Understanding Experience of Patients With Highly Infectious Diseases During Extended Isolation: A Design Perspective.

OBJECTIVES: This study aimed to develop a better understanding of the unique needs of patients with highly infectious diseases and their perceptions of being placed in isolation. We explore the subjective experiences of patients treated for Ebola in a biocontainment unit (BCU) and the healthcare personnel who cared for them. BACKGROUND: The 2014 Ebola outbreak and the COVID-19 pandemic have brought to focus some major challenges of caring for patients with serious infectious diseases. Previous studies on BCU design have looked at ways to prevent self- and cross-contamination, but very few have examined how the built environment can support an improved patient experience. METHOD: A qualitative study was conducted with four patients treated for Ebola and two critical care nurses who provided direct care to them at a single BCU in the U.S. Data were collected through in-depth semi-structured interviews to capture the actual patients' perception and experience of isolation. The interviews were analyzed using the thematic analysis approach. RESULTS: The Ebola patients placed in source isolation perceived the BCU as an artificial environment where they lacked control, agency, autonomy, and independence. The physical separation from other patients, visitor restrictions, and staff wearing PPE contributed to feelings of social and emotional isolation, and loneliness. CONCLUSIONS: The isolation can take a toll on physiological and psychological well-being. A thoughtful design of isolation units may improve patients' experience by supporting human and social interactions, empowering patients through space flexibility and personalization of space, and supporting a more holistic approach to isolation care.

Unrecognized introductions of SARS-CoV-2 into the US state of Georgia shaped the early epidemic.

In early 2020, as diagnostic and surveillance responses for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ramped up, attention focused primarily on returning international travelers. Here, we build on existing studies characterizing early patterns of SARS-CoV-2 spread within the USA by analyzing detailed clinical, molecular, and viral genomic data from the state of Georgia through March 2020. We find evidence for multiple early introductions into Georgia, despite relatively sparse sampling. Most sampled sequences likely stemmed from a single or small number of introductions from Asia three weeks prior to the state's first detected infection. Our analysis of sequences from domestic travelers demonstrates widespread circulation of closely related viruses in multiple US states by the end of March 2020. Our findings indicate that the exclusive focus on identifying SARS-CoV-2 in returning international travelers early in the pandemic may have led to a failure to recognize locally circulating infections for several weeks and point toward a critical need for implementing rapid, broadly targeted surveillance efforts for future pandemics.

Early warning of a COVID-19 surge on a university campus based on wastewater surveillance for SARS-CoV-2 at residence halls.

As COVID-19 continues to spread globally, monitoring the disease at different scales is critical to support public health decision making. Surveillance for SARS-CoV-2 RNA in wastewater can supplement surveillance based on diagnostic testing. In this paper, we report the results of wastewater-based COVID-19 surveillance on Emory University campus that included routine sampling of sewage from a hospital building, an isolation/quarantine building, and 21 student residence halls between July 13th, 2020 and March 14th, 2021. We examined the sensitivity of wastewater surveillance for detecting COVID-19 cases at building level and the relation between Ct values from RT-qPCR results of wastewater samples and the number of COVID-19 patients residing in the building. Our results show that weekly wastewater surveillance using Moore swab samples was not sensitive enough (6 of 63 times) to reliably detect one or two sporadic cases in a residence building. The Ct values of the wastewater samples over time from the same sampling location reflected the temporal trend in the number of COVID-19 patients in the isolation/quarantine building and hospital (Pearson's r < -0.8), but there is too much uncertainty to directly estimate the number of COVID-19 cases using Ct values. After students returned for the spring 2021 semester, SARS-CoV-2 RNA was detected in the wastewater samples from most of the student residence hall monitoring sites one to two weeks before COVID-19 cases surged on campus. This finding suggests that wastewater-based surveillance can be used to provide early warning of COVID-19 outbreaks at institutions.

SER-109, an Oral Microbiome Therapy for Recurrent Clostridioides difficile Infection.

