Immunogenicity and Safety of Vaccines against Coronavirus Disease in Actively Treated Patients with Solid Tumors: A Prospective Cohort Study / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#We aimed to assess the humoral response to and reactogenicity of coronavirus disease 2019 (COVID-19) vaccination according to the vaccine type and to analyze factors associated with immunogenicity in actively treated solid cancer patients (CPs). @*Materials and Methods@#Prospective cohorts of CPs, undergoing anticancer treatment, and healthcare workers (HCWs) were established. The participants had no history of previous COVID-19 and received either mRNA-based or adenovirus vector–based (AdV) vaccines as the primary series. Blood samples were collected before the first vaccination and after 2 weeks for each dose vaccination. Spike-specific binding antibodies (bAbs) in all participants and neutralizing antibodies (nAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) wild-type, Delta, and Omicron variants in CPs were analyzed and presented as the geometric mean titer. @*Results@#Age-matched 20 HCWs and 118 CPs were included in the analysis. The bAb seroconversion rate and antibody concentrations after the first vaccination were significantly lower in CPs than in HCWs. After the third vaccination, antibody levels in CPs with a primary series of AdV were comparable to those in HCWs, but nAb titers against the Omicron variant did not quantitatively increase in CPs with AdV vaccine as the primary series. The incidence and severity of adverse reactions post-vaccination were similar between CPs and HCWs. @*Conclusion@#CPs displayed delayed humoral immune response after SARS-CoV-2 vaccination. The booster dose elicited comparable bAb concentrations between CPs and HCWs, regardless of the primary vaccine type. Neutralization against the Omicron variant was not robustly elicited following the booster dose in some CPs, implying the need for additional interventions to protect them from COVID-19.

Cost-Benefit Analysis of Tafenoquine for Radical Cure of Plasmodium vivax Malaria in Korea

Background@#Plasmodium vivax malaria has a persistent liver stage that causes relapse, and introducing tafenoquine to suppress relapse could aid in disease eradication. Therefore, we assessed the impact of tafenoquine introduction on P. vivax malaria incidence and performed a cost-benefit analysis from the payer’s perspective. @*Methods@#We expanded the previously developed P. vivax malaria dynamic transmission model and calibrated it to weekly civilian malaria incidences in 2014–2018. Primaquine and tafenoquine scenarios were considered by assuming different relapse probabilities, and relapse and total P. vivax malaria cases were predicted over the next decade for each scenario. We then estimated the number of cases prevented by replacing primaquine with tafenoquine. The cost and benefit of introducing tafenoquine were obtained using medical expenditure from a nationwide database, and a cost-benefit analysis was conducted. A probabilistic sensitivity analysis was performed to assess the economic feasibility robustness of tafenoquine introduction under uncertainties of model parameters, costs, and benefits. @*Results@#Under 0.04 primaquine relapse probability, the introduction of tafenoquine with relapse probability of 0.01 prevented 129 (12.27%) and 35 (77.78%) total and relapse cases, respectively, over the next decade. However, under the same relapse probability as primaquine, introducing tafenoquine had no additional preventative effect. The 14-day primaquine treatment cost was $3.71. The tafenoquine and the glucose-6-phosphate dehydrogenase rapid diagnostic testing cost $57.37 and $7.76, totaling $65.13. The average medical expenditure per malaria patient was estimated at $1444.79. The cost-benefit analysis results provided an incremental benefit-cost ratio (IBCR) from 0 to 3.21 as the tafenoquine relapse probability decreased from 0.04 to 0.01. The probabilistic sensitivity analysis showed an IBCR > 1, indicating that tafenoquine is beneficial, with a probability of 69.1%. @*Conclusion@#Tafenoquine could reduce P. vivax malaria incidence and medical costs and bring greater benefits than primaquine.

