Real-World Effectiveness of Nirmatrelvir-Ritonavir and Its Acceptability in High-Risk COVID-19Patients

Background@#Nirmatrelvir-ritonavir is highly effective in preventing severe coronavirus disease 2019 (COVID-19) in high-risk patients with mild-to-moderate severity. However, real-world performance data are limited, and the drug is not so acceptable to the COVID-19 patients at high risk who need it in Korea. @*Methods@#To evaluate the effectiveness of nirmatrelvir-ritonavir, we conducted a propensity score-matched retrospective cohort study on patients with mild-to-moderate COVID-19 at high risk for a severe disease who were hospitalized at four hospitals in South Korea from February 2022 to April 2022. A total of 236 patients in the treatment group (administered nirmatrelvir-ritonavir) and 236 in the matched control group (supportive care only) were analyzed for the primary outcome, i.e., the time to oxygen support-free survival. The secondary outcome was a composite result of disease progression. The reason for not prescribing nirmatrelvir-ritonavir to the indicated patients was also investigated. @*Results@#The treatment group showed significantly longer oxygen support-free survival than the matched control group (adjusted hazard ratio [aHR], 0.07; 95% confidence interval [CI], 0.01–0.31; P < 0.001). Multivariate Cox regression analysis showed that age (aHR, 1.03; 95% CI, 1.00–1.07), National Early Warning Score-2 at admission (aHR, 1.36; 95% CI, 1.08–1.71), nirmatrelvir-ritonavir treatment, female sex (aHR, 0.37; 95% CI, 0.15–0.88), and time from symptom onset to admission (aHR, 0.67; 95% CI, 0.48–0.95) were significantly associated with oxygen therapy. However, none of the factors were related to the composite outcome. In the unmatched control group, 19.9% of 376 patients had documented explanations for nirmatrelvir-ritonavir non-prescription, and 44.0% of these were due to contraindication criteria. In the treatment group, 10.9% of patients discontinued the medication primarily because of adverse events (71.4%), with gastrointestinal symptoms being the most common (50.0%). @*Conclusion@#Nirmatrelvir-ritonavir treatment significantly reduced oxygen therapy requirements in high-risk patients with COVID-19 during the omicron variant surge in South Korea. Physicians are encouraged to consider the active use of nirmatrelvir-ritonavir and to be watchful for gastrointestinal symptoms during medication.

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 (ND 50 ) titers in serum samples. ND 50 titers against the omicron variant (median [interquartile range], 5.3 [50 titers than the detection threshold (50 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.

Similar Durability of Two Single Tablet Regimens, Dolutegravir/Abacavir/Lamivudine and Elvitegravir/Cobicistat/Tenofovir/Emtricitabine: Single Center Experience

Integrase inhibitor is uniquely available as single tablet regimen (STR) in Korea. In this study, the durability until 96 weeks was compared between dolutegravir/abacavir/lamivudine (D/A/L) and elvitegravir/cobicistat/tenofovir/emtricitabine (E/T/E) in treatment naïve human immunodeficiency virus 1 (HIV-1) infected individuals. From 2014 to 2017, 153 and 234 subjects started D/A/L and E/T/E, respectively. During 96 weeks, 73 discontinued initial STR and the reason of discontinuation was typable in 44. The frequency of drug adverse event related discontinuation (AEDC) was higher in D/A/L (13.1% vs. 6.4%, P = 0.023) while most non-AE related discontinuations occurred in E/T/E (8/9), such as drug-drug interaction, meal requirement and virologic failure. AEDC occurred usually within 24 weeks (20/35) and D/A/L to E/T/E AEDC incidence rate ratio was 3.71 (95% confidence interval, 1.36–10.10) in this period. Regarding the durability, D/A/L and E/T/E revealed no significant difference at week 96 (P = 0.138) while durability of D/A/L was worse in the aspect of AEDC (P = 0.013).

