A Tale of Two Tumors: A Collision Tumor of Atypical Fibroxanthoma and Basal Cell Carcinoma.

ABSTRACT: A collision tumor is an infrequent phenomenon characterized by the presence of 2 histologically distinct tumor types (either benign or malignant) occurring within the same specific anatomical site. We describe a rare case of co-occurrence of basal cell carcinoma and atypical fibroxanthoma presenting as a single lesion on the scalp in a 76-year-old man. The lesion was clinically suspicious for basal cell carcinoma and biopsied. Histologic examination showed 2 distinct tumors, one with basaloid cells and the other one with pleomorphic spindle cells colliding and growing together. Immunohistochemical stains were crucial in establishing the diagnosis. This presentation is exceedingly rare and requires additional evaluation for diagnosis.

Intrathecal delivery of adipose-derived mesenchymal stem cells in traumatic spinal cord injury: Phase I trial.

Intrathecal delivery of autologous culture-expanded adipose tissue-derived mesenchymal stem cells (AD-MSC) could be utilized to treat traumatic spinal cord injury (SCI). This Phase I trial (ClinicalTrials.gov: NCT03308565) included 10 patients with American Spinal Injury Association Impairment Scale (AIS) grade A or B at the time of injury. The study's primary outcome was the safety profile, as captured by the nature and frequency of adverse events. Secondary outcomes included changes in sensory and motor scores, imaging, cerebrospinal fluid markers, and somatosensory evoked potentials. The manufacturing and delivery of the regimen were successful for all patients. The most commonly reported adverse events were headache and musculoskeletal pain, observed in 8 patients. No serious AEs were observed. At final follow-up, seven patients demonstrated improvement in AIS grade from the time of injection. In conclusion, the study met the primary endpoint, demonstrating that AD-MSC harvesting and administration were well-tolerated in patients with traumatic SCI.

Hidden risk of gadolinium-based contrast agents during interventional pain medicine procedures: a retrospective chart review.

INTRODUCTION: Epidural steroid injections and epidural blood patches commonly involve the injection of a small amount of radiocontrast media under fluoroscopy to properly identify the target tissue or anatomic space and prevent off-target or intravascular delivery of therapeutic or diagnostic drugs. Iodinated low osmolar non-ionic contrast media is the standard preparation used as it is considered safe and cost-effective, but gadolinium-based preparations have been used as an alternative for patients with an 'iodine'-related or radiocontrast media allergy label to prevent hypersensitivity reactions. The risk of neurotoxic events when gadolinium is inadvertently injected into the intrathecal space has been reported in recent years, raising concerns when gadolinium-based contrast media is used in lieu of iodinated low osmolar non-ionic contrast media. METHODS: A retrospective review was conducted of patients who received gadolinium-based contrast media for procedures with risk of inadvertent intrathecal access from January 1, 2019 to May 1, 2022. Information on patient demographics, allergy label information, and procedure description was documented for all patients who received gadolinium-based contrast media for axial spine procedures (including epidural steroid injections, epidural blood patch procedures, and selective nerve root blocks), and all side effects reported within 1 month of the procedure were recorded. Saved fluoroscopy images of all procedures for which there was concern for possible gadolinium-based contrast media-related side effect were reviewed for evidence of inadvertent intrathecal gadolinium-based contrast media administration. Descriptive statistical analysis was performed using REDCap and IBM SPSS Statistics V.28. RESULTS: We identified 508 patients who received gadolinium-based contrast media during a fluoroscopically guided axial spine procedure. These patients underwent 697 epidural procedures and 23 patients were identified as experiencing an adverse event that could be consistent with possible, probable, or clear signs of exposure to intrathecal gadolinium. Our calculated adverse event rate was 3.3%. Ten patients required additional medical evaluation or treatment. DISCUSSION: Almost all patients in our cohort had an allergy label on their chart that guided the provider to switch to gadolinium-based contrast media, but most were incomplete, ill-defined, or related to allergy to iodine but not iodinated contrast media. Such practice is not recommended based on current guidelines. The current study raises concern regarding the use of gadolinium-based contrast media in axial spine procedures, with the risk of potential severe adverse events, without evidence-based need for avoiding iodinated contrast media.

