Bacterial Superinfection Research Articles

Rapid Detection of Bacterial and Fungal Pathogens Using the T2MR versus Blood Culture in Patients with Severe COVID-19.

ABSTRACTA high rate of bacterial and fungal superinfections was reported in critically ill patients with COVID-19. However, diagnosis can be challenging. The aim of this study is to evaluate the sensitivity and the clinical utility of the point-of-care method T2 magnetic resonance (T2MR) with the gold standard: the blood culture. T2MR can potentially detect five different Candida species and six common bacteria (so-called “ESKAPE” pathogens including Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Acinet`obacter baumanii, Pseudomonas aeruginosa, and Enterococcus faecium). If superinfection was suspected in patients with COVID-19 admitted to the intensive care unit, blood culture and two panels of T2MR were performed. Eighty-five diagnostic bundles were performed in 60 patients in total. T2MR detected an ESKAPE pathogen in 9 out of 85 (10.6%) samples, compared to BC in 3 out of 85 (3.5%). A Candida species was detected in 7 of 85 (8.2%) samples of T2MR compared to 1 out of 85(1.2%) in blood culture. The mean time to positive test result in samples with concordant positive results was 4.5 h with T2MR and 52.5 h with blood culture. The additional use of T2MR enables a highly sensitive and rapid detection of ESKAPE and Candida pathogens.IMPORTANCE Coronavirus disease 2019 (COVID-19) has led to a high number of deaths since the beginning of the pandemic worldwide. One of the reasons is the high number of bacterial and fungal superinfections in patients suffering from critical disease. However, diagnosis is often challenging. In this study we could show that the additional use of the culture-independent method T2MR did not only show a much higher detection rate of bacterial and fungal pathogens but also a significantly shorter time until detection and therapy change compared to the gold standard: the blood culture. The implementation of T2MRin the care of patients with severe course of COVID-19 might lead to an earlier sufficient antimicrobial therapy and as a result lower mortality and less use of broad-spectrum unnecessary therapy reducing the risk of resistance development.

Antimicrobial Resistance in the COVID-19 Landscape: Is There an Opportunity for Anti-Infective Antibodies and Antimicrobial Peptides?

Although COVID-19 has captured most of the public health attention, antimicrobial resistance (AMR) has not disappeared. To prevent the escape of resistant microorganisms in animals or environmental reservoirs a “one health approach” is desirable. In this context of COVID-19, AMR has probably been affected by the inappropriate or over-use of antibiotics. The increased use of antimicrobials and biocides for disinfection may have enhanced the prevalence of AMR. Antibiotics have been used empirically in patients with COVID-19 to avoid or prevent bacterial coinfection or superinfections. On the other hand, the measures to prevent the transmission of COVID-19 could have reduced the risk of the emergence of multidrug-resistant microorganisms. Since we do not currently have a sterilizing vaccine against SARS-CoV-2, the virus may still multiply in the organism and new mutations may occur. As a consequence, there is a risk of the appearance of new variants. Nature-derived anti-infective agents, such as antibodies and antimicrobial peptides (AMPs), are very promising in the fight against infectious diseases, because they are less likely to develop resistance, even though further investigation is still required.

