Respiratory Co-infection Research Articles

SARS-CoV-2 and Chlamydia pneumoniae co-infection: A review of the literature

Bacterial co-pathogens are commonly identified in viral respiratory infections and are important causes of morbid-mortality. The prevalence of Chlamydia (C.) pneumoniae infection in patients infected with SARS-CoV-2 has not been sufficiently studied. The objective of the present review was to describe the prevalence of C. pneumoniae in patients with coronavirus disease 2019 (COVID-19). A search in MEDLINE and Google Scholar databases for English language literature published between January 2020 and August 2021 was performed. Studies evaluating patients with confirmed COVID-19 and reporting the simultaneous detection of C. pneumoniae were included. Eleven articles were included in the systematic review (5 case cross-sectional studies and 6 retrospective studies). A total of 18450 patients were included in the eleven studies. The detection of laboratory-confirmed C. pneumoniae infection varied between 1.78 and 71.4% of the total number of co-infections. The median age of patients ranged from 35 to 71 years old and 65% were male. Most of the studies reported one or more pre-existing comorbidities and the majority of the patients presented with fever, cough and dyspnea. Lymphopenia and eosinopenia were described in COVID-19 co-infected patients. The main chest CT scan showed a ground glass density shadow, consolidation and bilateral pneumonia. Most patients received empirical antibiotics. Bacterial co-infection was not associated with increased ICU admission and mortality. Despite frequent prescription of broad-spectrum empirical antimicrobials in patients with coronavirus 2-associated respiratory infections, there is a paucity of data to support the association with respiratory bacterial co-infection. Prospective evidence generation to support the development of an antimicrobial policy and appropriate stewardship interventions specific for the COVID-19 pandemic are urgently required.

Low prevalence of community-acquired influenza coinfections among COVID-19 patients in Al-Madinah, Saudi Arabia: A retrospective cohort study

BackgroundCoinfections with respiratory viruses among SARS CoV-2 patients have been reported by several studies during the current COVID-19 pandemic. Most of these studies designated these coinfections as being hospital-acquired infections; however, there is inadequate knowledge about community-acquired respiratory coinfections among SARS CoV-2 patients. MethodsIn this retrospective cohort study, we investigated the seroprevalence of influenza A, influenza B, and parainfluenza-2 among newly hospitalized patients with confirmed COVID-19 infections (n = 163). The study was conducted during the early phase of the COVID-19 pandemic in Saudi Arabia (from April to October 2020). The patients’ serum samples were subjected to commercial immunoglobulin M (IgM) antibody tests against the three aforementioned viruses. ResultsSeropositivity for influenza A and B and parainfluenza-2 occurred only in 4.2% (7/163) of COVID-19 patients, indicating simultaneous acute infections of these three viruses with SARS CoV-2 infection. All coinfection cases were mild and misdiagnosed during the care period in the hospital. ConclusionThis study highlights the low prevalence of community-acquired respiratory infections among COVID-19 patients in the current pandemic and we discussed the possible factors for this finding. During newly emerging epidemics or pandemics, considering other respiratory viruses circulating in the community is essential to avoid their misdiagnosis and account for their possible negative effects on pandemic disease management and prognosis.

Respiratory viral co-infections in patients with COVID-19 and associated outcomes: A systematic review and meta-analysis.

The aim of this systematic review and meta‐analysis was to critically assess the published literature related to community‐acquired viral co‐infections and COVID‐19 and to evaluate the prevalence, most identified co‐pathogens, and relevant risk factors. Furthermore, we aimed to examine the clinical features and outcomes of co‐infected compared to mono‐infected COVID‐19 patients. We systematically searched PubMed, Web of Science, Embase, Scopus, and The Cochrane Library for studies published from 1 November 2019 to 13 August 2021. We included patients of all ages and any COVID‐19 severity who were screened for respiratory viral co‐infection within 48 h of COVID‐19 diagnosis. The main outcome was the proportion of patients with a respiratory viral co‐infection. The systematic review was registered to PROSPERO (CRD42021272235). Out of 6053 initially retrieved studies, 59 studies with a total of 16,643 SARS‐CoV‐2 positive patients were included. The global pooled prevalence was 5.01% (95% CI 3.34%–7.27%; I 2 = 95%) based on a random‐effects model, with Influenza Viruses (1.54%) and Enteroviruses (1.32%) being the most prevalent pathogens. Subgroup analyses showed that co‐infection was significantly higher in paediatric (9.39%) than adult (3.51%) patients (p‐value = 0.02). Furthermore, co‐infected patients were more likely to be dyspnoeic and the odds of fatality (OR = 1.66) were increased. Although a relatively low proportion of COVID‐19 patients have a respiratory viral co‐infection, our findings show that multiplex viral panel testing may be advisable in patients with compatible symptoms. Indeed, respiratory virus co‐infections may be associated with adverse clinical outcomes and therefore have therapeutic and prognostic implications.