Surveillance of Close Contacts and Implications of Pediatric Patients with COVID-19–Experiences from a Single Residential Treatment Center

Residential treatment centers (RTCs) are successful in isolating and closely monitoring adults confirmed with coronavirus disease 2019 (COVID-19), but there are concerns for children who need care. This study was conducted as a retrospective analysis of the surveillance of guardians who entered an RTC with infected pediatric patients to identify the secondary attack rate of COVID-19 to close contacts in a single RTC and to provide directions for developing guidelines for caregivers who co-isolate with infected children. When caregivers were admitted to this RTC, aside from negative confirmation before discharge, tests were additionally performed one or two times. There were 57 index children and adolescent patients who entered the RTC with their parents as caregivers. The secondary attack rate by pediatric patients to close contacts outside their households was 25% (95% confidence interval, 10.0 to 40.0) (8 out of 32 contacts). The transmissibility of SARS-CoV-2 in children was close to zero at 6 days after the confirmation tests. It is reasonable to test the close contacts of pediatric patients after 7 days of isolation to identify infections among caregivers.

Four Times of Relapse of Plasmodium vivax Malaria Despite Primaquine Treatment in a Patient with Impaired Cytochrome P450 2D6 Function

Plasmodium vivax exhibits dormant liver-stage parasites, called hypnozoites, which can cause relapse of malaria. The only drug currently used for eliminating hypnozoites is primaquine. The antimalarial properties of primaquine are dependent on the production of oxidized metabolites by the cytochrome P450 isoenzyme 2D6 (CYP2D6). Reduced primaquine metabolism may be related to P. vivax relapses. We describe a case of 4 episodes of recurrence of vivax malaria in a patient with decreased CYP2D6 function. The patient was 52-year-old male with body weight of 52 kg. He received total gastrectomy and splenectomy 7 months before the first episode and was under chemotherapy for the gastric cancer. The first episode occurred in March 2019 and each episode had intervals of 34, 41, and 97 days, respectively. At the first and second episodes, primaquine was administered as 15 mg for 14 days. The primaquine dose was increased with 30 mg for 14 days at the third and fourth episodes. Seven gene sequences of P. vivax were analyzed and revealed totally identical for all the 4 samples. The CYP2D6 genotype was analyzed and intermediate metabolizer phenotype with decreased function was identified.

A Case of African Tick-Bite Fever in a Returning Traveler from Southern Africa

African tick-bite fever (ATBF), caused by Rickettsia africae, is the second most frequent cause of fever after malaria in travelers returning from Southern Africa. As the Korean outbound travelers are increasing every year, tick-borne rickettsial diseases as a cause of febrile illness are likely to increase. We describe a febrile Korean returning traveler who showed two eschars after visiting the rural field in Manzini, Swaziland. We performed nested polymerase chain reaction using the eschar and diagnosed the patient with ATBF. He was treated with oral doxycycline for 7 days, and recovered without any complications. We believe that the present case is the first ATBF case diagnosed in a Korean traveler.

A Profile of Glucose-6-Phosphate Dehydrogenase Variants and Deficiency of Multicultural Families in Korea

Vivax malaria incidence in Korea is now decreased and showing a low plateau. Nowadays, vivax malaria in Korea is expected to be successfully eliminated with anti-malaria chemotherapy, primaquine, and vector control. The glucose-6-phosphate dehydrogenase (G6PD) deficiency is associated with potential hemolytic anemia after primaquine administration. This inborn disorder has a pivotal polymorphism with genetic variants and is the most prevalent X-chromosome-linked disorder. The prevalence of G6PD deficiency was previously reported negligible in Korea. As the population of multicultural families pertaining marriage immigrants and their adolescents increases, it is necessary to check G6PD deficiency for them prior to primaquine treatment for vivax malaria. The prevalence of G6PD variants and G6PD deficiency in multicultural families was performed in 7 counties and 2 cities of Jeollanam-do (Province), Gyeonggi-do, and Gangwon-do. A total of 733 blood samples of multicultural family participants were subjected to test the phenotypic and genetic G6PD deficiency status using G6PD enzyme activity quantitation kit and PCR-based G6PD genotyping kit. The G6PD phenotypic deficiency was observed in 7.8% of male adolescent participants and 3.2% of materfamilias population. Based on the PCR-based genotyping, we observed total 35 participants carrying the mutated alleles. It is proposed that primaquine prescription should seriously be considered prior to malaria treatment.