The Spanish flu

The Spanish flu occurred at the end of the First world war, in disastrous epidemiological conditions on populations exhausted by four years of war. At that time, there were no vaccines, no antibiotics, no oxygen and no resuscitation. It was even thought that the infectious agent was a bacterium. Humanity was poorly equipped to fight against a pandemic that caused 50–100 million deaths. The first palpable signs of the outbreak were the rapidly spreading multiple epidemics among young recruits in the American military training camps in March 1918. The flu then spread to the civilian populations and circled the globe twice, sparing no country, even the most remote islands, in tropical as well as polar climates, evolving in successive waves up until April 1919. The first was mild (lethality 0.21%), the second was lethal (lethality 2–4%), and during the third wave, lethality declined (1%), after which the flu became seasonal, with low lethality (0.1%). Between 20 and 40 years of age, patients often died within a few days of pneumonia, with respiratory distress leading to cyanosis, frequently associated with bacterial superinfection. The influenza virus, Myxovirus influenzae, was first discovered in 1931 by Richard Shope in pigs, and then in 1933 by Wilson Smith, Patrick Laidlaw and Christopher Andrews in humans during a seasonal influenza epidemic in London. In 1943, it was first observed under the electron microscope. Hemagglutinin and neuraminidase, the two main virulence factors, were discovered in the 1940s by George Hirst and Alfred Gottschalk. An RNA virus composed of 13,500 nucleotides in eight segments, it was initially sequenced in the 1980s, when Jeffrey Taubenberger determined the complete nucleotide sequence of the 1918 virus from lung tissue samples from patients who died of influenza. The 1918 H1N1 virus was found to have originated in birds. In 2005, it was successfully resuscitated in cell culture. It is 40,000 times more virulent in primates than the seasonal H1N1 virus. The lethality of the second wave could have been due to mutations in the hemagglutinin H1 gene, which would have resulted in a stronger affinity for α,2–6 galactose sialic acids, the virus' receptors on human epithelial cells. That said, the origin of the Spanish flu virus remains controversial. It probably emerged and circulated in the population before March 1918 in America, although European origin has also been evoked. The high mortality in the 20–40 age group remains an enigma. Some experts point to reduced immune response in patients previously exposed to related viral hemagglutinins during the 1889 pandemic. In any event, even though it concerns a markedly different virus, the history of the Spanish flu sheds light on the difficulties of management during today's pandemic.

Factors Associated With The Covid-19 Infection Severity In Patients With Mental Disorders

IntroductionRecent research showed that persons with mental disorders may represent a population at increased risk for coronavirus disease (COVID-19) infection with more adverse outcomes.ObjectivesWe aimed to analyze clinical profile of psychiatric inpatients during their infection with COVID-19, and to explore factors associated with the disease progression.MethodsWe analyzed retrospectively the medical records of 32 psychiatric inpatients, hospitalized in psychiatry “B” department at Hedi Chaker hospital (Sfax, Tunisia), and who contracted the COVID-19 infection. We used “Charlson Comorbidity Index Score” (CCIS), predicting 10-year survival in patients with multiple comorbidities.ResultsSomatic history was reported in 50% of patients. The CCIS ranged between 0 and 4. Psychiatric diagnosis was schizophrenia in 81.3% and bipolar disorder in 18.7% of cases. The clinical symptoms reported were fever (50%), dry cough (75%); dyspnea (34.4%). Biological assessment showed a lymphopenia in 40.6% and a high C-Reactive Protein (CRP) in 53.1%. Among our patients, 37,5% needed oxygen, and 25% were transferred to the intensive care unit. The COVID-19 complications were mostly bacterial pulmonary superinfections (21.9%) and pulmonary embolism (9.4%). Only three (9.4%) patients died from the virus. Patients with medical history were more likely to need oxygen (p<0.001). Clinical and paraclinical parameters associated with oxygen need were: fever (p<0.001); dyspnea (p<0.001); lymphopenia (p<0.001); high CRP (p=0.001). Patients presenting pulmonary superinfection or embolism were more likely to require oxygen (p=0.006 and p=0.044 respectively).ConclusionsThis study highlighted factors that may worsen the COVID-19 infection evolution, and which require special attention, in order to improve the prognosis of this disease.DisclosureNo significant relationships.

Antibiotic Prescriptions in Hospitalized Patients with an Exacerbation COPD and a Proven Influenza or RS Virus Infection.