The circulation of Non-SARS-CoV-2 respiratory viruses and coinfections with SARS-CoV-2 during the surge of the Omicron variant.

BackgroundIn December 2021, the SARS-CoV-2 Omicron variant displaced the Delta variant and caused an unprecedented spike in the numbers of COVID-19 cases. This study reports the positivity rates of circulating non-SARS-CoV-2 respiratory viruses and evaluates coinfections of these viruses with SARS-CoV-2 during the Omicron surge.MethodsData from the multiplex respiratory panels used for diagnosis at the Johns Hopkins Microbiology Laboratory were used to assess positivity rates and respiratory virus coinfections in the time frame between November 2021 and February 2022. Clinical presentations and outcomes were assessed in the cohort of 46 patients who had SARS-CoV-2 coinfections with other respiratory viruses.ResultsBetween November 2021 and February 2022, the high positivity of SARS-CoV-2 outcompeted enterovirus/rhinovirus and other circulating respiratory viruses and was associated with a notable decrease in influenza A infections. Coinfections represented 2.3% of the samples tested by the extended multiplex respiratory panel. SARS-COV-2 coinfections represented 25% of the coinfections in this time frame and were mostly SARS-COV-2/enterovirus/rhinovirus. Of the SARS-CoV-2 coinfection cohort, 3 patients were hospitalized and were coinfected with influenza-A (2) or RSV (1). Cough and shortness of breath were the most frequent symptoms (29%) followed by fever (28%).ConclusionsThe SARS-CoV-2 Omicron surge was associated with a change in the circulation of other respiratory viruses. Coinfections were most prevalent with viruses that showed the highest positivity in this time frame.

Lower Respiratory Tract Coinfection in the ICU: Prevalence and Clinical Significance of Coinfection Detected via Microbiological Analysis of Bronchoalveolar Lavage Fluid With a Comparison of Invasive Methodologies.

OBJECTIVES:Pneumonia remains a significant cause of morbidity and mortality, with increasing interest in the detection and clinical significance of coinfection. Further investigation into the impact of bronchoalveolar lavage (BAL) sampling methodology and efficient clinical utilization of microbiological analyses is needed to guide the management of lower respiratory tract infection in the ICU.DESIGN:Retrospective observational study.SETTING:ICUs at a single center between August 1, 2012, and January 1, 2018.PATIENTS:Mechanically ventilated adult patients who underwent BAL testing during an ICU admission were included.INTERVENTIONS:None.MEASUREMENTS AND MAIN RESULTS:BAL methodology (bronchoscopic vs nonbronchoscopic), microbiological diagnostic testing, and clinical outcomes measures were obtained. Chi-square or Fisher exact tests assessed associations between categorical variables, whereas Kruskal-Wallis tests analyzed differences in distributions of measures. BAL samples from 803 patients met inclusion criteria. Coinfection was detected more frequently via bronchoscopic BAL compared with nonbronchoscopic BAL (26% vs 9%; p < 0.001). Viruses were detected more frequently in bronchoscopic (42% vs 13%; p < 0.001) and bacteria in nonbronchoscopic (42% vs 33%; p = 0.011) BALs. A positive correlation between mortality and the number of organisms isolated was identified, with 43%, 48%, and 58% 30-day mortality among those with 0, 1, and more than 2 organisms, respectively (p = 0.003). Viral organism detection was associated with increased 30-day mortality (56% vs 46%; p = 0.033).CONCLUSIONS:Even in the setting of standardized institutional techniques, retrospective evaluation of bronchoscopic and nonbronchoscopic BAL methodologies did not reveal similar microbiologic yield in critically ill patients, though bronchoscopic BAL overall yielded more organisms, and occurrence of multiple organisms in BAL was associated with worse outcome. Prospective data are needed for direct comparison of both methods to develop more standardized approaches for use in different patient groups.

