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1.
J Leukoc Biol ; 110(1): 21-26, 2021 07.
Article in English | MEDLINE | ID: covidwho-1574077

ABSTRACT

The global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly pathogenic RNA virus causing coronavirus disease 2019 (COVID-19) in humans. Although most patients with COVID-19 have mild illness and may be asymptomatic, some will develop severe pneumonia, acute respiratory distress syndrome, multi-organ failure, and death. RNA viruses such as SARS-CoV-2 are capable of hijacking the epigenetic landscape of host immune cells to evade antiviral defense. Yet, there remain considerable gaps in our understanding of immune cell epigenetic changes associated with severe SARS-CoV-2 infection pathology. Here, we examined genome-wide DNA methylation (DNAm) profiles of peripheral blood mononuclear cells from 9 terminally-ill, critical COVID-19 patients with confirmed SARS-CoV-2 plasma viremia compared with uninfected, hospitalized influenza, untreated primary HIV infection, and mild/moderate COVID-19 HIV coinfected individuals. Cell-type deconvolution analyses confirmed lymphopenia in severe COVID-19 and revealed a high percentage of estimated neutrophils suggesting perturbations to DNAm associated with granulopoiesis. We observed a distinct DNAm signature of severe COVID-19 characterized by hypermethylation of IFN-related genes and hypomethylation of inflammatory genes, reinforcing observations in infection models and single-cell transcriptional studies of severe COVID-19. Epigenetic clock analyses revealed severe COVID-19 was associated with an increased DNAm age and elevated mortality risk according to GrimAge, further validating the epigenetic clock as a predictor of disease and mortality risk. Our epigenetic results reveal a discovery DNAm signature of severe COVID-19 in blood potentially useful for corroborating clinical assessments, informing pathogenic mechanisms, and revealing new therapeutic targets against SARS-CoV-2.


Subject(s)
COVID-19/genetics , DNA Methylation/genetics , Epigenesis, Genetic , Genome, Human , COVID-19/virology , HIV Infections/genetics , Humans , Influenza, Human/genetics , SARS-CoV-2/physiology
2.
Front Microbiol ; 12: 653399, 2021.
Article in English | MEDLINE | ID: covidwho-1389208

ABSTRACT

Co-infection with ancillary pathogens is a significant modulator of morbidity and mortality in infectious diseases. There have been limited reports of co-infections accompanying SARS-CoV-2 infections, albeit lacking India specific study. The present study has made an effort toward elucidating the prevalence, diversity and characterization of co-infecting respiratory pathogens in the nasopharyngeal tract of SARS-CoV-2 positive patients. Two complementary metagenomics based sequencing approaches, Respiratory Virus Oligo Panel (RVOP) and Holo-seq, were utilized for unbiased detection of co-infecting viruses and bacteria. The limited SARS-CoV-2 clade diversity along with differential clinical phenotype seems to be partially explained by the observed spectrum of co-infections. We found a total of 43 bacteria and 29 viruses amongst the patients, with 18 viruses commonly captured by both the approaches. In addition to SARS-CoV-2, Human Mastadenovirus, known to cause respiratory distress, was present in a majority of the samples. We also found significant differences of bacterial reads based on clinical phenotype. Of all the bacterial species identified, ∼60% have been known to be involved in respiratory distress. Among the co-pathogens present in our sample cohort, anaerobic bacteria accounted for a preponderance of bacterial diversity with possible role in respiratory distress. Clostridium botulinum, Bacillus cereus and Halomonas sp. are anaerobes found abundantly across the samples. Our findings highlight the significance of metagenomics based diagnosis and detection of SARS-CoV-2 and other respiratory co-infections in the current pandemic to enable efficient treatment administration and better clinical management. To our knowledge this is the first study from India with a focus on the role of co-infections in SARS-CoV-2 clinical sub-phenotype.