BACKGROUND: Current therapies for recurrent Clostridioides difficile infection do not address the disrupted microbiome, which supports C. difficile spore germination into toxin-producing bacteria. SER-109 is an investigational microbiome therapeutic composed of purified Firmicutes spores for the treatment of recurrent C. difficile infection. METHODS: We conducted a phase 3, double-blind, randomized, placebo-controlled trial in which patients who had had three or more episodes of C. difficile infection (inclusive of the qualifying acute episode) received SER-109 or placebo (four capsules daily for 3 days) after standard-of-care antibiotic treatment. The primary efficacy objective was to show superiority of SER-109 as compared with placebo in reducing the risk of C. difficile infection recurrence up to 8 weeks after treatment. Diagnosis by toxin testing was performed at trial entry, and randomization was stratified according to age and antibiotic agent received. Analyses of safety, microbiome engraftment, and metabolites were also performed. RESULTS: Among the 281 patients screened, 182 were enrolled. The percentage of patients with recurrence of C. difficile infection was 12% in the SER-109 group and 40% in the placebo group (relative risk, 0.32; 95% confidence interval [CI], 0.18 to 0.58; P<0.001 for a relative risk of <1.0; P<0.001 for a relative risk of <0.833). SER-109 led to less frequent recurrence than placebo in analyses stratified according to age stratum (relative risk, 0.24 [95% CI, 0.07 to 0.78] for patients <65 years of age and 0.36 [95% CI, 0.18 to 0.72] for those ≥65 years) and antibiotic received (relative risk, 0.41 [95% CI, 0.22 to 0.79] with vancomycin and 0.09 [95% CI, 0.01 to 0.63] with fidaxomicin). Most adverse events were mild to moderate and were gastrointestinal in nature, with similar numbers in the two groups. SER-109 dose species were detected as early as week 1 and were associated with bile-acid profiles that are known to inhibit C. difficile spore germination. CONCLUSIONS: In patients with symptom resolution of C. difficile infection after treatment with standard-of-care antibiotics, oral administration of SER-109 was superior to placebo in reducing the risk of recurrent infection. The observed safety profile of SER-109 was similar to that of placebo. (Funded by Seres Therapeutics; ECOSPOR III ClinicalTrials.gov number, NCT03183128.).

Sampling for SARS-CoV-2 Aerosols in Hospital Patient Rooms.

Evidence varies as to how far aerosols spread from individuals infected with SARS-CoV-2 in hospital rooms. We investigated the presence of aerosols containing SARS-CoV-2 inside of dedicated COVID-19 patient rooms. Three National Institute for Occupational Safety and Health BC 251 two-stage cyclone samplers were set up in each patient room for a six-hour sampling period. Samplers were place on tripods, which each held two samplers at various heights above the floor. Extracted samples underwent reverse transcription polymerase chain reaction for selected gene regions of the SARS-CoV-2 virus nucleocapsid. Patient medical data were compared between participants in rooms where virus-containing aerosols were detected and those where they were not. Of 576 aerosols samples collected from 19 different rooms across 32 participants, 3% (19) were positive for SARS-CoV-2, the majority from near the head and foot of the bed. Seven of the positive samples were collected inside a single patient room. No significant differences in participant clinical characteristics were found between patients in rooms with positive and negative aerosol samples. SARS-CoV-2 viral aerosols were detected from the patient rooms of nine participants (28%). These findings provide reassurance that personal protective equipment that was recommended for this virus is appropriate given its spread in hospital rooms.

Single-Amplicon Multiplex Real-Time Reverse Transcription-PCR with Tiled Probes To Detect SARS-CoV-2 spike Mutations Associated with Variants of Concern.

To provide an accessible and inexpensive method to surveil for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutations, we developed a multiplex real-time reverse transcription-PCR (rRT-PCR) assay, the Spike single-nucleotide polymorphism (SNP) assay, to detect specific mutations in the spike receptor binding domain. A single primer pair was designed to amplify a 348-bp region of spike, and probes were initially designed to detect K417, E484K, and N501Y. The assay was evaluated using characterized variant sample pools and residual nasopharyngeal samples. Variant calls were confirmed by SARS-CoV-2 genome sequencing in a subset of samples. Subsequently, a fourth probe was designed to detect L452R. The lower limit of 95% detection was 2.46 to 2.48 log10 genome equivalents (GE)/ml for the three initial targets (∼1 to 2 GE/reaction). Among 253 residual nasopharyngeal swabs with detectable SARS-CoV-2 RNA, the Spike SNP assay was positive in 238 (94.1%) samples. All 220 samples with threshold cycle (CT) values of <30 for the SARS-CoV-2 N2 target were detected, whereas 18/33 samples with N2 CT values of ≥30 were detected. Spike SNP results were confirmed by sequencing in 50/50 samples (100%). Addition of the 452R probe did not affect performance for the original targets. The Spike SNP assay accurately identifies SARS-CoV-2 mutations in the receptor binding domain, and it can be quickly modified to detect new mutations that emerge.