Clinical Usefulness of Serum Lactate Dehydrogenase Levels in Mycoplasma pneumoniae Pneumonia in Children.

To elucidate the clinical usefulness of lactate dehydrogenase (LDH) levels in children with Mycoplasma pneumoniae(MP) pneumonia and identify cut-off levels in various clinical conditions. The study was retrospectively performed in 145 children who were hospitalized with MP pneumonia. Laboratory findings, including LDH levels at admission and clinical features were retrospectively reviewed from patients' electronic medical records. The mean age of the study population was 5.9 y, and the mean value of LDH was 809.7 U/L. Poor response to treatment for MP pneumonia, respiratory virus coinfection, severe MP pneumonia, development of postinfectious bronchiolitis obliterans (PIBO) after MP pneumonia, pleural effusion, and oxygen need during illness were significantly associated with serum LDH levels. The cutoff levels of LDH for predicting poor response to treatment for MP pneumonia and respiratory virus coinfection were 1058 U/L [area under the curve (AUC), 0.729] and 803 U/L (AUC, 0.682), respectively. Those for pneumonic lesions involving at least one-third of the total lung volume, prediction of PIBO development, and extrapulmonary manifestations were 1098 U/L (AUC, 0.715), 676 U/L (AUC, 0.714), and 859 U/L (AUC, 0.710), respectively. The cutoff levels for pleural effusion during illness and for the prediction of oxygen need were 894 U/L (AUC, 0.699) and 1114 U/L (AUC, 0.771), respectively. LDHlevels areelevatedin diverse clinical conditions in children with MP pneumonia and may be useful in the identification of severe clinical courses of MP pneumonia in children.

Comparative incidence of early and late bloodstream and respiratory tract co-infection in patients admitted to ICU with COVID-19 pneumonia versus Influenza A or B pneumonia versus no viral pneumonia: wales multicentre ICU cohort study

ObjectiveThe aim is to characterise early and late respiratory and bloodstream co-infection in patients admitted to intensive care units (ICUs) with SARS-CoV-2-related acute hypoxemic respiratory failure (AHRF) needing respiratory support in seven ICUs within Wales, during the first wave of the COVID-19 pandemic. We compare the rate of positivity of different secondary pathogens and their antimicrobial sensitivity in three different patient groups: patients admitted to ICU with COVID-19 pneumonia, Influenza A or B pneumonia, and patients without viral pneumonia.DesignMulticentre, retrospective, observational cohort study with rapid microbiology data from Public Health Wales, sharing of clinical and demographic data from seven participating ICUs.SettingSeven Welsh ICUs participated between 10 March and 31 July 2020. Clinical and demographic data for COVID-19 disease were shared by each participating centres, and microbiology data were extracted from a data repository within Public Health Wales. Comparative data were taken from a cohort of patients without viral pneumonia admitted to ICU during the same period as the COVID-19 cohort (referred to as no viral pneumonia or ‘no viral’ group), and to a retrospective non-matched cohort of consecutive patients with Influenza A or B admitted to ICUs from 20 November 2017. The comparative data for Influenza pneumonia and no viral pneumonia were taken from one of the seven participating ICUs.ParticipantsA total of 299 consecutive patients admitted to ICUs with COVID-19 pneumonia were compared with 173 and 48 patients admitted with no viral pneumonia or Influenza A or B pneumonia, respectively.Main outcome measuresPrimary outcome was to calculate comparative incidence of early and late co-infection in patients admitted to ICU with COVID-19, Influenza A or B pneumonia and no viral pneumonia. Secondary outcome was to calculate the individual group of early and late co-infection rate on a per-patient and per-sample basis, with their antimicrobial susceptibility and thirdly to ascertain any statistical correlation between clinical and demographic variables with rate of acquiring co-infection following ICU admission.ResultsA total of 299 adults (median age 57, M/F 2:1) were included in the COVID-19 ICU cohort. The incidence of respiratory and bloodstream co-infection was 40.5% and 15.1%, respectively. Staphylococcus aureus was the predominant bacterial pathogen within the first 48 h. Gram-negative organisms from Enterobacterales group were predominantly seen after 48 h in COVID-19 cohort. Comparative no viral pneumonia cohort had lower rates of respiratory tract infection and bloodstream infection. The influenza cohort had similar rates respiratory tract infection and bloodstream infection. Mortality in all three groups was similar, and no clinical or demographic variables were found to increase the rate of co-infection and ICU mortality.ConclusionsHigher incidence of bacterial co-infection was found in COVID-19 cohort as compared to the no viral pneumonia cohort admitted to ICUs for respiratory support.