BackgroundCOPD exacerbations (AE-COPD) add up to over 200,000 hospitalization days annually in the Netherlands. Viral respiratory infections play a role in about half of COPD exacerbations. Although the prevalence of bacterial superinfection is estimated 10–40% in admitted AE-COPD patients with an influenza infection, the majority is treated with antibiotics. Current national and international guidelines provide limited guidance regarding antibiotic use in hospitalized patients with an AE-COPD with proven viral respiratory pathogens.Study GoalWe aimed to investigate antibiotic prescription in hospitalized patients with a COPD exacerbation and an influenza- or RS virus infection.Patients and methodsWe performed a retrospective cohort study in patients admitted with an AE-COPD and influenza- or RS virus infection. We compared clinical characteristics of patients with and without antibiotic treatment on admission and estimated adequacy of antibiotic prescriptions.ResultsWe included 134 patients. Seventy-nine (59%) received antibiotics on admission. Chest X-ray infiltrates and plasma CRP level (≥50 mg/L) were correlated with the prescription of antibiotics. Outcomes, such as number of hospitalized days and mortality, were not significantly different between the groups with and without antibiotic treatment. Antibiotic treatment was considered “probably adequate” in 52/79 (65.8%) patients; “not necessary” in 12/79 patients (15.2%) and “probably not necessary” in another 15/79 patients (19.0%).ConclusionPrescription of antibiotics in hospitalized COPD patients is common practice despite a proven viral infection on admission. A significant antibiotic reduction of 34.2% in these patients seems feasible. Future guidelines should include recommendations regarding antibiotic stewardship in hospitalized patients with AE-COPD with a proven viral respiratory infection.

Varicella with secondary skin bacterial complications: case reports

Chickenpox is a very contagious childhood disease with a self-limited course. It is most common in children up to 10 years old, but can infect a person at any age. Varicella presents with itchy pseudo-polymorphic rash (macula, papula, vesicle, crust) and mild intoxication syndrome. The disease is benign and uncomplicated in general, but complications can occur regardless of immune status and concomitant diseases. Neurological and respiratory are among the most common complications. In the patients described in this article, we can observe secondary bacterial superinfection (pyoderma and phlegmon). These are the third most common complications of varicella, and may have serious consequences. These cases are presented to call attention to proper skincare in a patient with chickenpox and to the choice of an appropriate antipyretic to control fever. It is also important to emphasise the importance of vaccination against this disease and to combat the misconceptions of anti-vaxxers.

Immunocompromised patients have been neglected in COVID-19 trials: a call for action

Immunocompromised patients have been neglected in COVID-19 trials: a call for action

Functions of IFNλs in Anti-Bacterial Immunity at Mucosal Barriers.

Type III interferons (IFNs), or IFNλs, are cytokines produced in response to microbial ligands. They signal through the IFNλ receptor complex (IFNLR), which is located on epithelial cells and select immune cells at barrier sites. As well as being induced during bacterial or viral infection, type III IFNs are produced in response to the microbiota in the lung and intestinal epithelium where they cultivate a resting antiviral state. While the multiple anti-viral activities of IFNλs have been extensively studied, their roles in immunity against bacteria are only recently emerging. Type III IFNs increase epithelial barrier integrity and protect from infection in the intestine but were shown to increase susceptibility to bacterial superinfections in the respiratory tract. Therefore, the effects of IFNλ can be beneficial or detrimental to the host during bacterial infections, depending on timing and biological contexts. This duality will affect the potential benefits of IFNλs as therapeutic agents. In this review, we summarize the current knowledge on IFNλ induction and signaling, as well as their roles at different barrier sites in the context of anti-bacterial immunity.

The Contribution of Viral Proteins to the Synergy of Influenza and Bacterial Co-Infection.

