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1.
J Med Cases ; 11(12): 403-406, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-1227213

ABSTRACT

There has been increasing evidence of co-infections with coronavirus disease 2019 (COVID-19) pneumonia, which increases the severity of the disease. Organisms such as Klebsiella pneumoniae and Streptococcus pneumoniae have been previously isolated. We present a case of a COVID-19 patient treated with baricitinib and dexamethasone who later developed Klebsiella pneumoniae-carbapenem-resistant Enterobacteriaceae (CRE) and Candida dubliniensis bloodstream infections, treated with meropenem/vaborbactam and micafungin, respectively. These infections are exceedingly rare and are mostly reported in immunosuppressed patients. The finding of these bloodstream infections raises concerns on the cause of immunosuppression in this patient infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) treated with baricitinib and dexamethasone. There has been no report so far of COVID-19 associated with these co-infections.

2.
Medeni Med J ; 35(4): 338-343, 2020.
Article in English | MEDLINE | ID: covidwho-1016336

ABSTRACT

The aim of this review is to examine the effects of COVID-19 on Tuberculosis (TB) management and to highlight evidence of the extent of TB and COVID-19 co-infection. Current findings on TB and COVID-19 have been identified using six databases: Pubmed, Science Direct, Pubmed Central, MedXRiv, Wiley, and Google Scholar. This search in literature was conducted up to 8 May 2020. We included five studies that met the selection criteria. These selected studies have been performed in regions having various demographic characteristics including developed and developing countries, mainly China. The total number of participants in each study ranged from 24 to 203. The case fatality rate of patients with TB and COVID-19 co-infection was found to be high (6/49; 12.3 percent) while a combined diagnosis of TB and COVID-19 was found in 9/49 patients. This condition is linked to several complications, manifested as the need for ex novo oxygen supply, pneumothorax, and extreme hypoxia. Researches on BCG vaccination have shown that countries without vaccination policy are more likely to be seriously affected than those with BCG vaccination programs. COVID-19 infection in patients with TB or the lack of sufficient BCG vaccination may be associated with higher detrimental consequences, including mortality.

3.
Am J Trop Med Hyg ; 103(6): 2353-2356, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-1005552

ABSTRACT

American trypanosomiasis, also named Chagas disease (CD), is an anthropozoonosis caused by the protozoan parasite Trypanosoma cruzi. The disease affects millions of people worldwide, leading yearly to approximately 50,000 deaths. COVID-19, generated by SARS-CoV-2, can lead to lymphopenia and death. We hereby describe the first report of two patients with CD and COVID-19 coinfection, from hospitalization until patients' death.


Subject(s)
COVID-19/diagnosis , Chagas Cardiomyopathy/diagnosis , RNA, Viral/genetics , SARS-CoV-2/pathogenicity , Trypanosoma cruzi/pathogenicity , Aged , Brazil , COVID-19/parasitology , COVID-19/pathology , COVID-19/virology , COVID-19 Testing/methods , Chagas Cardiomyopathy/parasitology , Chagas Cardiomyopathy/pathology , Chagas Cardiomyopathy/virology , Coinfection , Disease Progression , Fatal Outcome , Female , Hospitalization , Humans , Male , Pacemaker, Artificial , SARS-CoV-2/genetics , Tomography, X-Ray Computed , Trypanosoma cruzi/genetics
4.
Am J Case Rep ; 21: e927628, 2020 Nov 05.
Article in English | MEDLINE | ID: covidwho-994258