Clinical significance of respiratory virus coinfection in children with Mycoplasma pneumoniae pneumonia

BackgroundThe prevalence of refractory Mycoplasma pneumoniae (MP) pneumonia has been increasing. However, few studies have investigated the impact of respiratory virus coinfection in patients with MP pneumonia, and their results have been inconclusive. This study aimed to investigate the impact of respiratory virus coinfection in children hospitalized with MP pneumonia.MethodsThis study enrolled 145 children hospitalized with MP pneumonia between May 2019 and March 2020. The patients were divided into two groups: the respiratory virus coinfection and non-coinfection groups. All the children underwent polymerase chain reaction testing for respiratory virus infection. Information on clinical, laboratory, and radiologic findings were obtained retrospectively via medical chart reviews.ResultsChildren in the respiratory virus coinfection group were younger than those in the non-coinfection group. Respiratory virus coinfection in children hospitalized with MP pneumonia was significantly associated with persistence of fever more than 6 days (adjusted odds ratio [aOR], 2.394; 95% confidence interval [95% CI], 1.172–4.892), severe pneumonia (aOR, 4.602; 95% CI, 1.154–18.353), and poor response to the stepwise approach for MP pneumonia (aOR, 4.354; 95% CI, 1.374–13.800). In addition, higher levels of liver enzymes and lactate dehydrogenase at admission were associated with respiratory virus coinfection in children with MP pneumonia.ConclusionsThe results of this study suggest that respiratory virus coinfection in children hospitalized with MP pneumonia may be associated with refractory MP pneumonia.

Priming With Rhinovirus Protects Mice Against a Lethal Pulmonary Coronavirus Infection.

Rhinoviruses (RV) have been shown to inhibit subsequent infection by heterologous respiratory viruses, including influenza viruses and severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). To better understand the mechanisms whereby RV protects against pulmonary coronavirus infection, we used a native murine virus, mouse hepatitis virus strain 1 (MHV-1), that causes severe disease in the lungs of infected mice. We found that priming of the respiratory tract with RV completely prevented mortality and reduced morbidity of a lethal MHV-1 infection. Replication of MHV-1 was reduced in RV-primed mouse lungs although expression of antiviral type I interferon, IFN-β, was more robust in mice infected with MHV-1 alone. We further showed that signaling through the type I interferon receptor was required for survival of mice given a non-lethal dose of MHV-1. RV-primed mice had reduced pulmonary inflammation and hemorrhage and influx of leukocytes, especially neutrophils, in the airways upon MHV-1 infection. Although MHV-1 replication was reduced in RV-primed mice, RV did not inhibit MHV-1 replication in coinfected lung epithelial cells in vitro. In summary, RV-mediated priming in the respiratory tract reduces viral replication, inflammation, and tissue damage, and prevents mortality of a pulmonary coronavirus infection in mice. These results contribute to our understanding of how distinct respiratory viruses interact with the host to affect disease pathogenesis, which is a critical step in understanding how respiratory viral coinfections impact human health.