A severe course of acute respiratory disease caused by influenza A virus (IAV) infection is often linked with subsequent bacterial superinfection, which is difficult to cure. Thus, synergistic influenza–bacterial co-infection represents a serious medical problem. The pathogenic changes in the infected host are accelerated as a consequence of IAV infection, reflecting its impact on the host immune response. IAV infection triggers a complex process linked with the blocking of innate and adaptive immune mechanisms required for effective antiviral defense. Such disbalance of the immune system allows for easier initiation of bacterial superinfection. Therefore, many new studies have emerged that aim to explain why viral–bacterial co-infection can lead to severe respiratory disease with possible fatal outcomes. In this review, we discuss the key role of several IAV proteins—namely, PB1-F2, hemagglutinin (HA), neuraminidase (NA), and NS1—known to play a role in modulating the immune defense of the host, which consequently escalates the development of secondary bacterial infection, most often caused by Streptococcus pneumoniae. Understanding the mechanisms leading to pathological disorders caused by bacterial superinfection after the previous viral infection is important for the development of more effective means of prevention; for example, by vaccination or through therapy using antiviral drugs targeted at critical viral proteins.

Bacterial and Fungal Co-Infections and Superinfections in a Cohort of COVID-19 Patients: Real-Life Data from an Italian Third Level Hospital.

The use of immune suppressive drugs combined with the natural immune suppression caused by SARS-CoV-2 can lead to a surge of secondary bacterial and fungal infections. The aim of this study was to estimate the incidence of superinfections in hospitalized subjects with COVID-19. We carried out an observational retrospective single center cohort study. We enrolled patients admitted at the “Garibaldi” hospital for ≥72 h, with a confirmed diagnosis of COVID-19. All patients were routinely investigated for bacterial, viral, and fungal pathogens. A total of 589 adults with COVID-19 were included. A total of 88 infections were documented in different sites among 74 patients (12.6%). As for the etiology, 84 isolates were bacterial (95.5%), while only 4 were fungal (4.5%). A total of 51 episodes of hospital-acquired infections (HAI) were found in 43 patients, with a bacterial etiology in 47 cases (92.2%). Community-acquired infections (CAIs) are more frequently caused by Streptococcus pneumoniae, while HAIs are mostly associated with Pseudomonas aeruginosa. A high rate of CAIs and HAIs due to the use of high-dose corticosteroids and long hospital stays can be suspected. COVID-19 patients should be routinely evaluated for infection and colonization. More data about antimicrobial resistance and its correlation with antibiotic misuse in COVID-19 patients are required.

Time-series analysis of multidimensional clinical-laboratory data by dynamic Bayesian networks reveals trajectories of COVID-19 outcomes

Background and ObjectiveCOVID-19 severity spans an entire clinical spectrum from asymptomatic to fatal. Most patients who require in-hospital care are admitted to non-intensive wards, but their clinical conditions can deteriorate suddenly and some eventually die. Clinical data from patients’ case series have identified pre-hospital and in-hospital risk factors for adverse COVID-19 outcomes. However, most prior studies used static variables or dynamic changes of a few selected variables of interest. In this study, we aimed at integrating the analysis of time-varying multidimensional clinical-laboratory data to describe the pathways leading to COVID-19 outcomes among patients initially hospitalised in a non-intensive care setting. MethodsWe collected the longitudinal retrospective data of 394 patients admitted to non-intensive care units at the University Hospital of Padova (Padova, Italy) due to COVID-19. We trained a dynamic Bayesian network (DBN) to encode the conditional probability relationships over time between death and all available demographics, pre-existing conditions, and clinical laboratory variables. We applied resampling, dynamic time warping, and prototyping to describe the typical trajectories of patients who died vs. those who survived. ResultsThe DBN revealed that the trajectory linking demographics and pre-existing clinical conditions to death passed directly through kidney dysfunction or, more indirectly, through cardiac damage. As expected, admittance to the intensive care unit was linked to markers of respiratory function. Notably, death was linked to elevation in procalcitonin and D-dimer levels. Death was associated with persistently high levels of procalcitonin from admission and throughout the hospital stay, likely reflecting bacterial superinfection. A sudden raise in D-dimer levels 3–6 days after admission was also associated with subsequent death, possibly reflecting a worsening thrombotic microangiopathy. ConclusionsThis innovative application of DBNs and prototyping to integrated data analysis enables visualising the patient's trajectories to COVID-19 outcomes and may instruct timely and appropriate clinical decisions.

