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1.
Clin Infect Dis ; 77(2): 186-193, 2023 07 26.
Article in English | MEDLINE | ID: mdl-36996150

ABSTRACT

BACKGROUND: The vast majority of coronavirus disease 2019 (COVID-19) disease occurs in outpatients where treatment is limited to antivirals for high-risk subgroups. Acebilustat, a leukotriene B4 inhibitor, has potential to reduce inflammation and symptom duration. METHODS: In a single-center trial spanning Delta and Omicron variants, outpatients were randomized to 100 mg/d of oral acebilustat or placebo for 28 days. Patients reported daily symptoms via electronic query through day 28 with phone follow-up on day 120 and collected nasal swab samples on days 1-10. The primary outcome was sustained symptom resolution to day 28. Secondary 28-day outcomes included time to first symptom resolution, area under the curve (AUC) for longitudinal daily symptom scores, duration of viral shedding through day 10, and symptoms on day 120. RESULTS: Sixty participants were randomized to each study arm. At enrollment, the median duration was 4 days (interquartile range, 3-5 days), and the median number of symptoms was 9 (7-11). Most patients (90%) were vaccinated, with 73% having neutralizing antibodies. A minority of participants (44%; 35% in the acebilustat arm and 53% in placebo) had sustained symptom resolution at day 28 (hazard ratio, 0.6 [95% confidence interval, .34-1.04]; P = .07 favoring placebo). There was no difference in the mean AUC for symptom scores over 28 days (difference in mean AUC, 9.4 [95% confidence interval, -42.1 to 60.9]; P = .72). Acebilustat did not affect viral shedding or symptoms at day 120. CONCLUSIONS: Sustained symptoms through day 28 were common in this low-risk population. Despite this, leukotriene B4 antagonism with acebilustat did not shorten symptom duration in outpatients with COVID-19. Clinical Trials Registration. NCT04662060.


Subject(s)
COVID-19 , Humans , SARS-CoV-2 , Leukotriene B4 , Outpatients , Double-Blind Method , Treatment Outcome
2.
Clin Infect Dis ; 75(1): e314-e321, 2022 08 24.
Article in English | MEDLINE | ID: mdl-35079772

ABSTRACT

BACKGROUND: An immunodiagnostic assay that sensitively detects a cell-mediated immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is needed for epidemiological investigation and for clinical assessment of T- cell-mediated immune response to vaccines, particularly in the context of emerging variants that might escape antibody responses. METHODS: The performance of a whole blood interferon-gamma (IFN-γ) release assay (IGRA) for the detection of SARS-CoV-2 antigen-specific T cells was evaluated in coronavirus disease 2019 (COVID-19) convalescents tested serially up to 10 months post-infection and in healthy blood donors. SARS-CoV-2 IGRA was applied in contacts of households with index cases. Freshly collected blood in the lithium heparin tube was left unstimulated, stimulated with a SARS-CoV-2 peptide pool, and stimulated with mitogen. RESULTS: The overall sensitivity and specificity of IGRA were 84.5% (153/181; 95% confidence interval [CI]: 79.0-89.0) and 86.6% (123/142; 95% CI: 80.0-91.2), respectively. The sensitivity declined from 100% (16/16; 95% CI: 80.6-100) at 0.5-month post-infection to 79.5% (31/39; 95% CI: 64.4-89.2) at 10 months post-infection (P < .01). The IFN-γ response remained relatively robust at 10 months post-infection (3.8 vs 1.3 IU/mL, respectively). In 14 households, IGRA showed a positivity rate of 100% (12/12) and 65.2% (15/23), and IgG of 50.0% (6/12) and 43.5% (10/23) in index cases and contacts, respectively, exhibiting a difference of + 50% (95% CI: +25.4 to +74.6) and +21.7% (95% CI: +9.23 to +42.3), respectively. Either IGRA or IgG was positive in 100% (12/12) of index cases and 73.9% (17/23) of contacts. CONCLUSIONS: The SARS-CoV-2 IGRA is a useful clinical diagnostic tool for assessing cell-mediated immune response to SARS-CoV-2.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , COVID-19/diagnosis , Humans , Immunoglobulin G , Interferon-gamma Release Tests , Sensitivity and Specificity
3.
Clin Infect Dis ; 73(9): e3130-e3132, 2021 11 02.
Article in English | MEDLINE | ID: mdl-33035306

ABSTRACT

We investigated feasibility and accuracy of an interferon-γ release assay (IGRA) for detection of T-cell responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Whole blood IGRA accurately distinguished between convalescent and uninfected healthy blood donors with a predominantly CD4+ T-cell response. SARS-CoV-2 IGRA may serve as a useful diagnostic tool in managing the coronavirus disease 2019 pandemic.


