score (33.25 ± 5.97) was within normal range and was lower than those reported in previous studies conducted before COVID-19 vaccination became available. Among the 93 HCWs who participated, 64 (68.8%) answered that their fear of contracting COVID-19 decreased after vaccination. The number of coveralls used per patient decreased from 33.6 to 0. However, a demand for more PPE than necessary was observed in situations where HCWs were exposed to body fluids and secretions (n = 38, 40.9%). Excessive demand for PPE was not related to age, working experience, or SAS score. CONCLUSION: Anxiety in HCWs exposed to COVID-19 was lower than it was during the early period of the pandemic, and the period before vaccination was introduced. The number of coveralls used per patient also decreased although an excessive demand for PPE was observed.

The association between greenness exposure and COVID-19 incidence in South Korea: An ecological study.

BACKGROUND: The rapid spread of COVID-19 has caused an emergency situation worldwide. Investigating the association between environmental characteristics and COVID-19 incidence can be of the occurrence and transmission. The objective of this study was to evaluate the association between greenness exposure and COVID-19 cases at the district levels in South Korea. We also explored this association by considering several environmental indicators. METHODS: District-level data from across South Korea were used to model the cumulative count of COVID-19 cases per 100,000 persons between January 20, 2020, and February 25, 2021. Greenness exposure data were derived from the Environmental Geographic Information Service of the Korean Ministry of Environment. A negative binomial mixed model evaluated the association between greenness exposure and COVID-19 incidence rate at the district level. Furthermore, we assessed this association between demographic, socioeconomic, environmental statuses, and COVID-19 incidence. RESULTS: Data from 239 of 250 districts (95.6%) were included in the analyses, resulting in 127.89 COVID-19 cases per 100,000 persons between January 20, 2020 and February 25, 2021. Several demographic and socioeconomic variables, districts with a higher rate of natural greenness exposure, were significantly associated with lower COVID-19 incidence rates (incidence rate ratio (IRR), 0.70; 95% confidence interval (CI), 0.54-0.90; P-value = 0.008) after adjusting covariates, but no evidence for the association between built greenness and COVID-19 incidence rates was found. CONCLUSION: In this ecological study of South Korea, we found that higher rates of exposure to natural greenness were associated with lower rates of COVID-19 cases.

Booster BNT162b2 COVID-19 Vaccination Increases Neutralizing Antibody Titers Against the SARS-CoV-2 Omicron Variant in Both Young and Elderly Adults.

Concerns about the effectiveness of current vaccines against the rapidly spreading severe acute respiratory syndrome-coronavirus-2 omicron (B.1.1.529) variant are increasing. This study aimed to assess neutralizing antibody activity against the wild-type (BetaCoV/Korea/KCDC03/2020), delta, and omicron variants after full primary and booster vaccinations with BNT162b2. A plaque reduction neutralization test was employed to determine 50% neutralizing dilution (ND50) titers in serum samples. ND50 titers against the omicron variant (median [interquartile range], 5.3 [< 5.0-12.7]) after full primary vaccination were lower than those against the wild-type (144.8 [44.7-294.0]) and delta (24.3 [14.3-81.1]) variants. Furthermore, 19/30 participants (63.3%) displayed lower ND50 titers than the detection threshold (< 10.0) against omicron after full primary vaccination. However, the booster vaccine significantly increased ND50 titers against BetaCoV/Korea/KCDC03/2020, delta, and omicron, although titers against omicron remained lower than those against the other variants (P < 0.001). Our study suggests that booster vaccination with BNT162b2 significantly increases humoral immunity against the omicron variant.

Treatment for Immune Thrombocytopenia in Coronavirus Disease 2019 (COVID-19) Infection after COVID-19 Vaccination: A Case Report.

Thrombocytopenia is one of the rare signs of both the coronavirus disease 2019 (COVID-19) and COVID-19 vaccination. An 85-year-old man was diagnosed with immune thrombocytopenia and COVID-19, 7 days after COVID-19 vaccination. The patient was successfully treated with a short course of intravenous immunoglobulin and oral corticosteroids.

