Streptococcus pneumoniae re-emerges as a cause of community-acquired pneumonia, including frequent co-infection with SARS-CoV-2, in Germany, 2021

BackgroundThe COVID-19 pandemic and the associated containment measures had a substantial impact on pathogens causing pneumonia in adults. The objective of this study was to determine the etiology of hospitalized community-acquired pneumonia (CAP) among adults in Germany in 2021, the second year of the COVID-19 pandemic. MethodsSince January 2021, this on-going, prospective, population-based surveillances study enrolled adult patients with clinically and radiographically confirmed CAP at three hospitals in Thuringia, Germany, serving a population of approximately 280,000. Urine samples were collected from patients and tested for S. pneumoniae using the pneumococcal urinary antigen test (PUAT, BinaxNOW S. pneumoniae) and the proprietary serotype-specific urinary antigen detection (UAD) assays. Nasopharyngeal swabs were tested for 10 respiratory viruses by PCR. ResultsA total of 797 patients were enrolled, of whom 760 were included in the analysis. The median age of patients with CAP was 67 years; in-hospital case-fatality rate was 8.4%. A respiratory pathogen was detected in 553 (72.8%) patients. The most common pathogen was SARS-CoV-2 (n=498, 68.2%), followed by S. pneumoniae (n=40, 6.4%). Serotypes contained in the 13-valent, 15-valent and 20-valent pneumococcal conjugate vaccine were detected in 42.5%, 45.0%, and 70.0% of the pneumococcal CAP cases. Between the first and second half of 2021, the proportion of CAP cases associated with S. pneumoniae increased from 1.1% to 5.6% in patients aged 18-59 years and from 2.5% to 12.4% in those aged [≥]60 years; coinfection of SARS-CoV-2 and S. pneumoniae among COVID-19 patients increased from 0.7% (2/283 cases) to 6.0% (13/215) in patients aged [≥]18 years, and from 1.0% (2/195) to 8.7% (11/127) in those aged [≥]60 years. ConclusionIn Germany, the proportion of CAP cases associated with S. pneumoniae rebounded to a near-pandemic level in the second half of 2021 and many pneumococcal infections occurred in patients with COVID-19. Vaccination uptake against respiratory pathogens, including S. pneumoniae, should be strengthened.

A scoping review of regulatory T cell dynamics in convalescent COVID-19 patients - Implications for Long COVID?

BackgroundRecovery from coronavirus disease 2019 (COVID-19) can be impaired by the persistence of symptoms or new-onset health complications, commonly referred to as Long COVID. In a subset of patients, Long COVID is associated with immune system perturbations of unknown etiology, which could be related to compromised immunoregulatory mechanisms. ObjectiveThe aim of this scoping review was to investigate if regulatory T cell (Treg) dysregulation is observable beyond the acute illness and if it might be involved in Long COVID immunopathology. DesignA systematic search of studies investigating Tregs during COVID-19 convalescence was conducted on MEDLINE (via Pubmed) and Web of Science. ResultsThe literature search yielded 17 relevant studies, of which three included a distinct cohort of patients with Long COVID. The reviewed studies suggest that the Treg population of COVID-19 patients can reconstitute quantitatively and functionally during recovery. However, the comparison between recovered and seronegative controls revealed that an infection-induced dysregulation of the Treg compartment can be sustained for at least several months. The small number of studies investigating Tregs in Long COVID allowed no firm conclusions to be drawn about their involvement in the syndromes etiology. Yet, even almost one year post-infection Long COVID patients exhibit significantly altered proportions of Tregs within the CD4+ T cell population. ConclusionsPersistent alterations in cell frequency in Long COVID patients indicate that Treg dysregulation might be linked to immune system-associated sequelae. Future studies should aim to address the association of Treg adaptations with different symptom clusters and blood parameters beyond the sole quantification of cell frequencies while adhering to consensualized phenotyping strategies.