ABSTRACT

BACKGROUND Coinfection with severe acute respiratory syndrome-associated coronavirus 2 (SARS-CoV-2) and Mycobacterium tuberculosis (MBT) has been reported, albeit rarely, in various parts of the world and has received attention from health systems because up to one-third of the world's population has been infected with SARS-CoV-2. Mexico was not included in the first-ever report on a global cohort of patients with this coinfection. We report on a case of SARS-CoV-2/MBT coinfection in a 51-year-old taxi driver from Mexico City that underscores the importance of rapid and accurate laboratory testing, diagnosis, and treatment. CASE REPORT We present the case of a man in the sixth decade of life who was admitted to the National Institute of Respiratory Diseases (INER) with a diagnosis of COVID-19 pneumonia, which was confirmed by nasopharyngeal exudate using real-time polymerase chain reaction (RT-PCR) for the identification of SARS-CoV-2. Findings from imaging studies suggested that the patient might be coinfected with MBT. That suspicion was confirmed with light microscopy of a sputum sample after Ziehl-Neelsen staining and when a Cepheid Xpert MTB/RIF assay, an automated semi-quantitative RT-PCR assay, failed to detect rifampicin resistance. The patient was discharged from the hospital 10 days later. CONCLUSIONS The present report underscores the importance of using validated molecular diagnostic tests to identify coinfections in areas where there is a high prevalence of other causes of pneumonia, such as MBT, as a way to improve clinical outcomes in patients during the COVID-19 pandemic. While it is imperative to control the COVID-19 pandemic, the medical community must not forget about the other pandemics to which populations are still prey, and tuberculosis is one of them. We must remain alert to any clinical subtleties so as to ensure timely and accurate diagnosis and stay one step ahead of COVID-19.


Subject(s)
COVID-19/diagnosis , Coinfection , Mycobacterium tuberculosis/immunology , Pandemics , SARS-CoV-2/genetics , Tuberculosis, Pulmonary/diagnosis , Antibodies, Bacterial/analysis , COVID-19/complications , COVID-19/epidemiology , Humans , Male , Mexico/epidemiology , Middle Aged , RNA, Viral/analysis , Tomography, X-Ray Computed , Tuberculosis, Pulmonary/complications
5.
Case Rep Pulmonol ; 2020: 8849068, 2020.
Article in English | MEDLINE | ID: covidwho-991972

ABSTRACT

Bacterial coinfections are not uncommon with respiratory viral pathogens. These coinfections can add to significant mortality and morbidity. We are currently dealing with the SARS-CoV-2 pandemic, which has affected over 15 million people globally with over half a million deaths. Previous respiratory viral pandemics have taught us that bacterial coinfections can lead to higher mortality and morbidity. However, there is limited literature on the current SARS-CoV-2 pandemic and associated coinfections, which reported infection rates varying between 1% and 8% based on various cross-sectional studies. In one meta-analysis of coinfections in COVID-19, rates of Streptococcus pneumoniae coinfections have been negligible when compared to previous influenza pandemics. Current literature does not favor the use of empiric, broad-spectrum antibiotics in confirmed SARS-CoV-2 infections. We present three cases of confirmed SARS-CoV-2 infections complicated by Streptococcus pneumoniae coinfection. These cases demonstrate the importance of concomitant testing for common pathogens despite the need for antimicrobial stewardship.

6.
J Clin Microbiol ; 59(1)2020 12 17.
Article in English | MEDLINE | ID: covidwho-991749

ABSTRACT

Broad testing for respiratory viruses among persons under investigation (PUIs) for SARS-CoV-2 has been performed inconsistently, limiting our understanding of alternative viral infections and coinfections in these patients. RNA metagenomic next-generation sequencing (mNGS) offers an agnostic tool for the detection of both SARS-CoV-2 and other RNA respiratory viruses in PUIs. Here, we used RNA mNGS to assess the frequencies of alternative viral infections in SARS-CoV-2 RT-PCR-negative PUIs (n = 30) and viral coinfections in SARS-CoV-2 RT-PCR-positive PUIs (n = 45). mNGS identified all viruses detected by routine clinical testing (influenza A [n = 3], human metapneumovirus [n = 2], and human coronavirus OC43 [n = 2], and human coronavirus HKU1 [n = 1]). mNGS also identified both coinfections (1, 2.2%) and alternative viral infections (4, 13.3%) that were not detected by routine clinical workup (respiratory syncytial virus [n = 3], human metapneumovirus [n = 1], and human coronavirus NL63 [n = 1]). Among SARS-CoV-2 RT-PCR-positive PUIs, lower cycle threshold (CT ) values correlated with greater SARS-CoV-2 read recovery by mNGS (R 2, 0.65; P < 0.001). Our results suggest that current broad-spectrum molecular testing algorithms identify most respiratory viral infections among SARS-CoV-2 PUIs, when available and implemented consistently.