Mixed Infection with Plasmodium falciparum and Plasmodium ovale in a Returned Traveller: the First Case in Korea

Mixed-species malaria infections are often unrecognized or underestimated. We hereby report the first described case of mixed infection with Plasmodium falciparum and Plasmodium ovale malaria in a returned traveller in Korea. In August 2016, a 25-year-old returned traveller from Cameroon and Democratic Republic of Congo presented with fever. He was diagnosed as P. falciparum malaria and successfully treated with artesunate. And 5 weeks after the completion of treatment, he presented with fever and diagnosed as P. ovale infection. P. ovale infection is a rare cause of malaria and often shows delayed presentation due to its dormant liver stage as hypnozoites. At re-presentation, the immunochromatographic test and microscopic examinations of our patient did not reveal P. ovale, which was only detected via polymerase chain reaction (PCR) assay. This case highlights the importance of considering malaria infection even in persons who have previously received malaria treatment. It also shows the usefulness of PCR testing for diagnosing P. ovale infections, which often present with a low level of parasitaemia.

Correlation between Pneumonia Severity and Pulmonary Complications in Middle East Respiratory Syndrome

This nationwide, prospective cohort study evaluated pulmonary function and radiological sequelae according to infection severity in 73 survivors from the 2015 Middle East respiratory syndrome (MERS) outbreak in Korea. Patients with severe pneumonia in MERS-coronavirus infection had more impaired pulmonary function than those with no or mild pneumonia at the 1-year follow-up, which was compatible with the radiological sequelae. Severe pneumonia significantly impairs pulmonary function and makes long radiological sequelae in MERS.

Integrase Strand Transfer Inhibitor Resistance Mutations in Antiretroviral Treatment-naïve Patients in Korea: a Prospective, Observational Study

The present study investigated prevalence of integrase strand transfer inhibitors (INSTI) resistance mutations in HIV-1-infected antiretroviral therapy (ART)-naïve patients in Korea. From 106 plasma samples, amplification and sequencing of integrase genes was performed, and major or minor mutations were calculated by the Stanford HIV drug resistance mutation interpretation algorithm. No major INSTI resistance mutations were found, and 14 minor mutations were detected in 13 (12.3%) patients. The present data support the recommendation that routine testing for INSTI resistance mutations before starting ART is not necessary.

Clinical Presentation and Outcomes of Middle East Respiratory Syndrome in the Republic of Korea / 감염과화학요법

BACKGROUND: From May to July 2015, the Republic of Korea experienced the largest outbreak of Middle East respiratory syndrome (MERS) outside the Arabian Peninsula. A total of 186 patients, including 36 deaths, had been diagnosed with MERS-coronavirus (MERS-CoV) infection as of September 30th, 2015. MATERIALS AND METHODS: We obtained information of patients who were confirmed to have MERS-CoV infection. MERS-CoV infection was diagnosed using real-time reverse-transcriptase polymerase chain reaction assay. RESULTS: The median age of the patients was 55 years (range, 16 to 86). A total of 55.4% of the patients had one or more coexisting medical conditions. The most common symptom was fever (95.2%). At admission, leukopenia (42.6%), thrombocytopenia (46.6%), and elevation of aspartate aminotransferase (42.7%) were observed. Pneumonia was detected in 68.3% of patients at admission and developed in 80.8% during the disease course. Antiviral agents were used for 74.7% of patients. Mechanical ventilation, extracorporeal membrane oxygenation, and convalescent serum were employed for 24.5%, 7.1%, and 3.8% of patients, respectively. Older age, presence of coexisting medical conditions including diabetes or chronic lung disease, presence of dyspnea, hypotension, and leukocytosis at admission, and the use of mechanical ventilation were revealed to be independent predictors of death. CONCLUSION: The clinical features of MERS-CoV infection in the Republic of Korea were similar to those of previous outbreaks in the Middle East. However, the overall mortality rate (20.4%) was lower than that in previous reports. Enhanced surveillance and active management of patients during the outbreak may have resulted in improved outcomes.

