Virus-Induced Changes of the Respiratory Tract Environment Promote Secondary Infections With Streptococcus pneumoniae

Sender, Vicky; Hentrich, Karina; Henriques‐Normark, Birgitta

doi:10.3389/fcimb.2021.643326

Cited by 60 publications

(52 citation statements)

References 176 publications

(233 reference statements)

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“… 43 Another suggestion was that pneumonia vaccination may prevent COVID‐19 exacerbation due to co‐infections or secondary bacterial infections. 44 , 45 Compared with Streptococcus pneumoniae vaccines, the results of diphtheria, tetanus, and acellular pertussis vaccines should be interpreted with caution because not all sensitivity analyses indicate their corresponding associations as significant. Nevertheless, in support of our results, an in silico study found that combinations of diphtheria, tetanus, and acellular pertussis vaccines induce potential cross‐reactive immunity to SARS‐CoV‐2.…”

Section: Discussionmentioning

confidence: 99%

DrugWAS: Drug‐wide Association Studies for COVID‐19 Drug Repurposing

Bejan

Cahill

Staso

et al. 2021

Clin Pharma and Therapeutics

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This study aimed to systematically investigate if any of the available drugs in the electronic health record (EHR) can be repurposed as potential treatment for coronavirus disease 2019 . Based on a retrospective cohort analysis of EHR data, drug-wide association studies (DrugWAS) were performed on 9,748 patients with COVID-19 at Vanderbilt University Medical Center (VUMC). For each drug study, multivariable logistic regression with overlap weighting using propensity score was applied to estimate the effect of drug exposure on COVID-19 disease outcomes. Patient exposure to a drug between 3-months prior to the pandemic and the COVID-19 diagnosis was chosen as the exposure of interest. All-cause of death was selected as the primary outcome. Hospitalization, admission to the intensive care unit, and need for mechanical ventilation were identified as secondary outcomes. Overall, 17 drugs were significantly associated with decreased COVID-19 severity. Previous exposure to two types of 13-valent pneumococcal conjugate vaccines, PCV13 (odds ratio (OR), 0.31, 95% confidence interval (CI), 0.12-0.81 and OR, 0.33, 95% CI, 0.15-0.73), diphtheria toxoid and tetanus toxoid vaccine (OR, 0.38, 95% CI, 0.15-0.93) were significantly associated with a decreased risk of death (primary outcome). Secondary analyses identified several other significant associations showing lower risk for COVID-19 outcomes: acellular pertussis vaccine, 23-valent pneumococcal polysaccharide vaccine (PPSV23), flaxseed extract, ethinyl estradiol, estradiol, turmeric extract, ubidecarenone, azelastine, pseudoephedrine, dextromethorphan, omega-3 fatty acids, fluticasone, and ibuprofen. In conclusion, this cohort study leveraged EHR data to identify a list of drugs that could be repurposed to improve COVID-19 outcomes. Further randomized clinical trials are needed to investigate the efficacy of the proposed drugs.Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has triggered a pandemic infection leading to unprecedented excess mortality and adverse consequences to global economy. 1,2 According to the World Health Organization (WHO), SARS-CoV-2 has spread to over 222 countries and territories resulting in > 81 million

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Section: Discussionmentioning

confidence: 99%

DrugWAS: Drug‐wide Association Studies for COVID‐19 Drug Repurposing

Bejan

Cahill

Staso

et al. 2021

Clin Pharma and Therapeutics

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“…( 24) Mobility metrics showed a return to near-baseline levels of activity, which could allow the usual avenues of pneumococcal transmission to resume. There is also the possibility of post-SARS-CoV-2 vulnerability to pneumococcal infection, (27) and when ~5% of the population has had a confirmed SARS-CoV-2 infection, this may compromise the baseline health of the population. A further possibility is a mutualistic relationship between IPD and RSV.…”

Section: Discussionmentioning

confidence: 99%

Re-emergence of Invasive Pneumococcal Disease in Germany during the Spring and Summer of 2021

Perniciaro

Linden

Weinberger

2021

Preprint

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Background: The incidence of invasive pneumococcal disease (IPD) decreased worldwide in 2020 and the first quarter of 2021, concurrent with non-pharmaceutical interventions (NPIs) intended to stymie transmission of SARS-CoV-2. In 2021, stringency of these NPI strategies has varied. We investigated age- and serotype-specific variations in IPD case counts in Germany in 2020-2021. Methods: IPD cases through July 31, 2021 were stratified by age group, serotype, or geographic location. IPD surveillance data in 2020-2021 were compared with: 1) IPD surveillance data from 2015-2019, 2) mobility data during 2020 and 2021, and 3) NPI stringency data in 2020 and 2021. Results: IPD began to return towards baseline values among children 0 to 4 years old in April 2021 and exceeded baseline levels by June 2021 (a 9% increase over the average monthly values for 2015-2019). Children 5 to 14, adults aged 15-34 and adults 80 years and older showed increases in IPD cases which went over baseline values starting in July 2021, with increases also starting in Spring 2021. The age distribution and proportion of vaccine serotype IPD remained comparable to previous years despite lower overall case counts in 2020 and 2021. The percent change in IPD incidence compared to the previous five years correlated with changes in mobility and with NPI stringency. Conclusions: IPD levels began to return to and exceed seasonal levels in Spring/Summer 2021 in Germany following sharp declines in 2020 that coincided with NPIs related to the COVID-19 pandemic. Proportions of vaccine serotypes remained largely consistent throughout 2020-2021.

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“…The prevalent etiological agents of bacterial pneumonia following antecedent influenza infection (S. aureus, S. pneumoniae, and H. influenzae) are common, persistent, and asymptomatic colonizers of upper respiratory tract [35][36][37][38]. Curiously, this is a trait shared by other microorganisms that are less frequent causes of secondary pneumonia such as S. pyogenes (S. pyogenes) [38,39].…”

Section: Dysregulation Of Innate Immunitymentioning

confidence: 99%

“…In general, susceptibility to bacterial co-infection peaks 6-7 days post influenza infection and corresponds with increases in tissue damage and dysregulation of cytokine production [36,45,46]. In immunocompetent individuals, alveolar macrophages and neutrophils are the primary cell types responsible for controlling bacteria invading the lower respiratory tract (LRT).…”

Section: Dysregulation Of Innate Immunitymentioning

confidence: 99%

“…Similarly, the incumbent infection elicits production of the regulatory cytokine IL-10 in the lung epithelia. IL-10 reduces phagocytic activity in neutrophils [36,43,52]. Pretreatment of mice with a neutralizing monoclonal antibody against IL-10 after viral infection, but prior to onset of bacterial infection, significantly increases mouse survival [34].…”

Section: Dysregulation Of Innate Immunitymentioning

confidence: 99%

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Examining the Executioners, Influenza Associated Secondary Bacterial Pneumonia

Borgogna¹,

Voyich²

2022

Infectious Diseases

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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.

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Virus-Induced Changes of the Respiratory Tract Environment Promote Secondary Infections With Streptococcus pneumoniae

Cited by 60 publications

References 176 publications

DrugWAS: Drug‐wide Association Studies for COVID‐19 Drug Repurposing

DrugWAS: Drug‐wide Association Studies for COVID‐19 Drug Repurposing

Re-emergence of Invasive Pneumococcal Disease in Germany during the Spring and Summer of 2021

Examining the Executioners, Influenza Associated Secondary Bacterial Pneumonia

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