Antimicrobial resistance (AMR) in COVID-19 patients: a systematic review and meta-analysis (November 2019-June 2021).

BACKGROUND: Pneumonia from SARS-CoV-2 is difficult to distinguish from other viral and bacterial etiologies. Broad-spectrum antimicrobials are frequently prescribed to patients hospitalized with COVID-19 which potentially acts as a catalyst for the development of antimicrobial resistance (AMR). OBJECTIVES: We conducted a systematic review and meta-analysis during the first 18 months of the pandemic to quantify the prevalence and types of resistant co-infecting organisms in patients with COVID-19 and explore differences across hospital and geographic settings. METHODS: We searched MEDLINE, Embase, Web of Science (BioSIS), and Scopus from November 1, 2019 to May 28, 2021 to identify relevant articles pertaining to resistant co-infections in patients with laboratory confirmed SARS-CoV-2. Patient- and study-level analyses were conducted. We calculated pooled prevalence estimates of co-infection with resistant bacterial or fungal organisms using random effects models. Stratified meta-analysis by hospital and geographic setting was also performed to elucidate any differences. RESULTS: Of 1331 articles identified, 38 met inclusion criteria. A total of 1959 unique isolates were identified with 29% (569) resistant organisms identified. Co-infection with resistant bacterial or fungal organisms ranged from 0.2 to 100% among included studies. Pooled prevalence of co-infection with resistant bacterial and fungal organisms was 24% (95% CI 8-40%; n = 25 studies: I2 = 99%) and 0.3% (95% CI 0.1-0.6%; n = 8 studies: I2 = 78%), respectively. Among multi-drug resistant organisms, methicillin-resistant Staphylococcus aureus, carbapenem-resistant Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa and multi-drug resistant Candida auris were most commonly reported. Stratified analyses found higher proportions of AMR outside of Europe and in ICU settings, though these results were not statistically significant. Patient-level analysis demonstrated > 50% (n = 58) mortality, whereby all but 6 patients were infected with a resistant organism. CONCLUSIONS: During the first 18 months of the pandemic, AMR prevalence was high in COVID-19 patients and varied by hospital and geography although there was substantial heterogeneity. Given the variation in patient populations within these studies, clinical settings, practice patterns, and definitions of AMR, further research is warranted to quantify AMR in COVID-19 patients to improve surveillance programs, infection prevention and control practices and antimicrobial stewardship programs globally.

Detection of microorganisms in hospital air before and during the SARS-CoV-2 pandemic.

OBJECTIVE: Microorganisms present a global public health problem and are the leading cause of hospital-acquired infections. Therefore, it is essential to study the prevalence of microorganisms in hospital environments. The conclusion from such a study can contribute to identify the areas most likely to be contaminated in a hospital and appropriate measures that can decrease the exposure risk. MATERIALS AND METHODS: The prevalence of microorganisms in hospital air was examined in different departments by obtaining air samples with an impactor before and during the SARS-CoV-2 pandemic. A total of 2145 microorganisms were identified, and the corresponding data were jointly analyzed by area, sampling period, and concentration. RESULTS: The most frequently detected microorganisms in hospital air were Staphylococcus, Micrococcus, Neisseria, and fungi, and the more polluted departments were the hemodialysis department, respiratory department, treatment room, and toilet. Significant differences were found between the concentration of bacteria and fungi before and during the pandemic, which could be related to multiple environmental conditions. Furthermore, SARS-CoV-2 was negative in all the air samples. CONCLUSIONS: Overall, this study confirmed the existence and dynamic characteristics of airborne microorganisms in a hospital. The results contribute to the adaptation of specific measures which can decrease the exposure risk of patients, visitors, and staff.

COVID-19-associated-mucormycosis: possible role of free iron uptake and immunosuppression.

COVID-19-associated-mucormycosis, commonly referred to as the "Black Fungus," is a rare secondary fungal infection in COVID-19 patients prompted by a group of mucor molds. Association of this rare fungal infection with SARS-CoV-2 infection has been declared as an endemic in India, with minor cases in several other countries around the globe. Although the fungal infection is not contagious like the viral infection, the causative fungal agent is omnipresent. Infection displays an overall mortality rate of around 50%, with many other secondary side effects posing a potential threat in exacerbating COVID-19 mortality rates. In this review, we have accessed the role of free iron availability in COVID-19 patients that might correlate to the pathogenesis of the causative fungal agent. Besides, we have analyzed the negative consequences of using immunosuppressive drugs in encouraging this opportunistic fungal infection.