Subject(s)
Betacoronavirus/isolation & purification , COVID-19/diagnosis , Coronavirus OC43, Human/isolation & purification , Influenza A virus/isolation & purification , Metapneumovirus/isolation & purification , SARS-CoV-2/isolation & purification , Betacoronavirus/genetics , COVID-19 Nucleic Acid Testing/methods , Coinfection/virology , Coronavirus OC43, Human/genetics , Genome, Viral/genetics , High-Throughput Nucleotide Sequencing , Humans , Influenza A virus/genetics , Metagenome , Metagenomics , Metapneumovirus/genetics , SARS-CoV-2/genetics
7.
J Med Virol ; 92(10): 2181-2187, 2020 10.
Article in English | MEDLINE | ID: covidwho-935110

ABSTRACT

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is spreading at a rapid pace, and the World Health Organization declared it as pandemic on 11 March 2020. Mycoplasma pneumoniae is an "atypical" bacterial pathogen commonly known to cause respiratory illness in humans. The coinfection from SARS-CoV-2 and mycoplasma pneumonia is rarely reported in the literature to the best of our knowledge. We present a study in which 6 of 350 patients confirmed with COVID-19 were also diagnosed with M. pneumoniae infection. In this study, we described the clinical characteristics of patients with coinfection. Common symptoms at the onset of illness included fever (six [100%] patients); five (83.3%) patients had a cough, shortness of breath, and fatigue. The other symptoms were myalgia (66.6%), gastrointestinal symptoms (33.3%-50%), and altered mental status (16.7%). The laboratory parameters include lymphopenia, elevated erythrocyte sedimentation rate, C-reactive protein, lactate dehydrogenase, interleukin-6, serum ferritin, and D-dimer in all six (100%) patients. The chest X-ray at presentation showed bilateral infiltrates in all the patients (100%). We also described electrocardiogram findings, complications, and treatment during hospitalization in detail. One patient died during the hospital course.


Subject(s)
COVID-19/physiopathology , Hypertension/physiopathology , Mycoplasma pneumoniae/pathogenicity , Pneumonia, Mycoplasma/physiopathology , SARS-CoV-2/pathogenicity , Adult , Anti-Bacterial Agents/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/diagnostic imaging , COVID-19/mortality , COVID-19/therapy , Coinfection , Comorbidity , Cough/physiopathology , Dyspnea/physiopathology , Fatigue/physiopathology , Female , Fever/physiopathology , Humans , Hypertension/diagnostic imaging , Hypertension/mortality , Hypertension/therapy , Lymphocytes/pathology , Lymphocytes/virology , Male , Middle Aged , Myalgia/physiopathology , Mycoplasma pneumoniae/drug effects , Pneumonia, Mycoplasma/diagnostic imaging , Pneumonia, Mycoplasma/mortality , Pneumonia, Mycoplasma/therapy , Retrospective Studies , SARS-CoV-2/drug effects , Severity of Illness Index , Survival Analysis , Tomography, X-Ray Computed , Treatment Outcome
8.
J Pediatric Infect Dis Soc ; 9(5): 630-635, 2020 Nov 10.
Article in English | MEDLINE | ID: covidwho-919287

ABSTRACT

Most severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in pediatric patients are mild or asymptomatic. However, infants have emerged at higher risk of hospitalization and severe outcomes in pediatric coronavirus disease 2019 (COVID-19). We report a case series of 4 full-term neonates hospitalized with fever and found to have SARS-CoV-2 infection with a spectrum of illness severities. Two neonates required admission to the intensive care unit for respiratory insufficiency and end organ involvement. Half of the patients were found to have a coinfection. One neonate received antiviral therapy with remdesivir and is, to our knowledge, the youngest patient to receive this drug for COVID-19. All neonates had favorable outcomes.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections , Pandemics , Pneumonia, Viral , Biomarkers/blood , Blood Chemical Analysis , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques , Coronavirus Infections/complications , Coronavirus Infections/diagnosis , Electrocardiography , Fever/etiology , Humans , Infant, Newborn , Male , Pneumonia, Viral/complications , Pneumonia, Viral/diagnosis , Reverse Transcriptase Polymerase Chain Reaction , Risk Factors , SARS-CoV-2 , Socioeconomic Factors
9.
Infect Genet Evol ; 86: 104602, 2020 12.
Article in English | MEDLINE | ID: covidwho-899330