Renal Complications and Their Prognosis in Korean Patients with Middle East Respiratory Syndrome-Coronavirus from the Central MERS-CoV Designated Hospital

Some cases of Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) infection presented renal function impairment after the first MERS-CoV patient died of progressive respiratory and renal failure. Thus, MERS-CoV may include kidney tropism. However, reports about the natural courses of MERS-CoV infection in terms of renal complications are scarce. We examined 30 MERS-CoV patients admitted to National Medical Center, Korea. We conducted a retrospective analysis of the serum creatinine (SCr), estimated glomerular filtration rate (eGFR), urine dipstick tests, urinary protein quantitation (ACR or PCR), and other clinical parameters in all patients. Two consecutive results of more than trace (or 1+) of albumin and blood on dipstick test occurred in 18 (60%) (12 [40%]) and 22 (73.3%) (19 [63.3%]) patients, respectively. Fifteen (50.0%) patients showed a random urine ACR or PCR more than 100 mg/g Cr. Eight (26.7%) patients showed acute kidney injury (AKI), and the mean and median durations to the occurrence of AKI from symptom onset were 18 and 16 days, respectively. Old age was associated with a higher occurrence of AKI in the univariate analysis (HR [95% CI]: 1.069 [1.013-1.128], P = 0.016) and remained a significant predictor of the occurrence of AKI after adjustment for comorbidities and the application of a mechanical ventilator. Diabetes, AKI, and the application of a continuous renal replacement therapy (CRRT) were risk factors for mortality in the univariate analysis (HR [95% CI]: diabetes; 10.133 [1.692-60.697], AKI; 12.744 [1.418-114.565], CRRT; 10.254 [1.626-64.666], respectively). Here, we report renal complications and their prognosis in 30 Korean patients with MERS-CoV.

A Case of Infectious Spondylodiscitis due to Parvimonas Micra / 대한내과학회지

Parvimonas micra is frequently associated with periodontal disease as well as respiratory, gastrointestinal, and female genitourinary tract infections, but only rarely has it been reported as a pathogenic agent of infectious spondylodiscitis. We describe the case of a 38-year-old woman with spondylodiscitis caused by P. micra. P. micra was cultured from the patient's blood and vertebral tissue. This case was treated with vertebral corpectomy followed by intravenous ampicillin-sulbactam for four weeks. Her symptoms and vital signs improved, and elevated inflammatory markers were normalized after treatment.

A Case of Infectious Spondylodiscitis due to Parvimonas Micra / 대한내과학회지

Parvimonas micra is frequently associated with periodontal disease as well as respiratory, gastrointestinal, and female genitourinary tract infections, but only rarely has it been reported as a pathogenic agent of infectious spondylodiscitis. We describe the case of a 38-year-old woman with spondylodiscitis caused by P. micra. P. micra was cultured from the patient's blood and vertebral tissue. This case was treated with vertebral corpectomy followed by intravenous ampicillin-sulbactam for four weeks. Her symptoms and vital signs improved, and elevated inflammatory markers were normalized after treatment.

An Outbreak of Trichinellosis with Detection of Trichinella Larvae in Leftover Wild Boar Meat

The clinical diagnosis of trichinellosis can be difficult due to lack of pathognomonic signs or symptoms. In Korea, since the first report of human infection by Trichinella spiralis in 1997 following the consumption of raw badger meat, there have been occasional trichinellosis outbreaks. We describe an outbreak of 12 cases of trichinellosis in Korea and implicate raw wild boar meat as the culprit. A total of 27 larvae of Trichinella (0.54 larvae per gram of meat) were recovered from the leftover raw wild boar meat.

A Case of Group G Streptococcal Toxic Shock Syndrome / 감염과화학요법

Toxic shock syndrome is an acute, multi-systemic, toxin-mediated illness caused by toxin-producing strains of Staphylococcus aureus and Streptococcus species. Streptococcal toxic shock syndrome is usually caused by Streptococcus pyogenes but Group G streptococcal toxic shock syndrome is rare. Herein, we report a case of group G streptococcal toxic shock syndrome that was successfully treated with toxin reducing antibiotics and intravenous immunoglobulin therapies.