Routine Antigen Testing Is Not a Substitute for Health Care Worker Vaccination against SARS-CoV-2.

The utility of rapid antigen testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is measured within the context for which it is applied; diagnostic accuracy must be considered in determining if rapid antigen testing is appropriate for the clinical situation. In this issue of the Journal of Clinical Microbiology, J. N. Kanji, D. T. Proctor, W. Stokes, B. M. Berenger, et al. (J Clin Microbiol 59:e01411-21, 2021, https://doi.org/10.1128/JCM.01411-21) evaluate two rapid antigen tests that demonstrate high false-positive rates in asymptomatic health care workers. The assays may not be useful in situations where there is a shortage of staff, such as health care settings, since isolation would occur unnecessarily for these employees.

Bioaerosol Sampling for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in a Referral Center with Critically Ill Coronavirus Disease 2019 (COVID-19) Patients March-May 2020.

BACKGROUND: Previous research has shown that rooms of patients with coronavirus disease 2019 (COVID-19) present the potential for healthcare-associated transmission through aerosols containing severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). However, data on the presence of these aerosols outside of patient rooms are limited. We investigated whether virus-containing aerosols were present in nursing stations and patient room hallways in a referral center with critically ill COVID-19 patients. METHODS: Eight National Institute for Occupational Safety and Health BC 251 2-stage cyclone samplers were set up throughout 6 units, including nursing stations and visitor corridors in intensive care units and general medical units, for 6 h each sampling period. Samplers were placed on tripods which held 2 samplers positioned 102 cm and 152 cm above the floor. Units were sampled for 3 days. Extracted samples underwent reverse transcription polymerase chain reaction for selected gene regions of the SARS-CoV-2 virus nucleocapsid and the housekeeping gene human RNase P as an internal control. RESULTS: The units sampled varied in the number of laboratory-confirmed COVID-19 patients present on the days of sampling. Some of the units included patient rooms under negative pressure, while most were maintained at a neutral pressure. Of 528 aerosol samples collected, none were positive for SARS-CoV-2 RNA by the estimated limit of detection of 8 viral copies/m3 of air. CONCLUSIONS: Aerosolized SARS-CoV-2 outside of patient rooms was undetectable. While healthcare personnel should avoid unmasked close contact with each other, these findings may provide reassurance for the use of alternatives to tight-fitting respirators in areas outside of patient rooms during the current pandemic.

The Effect of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Mitigation Strategies on Seasonal Respiratory Viruses: A Tale of 2 Large Metropolitan Centers in the United States.

To assess the impact of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic on seasonal respiratory viruses, absolute case counts and viral reproductive rates from 2019-2020 were compared against previous seasons. Our findings suggest that the public health measures implemented to reduce SARS-CoV-2 transmission significantly reduced the transmission of other respiratory viruses.

Retinopathy and Systemic Disease Morbidity in Severe COVID-19.

PURPOSE: To assess the prevalence of retinopathy and its association with systemic morbidity and laboratory indices of coagulation and inflammatory dysfunction in severe COVID-19. DESIGN: Retrospective, observational cohort study. METHODS: Adult patients hospitalized with severe COVID-19 who underwent ophthalmic examination from April to July 2020 were reviewed. Retinopathy was defined as one of the following: 1) Retinal hemorrhage; 2) Cotton wool spots; 3) Retinal vascular occlusion. We analyzed medical comorbidities, sequential organ failure assessment (SOFA) scores, clinical outcomes, and laboratory values for their association with retinopathy. RESULTS: Thirty-seven patients with severe COVID-19 were reviewed, the majority of whom were female (n = 23, 62%), Black (n = 26, 69%), and admitted to the intensive care unit (n = 35, 95%). Fourteen patients had retinopathy (38%) with retinal hemorrhage in 7 (19%), cotton wool spots in 8 (22%), and a branch retinal artery occlusion in 1 (3%) patient. Patients with retinopathy had higher SOFA scores than those without retinopathy (8.0 vs. 5.3, p = .03), higher rates of respiratory failure requiring invasive mechanical ventilation and shock requiring vasopressors (p < .01). Peak D-dimer levels were 28,971 ng/mL in patients with retinopathy compared to 12,575 ng/mL in those without retinopathy (p = .03). Peak CRP was higher in patients with cotton wool spots versus those without cotton wool spots (354 mg/dL vs. 268 mg/dL, p = .03). Multivariate logistic regression modeling showed an increased risk of retinopathy with higher peak D-dimers (aOR 1.32, 95% CI 1.01-1.73, p = .04) and male sex (aOR 9.6, 95% CI 1.2-75.5, p = .04). CONCLUSION: Retinopathy in severe COVID-19 was associated with greater systemic disease morbidity involving multiple organs. Given its association with coagulopathy and inflammation, retinopathy may offer insight into disease pathogenesis in patients with severe COVID-19.