ABSTRACT

BACKGROUND: SARS-CoV-2 coinfection with other viral and bacterial pathogens and their interactions are increasingly recognized in the literature as potential determinants of COVID-19 phenotypes. The aim of this study was to determine infection induced, host transcriptomic overlap between SARS-CoV-2 and other pathogens. MATERIALS AND METHODS: SARS-CoV-2 infection induced gene expression data were used for gene set enrichment analysis (GSEA) via the Enrichr platform. GSEA compared the extracted signature to VirusMINT, Virus and Microbe perturbations from Gene Expression Omnibus (GEO) in order to detect overlap with other pathogen induced host gene signatures. For all analyses, a false discovery rate (FDR) <0.05 was considered statistically significant. RESULTS: GSEA via Enrichr revealed several significantly enriched sub-signatures associated with HSV1, EBV, HIV1, IAV, RSV, P.Aeruginosa, Staph. Aureus and Strep. Pneumoniae infections, among other pathogens (FDR < 0.05). These signatures were detected in at least 6 infection-induced transcriptomic studies from GEO and involved both bronchial epithelial and peripheral blood immune cells. DISCUSSION: SARS-CoV-2 infection may function synergistically with other viral and bacterial pathogens at the transcriptomic level. Notably, several meta-analyses of COVID-19 cohorts have furthermore corroborated viral and bacterial pathogens reported herein as coinfections with SARS-CoV-2. The identification of common, perturbed gene networks outlines a common host targetome for these pathogens, and furthermore provides candidates for biomarker discovery and drug design.


Subject(s)
COVID-19 , Host-Pathogen Interactions/genetics , SARS-CoV-2/pathogenicity , Transcriptome , Virus Diseases , COVID-19/genetics , COVID-19/metabolism , COVID-19/virology , Cells, Cultured , Coinfection , Computer Simulation , Humans , Systems Biology , Transcriptome/genetics , Transcriptome/physiology , Virus Diseases/genetics , Virus Diseases/metabolism , Virus Diseases/virology , Viruses/pathogenicity
10.
Future Microbiol ; 15: 1405-1413, 2020 09.
Article in English | MEDLINE | ID: covidwho-883809

ABSTRACT

As the global COVID-19 pandemic spreads worldwide, new challenges arise in the clinical landscape. The need for reliable diagnostic methods, treatments and vaccines for COVID-19 is the major worldwide urgency. While these goals are especially important, the growing risk of co-infections is a major threat not only to the health systems but also to patients' lives. Although there is still not enough published statistical data, co-infections in COVID-19 patients found that a significant number of patients hospitalized with COVID-19 developed secondary systemic mycoses that led to serious complications and even death. This review will discuss some of these important findings with the major aim to warn the population about the high risk of concomitant systemic mycoses in individuals weakened by COVID-19.


Subject(s)
Coronavirus Infections/complications , Mycoses/complications , Opportunistic Infections/complications , Pneumonia, Viral/complications , Betacoronavirus/pathogenicity , COVID-19 , Coronavirus Infections/drug therapy , Coronavirus Infections/pathology , Glucocorticoids/adverse effects , Humans , Invasive Fungal Infections/complications , Invasive Fungal Infections/diagnosis , Invasive Fungal Infections/epidemiology , Invasive Fungal Infections/microbiology , Lung Diseases, Fungal/complications , Lung Diseases, Fungal/diagnosis , Lung Diseases, Fungal/epidemiology , Lung Diseases, Fungal/microbiology , Mycoses/diagnosis , Mycoses/epidemiology , Mycoses/microbiology , Opportunistic Infections/diagnosis , Opportunistic Infections/epidemiology , Opportunistic Infections/microbiology , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/pathology , Risk , SARS-CoV-2
11.
West J Emerg Med ; 21(6): 1-4, 2020 Sep 28.
Article in English | MEDLINE | ID: covidwho-869240

