BA.5 sub-lineages associated with higher severity of COVID-19 infection: A cross-sectional study in Indonesia.

Objectives: We aimed to compare the clinical severity and outcome among laboratory-confirmed Omicron variant cases admitted between January and December 2022. Methods: This is a cross-sectional study conducted in Hasan Sadikin General Hospital between January and December 2022. We enrolled patients aged ≥18 years with laboratory-confirmed Omicron infection. Data were collected from clinical records and a whole genome sequencing database. We compared the risk of severe symptoms and mortality using a logistic regression analysis adjusted for sex, age, comorbidities, and vaccination status. Results: We enrolled 255 patients and the main sub-lineages were BA.1 (16.1%), BA.2 (11.4%), BA.5 (35.7%), XBB (22.7%), and BQ.1 (14.1%). Compared with BA.1/BA.2, BA.5 sub-lineages were associated with severe symptoms (adjusted odds ratio of 2.9, 95% confidence interval 1.1-8.2, P <0.05). The highest risk of severe symptoms and mortality was linked with a high number of comorbidities (adjusted odds ratio of 7.8, 95% confidence interval 1.7-22.4, P <0.05). Booster vaccination was protective of severity and mortality. Conclusions: Disease severity was associated with BA.5 sub-lineages and multiple comorbidities. Good management is particularly important for people with comorbidities. Furthermore, booster vaccination is also required to reduce severity and mortality.

Antibody Response to SARS-CoV-2 Vaccination in Patients with End-Stage Kidney Disease on Hemodialysis.

Patients with end-stage kidney disease on hemodialysis (ESKD-HD) have a high risk of contracting severe COVID-19. Vaccination can help reduce disease severity, but the immune dysregulation observed in these patients may result in an inadequate antibody response. Therefore, we aimed to evaluate the immune response postvaccination in ESKD-HD patients. This prospective cohort study was conducted in two hemodialysis centers in Indonesia. We enrolled ESKD-HD patients (n = 143) pre- and postvaccination and compared them to healthy subjects (n = 67). SARS-CoV-2 antibody response was assessed using anti-S-RBD antibodies and SVNT % inhibition tests. We performed bivariate and multivariate analysis to determine factors associated with SARS-CoV-2 antibody levels. Seropositive conversion was observed in 97% ESKD-HD subjects postvaccination. Compared with healthy subjects, ESKD-HD patients showed a comparable anti-S-RBD antibody titer postvaccination. mRNA vaccines remained a significant factor for the high immune response, while hypoalbuminemia correlated with lower immune response. In conclusion, ESKD-HD patients showed a robust immune response postvaccination. mRNA vaccines induced a stronger antibody response than other vaccines. Lower levels of serum albumin correlate with lower immune responses in ESKD-HD patients after vaccination.

Anti-SARS-CoV-2 Antibody Level Is Associated with a History of COVID-19 Infection and mRNA Vaccination in Patients with Diabetes.

Type 2 diabetes mellitus (T2DM) is associated with higher severity and mortality in SARS-CoV-2 infections. Vaccination has been encouraged to boost immunity and prevent these unfortunate outcomes. Few studies have evaluated antibody levels after COVID-19 vaccination in patients with T2DM. Therefore, we examined the vaccination status and anti-SARS-CoV-2 antibody levels to identify the factors that affect the antibody levels in patients with T2DM. This cross-sectional study was conducted at the Dr. Hasan Sadikin Hospital and Bandung Kiwari Hospital, Bandung, West Java, Indonesia, between October and November 2022. Adult participants with and without T2DM were tested for SARS-CoV-2 antibodies using a point-of-care quantitative immunochromatographic assay. We enrolled 289 participants: 201 participants with T2DM and 88 participants without T2DM. The T2DM participants had a lower vaccination rate compared with the non-T2DM participants. However, no significant differences in antibody levels were observed between the two groups. Higher antibody levels among the T2DM participants were associated with mRNA vaccination and a history of COVID-19 illness. The lower antibody response observed among the T2DM participants with chronic obstructive pulmonary disease suggests that such patients may need antibody level measurement and an additional booster vaccine.

The Diagnostic Value of Kinetics of NLR to Identify Secondary Pulmonary Bacterial Infection Among COVID-19 Patients at Single Tertiary Hospital in Indonesia.

