Introduction
Community acquired pneumonia (CAP) is a leading cause of hospital admissions and mortality in all age groups and most parts of the world [
1‐
3]. Our understanding of CAP has evolved in the last years. The introduction of PCR-based methods for detecting viruses and bacteria in respiratory specimens has shown a large proportion of bacterial-/viral coinfections and pure viral infections [
4‐
6]. Several studies have demonstrated a close interaction between different viral and bacterial pathogens, especially for coinfections with
Streptococcus pneumoniae and influenza virus [
7‐
10].
The global pandemic of SARS-Coronavirus-2 (SARS-CoV-2) with corresponding coronavirus disease 2019 (COVID-19) was met with different containment strategies within countries, to reduce the spread of the virus. Most European countries, including Norway, introduced during March 2020 strict public infection control measures. These included imposing social distancing, prohibiting social gatherings, use of face masks, encouraging work from home solutions, increased border control and the closure of kindergartens, schools, and universities. The extent of lockdown implemented during the outbreak of COVID-19 is unprecedented. Recent studies have shown that such measures not only decreased the transmission of SARS-CoV-2, but also contributed to a massive reduction of circulating seasonal viruses [
11‐
13]. We hypothesized that societal infection control measures would impact the number of hospital admissions for respiratory tract infections (RTIs), as well as, the spectrum of pathogens detected in patients with suspected CAP. Thus, we analysed both aggregated patient admission data (2017–2021) to compute numbers admitted with respiratory symptoms to the emergency department (ED), and furthermore studied the detection rates for common respiratory pathogens in two cohorts with acute community acquired RTIs, recruited before and during the COVID-19 pandemic at our tertiary care hospital. To our knowledge, this is the first study to both analyse admission data and systematically compare microbiological detections by syndromic PCR-based testing of lower respiratory tract samples in adult patients hospitalized with community acquired RTIs admitted before and during the outbreak of SARS-CoV-2.
Discussion
The Norwegian COVID-19 restrictions were comprehensive and intrusive, but comparable to other European countries [
17]. During the inclusion period of our COVID cohort, strict national restrictions were still in place. This likely resulted in important lifestyle changes and an increased awareness in the general population on measures to avoid respiratory tract infections, especially in combination with continued widespread use of hand disinfection fluids and face masks. Based on retrospective surveillance of ICD-10 codes, we demonstrated a large reduction in patients admitted to our hospital with acute respiratory infections, corresponding to the period with imposed COVID-19 restrictions. The reduction was specific for acute respiratory diseases as there was no reduction in the total number of admissions. Code-based surveillance of microbiological data has several pit-falls, including physician adherence to coding-practices and an unawareness of the diagnostic repertoire performed during hospitalization. Consequently, high-quality, microbiological data cannot be collected through code-based surveillance data. This study is one of the first to compare the microbiological aetiology of lower respiratory tract infections in patients with suspected CAP included from two prospective hospital cohorts, one recruited just prior to the outbreak of the COVID-19 pandemic and the other during the pandemic. The microbiological aetiology was rigorously ascertained by a comprehensive molecular pneumonia panel combined with conventional methods. Our results confirm recent reports of substantially decreased viral detections in patients with acute respiratory tract infections after the outbreak of the COVID-19 pandemic compared to earlier years. Although, the proportion of detected bacteria remained stable in both cohorts, a difference was observed in the bacterial spectrum in the two cohorts. Further, a significant reduction in hospital admissions with acute respiratory tract infections, including bacterial pneumonia, was observed during the first year of the pandemic compared to the previous years.