ABSTRACT

INTRODUCTION: The novel coronavirus (SARS-CoV-2) is the cause of COVID-19, which has had a devastating international impact. Prior reports of testing have reported low sensitivities of nasopharyngeal polymerase chain reaction (PCR), and reports of viral co-infections have varied from 0-20%. Therefore, we sought to determine the accuracy of nasopharyngeal PCR for COVID-19 and rates of viral co-infection. METHODS: We conducted a retrospective chart review of all patients who received viral testing between March 1, 2020-April 28, 2020. Test results of a complete viral pathogen panel and COVID-19 testing were abstracted. We compared patients with more than one COVID-19 test for diagnostic accuracy against the gold standard of chart review. RESULTS: We identified 1950 patients, of whom 1024 were tested for COVID-19. There were 221 repeat tests for COVID-19. Among patients with a repeat test, COVID-19 swabs had a sensitivity of 84.6% (95% confidence interval (CI), 69.5-94.4%) and a specificity of 99.5% (95%CI, 97-100%) compared to a clinical and radiographic criterion reference by chart review. We found viral co-infection rates of 2.3% in patients without COVID-19 and 6.1% in patients with COVID-19. Rates of co-infection appeared to be related to base rates of infection in the community and not a specific property of COVID-19. CONCLUSION: COVID-19 nasopharyngeal PCR specimens are accurate but have imperfect sensitivity. Repeat testing for high-risk patients should be considered, and presence of an alternative virus should not be used to limit testing for COVID-19 for patients where it would affect treatment or isolation.


Subject(s)
COVID-19 Testing , COVID-19/diagnosis , Nasopharynx/virology , SARS-CoV-2/isolation & purification , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Coinfection/diagnosis , Female , Humans , Infant , Male , Middle Aged , Polymerase Chain Reaction , Retrospective Studies , SARS-CoV-2/genetics , Sensitivity and Specificity , Young Adult
12.
Infect Drug Resist ; 13: 3409-3422, 2020.
Article in English | MEDLINE | ID: covidwho-845743

ABSTRACT

Background: The emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulted in a worldwide devastating effect with a diagnostic challenge. Identifying risk factors of severity aids in assessment for the need of early hospitalization. We aimed to demonstrate, for the first time, the clinical, laboratory and radiological characteristics of coronavirus disease 2019 (COVID-19) patients, to identify the predictors of severity and to describe the antimicrobial resistance profile in patients from Upper Egypt. Materials and Methods: Demographic characters, clinical presentations, laboratory, and radiological data were recorded and analyzed. Presence of other respiratory microorganisms and their sensitivity patterns were identified using the VITEK2 system. Resistance-associated genes were tested by PCR. Results: The study included 260 COVID-19 patients. The majority were males (55.4%) aged between 51 and 70 years. Hypertension, diabetes, and ischemic heart disease were common comorbidities. Main clinical manifestations were fever (63.8%), cough (57.7%), dyspnea (40%) and fatigue (30%). According to severity, 51.5% were moderate, 25.4% mild and 23% severe/critical. Lymphopenia, elevated CRP, ferritin, and D-dimer occurred in all patients with significantly higher value in the severe group. Age >53 years and elevated ferritin ≥484 ng/mL were significant risk factors for severity. About 10.7% of the COVID-19 patients showed bacterial and/or fungal infections. Klebsiella pneumoniae, Acinetobacter baumannii, and Staphylococcus aureus were the predominant isolated bacteria while Candida albicans and Candida glabrata were the predominant isolated fungi. All Staphylococci were methicillin-resistant and carried the mecA gene. Gram-negative isolates were multidrug-resistant and carried different resistance-associated genes, including NDM-1, KPC, TEM, CTX-M, and SHV. Conclusion: Older age and elevated serum ferritin were significant risk factors for severe COVID-19. Bacterial co-infection and multidrug resistance among patients with COVID-19 in Upper Egypt is common. Testing for presence of other co-infecting agents should be considered, and prompt treatment should be carried out according to the antimicrobial sensitivity reports.