3.
J Med Virol ; 93(9): 5310-5322, 2021 09.
Article in English | MEDLINE | ID: covidwho-1274726

ABSTRACT

The most consequential challenge raised by coinfection is perhaps the inappropriate generation of recombinant viruses through the exchange of genetic material among different strains. These genetically similar viruses can interfere with the replication process of each other and even compete for the metabolites required for the maintenance of the replication cycle. Due to the similarity in clinical symptoms of most viral respiratory tract infections, and their coincidence with COVID-19, caused by SARS-CoV-2, it is recommended to develop a comprehensive diagnostic panel for detection of respiratory and nonrespiratory viruses through the evaluation of patient samples. Given the resulting changes in blood markers, such as coagulation factors and white blood cell count following virus infection, these markers can be of diagnostic value in the detection of mixed infection in individuals already diagnosed with a certain viral illness. In this review, we seek to investigate the coinfection of SARS-CoV-2 with other respiratory and nonrespiratory viruses to provide novel insights into the development of highly sensitive diagnostics and effective treatment modalities.


Subject(s)
COVID-19/epidemiology , Coinfection , Virus Diseases/epidemiology , Coinfection/epidemiology , Coinfection/virology , Humans
4.
Clin Infect Dis ; 2021 Jun 18.
Article in English | MEDLINE | ID: covidwho-1276160

ABSTRACT

BACKGROUND: The COVID-19 pandemic has resulted in unprecedented healthcare challenges, and COVID-19 has been linked to secondary infections. Candidemia, a fungal healthcare-associated infection, has been described in patients hospitalized with severe COVID-19. However, studies of candidemia and COVID-19 co-infection have been limited in sample size and geographic scope. We assessed differences in patients with candidemia with and without a COVID-19 diagnosis. METHODS: We conducted a case-level analysis using population-based candidemia surveillance data collected through the Centers for Disease Control and Prevention's Emerging Infections Program during April-August 2020 to compare characteristics of candidemia patients with and without a positive test for COVID-19 in the 30 days before their Candida culture using chi-square or Fisher exact tests. RESULTS: Of the 251 candidemia patients included, 64 (25.5%) were positive for SARS-CoV-2. Liver disease, solid organ malignancies, and prior surgeries were each >3 times more common in patients without COVID-19 co-infection, whereas intensive care unit-level care, mechanical ventilation, having a central venous catheter, and receipt of corticosteroids and immunosuppressants were each >1.3 times more common in patients with COVID-19. All cause in-hospital fatality was two times higher among those with COVID-19 (62.5%) than without (32.1%). CONCLUSIONS: One quarter of candidemia patients had COVID-19. These patients were less likely to have certain underlying conditions and recent surgery commonly associated with candidemia and more likely to have acute risk factors linked to COVID-19 care, including immunosuppressive medications. Given the high mortality, it is important for clinicians to remain vigilant and take proactive measures to prevent candidemia in patients with COVID-19.

5.
J Microbiol Immunol Infect ; 54(1): 105-108, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-1272568

ABSTRACT

Cases of co-infection and secondary infection emerging during the current Coronavirus Disease-19 (COVID-19) pandemic are a major public health concern. Such cases may result from immunodysregulation induced by the SARS-CoV-2 virus. Pandemic preparedness must include identification of disease natural history and common secondary infections to implement clinical solutions.


Subject(s)
COVID-19/immunology , COVID-19/microbiology , Coinfection/immunology , Coinfection/virology , SARS-CoV-2/immunology , COVID-19/epidemiology , COVID-19/virology , Coinfection/epidemiology , Humans , Lymphopenia/immunology , Lymphopenia/microbiology , Lymphopenia/virology , Pandemics , Prevalence , Public Health , Superinfection/immunology , Superinfection/microbiology , Superinfection/virology
6.
Virol J ; 18(1): 127, 2021 06 14.
Article in English | MEDLINE | ID: covidwho-1269882

ABSTRACT

BACKGROUND: In COVID-19 patients, undetected co-infections may have severe clinical implications associated with increased hospitalization, varied treatment approaches and mortality. Therefore, we investigated the implications of viral and bacterial co-infection in COVID-19 clinical outcomes. METHODS: Nasopharyngeal samples were obtained from 48 COVID-19 patients (29% ICU and 71% non-ICU) and screened for the presence of 24 respiratory pathogens using six multiplex PCR panels. RESULTS: We found evidence of co-infection in 34 COVID-19 patients (71%). Influenza A H1N1 (n = 17), Chlamydia pneumoniae (n = 13) and human adenovirus (n = 10) were the most commonly detected pathogens. Viral co-infection was associated with increased ICU admission (r = 0.1) and higher mortality (OR 1.78, CI = 0.38-8.28) compared to bacterial co-infections (OR 0.44, CI = 0.08-2.45). Two thirds of COVID-19 critically ill patients who died, had a co-infection; and Influenza A H1N1 was the only pathogen for which a direct relationship with mortality was seen (r = 0.2). CONCLUSIONS: Our study highlights the importance of screening for co-infecting viruses in COVID-19 patients, that could be the leading cause of disease severity and death. Given the high prevalence of Influenza co-infection in our study, increased coverage of flu vaccination is encouraged to mitigate the transmission of influenza virus during the on-going COVID-19 pandemic and reduce the risk of severe outcome and mortality.