COVID-19 as cause of viral sepsis: A Systematic Review and Meta-Analysis

ImportanceCOVID-19 is a heterogenous disease most frequently causing respiratory tract infection but in its severe forms, respiratory failure and multiple organ dysfunction syndrome may occur, resembling sepsis. The prevalence of viral sepsis among COVID-19 patients is still unclear. ObjectiveWe aimed to describe this in a systematic review. Data sourcesMEDLINE(PubMed), Cochrane and Google Scholar databases were searched for studies reporting on patients hospitalized with confirmed COVID-19, diagnosed with sepsis or infection-related organ dysfunctions or receiving organ replacement therapy. Study selectionEligible were full-text English articles of randomized and non-randomized clinical trials and observational studies reporting on patients with confirmed COVID-19, who are diagnosed with sepsis or have infection-related organ dysfunctions. Systematic reviews, editorials, conference abstracts, animal studies, case reports, articles neither in English nor full-text, and studies with fewer than 30 participants were excluded. Data extraction and synthesisAll eligible studies were included in a narrative synthesis of results and after reviewing all included studies a meta-analysis was conducted. Separate sensitivity analyses were conducted per adult vs pediatric populations and per Intensive Care Unit (ICU) vs non-ICU populations. Main outcomes and measuresPrimary endpoint was the prevalence of sepsis using Sepsis-3 criteria among patients with COVID-19 and among secondary, new onset of infection-related organ dysfunction. Outcomes were expressed as proportions with respective 95% confidence interval (CI). ResultsOf 1,903 articles, 104 were analyzed. The prevalence of sepsis in COVID-19 was 39.9% (95% CI, 35.9-44.1; I2, 99%). In sensitivity analysis, sepsis was present in 25.1% (95% CI, 21.8-28.9; I2 99%) of adult patients hospitalized in non-Intensive-Care-Unit (ICU) wards (40 studies) and in 83.8 (95% CI, 78.1-88.2; I2,91%) of adult patients hospitalized in the ICU (31 studies). Sepsis in children hospitalized with COVID-19 was as high as 7.8% (95% CI, 0.4-64.9; I2, 97%). Acute Respiratory Distress Syndrome was the most common organ dysfunction in adult patients in non-ICU (27.6; 95% CI, 21.6-34.5; I2, 99%) and ICU (88.3%; 95% CI, 79.7-93.5; I2, 97%) Conclusions and relevanceDespite the high heterogeneity in reported results, sepsis frequently complicates COVID-19 among hospitalized patients and is significantly higher among those in the ICU. PROSPERO registration number: CRD42020202018. No funding. KEY POINTSO_ST_ABSQuestionC_ST_ABSWhat is the prevalence of viral sepsis by Sepsis-3 definition among hospitalized patients with COVID-19? FindingsIn this systematic review and meta-analysis, we systematically reviewed published literature for evidence of organ failure in COVID-19, to estimate the prevalence of viral sepsis in this setting, by means of SOFA score calculation. The prevalence of sepsis in COVID-19 was 39.9% (95% CI, 35.9-44.1; I2, 99%). MeaningThis is the first study to address the burden of viral sepsis in hospitalized patients with COVID-19, a highly heterogenous infection ranging from asymptomatic cases to severe disease leading to death, as reflected in the high heterogeneity of this study.

Seroprevalence of SARS CoV-2 antibodies in healthcare workers and administration employees: a prospective surveillance study at a 1,400-bed university hospital in Germany

Background: Healthcare workers (HCWs) are at particular risk to acquire SARS-CoV-2 infections. Aim: The objectives of this study were to compare SARS-CoV-2 IgG seroprevalence and compliance to wear personal protective equipment (PPE) between HCWs working within (high-risk) or outside (intermediate-risk) units treating suspected or confirmed COVID-19 patients. In addition, administration staff (low-risk) was included. Materials: Co-HCW is a prospective cohort study among employees at the Jena University Hospital, Germany. Since 16th March 2020, 50 SARS-CoV-2 inpatients and 73 outpatients were treated in our hospital. Mandatory masking was implemented on 20th March 2020. We here evaluated seroprevalence using two IgG detecting immunoassays, assessed COVID-19 exposure, clinical symptoms and compliance to wear PPE. Findings: Between 19th May and 19th June 2020 we analysed 660 employees [out of 3,228; 20.4%]. Eighteen participants (2.7%) had SARS-CoV-2 antibodies in at least one immunoassay. Among them, 13 (72.2%) were not aware of direct COVID-19 exposure and 9 (50.0%) did not report any clinical symptoms. We observed no evidence for an association between seroprevalence and risk area (high-risk: 2 of 137 HCWs (1.5%), intermediate-risk: 10 of 343 HCWs (2.9%), low-risk: 6 of 180 administration employees (3.3%); p=0.574). Reported compliance to wear PPE differed (p<0.001) between working in high-risk (98.3%) and in intermediate-risk areas (69.8%). Conclusion: No evidence for higher seroprevalence against SARS-CoV-2 in HCWs working in high-risk COVID-19 areas could be observed, probably due to high compliance to wear PPE. Compared to administration employees, we observed no additional risk to acquire SARS-CoV-2 infections by patient care.

