Utility of Differential White Cell Count and Cell Population Data for Ruling Out COVID-19 Infection in Patients With Community-Acquired Pneumonia

IntroductionThe main aim of this study was to assess the utility of differential white cell count and cell population data (CPD) for the detection of COVID-19 in patients admitted for community-acquired pneumonia (CAP) of different etiologies.MethodsThis was a multicenter, observational, prospective study of adults aged ≥18 years admitted to three teaching hospitals in Spain from November 2019 to November 2021 with a diagnosis of CAP. At baseline, a Sysmex XN-20 analyzer was used to obtain detailed information related to the activation status and functional activity of white cells.ResultsThe sample was split into derivation and validation cohorts of 1065 and 717 patients, respectively. In the derivation cohort, COVID-19 was confirmed in 791 patients and ruled out in 274 patients, with mean ages of 62.13 (14.37) and 65.42 (16.62) years, respectively (p < 0.001). There were significant differences in all CPD parameters except MO-Y. The multivariate prediction model showed that lower NE-X, NE-WY, LY-Z, LY-WY, MO-WX, MO-WY, and MO-Z values and neutrophil-to-lymphocyte ratio were related to COVID-19 etiology with an AUC of 0.819 (0.790, 0.846). No significant differences were found comparing this model to another including biomarkers (p = 0.18).ConclusionsAbnormalities in white blood cell morphology based on a few cell population data values as well as NLR were able to accurately identify COVID-19 etiology. Moreover, systemic inflammation biomarkers currently used were unable to improve the predictive ability. We conclude that new peripheral blood biomarkers can help determine the etiology of CAP fast and inexpensively.     

Lower incidence of hospital-treated infections in infants under 3 months of age vaccinated with BCG

BackgroundLive vaccines potentially have non-specific effects that protect against other infections than those the vaccines are targeted against. The national vaccination program (NVP) in Finland was changed on September 1st, 2006: before BCG vaccine was given to all newborn babies and afterwards to babies in risk groups only. We used this natural experiment to study the non-specific effects of BCG in the frame of NVP using before-after design.MethodsWe compared the incidence of several outcomes obtained from Finnish health registers between children born between July 1st, 2004, and June 30th, 2006 (BCG-eligible) and an age- and season-matched reference cohort born between July 1st, 2007, and June 30th, 2009 (BCG-non-eligible) using Poisson regression. These cohorts were restricted to full-term children whose parents were born in Finland. Follow-up began at birth and lasted 3 months, which is the scheduled age for DTaP-IPV-Hib vaccination, and from 4 months until first birthday. The outcomes included all infections, pneumonia and injuries as a negative control outcome.ResultsThe incidence rate ratio (IRR) of the BCG-eligible cohort (N = 93,658) compared to BCG-non-eligible cohort (N = 94,712) for hospital-diagnosed infections was 0.89 (95 %Cl 0.86–0.93) for the 3-month follow-up. The decrease was mainly caused by respiratory infections. In 4–12 months follow-up the BCG-eligible had slightly more infections than BCG-non-eligible children (IRR 1.03, 1.01–1.06).ConclusionsBCG vaccination was associated with a lower incidence of all hospital-diagnosed infections during the first three months of life. The difference cannot be attributed to lung tuberculosis, since only few paediatric cases occurred in Finland during 2000s. The disappearance of non-specific effect after administration of an inactivated vaccine is compatible with previous studies.     

Clinical manifestations and radiological features by chest computed tomographic findings of a novel coronavirus disease-19 pneumonia among 92 patients in Japan