Subject(s)
COVID-19/mortality , Coinfection/mortality , Influenza, Human/mortality , Adult , Aged , Bacterial Infections/epidemiology , Bacterial Infections/mortality , Bacterial Infections/pathology , COVID-19/epidemiology , COVID-19/pathology , Coinfection/epidemiology , Coinfection/pathology , Female , Hospitalization , Humans , Influenza A Virus, H1N1 Subtype/isolation & purification , Influenza, Human/epidemiology , Influenza, Human/pathology , Intensive Care Units , Male , Middle Aged , Nasopharynx/microbiology , Nasopharynx/virology , Prevalence , SARS-CoV-2/isolation & purification , Saudi Arabia/epidemiology
7.
Sci Rep ; 11(1): 10902, 2021 05 25.
Article in English | MEDLINE | ID: covidwho-1243311

ABSTRACT

The objective of this study was to detect the Epstein-Barr virus (EBV) coinfection in coronavirus disease 2019 (COVID-19). In this retrospective single-center study, we included 67 COVID-19 patients with onset time within 2 weeks in Renmin Hospital of Wuhan University from January 9 to February 29, 2020. Patients were divided into EBV/SARS-CoV-2 coinfection group and SARS-CoV-2 infection alone group according to the serological results of EBV, and the characteristics differences between the two groups were compared. The median age was 37 years, with 35 (52.2%) females. Among these COVID-19 patients, thirty-seven (55.2%) patients were seropositive for EBV viral capsid antigen (VCA) IgM antibody. EBV/SARS-CoV-2 coinfection patients had a 3.09-fold risk of having a fever symptom than SARS-CoV-2 infection alone patients (95% CI 1.11-8.56; P = 0.03). C-reactive protein (CRP) (P = 0.02) and the aspartate aminotransferase (AST) (P = 0.04) in EBV/SARS-CoV-2 coinfection patients were higher than that in SARS-CoV-2 infection alone patients. EBV/SARS-CoV-2 coinfection patients had a higher portion of corticosteroid use than the SARS-CoV-2 infection alone patients (P = 0.03). We find a high incidence of EBV coinfection in COVID-19 patients. EBV/SARS-CoV-2 coinfection was associated with fever and increased inflammation. EBV reactivation may associated with the severity of COVID-19.


Subject(s)
Antibodies, Viral/blood , COVID-19/pathology , Epstein-Barr Virus Infections/pathology , Herpesvirus 4, Human/isolation & purification , Adrenal Cortex Hormones/therapeutic use , Adult , Aspartate Aminotransferases/blood , C-Reactive Protein/analysis , COVID-19/complications , COVID-19/virology , Capsid Proteins/immunology , Epstein-Barr Virus Infections/complications , Epstein-Barr Virus Infections/drug therapy , Epstein-Barr Virus Infections/virology , Female , Fever/etiology , Herpesvirus 4, Human/immunology , Herpesvirus 4, Human/metabolism , Humans , Immunoglobulin M/blood , Male , Middle Aged , Risk Factors , SARS-CoV-2/isolation & purification , Severity of Illness Index
8.
Vopr Virusol ; 66(2): 152-161, 2021 05 15.
Article in Russian | MEDLINE | ID: covidwho-1229649