Effectiveness of Convalescent Plasma Therapy in Severe or Critically Ill COVID-19 Patients:A Retrospective Cohort Study

Purpose@#Coronavirus disease-2019 (COVID-19) is a novel respiratory infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); there are few specific treatments. Convalescent plasma (CP), donated by people who have recovered from COVID-19, is an investigational therapy for severe or critically ill patients with COVID-19. @*Materials and Methods@#This retrospective cohort study evaluated the effectiveness of CP therapy in patients with severe or lifethreatening cases of COVID-19 at two hospitals in Seoul, Korea, between May and September 2020. Clinical outcomes were evaluated in 20 patients with CP therapy in a descriptive manner. Additionally, the changes in cycle threshold (Ct) values of 10 patients with CP therapy were compared to those of 10 controls who had the same (±0.8) initial Ct values but did not receive CP. @*Results@#Of the 20 patients (mean age 66.6 years), 18 received high-dose oxygen therapy using mechanical ventilators or high-flow nasal cannulas. Systemic steroids were administered to 19 patients who received CP. The neutralizing antibody titers of the administered CP were between 1:80 and 1:10240. There were two ABO-mismatched transfusions. The World Health Organization ordinal scale score and National Institutes of Health severity score improved in half of the patients within 14 days. Those who received CP showed a higher increase in Ct values at 24 h and 72 h after CP therapy compared to controls with similar initial Ct values (p=0.002).No transfusion-related side effects were observed. @*Conclusion@#CP therapy may be a potential therapeutic option in severe or critically ill patients with COVID-19.

Current advances in pharmacological treatments for patients with COVID-19

Since the coronavirus disease 2019 (COVID-19) outbreak, more than 150 million people in over 200 countries have been infected, with over 3 million people dying due to it, as of May 1, 2021. Many researchers are working continuously to find effective drug treatments for COVID-19; however, the optimal treatment approach remains unclear. In this article, current advances in pharmacological treatments for patients with COVID-19 are discussed. Data obtained from recent studies indicate a mortality benefit with the administration of dexamethasone or adjunctive tocilizumab and potential clinical benefits with remdesivir (with or without baricitinib). Several monoclonal antibodies against severe acute respiratory syndrome coronavirus 2 have been developed. The US Food and Drug Administration issued two emergency use authorizations: one for bamlanivimab/etesevimab and another for casirivimab/imdevimab for patients with mild to moderate COVID-19, at high risk of progression to severe disease and/or hospitalization. The pathogenesis of COVID-19 indicates that antiviral treatments would be most beneficial in the early phase of the infection that is primarily driven by replication of severe acute respiratory syndrome coronavirus 2, whereas immunosuppressive/anti-inflammatory therapies are likely to be more beneficial during the late phase of the infection, when the disease is driven by an exaggerated immune/inflammatory response to the virus that causes tissue damage.

Revised Korean Society of Infectious Diseases/National Evidence-based Healthcarea Collaborating Agency Guidelines on the Treatment of Patients with COVID-19

Despite the global effort to mitigate the spread, coronavirus disease 2019 (COVID-19) has become a pandemic that took more than 2 million lives. There are numerous ongoing clinical studies aiming to find treatment options and many are being published daily. Some effective treatment options, albeit of variable efficacy, have been discovered. Therefore, it is necessary to develop an evidence-based methodology, to continuously check for new evidence, and to update recommendations accordingly. Here we provide guidelines on pharmaceutical treatment for COVID-19 based on the latest evidence.