Clinical Characteristics of 40 Patients Infected With the SARS-CoV-2 Omicron Variant in Korea.

Since severe acute respiratory syndrome-coronavirus-2 variant B.1.1.529 (omicron) was first reported to the World Health Organization on November 24, 2021, the cases of the omicron variant have been detected in more than 90 countries over the last month. We investigated the clinical and epidemiological characteristics of the first 40 patients with the omicron variant who had been isolated at the National Medical Center in South Korea during December 4-17, 2021. The median age of the patients was 39.5 years. Twenty-two patients (55%) were women. Seventeen patients (42.5%) were fully vaccinated, and none were reinfected with the omicron. Eighteen (45%) had recent international travel history. Half of the patients (19, 47.5%) were asymptomatic, while the others had mild symptoms. Six patients (15%) showed lung infiltrations on chest image; however, none required supplemental oxygen. These mild clinical features are consistent with recent case reports on the omicron variant from other countries.

Prevalence of Multidrug-Resistant Tuberculosis in HIV/Tuberculosis Co-Infected Patients.

Tuberculosis (TB) is a common opportunistic infection in human immunodeficiency virus (HIV)-infected patients. Patients with multidrug-resistant (MDR)-TB have poor outcomes. This study aimed to determine the prevalence of MDR-TB in HIV/TB co-infected patients in the Korea. We reviewed the medical records of HIV/TB co-infected patients at two university hospitals between January 1998 and December 2020. During the study period, a total of 87 HIV/TB co-infected patients were identified, and drug susceptibility test results were available for 44 of them. The prevalence of MDR-TB in the study population was 15.9% (7/44, 95% confidence interval, 5.1 - 26.7).

Different therapeutic associations of renin-angiotensin system inhibitors with coronavirus disease 2019 compared with usual pneumonia.

BACKGROUND/AIMS: Although it is near concluded that renin-angiotensin system inhibitors do not have a harmful effect on coronavirus disease 2019 (COVID-19), there is no report about whether angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) offer any protective role. This study aimed to compare the association of ARBs and ACEIs with COVID-19-related mortality. METHODS: All patients with COVID-19 in Korea between January 19 and April 16, 2020 were enrolled. The association of ARBs and ACEIs with mortality within 60 days were evaluated. A comparison of hazard ratio (HR) was performed between COVID-19 patients and a retrospective cohort of pneumonia patients hospitalized in 2019 in Korea. RESULTS: Among 10,448 COVID-19 patients, ARBs and ACEIs were prescribed in 1,231 (11.7%) and 57 (0.6%) patients, respectively. After adjusting for age, sex, and history of comorbidities, the ARB group showed neutral association (HR, 1.034; 95% CI, 0.765 to 1.399; p = 0.8270) and the ACEI groups showed no significant associations likely owing to the small population size (HR, 0.736; 95% CI, 0.314 to 1.726; p = 0.4810). When comparing HR between COVID-19 patients and a retrospective cohort of patients hospitalized with pneumonia in 2019, the trend of ACEIs showed similar benefits, whereas the protective effect of ARBs observed in the retrospective cohort was absent in COVID-19 patients. Meta-analyses showed significant positive correlation with survival of ACEIs, whereas a neutral association between ARBs and mortality. CONCLUSION: Although ARBs or ACEIs were not associated with fatal outcomes, potential beneficial effects of ARBs observed in pneumonia were attenuated in COVID-19.

High Prevalence of Human Immunodeficiency Virus Infection among Inmates in Korean Correctional Facilities.