IntroductionThe novel coronavirus disease (COVID-19) could cause a severe acute respiratory infectious disease, showing a high mortality rate of 12–45% among cases who required intensive care unit admission. COVID-19 pneumoniaPatients and methodsFor the purpose of identifying clinical manifestations and radiological findings of COVID-19 pneumonia, we reviewed all cases of COVID-19 pneumonia which were published by the homepage of the Japanese Association for Infectious Diseases from Feb 5 2020 until April 30 2020, including our cases. All patients were diagnosed based on positive results of the novel coronavirus-real-time RT-PCR with chest computed tomography (CT) findings.ResultsA total of 92 patients were enrolled in this study. The median age was 66 years (range 16–92 years). For all, 50 (54%) were males. The most common underlying disease was hypertension in 32 (36%). Any comorbidity was seen in 60 (67%). The mortality rate was 4 (6%). In terms of clinical symptoms on an initial visit, fever and cough were confirmed in 66 (72%) and 37 (40%). Forty-three (47%) had no respiratory symptoms. As for radiological findings by chest CT scan, ground-glass opacities (GGO)s, peripheral distribution, bilateral lung involvements were seen in 88 (96%), 76 (83%) and 78 (85%), respectively.ConclusionIt is difficult to diagnose as COVID-19 pneumonia due to poor respiratory symptoms. Chest CT findings typically show GGO, peripheral and bilateral shadows. Patients should have chest CT performed if suspected for early diagnosis and therapeutic intervention, resulting in a favorable outcome and prevention of secondary nosocomial transmitted infection.     

中医药调控益生菌防治肺炎的研究进展＊

肺炎是呼吸系统疾病中的常见疾病，发病率高，可伴有多种并发症，严重时可危及生命健康。肺炎患者多伴有肠道菌群失调，表现为有益菌减少，且益生菌可通过“肠-肺轴”影响肺部免疫参与肺炎的发生发展。中医以“肺”与“大肠”两者之间的生理及病理关系为基础，通过整体观念和辨证论治发挥了治疗肺炎的独特的优势。近年来，许多研究表明中医药在治疗肺炎的过程中具有改善肠道微生态作用，但肺炎的中医辨证分型与肠道菌群的相关性尚不明确。本文从中医辨证分型论治肺炎的角度出发，总结不同辨证分型的肺炎与肠道菌群结构特征，阐述中医治疗肺炎过程中对于益生菌的调节作用和“证型—中药—益生菌”的对应关系。通过讨论益生菌在防治肺炎中的关键作用，展望中医辩证联合益生菌治疗肺炎的应用前景，以期为肺炎的防治提供新思路和新靶点，也为将来指导不同肺炎证型患者选择适合的中药及益生菌提供理论依据。     

Retrospective study of pneumonia due to Panton-Valentine leukocidin-producing Staphylococcus aureus in Reunion

ObjectivePanton-Valentine leukocidin-producing Staphylococcus aureus necrotizing pneumonia is an unusual cause of community-acquired pneumonia, although associated with a high case fatality. This infection mainly affects young individuals, without any history, and is most often preceded by flu-like symptoms.MethodWe focused on patients presenting with Staphylococcus aureus necrotizing pneumonia in Reunion (Indian Ocean) admitted to the emergency department. We performed a retrospective study based on data collected from laboratory registers and medical files of patients presenting with Staphylococcus aureus necrotizing pneumonia in Reunion between December 2014 and December 2017.ResultsA total of 16 patients were recruited for this study, with a median age of 40.5 years. More than half of patients had previously been admitted to the emergency department for acute respiratory distress syndrome or severe sepsis. Fourteen patients were admitted to the intensive care unit and six patients died (five premature deaths).ConclusionPhysicians should be aware of this infection during the flu season and quickly adapt the specific antibiotic treatment, including a drug inhibiting toxin production. As methicillin-resistant Staphylococcus aureus is very rarely observed in Reunion, physicians can still adapt the empirical treatment, without glycopeptides.     

Effectiveness of the 10-valent pneumococcal conjugate vaccine among girls,boys, preterm and low-birth-weight infants – Results from a randomized,double-blind vaccine trial

BackgroundSeveral studies have shown differences in susceptibility to infections and immune response to vaccines by sex. Prematurely born infants are at higher risk for pneumococcal diseases, with lower effectiveness for some vaccines compared to term infants. We have reported the effectiveness of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10) on several endpoints in the Finnish Invasive Pneumococcal disease (FinIP) vaccine trial. Now, we present the results of a post-hoc analysis evaluating PHiD-CV10 effectiveness in subgroups by sex, gestational age, and birth weight.MethodsThe FinIP trial was a phase III/IV cluster-randomized, double-blind trial. Infants enrolled < 7 months of age received PHiD-CV10 in two thirds of clusters (3 + 1 or 2 + 1 schedule) and hepatitis B vaccine as control in remaining third. Outcome data included invasive pneumococcal disease, pneumonia, tympanostomy tube placements, and antimicrobial purchases collected through national, routinely used health registers. Negative binomial model was used in the incidence and vaccine effectiveness estimation, and differences in incidences between subgroups were tested among control children.ResultsOf the 30,527 infants enrolled 51% were boys. The incidences of hospital-diagnosed pneumonia and otitis-related outcomes were higher among boys in control groups. There were no significant sex differences in the vaccine effectiveness estimates.Altogether, 1519 (5%) infants were born before 37th gestational week. The incidences of pneumonia outcomes were higher among premature infants when compared to term infants.The vaccine effectiveness estimates among preterm infants were not statistically significant except for antimicrobial purchases, but all point estimates were at the same level among preterm infants as among term infants. There was no significant difference between 2 + 1 and 3 + 1 schedules in any of the subgroups analysed.ConclusionPHiD-CV10 had a similar effectiveness in both sexes, and seemed to be protective in preterm infants.Trial registration: ClinicalTrials.gov NCT00861380 and NCT00839254     