The role of viruses in CAP have been increasingly recognized in the last decades. The introduction of PCR-based methods capable of rapidly and accurately detecting viral pathogens, has led to a great increase of viral detections in CAP patients, either alone or in combination with bacteria [
4‐
6,
9,
18‐
20]. The high proportion of viral detections in our pre-COVID cohort, is consistent with these findings. However, the results from our COVID cohort, show a marked reduction in viral detections. Recent studies have shown a similar reduction of non-SARS-CoV-2 respiratory viruses during the pandemic compared to previous years [
11‐
13,
21]. Specifically, the prevalence of influenza and respiratory syncytial virus (RS-virus) are shown to be almost negligible. The drop in viral detections is shown to coincide with COVID-19 control measures introduced at the start of the pandemic, and probably is a direct result of reduced person to person spread of pathogens [
11‐
13,
21]. Interestingly, rhinoviruses showed a completely different trend with an increased rate of detection in the COVID cohort. This has also been observed in other studies, and correlates with the easing of social distancing and the reopening of schools after the summer in 2020 [
22,
23].
We observed a shift in the microbial patterns of detected bacteria in the COVID cohort, including, fewer bacterial- and viral co-detections. Notably, there was a reduced proportion of patients with detected
S. pneumoniae,
H. influenzae or a combination of these. A large study analysing surveillance data from 26 countries and territories across six continents on invasive disease due to
S. pneumoniae,
H. influenzae and
Neisseria meningitidis before and during the outbreak of SARS-CoV-2, showed a substantial and sustained reduction of hospital reported invasive disease for these pathogens [
24]. Although these findings were based on all invasive diseases, we find it likely that they also reflect a decrease in respiratory infections.
The development of LRTIs, including bacterial CAP, is complex and still not completely understood. Our data indicate a reduction of detected bacterial pathogens with a known potential to transmit by respiratory droplets, like
S. pneumoniae and
H. influenzae after the outbreak of SARS-CoV-2. This can be interpreted in support of the hypothesis that person-to-person transmission of microbes is an important cause of LRTIs for both viruses and bacteria. However, the proportion of detected
S. aureus, which also has the potential for person to person spread, increased in our COVID cohort. It is known that
S. aureus tend to colonize the upper respiratory tract of adults more frequently than
S. pneumoniae and
H. influenzae and this might explain why
S. aureus did not decrease in the same manner [
25‐
29]. Nasal carriage of
S. aureus is strongly associated with infection and clinical studies consistently describe a significantly greater risk of bacteremia among carriers [
30]. Societal restrictions, as imposed during the pandemic, might therefore play a lesser role in reducing
S. aureus invasive infections, than they do for other pathogens.
Many respiratory tract pathogens colonize the upper respiratory tract, especially among the children and elderly, without causing an infection [
26‐
29,
31]. Any change within the host or the environment, such as a change in circulating viruses, antimicrobial treatment or reduced person-to-person spread of microbes, could potentially alter the conditions for colonization and thereby the subsequent risk of infection. We found that
S. aureus was found more frequently in patients with detected SARS-CoV-2 compared with patients without (60% vs 17%, p = 0.0071). An interaction between viral and bacterial respiratory pathogens in CAP has been discussed for many years [
7,
10,
32‐
37]. It is believed that a bacterial CAP was the most frequent cause of death during the influenza pandemic of 1918–19 [
38]. Several reports have shown that influenza virus, by several complex interactions, can increase the potential of
S. pneumoniae both as a colonizer and as a pathogen [
10,
32,
34,
35,
37]. In our pre-COVID cohort, 79% (19/24) of all detected
S. pneumoniae were found in combination with a viral pathogen, most frequently with influenza virus.
In relation, data from the Norwegian Cause of Death Registry, show a decrease in age-adjusted death rate of LRTIs, including CAP, in 2020 compared with 2010–2019 [
39]. This indicates that the COVID-19 restrictions and dramatic decrease in circulating viral pathogens had an effect not only on the spectrum of bacterial patterns detected, but also in reducing the overall incidence of bacterial CAP.