14.
Crit Care Explor ; 2(9): e0211, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-800703

ABSTRACT

Objectives: Aspergillus coinfection in coronavirus disease 2019 patients has rarely been described but may be occurring among coronavirus disease 2019 patients admitted to ICUs. Previous reports of viral coinfections with Aspergillus, including influenza-associated pulmonary aspergillosis, suggest that coronavirus disease 2019-associated aspergillosis is plausible. This report aims to summarize what is known about coronavirus disease 2019 complicated by Aspergillus, introduces coronavirus disease 2019-associated pulmonary aspergillosis as a possible clinical entity, and describes reasons clinical suspicion of Aspergillus is warranted in the critical care setting. Data Sources: We summarize the available evidence suggesting the existence of Aspergillus coinfection among severe coronavirus disease 2019 patients. This includes published coronavirus disease 2019 patient case series, a case description, and a review of potential biologic mechanisms. Study Selection: Reports of coronavirus disease 2019 patient attributes were selected if they included clinical, microbiologic, or radiologic signs of invasive fungal infection. Data Extraction: Data included in summary tables were identified through a literature search for coronavirus disease 2019-associated pulmonary aspergillosis. Data Synthesis: We present descriptive data extracted from coronavirus disease 2019-associated pulmonary aspergillosis case series current at the time of article submission. Discussion: Pulmonary aspergillosis is known to occur among influenza patients requiring intensive care and is associated with increased mortality. If Aspergillus coinfections are occurring among coronavirus disease 2019 patients, early clinical suspicion and testing are needed to understand the epidemiology of these infections and prevent associated mortality. As the coronavirus disease 2019 pandemic unfolds, reports on the existence of this coinfection are needed, and opportunities to contribute cases of Aspergillus coinfection among coronavirus disease 2019 patients to an ongoing registry are described.

15.
Ann Ist Super Sanita ; 56(3): 359-364, 2020.
Article in English | MEDLINE | ID: covidwho-789696

ABSTRACT

Current literature shows that secondary bacterial infections, although less frequent than in previous influenza pandemics, affect COVID-19 patients. Mycoplasma pneumoniae, Staphylococcus aureus, Legionella pneumophila, Streptococcus pneumoniae, Haemophilus and Klebsiella spp. are the main species isolated. Of note, Mycobacterium tuberculosis-COVID-19 coinfections are also reported. However, bacterial coinfection rates increase in patients admitted in the intensive care units, and those diseases can be due to super-infections by nosocomial antibiotic-resistant bacteria. This highlights the urgency to revise frequent and empiric prescription of broad-spectrum antibiotics in COVID-19 patients, with more attention to evidence-based studies and respect for the antimicrobial stewardship principles.


Subject(s)
Bacterial Infections/epidemiology , Betacoronavirus , Coinfection/epidemiology , Coronavirus Infections/epidemiology , Pandemics , Pneumonia, Viral/epidemiology , Antimicrobial Stewardship , Bacterial Infections/drug therapy , Bacterial Infections/microbiology , Bacterial Infections/transmission , COVID-19 , Cross Infection/epidemiology , Cross Infection/transmission , Drug Resistance, Microbial , Early Diagnosis , Humans , Intensive Care Units , Italy/epidemiology , Mycoses/epidemiology , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/microbiology , SARS-CoV-2 , Species Specificity , Tuberculosis/epidemiology
16.
Vaccines (Basel) ; 8(3)2020 Sep 18.
Article in English | MEDLINE | ID: covidwho-789519

ABSTRACT

COVID-19 might potentially give rise to a more severe infection in solid organ transplant recipients due to their chronic immunosuppression. These patients are at a higher risk of developing concurrent or secondary bacterial and fungal infections. Co-infections can increase systemic inflammation influencing the prognosis and the severity of the disease, and can in turn lead to an increased need of mechanical ventilation, antibiotic therapy and to a higher mortality. Here we describe, for the first time in Europe, a fatal case of co-infection between SARS-CoV-2 and Pneumocystis jirevocii in a kidney transplant recipient.