Pneumococcal conjugate vaccine against serotype 3 pneumococcal pneumonia in adults: A systematic review and pooled analysis

BackgroundSerotype 3 pneumococcal disease has not substantially declined at the population level after the routine introduction of 13-valent pneumococcal conjugate vaccine (PCV13) into pediatric immunization programs across the globe. This epidemiological finding has generated debate regarding the effectiveness of PCV13 against serotype 3 disease. Evaluating PCV13 effectiveness against serotype 3 is especially critical in adults, where serotype 3 makes up an important amount of remaining pneumococcal disease.MethodsWe performed a systematic review of the published literature to assess the direct effectiveness of PCV13 against serotype 3 community-acquired pneumonia (CAP) among adults. We then estimated overall vaccine effectiveness (VE) using a pooled analysis of the individual-level, raw data.ResultsTwo published studies met inclusion criteria. One was a randomized controlled trial conducted in the Netherlands and published in 2014. The other was a recently-published case-control study conducted in Louisville, Kentucky that used a test-negative design (TND). We also identified a third TND study conducted in Argentina that was recently presented as a conference abstract but is not yet published. All three studies were conducted in adults aged ≥65 years. PCV13 VE against serotype 3 hospitalized CAP was 52.5% (95%CI: 6.2–75.9%) from the pooled analysis of individual-level data from all three studies. Results were similar if the unpublished estimate was excluded (serotype 3 VE = 53.6% [95%CI: 6.7–76.9%]). No heterogeneity was observed.ConclusionsCurrently-available evidence, although limited to three studies, suggests that PCV13 provides direct protection against serotype 3 hospitalized CAP in adults aged ≥65 years.     

Risk of Infection Associated With Ibrutinib in Patients With B-Cell Malignancies: A Systematic Review and Meta-analysis of Randomized Controlled Trials

IntroductionB-cell malignancies confer an increased risk of infection due to associated immune defects. Conflicting evidence exists on the risk of infection in patients receiving ibrutinib. We conducted a systematic review and meta-analysis to estimate relative risk of infection with ibrutinib in B-cell malignancies.MethodsA systematic search of Embase, Medline, Web of Science, Scopus, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, European Union Clinical Trials Register, and ClinicalTrials.gov was performed through January 15, 2019, to identify randomized controlled trials comparing ibrutinib with other agents or placebo in B-cell malignancies. We pooled point estimates using the Der Simonian and Laird random-effects model. Statistical analyses were performed by Stata/SE 15.1.ResultsSeven studies randomizing 2167 patients were included in the final analysis. Treatment duration in studies ranged from 9.4 to 38.7 months. Ibrutinib was associated with a significantly increased risk of infection (any grade and grade 3-5) in patients with B-cell malignancies [pooled risk ratio (RR) = 1.34, 95% confidence interval [CI], 1.06-1.69, P = .015; and RR = 1.35, 95% CI, 1.05-1.74, P = .018, respectively]. In patients with chronic lymphocytic leukemia, a significantly increased risk of grade 3-5 infection was noted in the ibrutinib group [pooled RR = 1.24, 95% CI, 1.02-1.50, P = .028]. Incidences of pneumonia and upper respiratory tract infection were not significantly different between groups.ConclusionOur meta-analysis found that ibrutinib was associated with significantly higher risk of infections in patients with B-cell malignancies. Occurrence of major individual subtypes was not different between groups, possibly as a result of inconsistent reporting across studies.