ABSTRACT

INTRODUCTION: Immunodeficiency underlying the development of severe forms of new coronavirus infection may be the result of mixed infection with SARS-CoV-2 and other pathogens, including Epstein-Barr virus (EBV).The aim is to study the prevalence and epidemiological features of co-infection with SARS-CoV-2 and EBV. MATERIAL AND METHODS: A cross-sectional randomized study was conducted in Moscow region from March to May 2020. Two groups were examined for EBV-markers: hospital patients (n = 95) treated for SARS-CoV-2 infection and blood donors (n = 92). RESULTS: With equal EBV prevalence the detection of active infection markers in donors (10.9%) was noticeably lower than in SARS-CoV-2 patients (80%). Significant differences in this indicator were also found when patients from subgroups with interstitial pneumonia with the presence (96.6%) and absence (97.2%) of SARS-CoV-2 in the nasopharyngeal smear were compared with the subgroup of patients with mild COVID-19 (43.3%). The average IgG VCA and IgG EBNA positivity coefficients in donor group were higher than in patient group (p < 0.05). Patients with active EBV infection markers were significantly more likely to have pneumonia, exceeding the reference values of ALT and the relative number of monocytes (odds ratio - 23.6; 3.5; 9.7, respectively). DISCUSSION: The present study examined the incidence and analyzed epidemiological features of active EBV infection in patients with COVID-19. CONCLUSION: A significantly higher rate of detection of active EBV infection markers in hospital patients indicates a combined participation SARS-CoV-2 and EBV in the development of interstitial pneumonia. Low levels of specific IgG EBV serve as predictors of EBV reactivation. Exceeding the reference values of ALT and the relative number of monocytes in patients should serve as a reason for examination for active EBV infection markers.


Subject(s)
COVID-19/metabolism , Epstein-Barr Virus Infections/metabolism , Herpesvirus 4, Human/metabolism , SARS-CoV-2/metabolism , Virus Activation , Adolescent , Adult , COVID-19/epidemiology , COVID-19/pathology , Epstein-Barr Virus Infections/epidemiology , Epstein-Barr Virus Infections/pathology , Female , Humans , Male , Middle Aged
9.
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.

10.
Microb Pathog ; 156: 104941, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1213436

ABSTRACT

The novel coronavirus infectious disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has traumatized the whole world with the ongoing devastating pandemic. A plethora of microbial domains including viruses (other than SARS-CoV-2), bacteria, archaea and fungi have evolved together, and interact in complex molecular pathogenesis along with SARS-CoV-2. However, the involvement of other microbial co-pathogens and underlying molecular mechanisms leading to extortionate ailment in critically ill COVID-19 patients has yet not been extensively reviewed. Although, the incidence of co-infections could be up to 94.2% in laboratory-confirmed COVID-19 cases, the fate of co-infections among SARS-CoV-2 infected hosts often depends on the balance between the host's protective immunity and immunopathology. Predominantly identified co-pathogens of SARS-CoV-2 are bacteria such as Streptococcus pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, Acinetobacter baumannii, Legionella pneumophila and Clamydia pneumoniae followed by viruses including influenza, coronavirus, rhinovirus/enterovirus, parainfluenza, metapneumovirus, influenza B virus, and human immunodeficiency virus. The cross-talk between co-pathogens (especially lung microbiomes), SARS-CoV-2 and host is an important factor that ultimately increases the difficulty of diagnosis, treatment, and prognosis of COVID-19. Simultaneously, co-infecting microbiotas may use new strategies to escape host defense mechanisms by altering both innate and adaptive immune responses to further aggravate SARS-CoV-2 pathogenesis. Better understanding of co-infections in COVID-19 is critical for the effective patient management, treatment and containment of SARS-CoV-2. This review therefore necessitates the comprehensive investigation of commonly reported microbial co-pathogens amid COVID-19, their transmission pattern along with the possible mechanism of co-infections and outcomes. Thus, identifying the possible co-pathogens and their underlying molecular mechanisms during SARS-CoV-2 pathogenesis may shed light in developing diagnostics, appropriate curative and preventive interventions for suspected SARS-CoV-2 respiratory infections in the current pandemic.