A cytokine panel and procalcitonin in COVID-19, a comparison between intensive care and non-intensive care patients.

Procalcitonin (PCT) is an acute-phase reactant with concentrations ≥0.5 μg/L indicative of possible bacterial infection in patients with SARS-CoV-2 infection (COVID-19). Some with severe COVID-19 develop cytokine storm secondary to virally driven hyper-inflammation. However, increased pro-inflammatory cytokines are also seen in bacterial sepsis. This study aimed to assess the clinical utility of a cytokine panel in the assessment of COVID-19 with bacterial superinfections along with PCT and C-reactive protein (CRP). The retrospective analysis included serum cytokines (interleukins; IL-1β, IL-6, IL-8 and tumour necrosis factor (TNFα)) measured using Ella™ (Bio-Techne, Oxford, UK) and PCT measured by Roche Cobas (Burgess Hill, UK) in patients admitted with COVID-19 between March 2020 and January 2021. Patients enrolled into COVID-19 clinical trials, treated with Remdesivir/IL-6 inhibitors were excluded. The cytokine data was compared between intensive care unit (ICU) patients, age matched non-ICU patients and healthy volunteers as well as ICU patients with high and normal PCT (≥0.5 vs. <0.5 μg/L). Cytokine concentrations and CRP were higher in COVID-19 patients (76; ICU & non-ICU) vs. healthy controls (n = 24), all p<0.0001. IL-6, IL-8, TNFα and were higher in ICU patients (n = 46) vs. non-ICU patients (n = 30) despite similar CRP. Among 46 ICU patients, the high PCT group (n = 26) had higher TNFα (p<0.01) and longer ICU stay (mean 47 vs. 25 days, p<0.05). There was no difference in CRP and blood/respiratory culture results between the groups. Pro-inflammatory cytokines and PCT were higher in COVID-19 patients requiring ICU admission vs. non-ICU admissions despite no difference in CRP. Furthermore, TNFα was higher in those with high PCT and requiring longer ICU admission despite no difference in CRP or rate of bacterial superinfection.

Evaluation of respiratory tract bacterial co-infections in SARS-CoV-2 patients with mild or asymptomatic infection in Lagos, Nigeria

BackgroundA common complication of any respiratory disease by a virus could be a secondary bacterial infection, which is known to cause an increase in severity. It is, however, not clear whether the presence of some opportunistic pathogens called pathobionts contributes to the severity of the disease. In COVID-19 patients, undetected bacterial co-infections may be associated with the severity of the disease. Therefore, we investigated the implications of bacterial co-infections in COVID-19 cases.ResultsThis is a cross-sectional study that involved archived specimens collected from nasopharyngeal samples of 150 people for COVID-19 screening in Lagos. DNA extraction from the samples was carried out to determine the presence of five respiratory bacterial pathogens using nested real-time PCR, and data were analysed using the Chi-square test. Of the 150 samples collected, 121 (80.7%) were positive for SARs-CoV-2 infection and 29 were negative. The proportion of patients with bacteria co-infection in COVID-19-negative, asymptomatic, and mild cases were 93.1%, 70.7%, and 67.5%, respectively. There was no statistically significant difference between mild COVID-19 conditions and bacteria co-infection (p = 0.097). There was also no significant difference in the nasal carriage of Staphylococcus aureus, Mycoplasma pneumoniae, and Haemophilus spp. However, there was a statistically significant increase in the carriage of Moraxella catarrhalis and Chlamydophila pneumoniae among COVID-19-negative patients when compared with the positive patients (p value = 0.003 and 0.000 for Moraxella catarrhalis and Chlamydophila pneumoniae, respectively).ConclusionsThe current study shows that bacterial co-infection and superinfection with COVID-19 are not associated with mild and asymptomatic COVID-19 cases in our setting. However, given the high prevalence of Staphylococcus aureus and Mycoplasma pneumoniae among the mild COVID-19 cases seen in this study, early diagnosis and treatment of these bacterial co-infections are still encouraged to mitigate the effect on the severity of COVID-19.