Subject(s)
COVID-19 , Interferon-gamma Release Tests , Antibodies, Viral , Humans , SARS-CoV-2 , T-Lymphocytes
4.
Clin Case Rep ; 12(8): e9186, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39130813

ABSTRACT

Long COVID, often following SARS-CoV-2 infection, may stem from sustained inflammation, overlapping with autoimmune diseases like sarcoidosis. Though specific treatments lack, this link could shape future diagnostic and therapeutic methods.

5.
Antimicrob Agents Chemother ; 57(7): 2923-8, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23571552

ABSTRACT

Nineteen linezolid-resistant Staphylococcus epidermidis and two Staphylococcus aureus isolates recovered from two medical institutions in northeast Ohio and an S. aureus cfr index strain previously collected in the same facilities during the 2007 SENTRY Antimicrobial Surveillance Program were investigated for the genetic basis of oxazolidinone resistance and the location of cfr. S. aureus isolates were typed by pulsed-field gel electrophoresis (PFGE), spa typing, and multilocus sequence typing (MLST). The location of cfr was determined by Southern blotting and hybridization. Plasmid sequencing was performed using the 454 Life Sciences (Roche) GS-FLX DNA platform. The two S. aureus isolates showed unique PFGE patterns but were multilocus sequence type 5 (ST5) and spa type t002, whereas the S. aureus index strain was ST239 and t037. Southern blot and hybridization experiments showed that cfr was plasmid located and that the S. epidermidis isolates, one of the S. aureus isolates, and the S. aureus index strain shared an identical cfr-carrying plasmid (39.3 kb). Sequencing results confirmed these findings. A 10-kb fragment containing cfr showed the highest identity (99.9%) to a 9.5-kb fragment of plasmid pSCFS3 from a bovine Staphylococcus lentus isolate from Germany. In addition, these 39.3-kb plasmids from human S. epidermidis and S. aureus exhibited BglII restriction profiles very similar to that observed for plasmid pSCFS3. The cfr-carrying plasmid detected in the remaining S. aureus isolate (7.9 kb) was distinct and showed the highest identity to the chromosomal cfr integrate found in the chromosomal DNA of a Proteus vulgaris isolate from a pig in China.


Subject(s)
Acetamides/pharmacology , Bacterial Proteins/genetics , Drug Resistance, Multiple, Bacterial , Oxazolidinones/pharmacology , Plasmids , Staphylococcal Infections/microbiology , Staphylococcus aureus/drug effects , Staphylococcus epidermidis/drug effects , Animals , Anti-Bacterial Agents/pharmacology , Base Sequence , Cattle , DNA, Bacterial/genetics , Humans , Linezolid , Microbial Sensitivity Tests , Molecular Sequence Data , Multilocus Sequence Typing , Ohio , Sequence Analysis, DNA , Staphylococcal Infections/drug therapy , Staphylococcal Infections/veterinary , Staphylococcus aureus/genetics , Staphylococcus aureus/isolation & purification , Staphylococcus epidermidis/genetics , Staphylococcus epidermidis/isolation & purification
6.
Cureus ; 15(12): e51286, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38288178

ABSTRACT

Post-acute sequelae of SARS-CoV-2 (PASC), or long COVID, is characterized by persistent symptoms after acute SARS-CoV-2 infection that can vary from patient to patient. Here, we present a case series of four patients with a history of SARS-CoV-2 infection referred to the Post-Acute COVID-19 Syndrome (PACS) Clinic at Stanford University for evaluation of persistent symptoms, who also experienced new-onset alcohol sensitivity. Alcohol reactions and sensitivity are not well characterized in the literature as it relates to post-viral illness. While there have been some anecdotal reports of new alcohol sensitivity in PASC patients in the media, there is a paucity of published data in the medical literature about this topic. During their medical consultation, the patients self-reported new changes in their symptoms or behaviors following the use of alcohol. A new onset of alcohol sensitivities should be assessed along with other post-COVID-19 symptoms and may provide novel avenues to explore the pathobiology of illness and potential interventions.