Autopsy study of fatal invasive pulmonary aspergillosis: Often undiagnosed premortem

Invasive aspergillosis (IA) is a serious complication in immunocompromised and critically ill patients but is difficult to diagnose. We sought to examine how often cases go undiagnosed and to understand the presenting clinical and radiologic features associated with fatal IA. We reviewed cases of fatal IA confirmed at autopsy (N = 67) between 1999 and 2019 at a tertiary academic hospital. At autopsy, pulmonary involvement was present in 97% of cases--46% were limited to the lungs and 51% had concomitant extrapulmonary involvement. Immunosuppression with either glucocorticoids and/or other immunosuppressive agents was present in 85%. Among those not immunocompromised (15%), chronic lung disease was present in 70%, and a respiratory coinfection was found in 50%. Chest imaging abnormalities including consolidation, ground glass opacities, halo sign, cavitation, and air crescent sign were present in 49%, 49%, 37%, 22%, and 7% of cases, respectively. Diagnostic bronchoscopy was performed in 61% of cases and yielded aspergillus in 63% of those cases by either bronchoalveolar lavage (galactomannan and/or culture), bronchial washings, or transbronchial biopsy cultures. Either a respiratory coinfection or other systemic coinfection was diagnosed in 64%. The performance of diagnostic bronchoscopy was associated with accurate pre-mortem identification of IA (p = 0.001). Clinicians correctly identified IA as the cause of death in only 27% of fatal IA cases identified at autopsy. Complex presenting features, high rates of co-infections, and low rates of invasive diagnostic procedures may have led to missed diagnoses of IA.

Respiratory pathogens co-infection in patients with COVID-19 pneumonia in Kazakhstan

Background Clinical evidence of the presence of bacterial co-infection in patients with SARS-CoV-2 pneumonia is important for an adequate treatment with antibacterial drugs. Objectives: to determine the secondary bacterial flora in patients with COVID pneumonia in patients in the Republic of Kazakhstan. Methods Prospective, microbiological, multicenter study, which was conducted at the Medical University of Karaganda in the Shared Resource Laboratory. Sputum samples were collected from three cities of Kazakhstan with the worst SARS-CoV-2 epidemiological situation. Microbiological examination was carried out using classical methods. All investigated isolates were identified to species by MALDI-TOF mass spectrometry. Susceptibility to antibiotics was performed by the disk diffusion method in accordance with the CLSI 2019 recommendations. Results 133 patients were included with a mean age of 60.9±12.7 years old, 53/133 (39.8%) had confirmed SARS-CoV-2 PCR test. Microbiological examination showed the growth of normal microflora in 31.45%. Difference in secondary bacterial co-infection etiology in COVID-19 positive and negative patients was not found. The leading place in general etiological structure belonged to K.pneumoniae - 22.64%, E.coli - 11.95% and A.baumannii - 11.32%. A significant relationship (p = 0.003) between such parameters as the use of antibacterial drugs and the isolated microflora was found. Conclusions Isolated microorganisms are etiologically significant and are pathogens of the ESKAPE group. It is important to limit the risk of infection and spread of resistant microorganisms by closely monitoring nosocomial infections and drawing attention to secondary infections caused by resistant bacteria that can increase the mortality rate of patients with COVID-19.

Meta-genomic detection of Candida spp. in the nasopharynx and upper airway of patients with severe COVID-19