Subject(s)
COVID-19 , Coinfection , Communicable Diseases , Microbiota , Humans , SARS-CoV-2
11.
Infect Drug Resist ; 14: 1645-1648, 2021.
Article in English | MEDLINE | ID: covidwho-1211754

ABSTRACT

Background: Coronavirus infectious disease 2019 (COVID-19) is primarily a respiratory disease. However, it may manifest with gastrointestinal symptoms that may overlap with Clostridioides difficile infection (CDI). COVID-19 appears to have higher mortality in those with comorbidities. We aimed to assess the outcomes of coinfection in these patients. Methods: A retrospective chart review was conducted to identify patients with CDI and COVID-19 from January 1st, 2020 to November 17th, 2020. Both infections were diagnosed via PCR. Clinical features, treatment for COVID-19 and CDI and outcomes including intensive care unit admission, colectomy, 30 day-mortality and long-term complications were analyzed. Results: Overall, 21 patients (20 hospitalized) with median age 70.9 years (range 51.8-90.7 years) had CDI and COVID-19 within 4 weeks of each other. Of these, 4 patients (19%) with CDI were diagnosed with COVID-19 at the time of admission, 12 (57%) had CDI diagnosed after COVID-19, and 5 (23.9%) developed COVID-19 within 4 weeks after CDI. Fourteen patients (66.7%) were treated with medications directed against COVID-19 including remdesivir and dexamethasone (n=7), remdesivir with convalescent plasma (n= 1), remdesivir (n= 5) and dexamethasone (n=1). The most common treatment for CDI was oral vancomycin in 20 patients (95.2%), and 1 patient received intravenous metronidazole. No patient required colectomy for CDI but 2 (9.5%) required ICU admission. Four patients (19%) died likely due to COVID-19 with median age 80 years (range 61-90 years). Conclusion: The relationship between COVID-19 and CDI is poorly understood, and studies are required to further investigate this association. Whether coinfection results in a worsening of outcomes, including mortality and clinical course, are questions that should be answered in future research studies. Diagnosing both infections for appropriate management is vital in light of overlapping symptoms.

12.
Trends Microbiol ; 29(10): 930-941, 2021 10.
Article in English | MEDLINE | ID: covidwho-1211155

ABSTRACT

Bacterial coinfections increase the severity of respiratory viral infections and were frequent causes of mortality in influenza pandemics but have not been well characterized in patients with coronavirus disease 2019 (COVID-19). The aim of this review was to identify the frequency and microbial etiologies of bacterial coinfections that are present upon admission to the hospital and that occur during hospitalization for COVID-19. We found that bacterial coinfections were present in <4% of patients upon admission and the yield of routine diagnostic tests for pneumonia was low. When bacterial coinfections did occur, Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae were the most common pathogens and atypical bacteria were rare. Although uncommon upon admission, bacterial infections frequently occurred in patients with prolonged hospitalization, and Pseudomonas aeruginosa, Klebsiella spp., and S. aureus were common pathogens. Antibacterial therapy and diagnostic testing for bacterial infections are unnecessary upon admission in most patients hospitalized with COVID-19, but clinicians should be vigilant for nosocomial bacterial infections.


Subject(s)
Bacterial Infections/complications , COVID-19/complications , Coinfection/microbiology , Coinfection/virology , Anti-Bacterial Agents/therapeutic use , Bacteria/classification , Bacteria/drug effects , Bacteria/genetics , Bacteria/isolation & purification , Bacterial Infections/drug therapy , Bacterial Infections/microbiology , Bacterial Physiological Phenomena , COVID-19/virology , Humans , SARS-CoV-2/genetics , SARS-CoV-2/physiology
13.
SN Compr Clin Med ; : 1-13, 2021 Apr 23.
Article in English | MEDLINE | ID: covidwho-1202894

ABSTRACT

The current frequency of COVID-19 in a pandemic era ensures that co-infections with a variety of co-pathogens will occur. Generally, there is a low rate of bonafide co-infections in early COVID-19 pulmonary infection as currently appreciated. Reports of high co-infection rates must be tempered by limitations in current diagnostic methods since amplification technologies do not necessarily confirm live pathogen and may be subject to considerable laboratory variation. Some laboratory methods may not exclude commensal microbes. Concurrent serodiagnoses have long been of concern for accuracy in these contexts. Presumed virus co-infections are not specific to COVID-19. The association of influenza viruses and SARS-CoV-2 in co-infection has been considerably variable during influenza season. Other respiratory virus co-infections have generally occurred in less than 10% of COVID-19 patients. Early COVID-19 disease is more commonly associated with bacterial co-pathogens that typically represent usual respiratory micro-organisms. Late infections, especially among severe clinical presentations, are more likely to be associated with nosocomial or opportunistic pathogens given the influence of treatments that can include antibiotics, antivirals, immunomodulating agents, blood products, immunotherapy, steroids, and invasive procedures. As anticipated, hospital care carries risk for multi-resistant bacteria. Overall, co-pathogen identification is linked with longer hospital stay, greater patient complexity, and adverse outcomes. As for other viral infections, a general reduction in the use of empiric antibiotic treatment is warranted. Further insight into co-infections with COVID-19 will contribute overall to effective antimicrobial therapies and disease control.