7.
Med ; 3(6): 371-387.e9, 2022 06 10.
Article in English | MEDLINE | ID: mdl-35434682

ABSTRACT

Background: COVID-19 manifests with respiratory, systemic, and gastrointestinal (GI) symptoms.1, SARS-CoV-2 RNA is detected in respiratory and fecal samples, and recent reports demonstrate viral replication in both the lung and intestinal tissue.2, 3, 4 Although much is known about early fecal RNA shedding, little is known about long-term shedding, especially in those with mild COVID-19. Furthermore, most reports of fecal RNA shedding do not correlate these findings with GI symptoms.5. Methods: We analyzed the dynamics of fecal RNA shedding up to 10 months after COVID-19 diagnosis in 113 individuals with mild to moderate disease. We also correlated shedding with disease symptoms. Findings: Fecal SARS-CoV-2 RNA is detected in 49.2% [95% confidence interval, 38.2%-60.3%] of participants within the first week after diagnosis. Whereas there was no ongoing oropharyngeal SARS-CoV-2 RNA shedding in subjects at 4 months, 12.7% [8.5%-18.4%] of participants continued to shed SARS-CoV-2 RNA in the feces at 4 months after diagnosis and 3.8% [2.0%-7.3%] shed at 7 months. Finally, we found that GI symptoms (abdominal pain, nausea, vomiting) are associated with fecal shedding of SARS-CoV-2 RNA. Conclusions: The extended presence of viral RNA in feces, but not in respiratory samples, along with the association of fecal viral RNA shedding with GI symptoms suggest that SARS-CoV-2 infects the GI tract and that this infection can be prolonged in a subset of individuals with COVID-19. Funding: This research was supported by a Stanford ChemH-IMA grant; fellowships from the AACR and NSF; and NIH R01-AI148623, R01-AI143757, and UL1TR003142.


Subject(s)
COVID-19 , Communicable Diseases , Gastrointestinal Diseases , COVID-19/diagnosis , COVID-19 Testing , Feces , Gastrointestinal Diseases/diagnosis , Humans , Lung , RNA, Viral/genetics , SARS-CoV-2/genetics
8.
Mayo Clin Proc ; 96(11): 2861-2878, 2021 11.
Article in English | MEDLINE | ID: mdl-34454716

ABSTRACT

Despite myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) affecting millions of people worldwide, many clinicians lack the knowledge to appropriately diagnose or manage ME/CFS. Unfortunately, clinical guidance has been scarce, obsolete, or potentially harmful. Consequently, up to 91% of patients in the United States remain undiagnosed, and those diagnosed often receive inappropriate treatment. These problems are of increasing importance because after acute COVID-19, a significant percentage of people remain ill for many months with an illness similar to ME/CFS. In 2015, the US National Academy of Medicine published new evidence-based clinical diagnostic criteria that have been adopted by the US Centers for Disease Control and Prevention. Furthermore, the United States and other governments as well as major health care organizations have recently withdrawn graded exercise and cognitive-behavioral therapy as the treatment of choice for patients with ME/CFS. Recently, 21 clinicians specializing in ME/CFS convened to discuss best clinical practices for adults affected by ME/CFS. This article summarizes their top recommendations for generalist and specialist health care providers based on recent scientific progress and decades of clinical experience. There are many steps that clinicians can take to improve the health, function, and quality of life of those with ME/CFS, including those in whom ME/CFS develops after COVID-19. Patients with a lingering illness that follows acute COVID-19 who do not fully meet criteria for ME/CFS may also benefit from these approaches.


Subject(s)
Family Practice/standards , Fatigue Syndrome, Chronic/therapy , Physician-Patient Relations , Adult , Attitude of Health Personnel , COVID-19/epidemiology , Fatigue Syndrome, Chronic/diagnosis , Humans , Practice Patterns, Physicians'
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