Characterization of fungal communities on shared bicycles in Southwest China.

BACKGROUND: The widespread use of shared bicycles has increased the demand and sanitary requirements for shared bicycles. Previous studies have identified potentially pathogenic bacteria on the surfaces of shared bicycles, but fungal communities have not been investigated. METHODS: We sampled shared-bicycle handles and saddles from five selected locations in a metropolis (Chengdu, China, n = 98) and used surrounding air deposition samples as controls (n = 12). Full-length ITS sequencing and multiple bioinformatic analyses were utilized to reveal fungal community structures and differences. RESULTS: Aspergillus was dominant on both the handles and saddles of shared bicycles, and Alternaria and Cladosporium were the most abundant families in the air samples. Significant differences in fungal community structures were found among the three groups. The handle samples contained higher abundances of Aureobasidium melanogenum and Filobasidium magnum than the saddle and air samples. The saddle samples had a higher abundance of Cladosporium tenuissimum than the other two sample types (P < 0·05). A higher abundance of fungal animal pathogens on shared-bicycle surfaces than in air by FUNGuild (P < 0·05). Moreover, the co-occurrence network of fungi on handles was more stable than that on saddles. CONCLUSION: There were more potential pathogens, including Aspergillus pseudoglaucus, Aureobasidium melanogenum, Kazachstania pintolopesii, Filobasidium magnum, Candida tropicalis, and Malassezia globose were found on shared bicycles than in air, suggesting that hands should not contact mucous membrane after cycling, especially in susceptible individuals, and hygiene management of shared bicycles should be given more attention by relevant organizations worldwide.

Fungal Infections in COVID-19 Intensive Care Patients.

Opportunistic fungal infections increase morbidity and mortality in COVID-19 patients monitored in intensive care units (ICU). As patients' hospitalization days in the ICU and intubation period increase, opportunistic infections also increase, which prolongs hospital stay days and elevates costs. The study aimed to describe the profile of fungal infections and identify the risk factors associated with mortality in COVID-19 intensive care patients. The records of 627 patients hospitalized in ICU with the diagnosis of COVID-19 were investigated from electronic health records and hospitalization files. The demographic characteristics (age, gender), the number of ICU hospitalization days and mortality rates, APACHE II scores, accompanying diseases, antibiotic-steroid treatments taken during hospitalization, and microbiological results (blood, urine, tracheal aspirate samples) of the patients were recorded. Opportunistic fungal infection was detected in 32 patients (5.10%) of 627 patients monitored in ICU with a COVID-19 diagnosis. The average APACHE II score of the patients was 28 ± 6. While 25 of the patients (78.12%) died, seven (21.87%) were discharged from the ICU. Candida parapsilosis (43.7%) was the opportunistic fungal agent isolated from most blood samples taken from COVID-19 positive patients. The mortality rate of COVID-19 positive patients with candidemia was 80%. While two out of the three patients (66.6%) for whom fungi were grown from their tracheal aspirate died, one patient (33.3%) was transferred to the ward. Opportunistic fungal infections increase the mortality rate of COVID-19-positive patients. In addition to the risk factors that we cannot change, invasive procedures should be avoided, constant blood sugar regulation should be applied, and unnecessary antibiotics use should be avoided.

Bacterial and fungal growth in sputum cultures from 165 COVID-19 pneumonia patients requiring intubation: evidence for antimicrobial resistance development and analysis of risk factors.