Bordetella hinzii Pneumonia in Patient with SARS-CoV-2 Infection

Abstract Patients infected with severe acute respiratory syndrome coronavirus 2 might have bacterial and fungal superinfections develop. We describe a clinical case of coronavirus disease with pulmonary aspergillosis associated with Bordetella hinzii pneumonia in an immunocompetent patient in France. B. hinzii infections are rare in humans and develop secondary to immunosuppression or debilitating diseases.

Description of a Newly Isolated Blautia faecis Strain and Its Benefit in Mouse Models of Post-Influenza Secondary Enteric and Pulmonary Infections.

The expanding knowledge on the systemic influence of the human microbiome suggests that fecal samples are underexploited sources of new beneficial strains for extra-intestinal health. We have recently shown that acetate, a main circulating microbiota-derived molecule, reduces the deleterious effects of pulmonary Streptococcus pneumoniae and enteric Salmonella enterica serovar Typhimurium bacterial post-influenza superinfections. Considering the beneficial and broad effects of acetate, we intended to isolate a commensal strain, producing acetate and potentially exploitable in the context of respiratory infections. We designed successive steps to select intestinal commensals that are extremely oxygen-sensitive, cultivable after a freezing process, without a proinflammatory effect on IL-8 induction, and producing acetate. We have identified the Blautia faecis DSM33383 strain, which decreased the TNFα-induced production of IL-8 by the intestinal epithelial cell line HT-29. The beneficial effect of this bacterial strain was further studied in two preclinical models of post-influenza Streptococcus pneumoniae (S.p) and Salmonella enterica serovar Typhimurium (S.t) superinfection. The intragastrical administration of Blautia faecis DSM33383 led to protection in influenza-infected mice suffering from an S.p. and, to a lesser extent, from an S.t secondary infection. Altogether, this study showed that Blautia faecis DSM33383 could be a promising candidate for preventive management of respiratory infectious diseases.

SARS-CoV-2 infection in the immediate post-transplant period: A report of five kidney transplant recipients

Introduction: The severe acute respiratory syndrome coronavirus 2 pandemic caused a negative impact on transplantation worldwide. One of the complexities is the management of the immunosuppression and anti-viral medication in transplant recipients. Herein we describe our experience managing five patients with coronavirus disease 2019 (COVID-19) immediately after kidney transplant. Description: we describe a series of five transplant recipients. Two were submitted to a low immunological risk induction immunosuppression: one developed severe disease, the other developed critical disease. The remaining three were submitted to a high immunologic risk immunosuppression: one developed mild disease, but approximately two months after diagnosis developed moderate COVID-19; another developed severe COVID-19; the remaining patient developed critical illness and perished. Both patients with critical COVID-19 developed bacterial and fungal superinfections in the Intensive Care Unit. All eligible patients were submitted to remdesivir and dexamethasone. The anti-metabolite was reduced or suspended. Despite worsening kidney function during the acute phase, kidney replacement therapy was only needed in one patient and the average serum creatinine at the time of discharge was lower that the pre-COVID-19 nadir. Discussion: There is still no definitive answer on whether solid organ transplant recipients carry a higher risk for morbimortality. Risk factors for the general population can also affect their outcome. The prolonged viral shedding in recipients may explain the irregular evolution of the patient who developed COVID-19 months after the initial diagnosis. The reduction of immunosuppression can be problematic in early post-transplant, but no apparent signs of rejection were noted. Literature addressing this specific context is scarce and studies are needed to clarify the optimal management of these patients.

The Impact of Multiplex PCR in Diagnosing and Managing Bacterial Infections in COVID-19 Patients Self-Medicated with Antibiotics.

