Examining the Executioners, Influenza Associated Secondary Bacterial Pneumonia

Influenza infections typically present mild to moderate morbidities in immunocompetent host and are often resolved within 14 days of infection onset. Death from influenza infection alone is uncommon; however, antecedent influenza infection often leads to an increased susceptibility to secondary bacterial pneumonia. Bacterial pneumonia following viral infection exhibits mortality rates greater than 10-fold of those of influenza alone. Furthermore, bacterial pneumonia has been identified as the major contributor to mortality during each of the previous four influenza pandemics. Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, and Streptococcus pyogenes are the most prevalent participants in this pathology. Of note, these lung pathogens are frequently found as commensals of the upper respiratory tract. Herein we describe influenza-induced host-changes that lead to increased susceptibility to bacterial pneumonia, review virulence strategies employed by the most prevalent secondary bacterial pneumonia species, and highlight recent findings of bacterial sensing and responding to the influenza infected environment.

Anti-Lethal Therapy of COVID-19 for Home Health Outpatient Therapy

The article presents the rationale for a new therapeutic strategy for treatment of patients with COVID-19, based on the combined use of biologic response modifiers and drugs targeting etiology and pathophysiology of the novel coronavirus infection, excluding disadvantages of polypharmacy, and providing a high clinical effect. This approach has been predominantly used in home health outpatient treatment of 324 patients with COVID-19 of variable severity using the biologic response modifiers “double drug cocktail” made of recombinant human interleukin-2 and recombinant human interferon alpha-2b in combination with alimemazine, nimesulide, rivaroxaban and antibiotic therapy (co-amoxiclav, or ceftriaxone) if secondary bacterial pneumonia was diagnosed. The results obtained indicate a dramatic improvement in the condition of patients, even with a severe COVID-19, which made possible to avoid artificial ventilation and prevent deaths.

The Prevalence and the Impacts of Pulmonary Bacterial Coinfections and Secondary Bacterial Pneumonia in Patients with Severe Influenza Pneumonitis

Background: This study investigated the prevalence and clinical outcomes of pulmonary bacterial coinfections and secondary bacterial pneumonia in patients with severe influenza pneumonitis. The causative pathogens and their clinical impacts were analyzed. Methods: We retrospectively analyzed the data of adult patients with severe influenza pneumonitis admitted to our medical ICUs from January 2014 to May 2018. Bacterial confection (in first 48 h) and secondary bacterial pneumonia (from 48 h to 1 week) were confirmed by chest radiographs and positive findings in the respiratory specimen obtained from lower airway. The risk factors of pulmonary coinfection were evaluated. The outcomes of patients with or without pulmonary coninfection or secondary bacterial pneumonia were also analyzed.Results: We identified 117 critically ill patients with laboratory-confirmed influenza pneumonitis admitted to the medical ICUs. Klebsiella pneumoniae (31.4%) and Staphylococcus aureus (22.8%) were the most commonly identified bacteria in patients with bacterial coinfection. A high proportion of methicillin-resistant Staphylococcus aureus was noted. Liver cirrhosis and diabetes mellitus were the independent risk factors for bacterial coinfection. Acinetobacter baumannii (28%) and S. aureus (25%) were the most often identified bacteria in patients with secondary bacterial pneumonia. Patients with secondary bacterial pneumonia had longer period of mechanical ventilation, longer ICU stay and hospital stay, and higher mortality.Conclusions: Bacterial coinfection or secondary infection in patients with severe influenza pneumonitis were associated with higher rates of morbidity and mortality in ICU patients. Earlier diagnosis and appropriate therapy, especially in patients with liver cirrhosis and diabetes mellitus, should be cautiously considered.

GP96 Drives Exacerbation of Secondary Bacterial Pneumonia following Influenza A Virus Infection

Secondary bacterial pneumonia following an influenza A virus (IAV) infection is a major cause of morbidity and mortality. Although it is generally accepted that preceding IAV infection leads to increased susceptibility to secondary bacterial infection, details regarding the pathogenic mechanism during the early stage of superinfection remain elusive.

Basil Polysaccharide Reverses Development of Experimental Model of Sepsis-Induced Secondary Staphylococcus aureus Pneumonia

Background. Basil polysaccharide (BPS) represents a main active ingredient extracted from basil (Ocimum basilicum L.), which can regulate secondary bacterial pneumonia development in the process of sepsis-mediated immunosuppression. Methods. In this study, a dual model of sepsis-induced secondary pneumonia with cecal ligation and puncture and intratracheal instillation of Staphylococcus aureus or Pseudomonas aeruginosa was constructed. Results. The results indicated that BPS-treated mice undergoing CLP showed resistance to secondary S. aureus pneumonia. Compared with the IgG-treated group, BPS-treated mice exhibited better survival rate along with a higher bacterial clearance rate. Additionally, BPS treatment attenuated cell apoptosis, enhanced lymphocyte and macrophage recruitment to the lung, promoted pulmonary cytokine production, and significantly enhanced CC receptor ligand 4 (CCL4). Notably, recombinant CCL4 protein could enhance the protective effect on S. aureus-induced secondary pulmonary infection of septic mice, which indicated that BPS-induced CCL4 partially mediated resistance to secondary bacterial pneumonia. In addition, BPS priming markedly promoted the phagocytosis of alveolar macrophages while killing S. aureus in vitro, which was related to the enhanced p38MAPK signal transduction pathway activation. Moreover, BPS also played a protective role in sepsis-induced secondary S. aureus pneumonia by inducing Treg cell differentiation. Conclusions. Collectively, these results shed novel lights on the BPS treatment mechanism in sepsis-induced secondary S. aureus pneumonia in mice.