Alternating Linezolid-Vancomycin Therapy for Persistent Endovascular Methicillin-resistant Staphylococcus aureus Infection: A Case Report / 감염과화학요법

Persistent Staphylococcus aureus bacteremia is frequently defined as bacteremia persisting for > or =7 days despite proper antibiotic therapy. Its treatment includes removal of all infection foci and proper antibiotic therapy. Vancomycin remains the antibiotic of choice in MRSA bacteremia. Alternative agents, linezolid or daptomycin, are available, but a consensus regarding management of persistent MRSA bacteremia on vancomycin failure is still lacking. We report a case of a 60-year-old male who received thoracoabdominal aorta replacement operation due to dissecting aneurysm of the ascending and descending aorta. Surgical site infection and bacteremia caused by MRSA occured, and wound debridement operations were performed. The patient was treated with vancomycin in therapeutic doses but MRSA bacteremia persisted for 168 days in a row. Although the inserted aortic graft was the most probable source of persistent bacteremia, surgical removal was impossible. Linezolid was administered as an alternative antibiotic but had to be discontinued from time to time due to thrombocytopenia induced by this agent. In the end, MRSA bacteremia was successfully managed by alternating vancomycin-linezolid therapy.

Alternating Linezolid-Vancomycin Therapy for Persistent Endovascular Methicillin-resistant Staphylococcus aureus Infection: A Case Report / 감염과화학요법

Persistent Staphylococcus aureus bacteremia is frequently defined as bacteremia persisting for > or =7 days despite proper antibiotic therapy. Its treatment includes removal of all infection foci and proper antibiotic therapy. Vancomycin remains the antibiotic of choice in MRSA bacteremia. Alternative agents, linezolid or daptomycin, are available, but a consensus regarding management of persistent MRSA bacteremia on vancomycin failure is still lacking. We report a case of a 60-year-old male who received thoracoabdominal aorta replacement operation due to dissecting aneurysm of the ascending and descending aorta. Surgical site infection and bacteremia caused by MRSA occured, and wound debridement operations were performed. The patient was treated with vancomycin in therapeutic doses but MRSA bacteremia persisted for 168 days in a row. Although the inserted aortic graft was the most probable source of persistent bacteremia, surgical removal was impossible. Linezolid was administered as an alternative antibiotic but had to be discontinued from time to time due to thrombocytopenia induced by this agent. In the end, MRSA bacteremia was successfully managed by alternating vancomycin-linezolid therapy.

A Case of Plasmodium vivax Malaria with Cerebral Complicatio / 감염과화학요법

Plasmodium vivax malaria is an endemic disease in Korea, which rarely causes severe complications including those occurring in the cerebrum. There are limited numbers of complicated cases that have been reported around the world. We experienced a case of vivax malaria with cerebral complication: cognitive impairment and ataxia. A 55-year-old female with diabetes mellitus presented to the emergency department with acute fever of two days' duration. She did not have any history of travelling abroad or receiving blood transfusions. Peripheral blood smear revealed vivax malaria with parasitemia density of 0.53 percent. She demonstrated loss of orientation, especially regarding time and place, and ataxia. Although the initial hydroxychloroquine treatment for malaria was successful, cognitive impairment and ataxia persisted and were not recovered. Brain MRI showed no structural abnormality. Brain PET showed diffuse hypometabolism in right parieto-temporal lobe of the brain.

A Case of Plasmodium vivax Malaria with Cerebral Complicatio / 감염과화학요법

Plasmodium vivax malaria is an endemic disease in Korea, which rarely causes severe complications including those occurring in the cerebrum. There are limited numbers of complicated cases that have been reported around the world. We experienced a case of vivax malaria with cerebral complication: cognitive impairment and ataxia. A 55-year-old female with diabetes mellitus presented to the emergency department with acute fever of two days' duration. She did not have any history of travelling abroad or receiving blood transfusions. Peripheral blood smear revealed vivax malaria with parasitemia density of 0.53 percent. She demonstrated loss of orientation, especially regarding time and place, and ataxia. Although the initial hydroxychloroquine treatment for malaria was successful, cognitive impairment and ataxia persisted and were not recovered. Brain MRI showed no structural abnormality. Brain PET showed diffuse hypometabolism in right parieto-temporal lobe of the brain.