17.
mBio ; 11(5)2020 09 10.
Article in English | MEDLINE | ID: covidwho-760223

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), is a recently emerged respiratory coronavirus that has infected >23 million people worldwide with >800,000 deaths. Few COVID-19 therapeutics are available, and the basis for severe infections is poorly understood. Here, we investigated properties of type I (ß), II (γ), and III (λ1) interferons (IFNs), potent immune cytokines that are normally produced during infection and that upregulate IFN-stimulated gene (ISG) effectors to limit virus replication. IFNs are already in clinical trials to treat COVID-19. However, recent studies highlight the potential for IFNs to enhance expression of host angiotensin-converting enzyme 2 (ACE2), suggesting that IFN therapy or natural coinfections could exacerbate COVID-19 by upregulating this critical virus entry receptor. Using a cell line model, we found that beta interferon (IFN-ß) strongly upregulated expression of canonical antiviral ISGs, as well as ACE2 at the mRNA and cell surface protein levels. Strikingly, IFN-λ1 upregulated antiviral ISGs, but ACE2 mRNA was only marginally elevated and did not lead to detectably increased ACE2 protein at the cell surface. IFN-γ induced the weakest ISG response but clearly enhanced surface expression of ACE2. Importantly, all IFN types inhibited SARS-CoV-2 replication in a dose-dependent manner, and IFN-ß and IFN-λ1 exhibited potent antiviral activity in primary human bronchial epithelial cells. Our data imply that type-specific mechanisms or kinetics shape IFN-enhanced ACE2 transcript and cell surface levels but that the antiviral action of IFNs against SARS-CoV-2 counterbalances any proviral effects of ACE2 induction. These insights should aid in evaluating the benefits of specific IFNs, particularly IFN-λ, as repurposed therapeutics.IMPORTANCE Repurposing existing, clinically approved, antiviral drugs as COVID-19 therapeutics is a rapid way to help combat the SARS-CoV-2 pandemic. Interferons (IFNs) usually form part of the body's natural innate immune defenses against viruses, and they have been used with partial success to treat previous new viral threats, such as HIV, hepatitis C virus, and Ebola virus. Nevertheless, IFNs can have undesirable side effects, and recent reports indicate that IFNs upregulate the expression of host ACE2 (a critical entry receptor for SARS-CoV-2), raising the possibility that IFN treatments could exacerbate COVID-19. Here, we studied the antiviral- and ACE2-inducing properties of different IFN types in both a human lung cell line model and primary human bronchial epithelial cells. We observed differences between IFNs with respect to their induction of antiviral genes and abilities to enhance the cell surface expression of ACE2. Nevertheless, all the IFNs limited SARS-CoV-2 replication, suggesting that their antiviral actions can counterbalance increased ACE2.


Subject(s)
Antiviral Agents/pharmacology , Coronavirus Infections/drug therapy , Interferon Type I/pharmacology , Interferon-gamma/pharmacology , Interferons/pharmacology , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/drug therapy , Aged , Angiotensin-Converting Enzyme 2 , Animals , Betacoronavirus/immunology , COVID-19 , Cell Line , Chlorocebus aethiops , Female , Humans , Immunotherapy/methods , Interferon Type I/adverse effects , Interferon-gamma/adverse effects , Interferons/adverse effects , Pandemics , Peptidyl-Dipeptidase A/genetics , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Receptors, Virus/metabolism , Respiratory Mucosa/cytology , Respiratory Mucosa/virology , SARS-CoV-2 , Up-Regulation/drug effects , Vero Cells , Virus Replication/drug effects
18.
Arch Pediatr ; 27(8): 509-510, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-753925

ABSTRACT

COVID-19 is a new disease leading to respiratory complications in adults. Children appear to have more modest symptoms than adults. Varicella is often described as a benign disease in the pediatric population. However, patients with varicella and COVID-19 co-infection can develop a more serious respiratory infection. We report the case of an infant who had a co-infection with both viruses that led to pleuropneumonia. The main question in the present case concerns the link between COVID-19 and varicella infection, and the possible modulation in immune response due to the two virus infections.