BACKGROUND: Coronavirus SARS-CoV-2 causes COVID-19 illness which can progress to severe pneumonia. Empiric antibacterials are often employed though frequency of bacterial coinfection superinfection is debated and concerns raised about selection of bacterial antimicrobial resistance. We evaluated sputum bacterial and fungal growth from 165 intubated COVID-19 pneumonia patients. Objectives were to determine frequency of culture positivity, risk factors for and outcomes of positive cultures, and timing of antimicrobial resistance development. METHODS: Retrospective reviews were conducted of COVID-19 pneumonia patients requiring intubation admitted to a 1058-bed four community hospital system on the east coast United States, March 1 to May 1, 2020. Length of stay (LOS) was expressed as mean (standard deviation); 95% confidence interval (95% CI) was computed for overall mortality rate using the exact binomial method, and overall mortality was compared across each level of a potential risk factor using a Chi-Square Test of Independence. All tests were two-sided, and significance level was set to 0.05. RESULTS: Average patient age was 68.7 years and LOS 19.9 days. Eighty-three patients (50.3% of total) originated from home, 10 from group homes (6.1% of total), and 72 from nursing facilities (43.6% of total). Mortality was 62.4%, highest for nursing home residents (80.6%). Findings from 253 sputum cultures overall did not suggest acute bacterial or fungal infection in 73 (45%) of 165 individuals sampled within 24 h of intubation. Cultures ≥ 1 week following intubation did grow potential pathogens in 72 (64.9%) of 111 cases with 70.8% consistent with late pneumonia and 29.2% suggesting colonization. Twelve (10.8% of total) of these late post-intubation cultures revealed worsened antimicrobial resistance predominantly in Pseudomonas, Enterobacter, or Staphylococcus aureus. CONCLUSIONS: In severe COVID-19 pneumonia, a radiographic ground glass interstitial pattern and lack of purulent sputum prior to/around the time of intubation correlated with no culture growth or recovery of normal oral flora ± yeast. Discontinuation of empiric antibacterials should be considered in these patients aided by other clinical findings, history of prior antimicrobials, laboratory testing, and overall clinical course. Continuing longterm hospitalisation and antibiotics are associated with sputum cultures reflective of hospital-acquired microbes and increasing antimicrobial resistance. TRIAL REGISTRATION: Not applicable as this was a retrospective chart review study without interventional arm.

Fast, Scalable, and Practical: An Alkaline DNA Extraction Pipeline for Emergency Microbiomics Biosurveillance.

Pandemics and environmental crises evident from the first two decades of the 21st century call for methods innovation in biosurveillance and early detection of risk signals in planetary ecosystems. In crises conditions, conventional methods in public health, biosecurity, and environmental surveillance do not work well. In addition, the standard laboratory amenities and procedures may become unavailable, irrelevant, or simply not feasible, for example, owing to disruptions in logistics and process supply chains. The COVID-19 pandemic has been a wakeup call in this sense to reintroduce point-of-need diagnostics with an eye to limited resource settings and biosurveillance solutions. We report here a methodology innovation, a fast, scalable, and alkaline DNA extraction pipeline for emergency microbiomics biosurveillance. We believe that the presented methodology is well poised for effective, resilient, and anticipatory responses to future pandemics and ecological crises while contributing to microbiome science and point-of-need diagnostics in nonelective emergency contexts. The alkaline DNA extraction pipeline can usefully expand the throughput in emergencies by deployment or to allow backup in case of instrumentation failure in vital facilities. The need for distributed public health genomics surveillance is increasingly evident in the 21st century. This study makes a contribution to these ends broadly, and for future pandemic preparedness in particular. We call for innovation in biosurveillance methods that remain important existentially on a planet under pressure from unchecked human growth and breach of the boundaries between human and nonhuman animal habitats.

Endogenous Endophthalmitis A Complication of COVID-19 Pandemic: A Case Series.

PURPOSE: To report six patients with endogenous endophthalmitis as a complication of COVID-19 infection. METHODS: A multicentric retrospective database review of patients with a diagnosis of endogenous endophthalmitis and a history of COVID-19 infection. RESULTS: Four of six patients were diabetics. All presented after an average duration of 40 days (Range 17-90 days) of COVID-19 infection. Two of six patients had bilateral involvement. Five of six patients had received intravenous corticosteroid for COVID-19. Two of six vitreous samples showed fungi (Candida and Bipolaris species), two showed bacteria (Staphylococcus species) and two samples were culture negative. Control of infection with good visual outcome in four out of eight eyes. CONCLUSIONS: COVID-19 patients with a history of hospitalization and prolonged use of systemic corticosteroids and comorbidities, for example, diabetes mellitus have a high risk of endogenous endophthalmitis. A high index of clinical suspicion with timely intervention can salvage many eyes.

Nosocomial infections associated to COVID-19 in the intensive care unit: clinical characteristics and outcome.

Bacterial and fungal co-infection has been reported in patients with COVID-19, but there is limited experience on these infections in critically ill patients. The objective of this study was to assess the characteristics and ouctome of ICU-acquired infections in COVID-19 patients. We conducted a retrospective single-centre, case-control study including 140 patients with severe COVID-19 admitted to the ICU between March and May 2020. We evaluated the epidemiological, clinical, and microbiological features, and outcome of ICU-acquired infections. Fifty-seven patients (40.7%) developed a bacterial or fungal nosocomial infection during ICU stay. Infection occurred after a median of 9 days (IQR 5-11) of admission and was significantly associated with the APACHE II score (p = 0.02). There were 91 episodes of infection: primary (31%) and catheter-related (25%) bloodstream infections were the most frequent, followed by pneumonia (23%), tracheobronchitis (10%), and urinary tract infection (8%) that were produced by a wide spectrum of Gram-positive (55%) and Gram-negative bacteria (30%) as well as fungi (15%). In 60% of cases, infection was associated with septic shock and a significant increase in SOFA score. Overall ICU mortality was 36% (51/140). Infection was significantly associated with death (OR 2.7, 95% CI 1.2-5.9, p = 0.015) and a longer ICU stay (p < 0.001). Bacterial and fungal nosocomial infection is a common complication of ICU admission in patients with COVID-19. It usually presents as a severe form of infection, and it is associated with a high mortality and longer course of ICU stay.