BACKGROUND: Epidemiological data are crucial in designing policies for the control of human immunodeficiency virus (HIV) infections. There is a lack of data on the epidemiology of HIV in Korean correctional facilities such as jails and prisons. METHODS: Clinical characteristics of the study population were collected through a medical record review. RESULTS: The number of people with HIV infection were 83 and the HIV infection prevalence in correctional facilities of Korea was 0.15%. Among them, 10 (12.0%) were diagnosed with the infection when they were incarcerated. The number of drug users was 38 (45.8%). Syphilis-HIV coinfection was observed in 21 (25.3%) patients. Individuals from the group comprising the drug users were more likely to belong to the lesbian, gay, bisexual, transgender, queer (LGBTQ) community, and had a higher incidence of psychological disorders (31.6% vs. 11.1%, P = 0.029; 50.0% vs. 28.9%, P = 0.049, respectively). CONCLUSION: Inmates of correctional facilities showed a five times higher prevalence of HIV infection in Korea, nearly half of whom were drug users.

Beneficial Effect of Statins in COVID-19-Related Outcomes-Brief Report: A National Population-Based Cohort Study.

OBJECTIVE: Although statins are widely prescribed lipid-lowering drugs, there are concerns about the safety of their use in the context of coronavirus disease 2019 (COVID-19), since statins increase the expression of ACE2 (angiotensin-converting enzyme 2). This study aimed to disclose the association between statins and 60-day COVID-19 mortality. Approach and Results: All patients hospitalized with laboratory-confirmed COVID-19 were enrolled in this study from January 19 to April 16, 2020, in Korea. We evaluated the association between the use of statins and COVID-19-related mortality in the overall and the nested 1:2 propensity score-matched study. Furthermore, a comparison of the hazard ratio for death was performed between COVID-19 patients and a retrospective cohort of patients hospitalized with pneumonia between January and June 2019 in Korea. The median age of the 10 448 COVID-19 patients was 45 years. Statins were prescribed in 533 (5.1%) patients. After adjusting for age, sex, and comorbidities, Cox regression showed a significant decrease in hazard ratio associated with the use of statins (hazard ratio, 0.637 [95% CI, 0.425-0.953]; P=0.0283). Moreover, on comparing the hazard ratio between COVID-19 patients and the retrospective cohort of hospitalized pneumonia patients, the use of statins showed similar benefits. CONCLUSIONS: The use of statins correlates significantly with lower mortality in patients with COVID-19, consistent with the findings in patients with pneumonia. Graphic Abstract: A graphic abstract is available for this article.

Impact of a computerised clinical decision support system on vancomycin loading and the risk of nephrotoxicity.

BACKGROUND: A vancomycin loading dose is recommended for the treatment of serious methicillin-resistant Staphylococcus aureus (MRSA) infections. However, clinicians often do not adhere to these recommendations, mainly due to nephrotoxicity risk, unfamiliarity with the guideline, or complexity of calculating an individual dose. Therefore, we introduced a computerised clinical decision support system (CDSS) for vancomycin loading (hereafter Vancomycin CDSS) to promote the use of vancomycin loading dose. METHODS: We describe a quasi-experimental study spanning 6 months before and 18 months after the deployment of a Vancomycin CDSS. The Vancomycin CDSS was integrated into the hospital's electronic medical record system in the form of a vancomycin order set. Our primary endpoint was the incidence of nephrotoxicity; the secondary endpoint was mean initial vancomycin trough levels. We also conducted a survey to evaluate the reasons why clinicians opted not to utilise a vancomycin loading dose. RESULTS: After implementation of Vancomycin CDSS, 363 out of 746 patients (49 %) who were first administered vancomycin received a loading dose. We did not find significant differences in nephrotoxicity between the pre- and post-intervention groups, nor between the loading- and non-loading groups. In the pre-intervention group, the mean initial vancomycin trough level was 7.10 mg/L, which was significantly lower than that in the post-intervention group of 11.11 mg/L. In the vancomycin loading group, the mean initial trough level was 11.95 mg/L, compared to 7.55 mg/L in the non-loading group. The main reason stated for not prescribing a vancomycin loading dose was concern about nephrotoxicity. CONCLUSION: Introduction of the Vancomycin CDSS did not increase nephrotoxicity and increased the mean initial dose and trough level of vancomycin.