Persistent chest pain following COVID-19 infection - A scoping review.

Persistent chest pain (PCP) following acute COVID-19 infection is a commonly reported symptom with an unclear etiology, making its management challenging. This scoping review aims to address the knowledge gap surrounding the characteristics of PCP following COVID-19, its causes, and potential treatments. This is a scoping review of 64 studies, including observational (prospective, retrospective, cross-sectional, case series, and case-control) and one quasi-experimental study, from databases including Embase, PubMed/MEDLINE, Cochrane CENTRAL, Google Scholar, Cochrane Database of Systematic Reviews, and Scopus. Studies on patients with PCP following mild, moderate, and severe COVID-19 infection were included. Studies with patients of any age, with chest pain that persisted following acute COVID-19 disease, irrespective of etiology or duration were included. A total of 35 studies reported PCP symptoms following COVID-19 (0.24%-76.6%) at an average follow-up of 3 months or longer, 12 studies at 1-3 months and 17 studies at less than 1-month follow-up or not specified. PCP was common following mild-severe COVID-19 infection, and etiology was mostly not reported. Fourteen studies proposed potential etiologies including endothelial dysfunction, cardiac ischemia, vasospasm, myocarditis, cardiac arrhythmia, pneumonia, pulmonary embolism, postural tachycardia syndrome, or noted cardiac MRI (cMRI) changes. Evaluation methods included common cardiopulmonary tests, as well as less common tests such as flow-mediated dilatation, cMRI, single-photon emission computed tomography myocardial perfusion imaging, and cardiopulmonary exercise testing. Only one study reported a specific treatment (sulodexide). PCP is a prevalent symptom following COVID-19 infection, with various proposed etiologies. Further research is needed to establish a better understanding of the causes and to develop targeted treatments for PCP following COVID-19.

Herpes Zoster Ophthalmicus Discovered During Pain Consult Possibly Complicated With Dural Sinus Thrombosis and Refractory Headache Managed With Ketamine: A Case Report.

Pain is a common symptom associated with shingles and may precede the onset of the characteristic rash. In the context of herpes zoster ophthalmicus, pain can manifest with severe headaches, posing challenges due to other potentially life-threatening conditions such as stroke and intracranial hypertension. In this report, we present the case of a 51-year-old male with severe headache and imaging findings of dural sinus thrombosis. He was later diagnosed with herpes zoster ophthalmicus and required aggressive inpatient management of neuropathic pain. Despite appropriate treatment, acute herpes zoster can progress to post-herpetic neuralgia, requiring long-term pain management.

Early Outcomes of SARS-CoV-2 Infection in a Multisite Prospective Cohort of Inpatient Veterans.

Background: Over 870 000 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have occurred among Veterans Health Administration users, and 24 000 have resulted in death. We examined early outcomes of SARS-CoV-2 infection in hospitalized veterans. Methods: In an ongoing, prospective cohort study, we enrolled veterans age ≥18 tested for SARS-CoV-2 and hospitalized at 15 Department of Veterans Affairs medical centers between February 2021 and June 2022. We estimated adjusted odds ratios (aORs), adjusted incidence rate ratios (aIRRs), and adjusted hazard ratios (aHRs) for maximum illness severity within 30 days of study entry (defined using the 4-category VA Severity Index for coronavirus disease 2019 [COVID-19]), as well as length of hospitalization and rehospitalization within 60 days, in relationship with demographic characteristics, Charlson comorbidity index (CCI), COVID-19 vaccination, and calendar period of enrollment. Results: The 542 participants included 329 (61%) who completed a primary vaccine series (with or without booster; "vaccinated"), 292 (54%) enrolled as SARS-CoV-2-positive, and 503 (93%) men, with a mean age of 64.4 years. High CCI scores (≥5) occurred in 61 (44%) vaccinated and 29 (19%) unvaccinated SARS-CoV-2-positive participants. Severe illness or death occurred in 29 (21%; 6% died) vaccinated and 31 (20%; 2% died) unvaccinated SARS-CoV-2-positive participants. SARS-CoV-2-positive inpatients per unit increase in CCI had greater multivariable-adjusted odds of severe illness (aOR, 1.21; 95% CI, 1.01-1.45), more hospitalization days (aIRR, 1.06; 95% CI, 1.03-1.10), and rehospitalization (aHR, 1.07; 95% CI, 1.01-1.12). Conclusions: In a cohort of hospitalized US veterans with SARS-CoV-2 infection, those with a higher CCI had more severe COVID-19 illness, more hospital days, and rehospitalization, after adjusting for vaccination status, age, sex, and calendar period.