Korean Society of Infectious Diseases/National Evidence-based Healthcare Collaborating Agency Recommendations for Anti-SARSCoV-2 Monoclonal Antibody Treatment of Patients with COVID-19

Neutralizing antibodies targeted at the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein have been developed and now under evaluation in clinical trials. The US Food and Drug Administration currently issued emergency use authorizations for neutralizing monoclonal antibodies in non-hospitalized patients with mild to moderate coronavirus disease 2019 (COVID-19) who are at high risk for progressing to severe disease and/or hospitalization. In terms of this situation, there is an urgent need to investigate the clinical aspects and to develop strategies to deploy them effectively in clinical practice. Here we provide guidance for the use of anti-SARS-CoV-2 monoclonal antibodies for the treatment of COVID-19 based on the latest evidence.

Effectiveness of Convalescent Plasma Therapy in Severe or Critically Ill COVID-19 Patients:A Retrospective Cohort Study

Purpose@#Coronavirus disease-2019 (COVID-19) is a novel respiratory infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); there are few specific treatments. Convalescent plasma (CP), donated by people who have recovered from COVID-19, is an investigational therapy for severe or critically ill patients with COVID-19. @*Materials and Methods@#This retrospective cohort study evaluated the effectiveness of CP therapy in patients with severe or lifethreatening cases of COVID-19 at two hospitals in Seoul, Korea, between May and September 2020. Clinical outcomes were evaluated in 20 patients with CP therapy in a descriptive manner. Additionally, the changes in cycle threshold (Ct) values of 10 patients with CP therapy were compared to those of 10 controls who had the same (±0.8) initial Ct values but did not receive CP. @*Results@#Of the 20 patients (mean age 66.6 years), 18 received high-dose oxygen therapy using mechanical ventilators or high-flow nasal cannulas. Systemic steroids were administered to 19 patients who received CP. The neutralizing antibody titers of the administered CP were between 1:80 and 1:10240. There were two ABO-mismatched transfusions. The World Health Organization ordinal scale score and National Institutes of Health severity score improved in half of the patients within 14 days. Those who received CP showed a higher increase in Ct values at 24 h and 72 h after CP therapy compared to controls with similar initial Ct values (p=0.002).No transfusion-related side effects were observed. @*Conclusion@#CP therapy may be a potential therapeutic option in severe or critically ill patients with COVID-19.

Current advances in pharmacological treatments for patients with COVID-19

Since the coronavirus disease 2019 (COVID-19) outbreak, more than 150 million people in over 200 countries have been infected, with over 3 million people dying due to it, as of May 1, 2021. Many researchers are working continuously to find effective drug treatments for COVID-19; however, the optimal treatment approach remains unclear. In this article, current advances in pharmacological treatments for patients with COVID-19 are discussed. Data obtained from recent studies indicate a mortality benefit with the administration of dexamethasone or adjunctive tocilizumab and potential clinical benefits with remdesivir (with or without baricitinib). Several monoclonal antibodies against severe acute respiratory syndrome coronavirus 2 have been developed. The US Food and Drug Administration issued two emergency use authorizations: one for bamlanivimab/etesevimab and another for casirivimab/imdevimab for patients with mild to moderate COVID-19, at high risk of progression to severe disease and/or hospitalization. The pathogenesis of COVID-19 indicates that antiviral treatments would be most beneficial in the early phase of the infection that is primarily driven by replication of severe acute respiratory syndrome coronavirus 2, whereas immunosuppressive/anti-inflammatory therapies are likely to be more beneficial during the late phase of the infection, when the disease is driven by an exaggerated immune/inflammatory response to the virus that causes tissue damage.

Revised Korean Society of Infectious Diseases/National Evidence-based Healthcarea Collaborating Agency Guidelines on the Treatment of Patients with COVID-19

Despite the global effort to mitigate the spread, coronavirus disease 2019 (COVID-19) has become a pandemic that took more than 2 million lives. There are numerous ongoing clinical studies aiming to find treatment options and many are being published daily. Some effective treatment options, albeit of variable efficacy, have been discovered. Therefore, it is necessary to develop an evidence-based methodology, to continuously check for new evidence, and to update recommendations accordingly. Here we provide guidelines on pharmaceutical treatment for COVID-19 based on the latest evidence.