The multiplex PCR is a powerful and efficient tool that was widely used during the COVID-19 pandemic to diagnose SARS-CoV-2 infections and that has applications for bacterial identification, as well as determining bacterial resistance to antibiotics. Therefore, this study aimed to determine the usability of multiplex PCR, especially in patients self-medicated with antibiotics, where bacterial cultures often give false-negative results. A cross-sectional study was developed in two COVID-19 units, where 489 eligible patients were included as antibiotic takers and non-antibiotic takers. Antibiotic takers used mostly over-the-counter medication; they suffered significantly more chronic respiratory conditions and were self-medicated most often with cephalosporins (41.4%), macrolide (23.2%), and penicillin (19.7%). The disease severity in these patients was significantly higher than in non-antibiotic takers, and bacterial superinfections were the most common finding in the same group (63.6%). Antibiotic takers had longer hospital and ICU admissions, although the mortality rate was not significantly higher than in non-antibiotic takers. The most common bacteria involved in secondary infections were Staphylococcus aureus (22.2%), Pseudomonas aeruginosa (27.8%), and Klebsiella spp (25.0%). Patients self-medicating with antibiotics had significantly higher rates of multidrug resistance. The multiplex PCR test was more accurate in identifying multidrug resistance and resulted in a quicker initiation of therapeutic antibiotics compared with instances where a bacterial culture was initially performed, with an average of 26.8 h vs. 40.4 h, respectively. The hospital stay was also significantly shorter by an average of 2.5 days when PCR was used as an initial assessment tool for secondary bacterial infections. When adjusted for age, COVID-19 severity, and pulmonary disease, over-the-counter use of antibiotics represented a significant independent risk factor for a prolonged hospitalization (AOR = 1.21). Similar findings were observed for smoking status (AOR = 1.44), bacterial superinfection (AOR = 1.52), performing only a conventional bacterial culture (AOR = 1.17), and a duration of more than 48 h for bacterial sampling from the time of hospital admission (AOR = 1.36). Multiplex PCR may be a very effective method for diagnosing secondary bacterial infections in COVID-19 individuals self-medicating with antibiotics. Utilizing this strategy as an initial screen in COVID-19 patients who exhibit signs of sepsis and clinical deterioration will result in a faster recovery time and a shorter period of hospitalization.

Routine laboratory test to assess the need of respiratory support in acute bronchiolitis

Accurate and readily available biomarkers to predict the clinical course of bronchiolitis would enable enhanced decision-making in this setting. We explored the relationship of several biochemical parameters available at the pediatric emergency care setting with the need of advanced respiratory support (ARS): continuous positive airway pressure (CPAP), biphasic positive airway pressure (BiPAP), or invasive mechanical ventilation (MV) in bronchiolitis. Single-center, prospective, observational, including infants aged less than 12 months diagnosed with acute bronchiolitis at the Pediatric Emergency Department. Determination of plasmatic values of several laboratory tests was performed at the time of hospital admission. Multivariate logistic analysis identified independent predictors for need of ARS. From October 1, 2018to May 1, 2020, we recruited 149 infants (58% males; median age of 1 [0.5-2.5]month). Thirty-seven (25%) cases required ARS. After adjusting by age, bacterial superinfection, and comorbidities in the multivariate analysis, only higher levels of glycemia (p = 0.001),C-reactive protein (CRP)(p = 0.028), CRP/albuminratio (p = 0.032), and NT-proBNP (p = 0.001) remained independently associated with ARS. These biomarkers reached moderate prediction accuracy with area under the curve of receiver operator curve curves ranging from 0.701 to 0.830 (p = 0.001). All they presented relatively high specificity (0.75-0.84) and negative predictive values (0.77-0.89) with low sensitivity and positive predictive values. They also correlated significantly with length of stay hospitalization (p = 0.001). Increased plasmatic levels of CRP, CRP/albumin ratio, glycemia, and NT-proBNP at hospital admission are associated with the need for ARS in infants with acute bronchiolitis.

Cytological patterns of bronchoalveolar lavage fluid in mechanically ventilated COVID-19 patients on extracorporeal membrane oxygenation.