14.
Indian J Crit Care Med ; 25(4): 465-466, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1197613

ABSTRACT

Thrombocytopenia in coronavirus disease-2019 (COVID-19) can be attributed to multiple factors. Most often it is disease related. It is usually mild and if severe often associated with severe COVID-19 disease. It can also be due to drugs (Remdesivir, Tocilizumab) or coinfection with other viruses. Here we report two cases of severe thrombocytopenia in COVID-19 due to dengue coinfection. Most often the thrombocytopenia in dengue is self-resolving, and a careful "wait and watch" should suffice unlike COVID-19, where steroids can help if the cytopenia is due to cytokine storm or immune-mediated effects. How to cite this article: Adarsh MB, Abraham A, Kavitha P, Nandakumar MM, Vaman RS. Severe Thrombocytopenia in COVID-19: A Conundrum in Dengue-endemic Areas. Indian J Crit Care Med 2021;25(4):465-466.

15.
J Med Virol ; 93(3): 1489-1495, 2021 03.
Article in English | MEDLINE | ID: covidwho-1196455

ABSTRACT

Bacterial coinfection is associated with poor outcomes in patients with viral pneumonia, but data on its role in the mortality of patients with coronavirus disease 2019 (COVID-19) is limited. This is a single-center retrospective analysis of 242 patients with confirmed COVID-19 admitted to both intensive care and non-intensive care settings. Bacterial coinfection was determined by the presence of characteristic clinical features and positive culture results. Multivariable logistic regression was used to analyze the association of concomitant bacterial infection with inpatient death after adjusting for demographic factors and comorbidities. Antibiotic use pattern was also determined. Bacterial coinfection was detected in 46 (19%) patients. Genitourinary source was the most frequent, representing 57% of all coinfections. The overall mortality rate was 21%. Concomitant bacterial infections were independently associated with increased inpatient mortality (OR, 5.838; 95% CI, 2.647-12.876). Patients with bacterial coinfection were relatively older (71.35 ± 11.20 vs 64.78 ± 15.23; P = .006). A total of 67% of patients received antibiotic therapy, yet 72% did not have an obvious source of bacterial infection. There was a significantly higher rate of inpatient mortality in patients who received antibiotics compared to those who did not (30% vs 5%; P < .0001). Bacterial coinfection in COVID-19 is associated with increased mortality.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Bacterial Infections/complications , Bacterial Infections/drug therapy , COVID-19/complications , COVID-19/mortality , Coinfection/mortality , Aged , Bacterial Infections/mortality , Female , Hospitalization , Humans , Intensive Care Units , Male , Middle Aged
16.
Infect Dis Now ; 51(4): 383-386, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1159611

ABSTRACT

Introduction: Invasive pulmonary aspergillosis is a well-known complication of acute respiratory distress syndrome, the most serious manifestation of COVID-19. Four recent studies have reported its incidence among ICU COVID-19 patients. However, they do not share the same case definition, and have provided conflicting results. In this paper we have aimed at reported the incidence of invasive pulmonary aspergillosis for COVID-19 patients in our ICU, and at comparing the different definitions in order to assess their respective relevance. Methods: Retrospective cohort study of critically ill patients with severe COVID-19 requiring ICU management between 1st March and 30th April 2020. Results: Our results showed significantly lower incidence of invasive pulmonary aspergillosis (1.8%;1/53), compared to three out of four previous studies, and wide variation in the numbers of cases with regard to the different definitions. Conclusion: Large-scale studies are needed for a better definition and a more accurate estimation of invasive pulmonary aspergillosis coinfection during COVID-19.