Abstract Recent case reports and epidemiological data suggest fungal infections represent an under-appreciated respiratory co-infection among people with severe COVID-19, however the frequency and clinical impact is currently unknown. We have previously generated a single-cell RNA-sequencing (scRNA-seq) dataset characterizing the upper respiratory microenvironment during COVID-19 and mapped the relationship between disease severity with the local behavior of nasal epithelial and immune cells. In agreement with other human cohorts, this prior study suggested that a deficiency in host immunity, particularly in type I/ III interferon signaling in the upper respiratory tract, is associated with rapid progression to severe disease and worse clinical outcomes. Here, we have performed further analysis of this cohort and identified a subset of participants with severe COVID-19 and concurrent nasal and/or endotracheal infection with Candida spp. We present the clinical characteristics of these individuals, including confirmatory testing demonstrating elevated serum (1,3)-β-D-glucan and/or a positive fungal culture. Finally, using the matched single-cell transcriptomic profiles of these individuals’ respiratory mucosa, in addition to blunted type I/III interferon signaling previously reported, we identified epithelial and mucosal immune signatures consistent with augmented IL-17 responses, suggestive of activated anti-fungal immunity. These results indicate that a subset of patients with severe COVID-19 exhibit increased frequency of concurrent fungal infections associated with augmented IL-17 responses and suggest that concurrent fungal infection may be contributing to SARS-C0V-2 mediated inflammatory pathology. This project has been made possible in part by grant number 2020-216949 from the Chan Zuckerberg Initiative DAF, an advised fund of Silicon Valley Community Foundation to Alex K. Shalek and Jose Ordovas-Montanes. Carly G. K. Ziegler was supported by T32GM007753 from the NIH. Jose Ordovas-Montanes is a New York Stem Cell Foundation – Robertson Investigator. Jose Ordovas-Montanes was supported by the Richard and Susan Smith Family Foundation, the AGA Research Foundation’s AGA-Takeda Pharmaceuticals Research Scholar Award in IBD – AGA2020-13-01, the Food Allergy Science Initiative, and The New York Stem Cell Foundation. Bruce H. Horwitz was supported by DK122532-01A1, NIH; 12019PG-CD002, The Leona M. and Harry B. Helmsley Charitable Trust; SRA #54518, and Crohn’s and Colitis Foundation. P.L. was supported by 5T32AG000222 from the NIH. Andrew W. Navia was supported by the Ludwig Center for Molecular Oncology at MIT. Alex K. Shalek was supported by the Bill and Melinda Gates Foundation, Sloan Fellowship in Chemistry, the NIH (5U24AI118672), and the Ragon Institute of MGH, MIT and Harvard.

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.

COVID-19 Autopsies Reveal Underreporting of SARS-CoV-2 Infection and Scarcity of Co-infections.

Coronavirus disease 2019 (COVID-19) mortality can be estimated based on reliable mortality data. Variable testing procedures and heterogeneous disease course suggest that a substantial number of COVID-19 deaths is undetected. To address this question, we screened an unselected autopsy cohort for the presence of SARS-CoV-2 and a panel of common respiratory pathogens. Lung tissues from 62 consecutive autopsies, conducted during the first and second COVID-19 pandemic waves in Switzerland, were analyzed for bacterial, viral and fungal respiratory pathogens including SARS-CoV-2. SARS-CoV-2 was detected in 28 lungs of 62 deceased patients (45%), although only 18 patients (29%) were reported to have COVID-19 at the time of death. In 23 patients (37% of all), the clinical cause of death and/or autopsy findings together with the presence of SARS-CoV-2 suggested death due to COVID-19. Our autopsy results reveal a 16% higher SARS-CoV-2 infection rate and an 8% higher SARS-CoV-2 related mortality rate than reported by clinicians before death. The majority of SARS-CoV-2 infected patients (75%) did not suffer from respiratory co-infections, as long as they were treated with antibiotics. In the lungs of 5 patients (8% of all), SARS-CoV-2 was found, yet without typical clinical and/or autopsy findings. Our findings suggest that underreporting of COVID-19 contributes substantially to excess mortality. The small percentage of co-infections in SARS-CoV-2 positive patients who died with typical COVID-19 symptoms strongly suggests that the majority of SARS-CoV-2 infected patients died from and not with the virus.

Contribution of Influenza Viruses, Other Respiratory Viruses and Viral Co-Infections to Influenza-like Illness in Older Adults.

Influenza-like illness (ILI) can be caused by a range of respiratory viruses. The present study investigates the contribution of influenza and other respiratory viruses, the occurrence of viral co-infections, and the persistence of the viruses after ILI onset in older adults. During the influenza season 2014–2015, 2366 generally healthy community-dwelling older adults (≥60 years) were enrolled in the study. Viruses were identified by multiplex ligation–dependent probe-amplification assay in naso- and oropharyngeal swabs taken during acute ILI phase, and 2 and 8 weeks later. The ILI incidence was 10.7%, which did not differ between vaccinated and unvaccinated older adults; influenza virus was the most frequently detected virus (39.4%). Other viruses with significant contribution were: rhinovirus (17.3%), seasonal coronavirus (9.8%), respiratory syncytial virus (6.7%), and human metapneumovirus (6.3%). Co-infections of influenza virus with other viruses were rare. The frequency of ILI cases in older adults in this 2014–2015 season with low vaccine effectiveness was comparable to that of the 2012–2013 season with moderate vaccine efficacy. The low rate of viral co-infections observed, especially for influenza virus, suggests that influenza virus infection reduces the risk of simultaneous infection with other viruses. Viral persistence or viral co-infections did not affect the clinical outcome of ILI.