Purpose: Coronavirus disease 2019 (COVID-19) is a new respiratory tract infection caused by severe acute respiratory syndrome coronavirus-2. The presence of secondary pulmonary bacterial infection (SPBI) made COVID-19 difficult to treat. Neutrophil-lymphocyte count ratio (NLR) is a systemic inflammatory marker used in the diagnosis and prognosis of viral or bacterial infection. At the first 3-5 days after hyperinflammation, it occurs in relation to clinical outcome. Therefore, this study aimed to evaluate the diagnostic value of NLR based on leukocyte kinetics upon admission and after 72 hours among COVID-19 patients with or without SPBI. Patients and Methods: This retrospective cross-sectional study analyzed medical records data of admitted patients with COVID-19 according to the International Classification of Disease 10th Revision (ICD-10) between January and December 2021. The list of patients was extracted and followed by a hand search to identify the inclusion or exclusion criteria and stratified into proven and non-proven SPBI based on clinical data. The study distinguished between SPBI by means of a cut-off value (COV) on the first (D1) and third day (D3), assessed using receiver operating characteristics (ROC), as well as determined the magnitude of sensitivity, specificity, and prevalence ratio. Results: A screening process was conducted on 2902 COVID-19 patients, of which 236 were included, accounting for 8.1%. Among these patients, 87 (36.9%) were found to have proven SPBI. A considerable difference in NLR value between proven and non-proven SPBI was observed on both D1 (11.1 vs 4.2) and D3 (15.3 vs 5.2), with optimal COV of NLR on D1, D3 was found to be 5.29, 9.47, respectively (p < 0.001). Conclusion: NLR on the D1 and D3 distinguished the occurrence of SPBI among COVID-19 patients. The application of NLR assisted in the early determination of bacterial infection and helped in controlling the empirical use of antibiotics.

Clinical and treatment factors associated with the mortality of COVID-19 patients admitted to a referral hospital in Indonesia.

Background: Indonesia had the second-highest number of COVID-19 cases and deaths in South-East Asia. We aimed to determine the factors associated with this mortality and the effect of the recommended COVID-19 treatment regimen during the first 10 months of the epidemic. Methods: This was a retrospective cohort study using secondary data from medical records. In total, 689 adult COVID-19 inpatients hospitalized between March and December 2020 were enrolled. Clinical characteristics, laboratory parameters, and treatments were analyzed by survival outcome. Kaplan-Meier statistics were used to estimate survival. Findings: Of the 689 patients enrolled, 103 (14.9%) died. Disease severity was highly associated with mortality (hazard ratio [HR]: 7.69, p < 0.001). Other clinical factors associated with mortality were older age and comorbidities. Based on laboratory parameters, higher procalcitonin and C-reactive protein contents and a neutrophil-to-lymphocyte ratio >3.53 were also linked to mortality. Favipiravir was associated with lower mortality, with adjusted HRs of 0.24 (0.11-0.54) and 0.40 (0.17-0.98) among the mild/moderate and severe cases, respectively. Among patients with severe disease, steroids showed some beneficial effects in the early days of hospitalization. Interpretation: Older age and comorbidities were associated with disease severity and, consequently, higher mortality. Higher mortality after the second week of hospitalization may be related to secondary bacterial infection. Favipiravir showed significant benefit for COVID-19 survival, while steroids showed benefit only in the early days of admission among patients with severe disease. Funding: This research did not receive a specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

MDR Pathogens Organisms as Risk Factor of Mortality in Secondary Pulmonary Bacterial Infections Among COVID-19 Patients: Observational Studies in Two Referral Hospitals in West Java, Indonesia.

Purpose: The coronavirus disease (COVID-19) outbreak has created a global health crisis. Secondary pulmonary bacterial infection is a COVID-19 complication, increasing morbidity and mortality. This study aimed to determine the pathogens, antibiotic susceptibility patterns, and risk factors for mortality in hospitalized COVID-19 patients. Patients and Methods: This retrospective study used secondary data from patients' electronic medical records at Hasan Sadikin General Hospital and Santo Borromeus Hospital between March 2020 and March 2021. Overall, 2230 hospitalized COVID-19 patients were screened, and 182 of them who were hospitalized ≥48 hours with a procalcitonin level of ≥0.25 ng/mL were enrolled. Culture examination was performed on sputum samples to determine pathogen and antibiotic susceptibilities. Univariate and multivariate analyses were used to determine mortality-related risk factors in hospitalized COVID-19 patients. Results: The prevalence of secondary pulmonary bacterial infections in COVID-19 patients was 8.2%, with 161/182 pathogen growth from sputum samples. Mainly gram-negative bacteria (64.8%) were present, including Acinetobacter baumannii (31.9%), Klebsiella pneumoniae (19.8%), and Pseudomonas aeruginosa (8.8%). High rate of multidrug-resistant (MDR) pathogens was found among isolate (45.9%), ie carbapenem-resistance A. baumannii (CR-Ab) was 84.2%, extended-spectrum ß-lactamase (ESBL) among K. pneumoniae was 61.1%. Secondary infection of MDR pathogens was associated with a higher risk of mortality (AOR 5.63, p = 0.001). Other associated factors were age ≥60 years, ventilator use, and female gender. Conclusion: Gram-negative bacteria are the predominant pathogens causing secondary pulmonary bacterial infection in COVID-19 patients, implying nosocomial infection. High resistance to first-line antimicrobial drugs was observed in Gram-negative bacteria and Gram-positive bacteria. High rate of MDR pathogens was found among isolate and was associated with a significant risk of mortality.

Polymorphisms of SLCO1B1 Gene in Sundanese Ethnic Population of Tuberculosis Patients in Indonesia.