Subject(s)
COVID-19/complications , Invasive Pulmonary Aspergillosis/etiology , Aged , Cohort Studies , Critical Illness , Female , Humans , Incidence , Invasive Pulmonary Aspergillosis/epidemiology , Male , Middle Aged , Retrospective Studies
17.
Assay Drug Dev Technol ; 19(3): 156-175, 2021 04.
Article in English | MEDLINE | ID: covidwho-1137927

ABSTRACT

Corona virus disease-2019 (COVID-19) emerged in Wuhan, China in December 2019 and was declared as a pandemic by the World Health Organization in March 2020. Although there is no complete treatment protocol for COVID-19, studies on this topic are ongoing, and it is known that broad-spectrum antibiotics such as cephalosporins are used for coinfections and symptoms in COVID-19 patients. Studies have shown that Staphylococcus aureus and Escherichia coli bacteria can cause symptoms such as diarrhea and coinfections accompanying COVID-19. Therefore, in this study, colon-targeted cefaclor monohydrate (CEF)-loaded poly(lactic-co-glycolic acid) (PLGA)-Eudragit S100 nanoparticles (NPs) were prepared using a nanoprecipitation technique. The particle sizes of the CEF-loaded NPs were between 171.4 and 198.8 nm. The encapsulation efficiency was in the range of 58.4%-81.2%. With dissolution studies, it has been concluded that formulations prepared with Eudragit S100 (E-coded) and Eudragit S100+PLGA (EP-coded) are pH-sensitive formulations and they are targetable to the colon, whereas the formulation prepared only with PLGA (P-coded) can release a higher CEF rate in the colon owing to the slow release properties of PLGA. The release kinetics were fitted to the Korsmeyer-Peppas and Weibull models. The antibacterial activity of E-, EP-, and P-coded formulations was 16-fold, 16-fold, and 2-fold higher than CEF, respectively, for S. aureus and E. coli according to the microdilution results. As a result of the time killing experiment, all formulations prepared were found to be more effective than the antibiotic itself for long periods. Consequently, all formulations prepared in this study hope to guide researchers/clinicians in treating both gram-positive and gram-negative bacteria-induced infections, as well as COVID-19 associated coinfections and symptoms.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Bacterial Infections/complications , Bacterial Infections/drug therapy , COVID-19/complications , Cefaclor/administration & dosage , Cefaclor/therapeutic use , Intestinal Diseases/complications , Intestinal Diseases/drug therapy , Anti-Bacterial Agents/pharmacology , Cefaclor/pharmacology , Coinfection , Drug Compounding , Escherichia coli/drug effects , Excipients , Kinetics , Microbial Sensitivity Tests , Nanoparticles , Particle Size , Polylactic Acid-Polyglycolic Acid Copolymer , Polymethacrylic Acids , Staphylococcus aureus/drug effects
18.
Front Immunol ; 12: 640644, 2021.
Article in English | MEDLINE | ID: covidwho-1133916

ABSTRACT

Infection with SARS-CoV-2 can lead to Coronavirus disease-2019 (COVID-19) and result in severe acute respiratory distress syndrome (ARDS). Recent reports indicate an increased rate of fungal coinfections during COVID-19. With incomplete understanding of the pathogenesis and without any causative therapy available, secondary infections may be detrimental to the prognosis. We monitored 11 COVID-19 patients with ARDS for their immune phenotype, plasma cytokines, and clinical parameters on the day of ICU admission and on day 4 and day 7 of their ICU stay. Whole blood stimulation assays with lipopolysaccharide (LPS), heat-killed Listeria monocytogenes (HKLM), Aspergillus fumigatus, and Candida albicans were used to mimic secondary infections, and changes in immune phenotype and cytokine release were assessed. COVID-19 patients displayed an immune phenotype characterized by increased HLA-DR+CD38+ and PD-1+ CD4+ and CD8+ T cells, and elevated CD8+CD244+ lymphocytes, compared to healthy controls. Monocyte activation markers and cytokines IL-6, IL-8, TNF, IL-10, and sIL2Rα were elevated, corresponding to monocyte activation syndrome, while IL-1ß levels were low. LPS, HKLM and Aspergillus fumigatus antigen stimulation provoked an immune response that did not differ between COVID-19 patients and healthy controls, while COVID-19 patients showed an attenuated monocyte CD80 upregulation and abrogated release of IL-6, TNF, IL-1α, and IL-1ß toward Candida albicans. This study adds further detail to the characterization of the immune response in critically ill COVID-19 patients and hints at an increased susceptibility for Candida albicans infection.