Korean Society of Infectious Diseases/National Evidence-based Healthcare Collaborating Agency Recommendations for Anti-SARSCoV-2 Monoclonal Antibody Treatment of Patients with COVID-19

Neutralizing antibodies targeted at the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein have been developed and now under evaluation in clinical trials. The US Food and Drug Administration currently issued emergency use authorizations for neutralizing monoclonal antibodies in non-hospitalized patients with mild to moderate coronavirus disease 2019 (COVID-19) who are at high risk for progressing to severe disease and/or hospitalization. In terms of this situation, there is an urgent need to investigate the clinical aspects and to develop strategies to deploy them effectively in clinical practice. Here we provide guidance for the use of anti-SARS-CoV-2 monoclonal antibodies for the treatment of COVID-19 based on the latest evidence.

Interim Guidelines on Antiviral Therapy for COVID-19

Since the first case was reported in Wuhan, Hubei Province, China on December 12, 2019, Coronavirus disease 2019 (COVID-19) has spread widely to other countries since January 2020. As of April 16, 2020, 10635 confirmed cases have been reported, with 230 deaths in Korea. COVID-19 patients may be asymptomatic or show various clinical manifestations, including acute symptoms such as fever, fatigue, sore throat; pneumonia presenting as acute respiratory distress syndrome; and multiple organ failure. As COVID-19 has such varied clinical manifestations and case fatality rates, no standard antiviral therapy regimen has been established other than supportive therapy. In the present guideline, we aim to introduce potentially helpful antiviral and other drug therapies based on in vivo and in vitro research and clinical experiences from many countries.

Identification of Fungal Species and Detection of Azole-Resistance Mutations in the Aspergillus fumigatus cyp51A Gene at a South Korean Hospital

Purpose@#With changing fungal epidemiology and azole resistance in Aspergillus species, identifying fungal species and susceptibility patterns is crucial to the management of aspergillosis and mucormycosis. The objectives of this study were to evaluate performance of panfungal polymerase chain reaction (PCR) assays on formalin-fixed paraffin embedded (FFPE) samples in the identification of fungal species and in the detection of azole-resistance mutations in the Aspergillus fumigatus cyp51A gene at a South Korean hospital. @*Materials and Methods@#A total of 75 FFPE specimens with a histopathological diagnosis of aspergillosis or mucormycosis were identified during the 10-year study period (2006–2015). After deparaffinization and DNA extraction, panfungal PCR assays were conducted on FFPE samples for fungal species identification. The identified fungal species were compared with histopathological diagnosis. On samples identified as A. fumigatus, sequencing to identify frequent mutations in the cyp51A gene [tandem repeat 46 (TR46), L98H, and M220 alterations] that confer azole resistance was performed. @*Results@#Specific fungal DNA was identified in 31 (41.3%) FFPE samples, and of these, 16 samples of specific fungal DNA were in accord with a histopathological diagnosis of aspergillosis or mucormycosis; 15 samples had discordant histopathology and PCR results. No azole-mediating cyp51A gene mutation was noted among nine cases of aspergillosis. Moreover, no cyp51A mutations were identified among three cases with history of prior azole use. @*Conclusion@#Panfungal PCR assay with FFPE samples may provide additional information of use to fungal species identification. No azole-resistance mediating mutations in the A. fumigatus cyp51A gene were identified among FFPE samples during study period.

Use of Convalescent Plasma Therapy in Two COVID-19 Patients with Acute Respiratory Distress Syndrome in Korea

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 not yet has established its treatment, but convalescent plasma has been expected to increase survival rates as in the case with other emerging viral infections. We describe two cases of COVID-19 treated with convalescent plasma infusion. Both patients presented severe pneumonia with acute respiratory distress syndrome and showed a favorable outcome after the use of convalescent plasma in addition to systemic corticosteroid. To our knowledge, this is the first report of the use of convalescent plasma therapy for COVID-19 in Korea.