Validation of High-Sensitivity Severe Acute Respiratory Syndrome Coronavirus 2 Testing for Stool-Toward the New Normal for Fecal Microbiota Transplantation.

INTRODUCTION: Mounting evidence demonstrates potential for fecal-oral transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The US Food and Drug Administration now requires SARS-CoV-2 testing of potential feces donors before the use of stool manufactured for fecal microbiota transplantation. We sought to develop and validate a high-sensitivity SARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR) procedure for testing stool specimens. METHODS: A modified extraction method was used with an RT-PCR assay adapted from the Centers for Disease Control and Prevention PCR protocol for respiratory specimens. Contrived specimens were created using pre-COVID-19 banked stool specimens and spiking in known concentrations of SARS-CoV-2-specific nucleic acid. The highest transcript concentration at which 2/2 or 1/2 SARS-CoV-2 targets were detected in 9/10 replicates was defined as the dual-target limit and single-target limit of detection, respectively. The clinical performance of the assay was evaluated with stool samples collected from 17 nasopharyngeal swab RT-PCR-positive patients and 14 nasopharyngeal RT-PCR-negative patients. RESULTS: The dual-target and single-target limit of detection were 56 copies/µL and 3 copies/µL, respectively. SARS-CoV-2 was detected at concentrations as low as 0.6 copies/µL. Clinical stool samples from known COVID-19-positive patients demonstrated the detection of SARS-CoV-2 in stool up to 29 days from symptom onset with a high agreement with nasopharyngeal swab tests (kappa statistic of 0.95, P value < 0.001). DISCUSSION: The described RT-PCR test is a sensitive and flexible approach for the detection of SARS-CoV-2 in stool specimens. We propose an integrated screening approach that incorporates this stool test to support continuation of fecal microbiota transplantation programs.

The interplay of SARS-CoV-2 and Clostridioides difficile infection.

The COVID-19 pandemic has changed the way we practice medicine and lead our lives. In addition to pulmonary symptoms; COVID-19 as a syndrome has multisystemic involvement including frequent gastrointestinal symptoms such as diarrhea. Due to microbiome alterations with COVID-19 and frequent antibiotic exposure, COVID-19 can be complicated by Clostridioides difficile infection. Co-infection with these two can be associated with a high risk of complications. Infection control measures in hospitals is enhanced due to the COVID-19 pandemic which in turn appears to reduce the incidence of hospital-acquired infections such as C. difficile infection. Another implication of COVID-19 and its potential transmissibility by stool is microbiome-based therapies. Potential stool donors should be screened COVID-19 symptoms and be tested for COVID-19.

Metagenomic Sequencing To Detect Respiratory Viruses in Persons under Investigation for COVID-19.

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 (R2, 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.

Novel approach to deployment of crisis situation supply of N95 respirator models in a healthcare system.

Given supply constraints of N95s in the United States during the COVID-19 pandemic, healthcare facilities have turned to extended use protocols and new sources of N95s. Because fit testing every employee for every new mask is not feasible, our Infection Prevention Department developed a method for rapid deployment of new N95s.

Bioaerosol sampling of a ventilated patient with COVID-19.

Bioaerosol samples were collected in an airborne infection isolation room, bathroom, and anteroom of a ventilated patient with coronavirus disease 2019. Twenty-eight samples were negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid, possibly due to the patient being on a closed-circuit ventilator or the efficiency of the air exchanges in the room.