Three-year outcome of rapid HIV testing at public health centers in Seoul, Republic of Korea: a short report.

Before 2014, the only test used for anonymous voluntary human immunodeficiency virus (HIV) screening at public health centers (PHCs) in the Republic of Korea was an enzyme-linked immunosorbent assay (ELISA), which takes around 3 days to obtain results. In 2014, to encourage voluntary anonymous HIV screening tests, the Seoul Metropolitan Government adopted a rapid HIV screening test at PHCs. The rapid HIV screening test was introduced at four PHCs in 2014 and all 25 PHCs after 2015. We compared the numbers of HIV screening tests and confirmed positive individuals before and after introduction of the rapid HIV screening test. In 2012-2013, before the introduction of rapid HIV screening test, an average of 330 HIV screening tests were performed monthly (355 in 2012 and 305 in 2013) and 69 individuals were confirmed to have HIV in 2012 and 93 in 2013. After the introduction of the rapid HIV screening test, anonymous voluntary HIV screening increased to a monthly average of 447 tests in 2014, 2099 in 2015, and 2409 in 2016. These identified 38 new cases in 2014, 116 in 2015, and 143 in 2016. Adoption of the rapid HIV screening test has increased the number of HIV screening tests and confirmed cases.

Waning Antibody Responses in Asymptomatic and Symptomatic SARS-CoV-2 Infection.

We investigated the kinetics of severe acute respiratory syndrome coronavirus 2 neutralizing antibodies in 7 asymptomatic persons and 11 patients with pneumonia. The geometric mean titer of neutralizing antibodies declined from 219.4 at 2 months to 143.7 at 5 months after infection, indicating a waning antibody response.

Suboptimal medication adherence in young women living with HIV infection: a Korean nationwide claims study.

The epidemiological characteristics of women living with human immunodeficiency virus (HIV) infection have gained little attention as the numbers are small compared with men living with HIV in the Republic of Korea. However, these data are important to achieve effective HIV infection control and to consider the influence of socioeconomic status on HIV transmission. This study utilized the claims database of the Korean National Health Insurance system to analyze women with a newly diagnosed HIV infection during the period 2009-2016. Adherence to antiretroviral agents was calculated using the medication possession ratio. Among 677 women with a newly diagnosed HIV infection, 219 (32.4%) were over 50 years of age; 291 (43.0%) were identified as having acquired immune deficiency syndrome (AIDS). A total of 99 women (14.6%) were National Medical Aid beneficiaries. Optimal medical adherence >95% was found in 62.2% of subjects. Teenage years (odds ratio(OR) 14.9, 95% confidence interval (95CI) 4.9-44.8), AIDS (OR 1.7, 95CI 1.2-2.3), and low economic status requiring National Medical Aid (OR 3.0, 95CI 2.0-4.6) were associated to adherence. Diagnosis prior to 2012 was also associated with poor adherence. In women, particularly young patients with low economic status, extra attention is required to enhance adherence to prescribed medication.

The Importance of Proper History Taking: Asking a Fever Pattern in Patients with Vivax Malaria.

Characteristic fever patterns of malarial infection are clues for diagnosis. However, checking fever patterns in febrile patients has been usually missed, and unnecessary tests have been performed. We reviewed electrical medical record to check whether history-taking included questions on fever pattern in febrile patients. Main outcomes were time interval between visit and diagnosis of vivax malaria and proportion of patients who had taken unnecessary tests. Among 134 vivax malarial patients, asking about fever pattern was done in 64 (47.8%). Median time interval between visit and diagnosis was significantly shorter in patients whose fever pattern was asked than those not asked (3.2 hours vs. 18.6 hours; P < 0.001). Unnecessary diagnostic tests were conducted in 27% (17/64) of patients asked about fever pattern and 71% (50/70) in patients not asked (P < 0.001). Proper history-taking can reduce time elapsed for diagnosis and performing unnecessary diagnostic tests in vivax malaria.