Clinical Characteristics and Causative Pathogens of Infective Arthritis and Risk Factors for Gram-Negative Bacterial Infections

Background@#The aim of this study was to describe the clinical and microbiological characteristics of infective arthritis and to analyze risk factors for Gram-negative bacterial infections that cause infective arthritis. @*Materials and Methods@#Patients admitted between 2009 - 2018 with infective arthritis in a single-tertiary hospital were evaluated retrospectively. @*Results@#A total of 181 patients were enrolled in this study. Of them, 135 were native joint infection patients and 46 were prosthetic joint infection patients. The most common site of infective arthritis was the knee (63.6%), followed by the shoulder (17.7%), and the hip (9.9%).The most frequently identified microorganisms were Staphylococcus aureus (51.1%), followed by Streptococci sp. (21.1%), Enterobacteriaceae (8.4%), and coagulase-negative-Staphylococci (CNS;8.4%). Infections due to Gram-negative bacteria and fungi made up 13.7% and 3.2% of all cases, respectively. Additionally, 20% and 4.2% of the cases involved methicillin-resistant S. aureus (MRSA) and MRCNS. We found that bacteriuria, infective arthritis in the hip, and steroid use at admission are independent risk factors for Gram-negative bacterial infections. @*Conclusion@#Infective arthritis with methicillin-resistant microorganisms reached up to about 25% in a single-tertiary hospital in Korea. In case of suspected urinary tract infection, infective arthritis of the hip joint, or steroid use at admission time among infective arthritis patients, empirical treatment covering Gram-negative microorganisms can be considered.

Use of Convalescent Plasma Therapy in Two COVID-19 Patients with Acute Respiratory Distress Syndrome in Korea

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 not yet has established its treatment, but convalescent plasma has been expected to increase survival rates as in the case with other emerging viral infections. We describe two cases of COVID-19 treated with convalescent plasma infusion. Both patients presented severe pneumonia with acute respiratory distress syndrome and showed a favorable outcome after the use of convalescent plasma in addition to systemic corticosteroid. To our knowledge, this is the first report of the use of convalescent plasma therapy for COVID-19 in Korea.

Clinical Characteristics and Causative Pathogens of Infective Arthritis and Risk Factors for Gram-Negative Bacterial Infections

Background@#The aim of this study was to describe the clinical and microbiological characteristics of infective arthritis and to analyze risk factors for Gram-negative bacterial infections that cause infective arthritis. @*Materials and Methods@#Patients admitted between 2009 - 2018 with infective arthritis in a single-tertiary hospital were evaluated retrospectively. @*Results@#A total of 181 patients were enrolled in this study. Of them, 135 were native joint infection patients and 46 were prosthetic joint infection patients. The most common site of infective arthritis was the knee (63.6%), followed by the shoulder (17.7%), and the hip (9.9%).The most frequently identified microorganisms were Staphylococcus aureus (51.1%), followed by Streptococci sp. (21.1%), Enterobacteriaceae (8.4%), and coagulase-negative-Staphylococci (CNS;8.4%). Infections due to Gram-negative bacteria and fungi made up 13.7% and 3.2% of all cases, respectively. Additionally, 20% and 4.2% of the cases involved methicillin-resistant S. aureus (MRSA) and MRCNS. We found that bacteriuria, infective arthritis in the hip, and steroid use at admission are independent risk factors for Gram-negative bacterial infections. @*Conclusion@#Infective arthritis with methicillin-resistant microorganisms reached up to about 25% in a single-tertiary hospital in Korea. In case of suspected urinary tract infection, infective arthritis of the hip joint, or steroid use at admission time among infective arthritis patients, empirical treatment covering Gram-negative microorganisms can be considered.