BACKGROUND: The blood level of rifampicin, one of the tuberculosis (TB) drugs, depends on the organic anion transporting polypeptide 1B1 (OATP1B1) in hepatocytes. This protein is encoded by the solute carrier organic anion 1B1 (SLCO1B1) gene. Its genetic variation has been reported to have an impact on clinical outcomes and drug efficacy. However, the polymorphism in the SLCO1B1 gene has not been examined in Indonesia yet. We aimed to identify the frequency of polymorphism in SLCO1B1 gene among pulmonary TB patients in Bandung, Indonesia. METHODS: Cross-sectional study was conducted in West Java. 145 pulmonary TB patients who were treated with first-line drugs treatment (including rifampicin 450 mg daily) were analyzed for polymorphism in SLCO1B1 gene. Patients aged between 18-64 years old and mainly came from Sundanese ethnic group (92.4%). Genetic variants were detected using Polymerase Chain Reaction (PCR) and Sanger sequencing. RESULTS: Polymorphism of c.463C>A(rs11045819) was not identified, while heterozygous and homozygous polymorphism of c.85-7793C>T(rs4149032) were identified in 74 (51.0%) and 56 (38.6%) patients, respectively. The minor allele frequency (MAF) of T (mutant) allele of c.85-7793C>T(rs4149032) was 64.13% (186/209), higher than in the general population, which the MAF of rs4149032 is 53.6% based on 1000 genome database. CONCLUSION: This study highlights the presence of different allele frequencies of polymorphisms within the population, which might affect treatment outcomes.

Chromobacterium violaceum: A Review of an Unexpected Scourge.

Chromobacterium violaceum is a common environmental bacterium that rarely causes disease in humans but has a high fatality rate if it does. Due to the rarity of the cases, clinicians are often unaware of the rapid progression of C. violaceum infection and its unexpected antibiotic resistance pattern, which contribute to the failure of patient management. Our review provides the clinical characteristics, possible sources of exposure, and comorbidities and determines factors associated with survival. We gathered information on 132 cases of C. violaceum causing disease in humans published between 1953 and 2020. Patients were predominantly male with a median age of 17.5, interquartile range (IQR) of 5.0-40.0 years, and a third of them were known to have immune deficiencies or comorbidities. Portals of entry were mainly through a wound in the leg and feet (28.0%), the torso (8.5%), or hands and arms (6.8%). It is not uncommon to acquire infection through unintended contact with contaminated water or dust through the mouth or inhalation. The median incubation period is 4.0 days (IQR 2.0-8.0 days) with a duration of clinical course of 17.5 days (IQR 8.0-30.8 days). The high rate of positive blood cultures (56.1%) and abscesses in internal organs (36.4%) shows the significant severity of this disease. Sepsis and Bacteremia were related to mortality with a risk ratio (RR) of 5.20 (95% CI, 0.831-32.58) and 2.14 (95% CI, 1.05-4.36), respectively. Appropriate antibiotic use prevented death at a RR 0.33 (95% CI, 0.21-0.52). Most patients who recovered and survived were treated with aminoglycosides, fluoroquinolones and carbapenems. This review shows the malignant nature of C. violaceum infection and the need for clinicians to be aware and provide prompt source management for patients. Appropriate empiric and targeted antibiotic regiment guided by susceptibility test results is of vital importance.

Calcitriol Ameliorates Kidney Injury Through Reducing Podocytopathy, Tubular Injury, Inflammation and Fibrosis in 5/6 Subtotal Nephrectomy Model in Rats.

Chronic kidney diseases (CKDs) lead to end-stage renal diseases (ESRD) which are characterized by glomerulosclerosis, tubular injury, anemia, inflammation, and interstitial fibrosis. Vitamin D is known to have renal protective effects. However, its effects relate to low and high doses of Vitamin D in CKD model is still unknown. CKD was performed using 5/6 subtotal nephrectomy procedure in male Sprague Dawley rats (3 months old, 200-300 grams, SN group; n=6), then rats were sacrificed on day 14 after operation. Sham operation was used for control (SO group; n=6). Calcitriol was administered in two doses : 0.01 µg/mL/100 gramsBW/day (SND1 group; n=6) and 0.05 µg/mL/100 gramsBW/day (SND2 group; n=6) intraperitoneally for 14 days. Glomerulosclerosis and tubular injury score were examined using PAS staining, meanwhile, interstitial fibrosis area fraction was assessed with Sirius Red staining. RT-PCR was performed for assessing nephrin, podocin, IL-6, CD68, Collagen-1, and TGF-ß1 mRNA expressions. Immunostaining (IHC) was carried out to observe macrophage (CD68) and myofibroblast (α-SMA). SN demonstrated CKD condition with higher tubular injury, glomerulosclerosis, interstitial fibrosis, and inflammation compared to SO. Calcitriol-treated group (especially SND2) demonstrated significant lower tubular injury, glomerulosclerosis, and interstitial fibrosis compared to SN. SND2 group showed not only significantly lower CD68, IL-6, Collagen-1, and TGF-ß1 mRNA expressions, but also higher mRNA expressions of nephrin and podocin. SND2 group also demonstrated reduction of macrophages infiltration and myofibroblasts expansion based on its histopathological appearance. Vitamin D may have a renoprotective effect on 5/6 subtotal nephrectomy model by attenuating podocytopathy, tubular injury, inflammation and interstitial fibrosis.