Comparison of Clinical, Demographic Features, and Costs in Respiratory Syncytial Virus, Rhinovirus, and Viral Co-infections in Children Hospitalized with Viral Infections of the Lower Respiratory Tract.

Viruses are the most common cause of lower respiratory tract infections (LRTIs) in children. Our study aimed to shed light on co-infection by comparing it with the most common single agents, such as respiratory syncytial virus (RSV) and rhinovirus (RV), in terms of epidemiological, clinical, laboratory findings, and cost. This retrospective study analyzed medical records pertaining to infants aged below 5 years, hospitalized with a diagnosis of LRTI with RSV, RV, or co-infection. The study group consisted of 199 children, RSV was detected in 116 patients (58.3%), RV in 46 (23.1%), and co-infections in 37 (18.6%). The average age of patients infected with RV was higher (P = 0.006), and the length of hospital stay of patients infected with RSV was longer (P = 0.03) than that with other agents. There was no significant difference between the groups in terms of oxygen requirement, intensive care unit admission, intubation, and development of complications. The cost was significantly higher in the RSV group (P = 0.02) compared to the other groups. Viral co-infections, RSV, and RV constitute an important part of the etiology in patients aged below 5 years; co-infections do not cause more severe clinical findings compared to single viral agents.

Predictors of severity and mortality in COVID-19 patients

BackgroundDue to limited capacity, health care systems worldwide have been put in challenging situations since the emergence of COVID-19. To prioritize patients who need hospital admission, a better understanding of the clinical predictors of disease severity is required. In the current study, we investigated the predictors of mortality and severity of illness in COVID-19 from a single center in Cairo, Egypt.MethodsThis retrospective cohort study included 175 patients hospitalized with COVID-19 pneumonia and had positive real-time polymerase chain reaction (RT-PCR) results for SARS-CoV-2 from 1 May 2020 to 1 December 2020. Severe COVID-19 was defined as requiring high-flow oxygen (flow rate of more than 8 L/min or use of high flow oxygen cannula), noninvasive ventilation, or invasive mechanical ventilation at any time point during the hospitalization. We used univariate and multivariate regression analyses to examine the differences in patient demographics and clinical and laboratory data collected during the first 24 h of hospitalization related to severe disease or death in all 175 patients.ResultsSixty-seven (38.3%) of the study subjects had a severe or critical disease. Elevated d-dimer, leukocytosis, and elevated CRP were found to be independent predictors of severe disease. In-hospital mortality occurred in 34 (19.4%) of the cases. Elevated TLC, urea, the use of invasive mechanical ventilation, and the presence of respiratory bacterial co-infection were found to be independently associated with mortality.ConclusionClinical and laboratory data of COVID-19 patients at their hospital admission may aid clinicians in the early identification and triage of high-risk patients.

Identification of Co-Infections by Viral and Bacterial Pathogens in Covid-19 Hospitalized Patients in Peru: Molecular Diagnosis and Clinical Characteristics

