Howell-Jolly Body-Like Inclusions in Coronavirus Disease 2019 (COVID-19): Possible Novel Findings.

Background: During COVID-19 pandemic, it is difficult to distinguish febrile patient infected by SARS-CoV-2 or bacterial causes. Howell-Jolly bodies are a well-known entity found in red blood cells. They are nuclear fragments, composed of deoxyribonucleic acid, commonly observed in the peripheral blood smears of hyposplenic or asplenic patients. Recently, similar inclusions often referred to as Howell-Jolly body-like inclusions (HJBLIs) have been reported in the neutrophils of patients with acquired immune deficiency syndrome (AIDS) and COVID-19 patient. Aim: To explore whether HJBLIs in peripheral blood smear could differentiate between patients with confirmed SARS-CoV-2 and bacterial pneumonia. Methods: We performed cross-sectional study using secondary data from COVID-19 database and re-evaluated peripheral blood smears to identify HJBLIs. We included confirmed COVID-19 adults age >18 years who were hospitalized in Dr. Hasan Sadikin General Hospital, Bandung, Indonesia from March 1st 2020-May 31st 2020. We also examined peripheral blood smears in patients with confirmed bacterial pneumonia as a control group. Clinical characteristics including disease severity, CURB-65 score, comorbidity, and the present of HJBLIs in peripheral blood smears were evaluated. Results: Overall, 33 patients were included: 22 were confirmed COVID-19 and 11 were confirmed bacterial pneumonia. The median (interquartile range) age in COVID-19 and patients with bacterial pneumonia were 53 years (40-64) vs 57 years (53-71), respectively. Compared with patients with bacterial pneumonia, HJBLIs were significantly higher in COVID-19 patients [21/22 (80.8%) vs 5/11 (45.5%), p 0.001]. Conclusion: Howell-Jolly body-like inclusions could be a potential feature to help differentiate between COVID-19 and bacterial pneumonia.

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.

Etiologies of severe acute respiratory infection (SARI) and misdiagnosis of influenza in Indonesia, 2013-2016.

BACKGROUND: Severe acute respiratory infection (SARI) accounts for a large burden of illness in Indonesia. However, epidemiology of SARI in tertiary hospitals in Indonesia is unknown. This study sought to assess the burden, clinical characteristics, and etiologies of SARI and concordance of clinical diagnosis with confirmed etiology. METHODS: Data and samples were collected from subjects presenting with SARI as part of the acute febrile Illness requiring hospitalization study (AFIRE). In tertiary hospitals, clinical diagnosis was ascertained from chart review. Samples were analyzed to determine the "true" etiology of SARI at hospitals and Indonesia Research Partnership on Infectious Diseases (INA-RESPOND) laboratory. Distribution and characteristics of SARI by true etiology and accuracy of clinical diagnosis were assessed. RESULTS: Four hundred and twenty of 1464 AFIRE subjects presented with SARI; etiology was identified in 242 (57.6%), including 121 (28.8%) viruses and bacteria associated with systemic infections, 70 (16.7%) respiratory bacteria and viruses other than influenza virus, and 51 (12.1%) influenza virus cases. None of these influenza patients were accurately diagnosed as having influenza during hospitalization. CONCLUSIONS: Influenza was misdiagnosed among all patients presenting with SARI to Indonesian tertiary hospitals in the AFIRE study. Diagnostic approaches and empiric management should be guided by known epidemiology. Public health strategies to address the high burden of influenza should include broad implementation of SARI screening, vaccination programs, clinician education and awareness campaigns, improved diagnostic capacity, and support for effective point-of-care tests.

C-reactive protein, procalcitonin, D-dimer, and ferritin in severe coronavirus disease-2019: a meta-analysis.

BACKGROUND: Patients critically ill with coronavirus disease-2019 (COVID-19) feature hyperinflammation, and the associated biomarkers may be beneficial for risk stratification. We aimed to investigate the association between several biomarkers, including serum C-reactive protein (CRP), procalcitonin (PCT), D-dimer, and serum ferritin, and COVID-19 severity. METHODS: We performed a comprehensive systematic literature search through electronic databases. The outcome of interest for this study was the composite poor outcome, which comprises mortality, acute respiratory distress syndrome, need for care in an intensive care unit, and severe COVID-19. RESULTS: A total of 5350 patients were pooled from 25 studies. Elevated CRP was associated with an increased composite poor outcome [risk ratio (RR) 1.84 (1.45, 2.33), p < 0.001; I2: 96%] and its severe COVID-19 (RR 1.41; I2: 93%) subgroup. A CRP ⩾10 mg/L has a 51% sensitivity, 88% specificity, likelihood ratio (LR) + of 4.1, LR- of 0.5, and an area under curve (AUC) of 0.84. An elevated PCT was associated with an increased composite poor outcome [RR 3.92 (2.42, 6.35), p < 0.001; I2: 85%] and its mortality (RR 6.26; I2: 96%) and severe COVID-19 (RR 3.93; I2: 63%) subgroups. A PCT ⩾0.5 ng/ml has an 88% sensitivity, 68% specificity, LR+ of 2.7, LR- of 0.2, and an AUC of 0.88. An elevated D-dimer was associated with an increased composite poor outcome [RR 2.93 (2.14, 4.01), p < 0.001; I2: 77%], including its mortality (RR 4.15; I2: 83%) and severe COVID-19 (RR 2.42; I2: 58%) subgroups. A D-dimer >0.5 mg/L has a 58% sensitivity, 69% specificity, LR+ of 1.8, LR- of 0.6, and an AUC of 0.69. Patients with a composite poor outcome had a higher serum ferritin with a standardized mean difference of 0.90 (0.64, 1.15), p < 0.0001; I2: 76%. CONCLUSION: This meta-analysis showed that an elevated serum CRP, PCT, D-dimer, and ferritin were associated with a poor outcome in COVID-19. The reviews of this paper are available via the supplemental material section.