Subject(s)
Aspergillus fumigatus/immunology , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Candida albicans/immunology , Listeria monocytogenes/immunology , SARS-CoV-2/physiology , Aged , Cells, Cultured , Cytokines/metabolism , Disease Susceptibility , Female , Humans , Immune Tolerance , Male , Middle Aged , Programmed Cell Death 1 Receptor/metabolism , Respiratory Distress Syndrome
19.
J Infect Dis ; 223(5): 765-774, 2021 03 03.
Article in English | MEDLINE | ID: covidwho-1117036

ABSTRACT

BACKGROUND: Pandemic coronavirus disease 2019 (COVID-19) disease represents a challenge for healthcare structures. The molecular confirmation of samples from infected individuals is crucial and therefore guides public health decision making. Clusters and possibly increased diffuse transmission could occur in the context of the next influenza season. For this reason, a diagnostic test able to discriminate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from influenza viruses is urgently needed. METHODS: A multiplex real-time reverse-transcription polymerase chain reaction (PCR) assay was assessed using 1 laboratory protocol with different real-time PCR instruments. Overall, 1000 clinical samples (600 from samples SARS-CoV-2-infected patients, 200 samples from influenza-infected patients, and 200 negative samples) were analyzed. RESULTS: The assay developed was able to detect and discriminate each virus target and to intercept coinfections. The limit of quantification of each assay ranged between 5 and 10 genomic copy numbers, with a cutoff value of 37.7 and 37.8 for influenza and SARS-CoV-2 viruses, respectively. Only 2 influenza coinfections were detected in COVID-19 samples. CONCLUSIONS: This study suggests that multiplex assay is a rapid, valid, and accurate method for the detection of SARS-CoV-2 and influenza viruses in clinical samples. The test may be an important diagnostic tool for both diagnostic and surveillance purposes during the seasonal influenza activity period.


Subject(s)
COVID-19/diagnosis , Influenza, Human/diagnosis , Orthomyxoviridae/isolation & purification , SARS-CoV-2/isolation & purification , Area Under Curve , COVID-19/complications , COVID-19/epidemiology , Diagnosis, Differential , Humans , Influenza, Human/complications , Influenza, Human/epidemiology , Multiplex Polymerase Chain Reaction , Orthomyxoviridae/genetics , RNA, Viral/isolation & purification , ROC Curve , Reproducibility of Results , SARS-CoV-2/genetics , Seasons , Sensitivity and Specificity
20.
Cell Res ; 31(4): 395-403, 2021 04.
Article in English | MEDLINE | ID: covidwho-1091494

ABSTRACT

The upcoming flu season in the Northern Hemisphere merging with the current COVID-19 pandemic raises a potentially severe threat to public health. Through experimental coinfection with influenza A virus (IAV) and either pseudotyped or live SARS-CoV-2 virus, we found that IAV preinfection significantly promoted the infectivity of SARS-CoV-2 in a broad range of cell types. Remarkably, in vivo, increased SARS-CoV-2 viral load and more severe lung damage were observed in mice coinfected with IAV. Moreover, such enhancement of SARS-CoV-2 infectivity was not observed with several other respiratory viruses, likely due to a unique feature of IAV to elevate ACE2 expression. This study illustrates that IAV has a unique ability to aggravate SARS-CoV-2 infection, and thus, prevention of IAV infection is of great significance during the COVID-19 pandemic.


Subject(s)
COVID-19/pathology , Coinfection/pathology , Influenza A virus/physiology , Orthomyxoviridae Infections/pathology , SARS-CoV-2/physiology , Angiotensin-Converting Enzyme 2/deficiency , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Animals , COVID-19/virology , Cathepsin L/genetics , Cathepsin L/metabolism , Cell Line , Coinfection/virology , Humans , Influenza A virus/isolation & purification , Lung/pathology , Mice , Mice, Transgenic , Orthomyxoviridae Infections/virology , RNA, Guide/metabolism , SARS-CoV-2/isolation & purification , Serine Endopeptidases/genetics , Serine Endopeptidases/metabolism , Severity of Illness Index , Viral Load , Virus Internalization
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