PurposeThe impact of respiratory coinfections in COVID-19 is still not well understood. This study sought to identify the respiratory pathogens causing coinfections in patients with moderate/severe SARS-CoV-2 pneumonia from a hospital in Peru. Also, to describe the clinical characteristics and outcomes of coinfected and non-coinfected patients.Methods & MaterialsA descriptive study was conducted on hospitalized patients with a confirmed diagnosis of moderate/severe pneumonia due to SARS-CoV-2 infection. The selection criteria included patients older than 18 years of age who were admitted to the Guillermo Almenara Irigoyen Hospital in Lima, Peru during the period July-November 2020. Pregnant women were excluded from the study. A nasopharyngeal swab sample was obtained from the patients included in the study. Diagnosis of SARS-CoV-2 infection was performed by reverse-transcriptase polymerase chain reaction (RT-PCR). The detection of the following respiratory viruses was performed by RT-PCR: Influenza A and B, Respiratory syncitial virus (RSV) A and B; and Adenovirus. The detection of atypical bacteria, Mycoplasma pneumoniae and Chlamydia pneumoniae was carried out using conventional polymerase chain reaction.ResultsA total of 295 patients with confirmed SARS-CoV-2 infection were enrolled during the study period. A coinfection with one or more respiratory pathogen was detected in 154 (52.20%) patients at hospital admission. The most common coinfections were Mycoplasma pneumoniae (28.12%), Chlamydia pneumoniae (8.81%) and with both bacteria (11.53%); followed by Adenovirus (1.70%), Mycoplasma pneumoniae/Adenovirus (0.71%), Chlamydia pneumoniae/Adenovirus (0.71%), RSV-B/Chlamydia pneumoniae (0.32%), Mycoplasma pneumoniae/Chlamydia pneumoniae/Adenovirus (0.32%). Sepsis was more frequent among coinfected patients than non coinfected (33.12% vs 20.57%, p = 0.018). Expectoration was less frequent in coinfected individuals compared to non coinfected (5.84% vs 12.77%, p = 0.045). We could highlight that the majority of patients were administered an antibiotic (69.50%). The correlation between the empirical use of macrolides in patients with Mycoplasma pneumoniae and Chlamydia pneumoniae was observed in 41% of the cases.ConclusionMycoplasma pneumoniae and Chlamydia pneumoniae were the main microorganisms associated with SARS-CoV-2 coinfection at hospital admission. The presence of multiple coinfections was described in some patients. Antibiotics should be carefully prescribed, as high rates of antibiotic use was found, particularly with macrolides.

Streptococcus pneumoniae and Influenza A Virus Co-Infection Induces Altered Polyubiquitination in A549 Cells.

Epithelial cells are an important line of defense within the lung. Disruption of the epithelial barrier by pathogens enables the systemic dissemination of bacteria or viruses within the host leading to severe diseases with fatal outcomes. Thus, the lung epithelium can be damaged by seasonal and pandemic influenza A viruses. Influenza A virus infection induced dysregulation of the immune system is beneficial for the dissemination of bacteria to the lower respiratory tract, causing bacterial and viral co-infection. Host cells regulate protein homeostasis and the response to different perturbances, for instance provoked by infections, by post translational modification of proteins. Aside from protein phosphorylation, ubiquitination of proteins is an essential regulatory tool in virtually every cellular process such as protein homeostasis, host immune response, cell morphology, and in clearing of cytosolic pathogens. Here, we analyzed the proteome and ubiquitinome of A549 alveolar lung epithelial cells in response to infection by either Streptococcus pneumoniae D39Δcps or influenza A virus H1N1 as well as bacterial and viral co-infection. Pneumococcal infection induced alterations in the ubiquitination of proteins involved in the organization of the actin cytoskeleton and Rho GTPases, but had minor effects on the abundance of host proteins. H1N1 infection results in an anti-viral state of A549 cells. Finally, co-infection resembled the imprints of both infecting pathogens with a minor increase in the observed alterations in protein and ubiquitination abundance.

Treatment of Respiratory Viral Coinfections.

With the advent of rapid multiplex PCR, physicians have been able to test for multiple viral pathogens when a patient presents with influenza-like illness. This has led to the discovery that many respiratory infections are caused by more than one virus. Antiviral treatment of viral coinfections can be complex because treatment of one virus will affect the time course of the other virus. Since effective antivirals are only available for some respiratory viruses, careful consideration needs to be given on the effect treating one virus will have on the dynamics of the other virus, which might not have available antiviral treatment. In this study, we use mathematical models of viral coinfections to assess the effect of antiviral treatment on coinfections. We examine the effect of the mechanism of action, relative growth rates of the viruses, and the assumptions underlying the interaction of the viruses. We find that high antiviral efficacy is needed to suppress both infections. If high doses of both antivirals are not achieved, then we run the risk of lengthening the duration of coinfection or even of allowing a suppressed virus to replicate to higher viral titers.