Sensors and Analytical Technologies for Air Quality: Particulate Matters and Bioaerosols.

Particulate matters (PMs), e. g. dusts, fibres, smokes, fumes, mists, liquid droplets and airborne respirable solid or liquid particles, are the major sources of air pollution concerning outdoor and indoor air quality. Among various PMs, bioaerosols are airborne particles that are either living organisms (bacteria, viruses, and fungi) or originate from living organisms (endotoxin, allergen, etc). PMs and/or bioaerosols have adverse health effects of infection, allergy, and irritation. Proper management and source identification of PMs and bioaerosols will reduce their negative health impact. In this review, we will discuss the analytical technologies and sensors for PMs and bioaerosols. We will first introduce four types of PM analysers, namely, filter-based gravimetric method (GMM), optical method, ß-ray absorption method (BAM), and tapered element oscillating microbalance (TEOM). We will provide examples of how commercial PM analyzers of different principles have been compared and calibrated for specific applications under different climate conditions of specific geographic locations. For bioaerosols, having more complex biological and biochemical identity, we will start from air sampling techniques, followed by a discussion of various detection methods (plate culture, molecular methods, immunoassays and biosensors) in association with compatible sampling technologies. Using Influenza A (H1 N1) virus and SARS-CoV-2 (COVID-19) virus as examples, we have highlighted air sampling and detection challenges for viral aerosols relative to bacterial and fungal aerosols. Finally, we provide a perspective for future trends according to the limitation of current commercial products and the key challenges in this field.

Alterations in Fecal Fungal Microbiome of Patients With COVID-19 During Time of Hospitalization until Discharge.

BACKGROUND & AIMS: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects intestinal cells, and might affect the intestinal microbiota. We investigated changes in the fecal fungal microbiomes (mycobiome) of patients with SARS-CoV-2 infection during hospitalization and on recovery. METHODS: We performed deep shotgun metagenomic sequencing analysis of fecal samples from 30 patients with coronavirus disease 2019 (COVID-19) in Hong Kong, from February 5 through May 12, 2020. Fecal samples were collected 2 to 3 times per week from time of hospitalization until discharge. We compared fecal mycobiome compositions of patients with COVID-19 with those from 9 subjects with community-acquired pneumonia and 30 healthy individuals (controls). We assessed fecal mycobiome profiles throughout time of hospitalization until clearance of SARS-CoV-2 from nasopharyngeal samples. RESULTS: Patients with COVID-19 had significant alterations in their fecal mycobiomes compared with controls, characterized by enrichment of Candia albicans and a highly heterogeneous mycobiome configuration, at time of hospitalization. Although fecal mycobiomes of 22 patients with COVID-19 did not differ significantly from those of controls during times of hospitalization, 8 of 30 patients with COVID-19 had continued significant differences in fecal mycobiome composition, through the last sample collected. The diversity of the fecal mycobiome of the last sample collected from patients with COVID-19 was 2.5-fold higher than that of controls (P < .05). Samples collected at all timepoints from patients with COVID-19 had increased proportions of opportunistic fungal pathogens, Candida albicans, Candida auris, and Aspergillus flavus compared with controls. Two respiratory-associated fungal pathogens, A. flavus and Aspergillus niger, were detected in fecal samples from a subset of patients with COVID-19, even after clearance of SARS-CoV-2 from nasopharyngeal samples and resolution of respiratory symptoms. CONCLUSIONS: In a pilot study, we found heterogeneous configurations of the fecal mycobiome, with enrichment of fungal pathogens from the genera Candida and Aspergillus, during hospitalization of 30 patients with COVID-19 compared with controls. Unstable gut mycobiomes and prolonged dysbiosis persisted in a subset of patients with COVID-19 up to 12 days after nasopharyngeal clearance of SARS-CoV-2. Studies are needed to determine whether alterations in intestinal fungi contribute to or result from SARS-CoV-2 infection, and the effects of these changes in disease progression.