IntroductionCoronavirus disease‐2019 (COVID‐19) may lead to acute respiratory distress syndrome requiring extracorporeal membrane oxygenation (ECMO). Patterns of inflammatory bronchoalveolar cells in COVID‐19 patients treated with ECMO are not well described.ObjectiveWe aimed to describe inflammatory cell subpopulations in blood and bronchoalveolar lavages (BALs) obtained in critically ill COVID‐19 patients shortly after ECMO implementation.MethodsBAL was performed in the middle lobe in 12 consecutive ECMO‐treated COVID‐19 patients. Trained cytologists analyzed peripheral blood and BAL cells using flow cytometry and routine staining, respectively. Data were interpreted in relation to dexamethasone administration and weaning from ECMO and ventilator.ResultsHigh neutrophil proportions (66% to 88% of total cells) were observed in the absence of bacterial superinfection and more frequently in dexamethasone‐free patients (83% [82–85] vs. 29% [8–68], P = 0.006), suggesting that viral infection could be responsible of predominantly neutrophilic lung inflammation. Successful weaning from ECMO/ventilator could not be predicted by the peripheral white blood and BAL cell pattern.ConclusionHigh neutrophil proportions can be observed in critically ill COVID‐19 patients despite the lack of microbiological evidence on BAL of bacterial superinfection. Dexamethasone was associated with lower neutrophil proportions in BAL. Our study was probably underpowered to provide BAL cell pattern helpful to predict weaning from ECMO/ventilator.

Impact of Hypogammaglobulinemia on the Course of COVID-19 in a Non-Intensive Care Setting: A Single-Center Retrospective Cohort Study.

BackgroundSeverity and mortality of COVID-19 largely depends on the ability of the immune system to clear the virus. Among various comorbidities potentially impacting on this process, the weight and the consequences of an antibody deficiency have not yet been clarified.MethodsWe used serum protein electrophoresis to screen for hypogammaglobulinemia in a cohort of consecutive adult patients with COVID-19 pneumonia, hospitalized in non-intensive care setting between December 2020 and January 2021. The disease severity, measured by a validated score and by the need for semi intensive (sICU) or intensive care unit (ICU) admission, and the 30-day mortality was compared between patients presenting hypogammaglobulinemia (HYPO) and without hypogammaglobulinemia (no-HYPO). Demographics, comorbidities, COVID-19 specific treatment during the hospital stay, disease duration, complications and laboratory parameters were also evaluated in both groups.ResultsWe enrolled 374 patients, of which 39 represented the HYPO cohort (10.4%). In 10/39 the condition was previously neglected, while in the other 29/39 hematologic malignancies were common (61.5%); 2/39 were on regular immunoglobulin replacement therapy (IgRT). Patients belonging to the HYPO group more frequently developed a severe COVID-19 and more often required sICU/ICU admission than no-HYPO patients. IgRT were administered in 8/39 during hospitalization; none of them died or needed sICU/ICU. Among HYPO cohort, we observed a significantly higher prevalence of neoplastic affections, of active oncologic treatment and bronchiectasis, together with higher prevalence of viral and bacterial superinfections, mechanical ventilation, convalescent plasma and SARS-CoV-2 monoclonal antibodies administration during hospital stay, and longer disease duration. Multivariate logistic regression analysis and Cox proportional hazard regression confirmed the impact of hypogammaglobulinemia on the COVID-19 severity and the probability of sICU/ICU admission. The analysis of the mortality rate in the whole cohort showed no significant difference between HYPO and no-HYPO.ConclusionsHypogammaglobulinemia, regardless of its cause, in COVID-19 patients hospitalized in a non-intensive care setting was associated to a more severe disease course and more frequent admission to s-ICU/ICU, particularly in absence of IgRT. Our findings emphasize the add-value of routine serum protein electrophoresis evaluation in patients admitted with COVID-19 to support clinicians in patient care and to consider IgRT initiation during hospitalization.