Subject(s)
Betacoronavirus , Chickenpox/diagnosis , Coinfection/diagnosis , Coronavirus Infections/diagnosis , Pleuropneumonia/diagnosis , Pneumonia, Viral/diagnosis , Betacoronavirus/isolation & purification , COVID-19 , Coinfection/virology , Humans , Infant , Male , Pandemics , Pleuropneumonia/virology , SARS-CoV-2
19.
Respir Med Case Rep ; 31: 101203, 2020.
Article in English | MEDLINE | ID: covidwho-733634

ABSTRACT

This is the first reported case, to our knowledge, of co-infection of Bordetella bronchiseptica and SARS-CoV-2 in a young patient with underlying idiopathic bronchiectasis and vitamin D3 deficiency that was treated successfully with a combination therapeutic regime integrating doxycycline, empiric therapies for COVID-19, vitamin D supplementation, and supportive ICU care. Large prospective studies are required to investigate further the role of co-infections in COVID-19 patients with bronchiectasis. Randomized control trials should examine the putative beneficial role of vitamin D supplementation in patients with COVID-19.

20.
Appl Microbiol Biotechnol ; 104(18): 7777-7785, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-709732

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel ß-coronavirus, is the main pathogenic agent of the rapidly spreading pneumonia called coronavirus disease 2019 (COVID-19). SARS-CoV-2 infects much more people, especially the elder population, around the world than other coronavirus, such as SARS-CoV and MERS-CoV, which is challenging current global public health system. Beyond the pathogenesis of SARS-CoV-2, microbial coinfection plays an important role in the occurrence and development of SARS-CoV-2 infection by raising the difficulties of diagnosis, treatment, prognosis of COVID-19, and even increasing the disease symptom and mortality. We summarize the coinfection of virus, bacteria and fungi with SARS-CoV-2, their effects on COVID-19, the reasons of coinfection, and the diagnosis to emphasize the importance of microbial coinfection in COVID-19. KEY POINTS: • Microbial coinfection is a nonnegligible factor in COVID-19. • Microbial coinfection exacerbates the processes of the occurrence, development and prognosis of COVID-19, and the difficulties of clinical diagnosis and treatment. • Different virus, bacteria, and fungi contributed to the coinfection with SARS-CoV-2.


Subject(s)
Bacterial Infections/epidemiology , Coronavirus Infections/epidemiology , Cytokine Release Syndrome/epidemiology , Lymphopenia/epidemiology , Mycoses/epidemiology , Pandemics , Pneumonia, Viral/epidemiology , Virus Diseases/epidemiology , Anti-Bacterial Agents/therapeutic use , Antiviral Agents/therapeutic use , Bacterial Infections/drug therapy , Bacterial Infections/microbiology , Bacterial Infections/virology , Betacoronavirus/drug effects , Betacoronavirus/immunology , Betacoronavirus/pathogenicity , COVID-19 , Coinfection , Coronavirus Infections/drug therapy , Coronavirus Infections/microbiology , Coronavirus Infections/virology , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/microbiology , Cytokine Release Syndrome/virology , Cytokines/biosynthesis , Disease Progression , Host-Pathogen Interactions/immunology , Humans , Immunity, Innate/drug effects , Lymphocytes/microbiology , Lymphocytes/virology , Lymphopenia/drug therapy , Lymphopenia/microbiology , Lymphopenia/virology , Mycoses/drug therapy , Mycoses/microbiology , Mycoses/virology , Pneumonia, Viral/drug therapy , Pneumonia, Viral/microbiology , Pneumonia, Viral/virology , SARS-CoV-2 , Virus Diseases/drug therapy , Virus Diseases/microbiology , Virus Diseases/virology
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