Impact of universal masking in health care and community on SARS-CoV-2 spread

Universal masking the health care setting and in the community to contain the spread of SARS-CoV-2 has been recently recommended by the WHO, but supporting data are rare. The City of Jena was the first community in Germany to issue an order on mandatory public masking. Here, we report the development of the number of novel infections in our hospital and in the city of Jena after implementation of universal masking in our hospital and the city.

SARS-CoV-2 causes severe alveolar inflammation and barrier dysfunction

Infections with SARS-CoV-2 lead to mild to severe coronavirus disease-19 (COVID-19) with systemic symptoms. Although the viral infection originates in the respiratory system, it is unclear how the virus can overcome the alveolar barrier, which is observed in severe COVID-19 disease courses. To elucidate the viral effects on the barrier integrity and immune reactions, we used mono-cell culture systems and a complex human alveolus-on-a-chip model composed of epithelial, endothelial, and mononuclear cells. Our data show that SARS-CoV-2 efficiently infected epithelial cells with high viral loads and inflammatory response, including the interferon expression. By contrast, the adjacent endothelial layer was no infected and did neither show productive virus replication or interferon release. With prolonged infection, both cell types are damaged, and the barrier function is deteriorated, allowing the viral particles to overbear. In our study, we demonstrate that although SARS-CoV-2 is dependent on the epithelium for efficient replication, the neighboring endothelial cells are affected, e.g., by the epithelial cytokine release, which results in the damage of the alveolar barrier function and viral dissemination.

Seroprevalence of SARS-CoV-2 antibodies in an entirely PCR-sampled and quarantined community after a COVID-19 outbreak - the CoNAN study

BackgroundDue to the substantial proportion of asymptomatic and mild courses many SARS-CoV-2 infections remain unreported. Therefore, assessment of seroprevalence may detect the real burden of disease. We aimed at determining and characterizing the rate of SARS-CoV-2 infections and the resulting immunity in a defined population. MethodsCoNAN is a population-based cohort study in the previously quarantined community Neustadt-am-Rennsteig, Germany six weeks after a SARS-CoV-2 outbreak with 49 cases identified by PCR screening of all 883 inhabitants. The primary objective of the study was to assess SARS-CoV-2 antibody seroconversion rate using six different IgG detecting immunoassays. Secondary objectives of the study were: i.) to determine the rate of seroconversion in children; ii.) to determine potential risk factors for symptomatic vs. asymptomatic Covid19 courses; iii.) to investigate the rate of virus persistence. FindingsWe enrolled 626 participants (71% of the community population). All actual SARS-CoV-2 PCR tests were negative; while a total of 8{middle dot}4% (52 of 620 tested) had antibodies against SARS-CoV-2 in at least two independent tests. Twenty of the antibody positive participants had previously a positive SARS-CoV-2 PCR. On the contrary, of those 38 participants with SARS-CoV-2 infection, only 20 (52{middle dot}6%) were antibody positive. InterpretationSeveral antibody tests conducted six weeks after an outbreak of SARS-CoV-2 did not detect all previously PCR-positive tested individuals. Cautious evaluation of antibody testing strategies to assess immunity against the infection is warranted. FundingCoNAN was funded by the Thuringian Ministry for Economic Affairs, Science and Digital Society (TMWWDG).