Impaired immune signaling and changes in the lung microbiome precede secondary bacterial pneumonia in COVID-19

Secondary bacterial infections, including ventilator-associated pneumonia (VAP), lead to worse clinical outcomes and increased mortality following viral respiratory infections including in patients with coronavirus disease 2019 (COVID-19). Using a combination of tracheal aspirate bulk and single-cell RNA sequencing (scRNA-seq) we assessed lower respiratory tract immune responses and microbiome dynamics in 28 COVID-19 patients, 15 of whom developed VAP, and eight critically ill uninfected controls. Two days before VAP onset we observed a transcriptional signature of bacterial infection. Two weeks prior to VAP onset, following intubation, we observed a striking impairment in immune signaling in COVID-19 patients who developed VAP. Longitudinal metatranscriptomic analysis revealed disruption of lung microbiome community composition in patients with VAP, providing a connection between dysregulated immune signaling and outgrowth of opportunistic pathogens. These findings suggest that COVID-19 patients who develop VAP have impaired antibacterial immune defense detectable weeks before secondary infection onset.

Basil Polysaccharide Reverses Development of Experimental Model of Sepsis-Induced Secondary Staphylococcus Aureus Pneumonia

Background: Basil polysaccharide (BPS) represents a main active ingredient extracted from Basil (Ocimum basilicum L.), which can regulate secondary bacterial pneumonia development in the process of sepsis-mediated immunosuppression.Methods: In this study, a dual model of sepsis-induced secondary pneumonia with cecal ligation and puncture and intratracheal instillation of Staphylococcus aureus or Pseudomonas aeruginosa was constructed.Results: The results indicated that BPS treated mice undergoing CLP showed resistance to secondary S. aureus pneumonia. Compared with the IgG treated group, BPS treated mice exhibited better survival rate along with higher bacterial clearance rate. Additionally, BPS treatment attenuated cell apoptosis, enhanced lymphocytes and macrophages recruitment to the lung, promoted pulmonary cytokine production, and significantly enhanced CC receptor ligand 4 (CCL4). Notably, recombinant CCL4 protein could enhance the protective effect on S. aureus-induced secondary pulmonary infection of septic mice, which indicated that BPS induced CCL4 partially mediated resistance to secondary bacterial pneumonia. In addition, BPS priming markedly promoted the phagocytosis of alveolar macrophages while killing S. aureus in vitro, which was related to the enhanced p38MAPK signal transduction pathway activation. Moreover, BPS also played a protective role in sepsis-induced secondary S. aureus pneumonia by inducing Treg cell differentiation.Conclusions: Collectively, these results shed novel lights on the BPS treatment mechanism in sepsis-induced secondary S. aureus pneumonia in mice.

The study of neuraminidase immunity in protection against secondary bacterial pneumonia induced by S. aureus after influenza infection in mice

Introduction. Pneumonia often occurs secondary to influenza infection and accounts for a large proportion of the morbidity and mortality associated with seasonal and pandemic influenza outbreaks. We previously have shown that vaccination with Virus-like particles (VLPs) containing hemagglutinin (HA) of influenza virus reduces mortality caused by bacterial infections after an influenza infections in mice.The aim of this work is to study whether this protective effect may be potentiated by supplementing the HA preparation with the influenza neuraminidase (NA).Materials and methods. We studied the effect of Gag-VLPs with the influenza HA or NA from А/PR/8/34 alone or in combination, in a lethal BALB/c mouse model of S. aureus infection after vaccine-matched or mismatched influenza virus challenge.Results. A cocktail of HA-Gag and NA-Gag-VLPs fully protected from weight loss, mortality and viral replication and significantly reduced the bacterial burden in the lungs of А/PR/8/34 infected animals. Immunization with this cocktail HA-Gag-VLPs 100 ng + NA-Gag-VLPs 20 ng also protected 60% of animals from mortality associated with secondary bacterial S. aureus infection following a heterologous H1N1 influenza virus challenge, and led to the significant protection from weight loss and pulmonary pathogen replication even in the absence of HA-inhibition and NA-inhibition antibodies.Conclusion. Our results indicate that influenza vaccination may improve the outcome of a secondary bacterial pneumonia induced by S. aureus after influenza even when the virus is antigenically different from the vaccine strain. At the same time, in our model, the significance of the immunity to influenza virus HA was prevalent.

Pneumothorax in Mechanically Ventilated Patients with COVID-19 Infection

Data on patient-related factors associated with pneumothorax among critically ill patients with COVID-19 pneumonia is limited. Reports of spontaneous pneumothorax in patients with coronavirus disease 2019 (COVID-19) suggest that the COVID-19 infection could itself cause pneumothorax in addition to the ventilator-induced trauma among mechanically ventilated patients. Here, we report a case series of five mechanically ventilated patients with COVID-19 infection who developed pneumothorax. Consecutive cases of intubated patients in the intensive care unit with the diagnosis of COVID-19 pneumonia and pneumothorax were included. Data on their demographics, preexisting risk factors, laboratory workup, imaging findings, treatment, and survival were collected retrospectively between March and July 2020. Four out of five patients (4/5; 80%) had a bilateral pneumothorax, while one had a unilateral pneumothorax. Of the four patients with bilateral pneumothorax, three (3/4; 75%) had secondary bacterial pneumonia, two had pneumomediastinum and massive subcutaneous emphysema, and one of these two had an additional pneumoperitoneum. A surgical chest tube or pigtail catheter was placed for the management of pneumothorax. Three out of five patients with pneumothorax died (3/5; 60%), and all of them had bilateral involvement. The data from these cases suggest that pneumothorax is a potentially fatal complication of COVID-19 infection. Large prospective studies are needed to study the incidence of pneumothorax and its sequelae in patients with COVID-19 infection.