The major strength of our work is that microbiological data were collected from two prospective studies with an attention to detail and accuracy of lower respiratory tract sampling. Lower respiratory tract samples were collected from all patients and tested with a comprehensive multiplex molecular panel in addition to standard methods in most patients. The study has limitations; the inclusion of CAP patients at a single hospital in Norway, a limited sample size and enrolment of patients restricted to fixed hours during weekdays. We excluded patients that were unable to provide a lower respiratory tract sample, e.g. due to confusion, severe hypoxemia, need of assisted ventilation, or a non-productive cough; symptoms which are often found in patients with COVID-19. In addition, in Norway, patients with mild COVID-19 were often treated outside the hospitals at designated COVID-19 wards. Finally, concerning surveillance data from electronic health records, ICD-10 diagnoses are registered by the treating physician and the primary diagnosis may have been influenced by the pandemic. Nevertheless, national surveillance data show that influenza, invasive pneumococcal disease, and systemic disease caused by
H. influenzae have decreased [
40].
In conclusion, admissions with pneumonia and microbiological detections in patients with suspected CAP during the first year of the COVID-19 pandemic, differed from the previous year, suggesting that infection control measures related to COVID-19 restrictions are effective beyond reducing the spread of SARS-CoV-2. The number of detected viruses declined, and accordingly, the proportion of patients with bacterial- and viral co-detections decreased. Furthermore, we observed a change in both the proportion and pattern of certain bacterial detections, implying that presence of viruses may facilitate colonization and infection by certain types of bacteria and play an important role in the etiopathogenesis of CAP.
Acknowledgements
We gratefully acknowledge the CAPNOR study group, the study nurses, the staff at the Emergency Care Clinic, and staff at the Department of Microbiology. Last, we thank all the enrolled patients.
CAPNOR study group: Rune O. Bjørneklett (Emergency Care Clinic, Haukeland University Hospital, Bergen, Norway; Department of Clinical Medicine, University of Bergen, Bergen, Norway), Tristan W. Clark (School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK), Marit H. Ebbesen (Department of Microbiology, Haukeland University Hospital, Bergen, Norway), Daniel Faurholt-Jepsen (Department of Clinical Science, Bergen Integrated Diagnostic Stewardship cluster, University of Bergen, Bergen, Norway; Department of Infectious Diseases, Rigshospitalet, Denmark), Harleen M. S. Grewal (Department of Clinical Science, Bergen Integrated Diagnostic Stewardship cluster, University of Bergen, Bergen, Norway; Department of Microbiology, Haukeland University Hospital, Bergen, Norway), Lars Heggelund (Department of Clinical Science, Bergen Integrated Diagnostic Stewardship cluster, University of Bergen, Bergen, Norway; Department of Internal Medicine, Vestre Viken Hospital Trust, Drammen, Norway), Siri T. Knoop (Department of Clinical Science, Bergen Integrated Diagnostic Stewardship cluster, University of Bergen, Bergen, Norway; Department of Microbiology, Haukeland University Hospital, Bergen, Norway), Øyvind Kommedal (Department of Clinical Science, Bergen Integrated Diagnostic Stewardship cluster, University of Bergen, Bergen, Norway; Department of Microbiology, Haukeland University Hospital, Bergen, Norway), Dagfinn L. Markussen (Emergency Care Clinic, Haukeland University Hospital, Bergen, Norway), Pernille Ravn (Department of Internal Medicine, Section for Infectious Diseases, Herlev and Gentofte Hospital, Hellerup, Denmark), Christian Ritz (Department of Clinical Science, Bergen Integrated Diagnostic Stewardship cluster, University of Bergen, Bergen, Norway; National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark), Sondre Serigstad (Emergency Care Clinic, Haukeland University Hospital, Bergen, Norway; Department of Clinical Medicine, University of Bergen, Bergen, Norway; Department of Clinical Science, Bergen Integrated Diagnostic Stewardship cluster, University of Bergen, Bergen, Norway), Elling Ulvestad (Department of Clinical Science, Bergen Integrated Diagnostic Stewardship cluster, University of Bergen, Bergen, Norway; Department of Microbiology, Haukeland University Hospital, Bergen, Norway), Cornelis H. van Werkhoven (Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands).
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