Pain Associated With Monkeypox Virus: A Rapid Review.

International concerns for another pandemic arose after emerging reports of an ongoing outbreak of the monkeypox virus (MPXV) in Europe and the United States in 2022. Severe pain is one of the most distressing complications for patients in the current outbreak, but there is a general paucity of relevant peer-reviewed medical literature from which to draw clear recommendations on appropriate pain therapies. The Centers for Disease Control recently published a letter in July 2022 urging providers to conduct further studies concerning pain management. Thus, a rapid literature search was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive search of several databases from inception until August 19, 2022, was conducted. All published studies describing pain in patients who tested positive for MPXV with original data and written in English were included. Sixty-nine studies were initially identified for screening. After initial screening, 27 papers were considered for full-text review, and 15 papers met the inclusion criteria. A total of 1043 positive cases were included in this study. Most patients were men. Treatment options proposed by the authors include acetaminophen, ibuprofen, opioids, lidocaine gel, metamizole, and rectal suppositories containing emollients or steroids with oral laxatives for severe anal pain. Although most cases were mild requiring outpatient treatment, a considerable number of patients were admitted due to serious complications. Severe pain was often the reason to seek medical attention and hospital admission for pain control. Analgesic plans included oral and topical analgesia. In severe cases, pain was managed with opioids. To our knowledge, this rapid review is the first study to comprehensively summarize proposed treatments for pain associated with MPXV. Guidelines may be needed to help direct the best management to avoid morbidity in patients, particularly as adjuvants may play a key role but are not commonly utilized in published reports.

Evidence-based consensus guidelines on patient selection and trial stimulation for spinal cord stimulation therapy for chronic non-cancer pain.

Spinal cord stimulation (SCS) has demonstrated effectiveness for neuropathic pain. Unfortunately, some patients report inadequate long-term pain relief. Patient selection is emphasized for this therapy; however, the prognostic capabilities and deployment strategies of existing selection techniques, including an SCS trial, have been questioned. After approval by the Board of Directors of the American Society of Regional Anesthesia and Pain Medicine, a steering committee was formed to develop evidence-based guidelines for patient selection and the role of an SCS trial. Representatives of professional organizations with clinical expertize were invited to participate as committee members. A comprehensive literature review was carried out by the steering committee, and the results organized into narrative reports, which were circulated to all the committee members. Individual statements and recommendations within each of seven sections were formulated by the steering committee and circulated to members for voting. We used a modified Delphi method wherein drafts were circulated to each member in a blinded fashion for voting. Comments were incorporated in the subsequent revisions, which were recirculated for voting to achieve consensus. Seven sections with a total of 39 recommendations were approved with 100% consensus from all the members. Sections included definitions and terminology of SCS trial; benefits of SCS trial; screening for psychosocial characteristics; patient perceptions on SCS therapy and the use of trial; other patient predictors of SCS therapy; conduct of SCS trials; and evaluation of SCS trials including minimum criteria for success. Recommendations included that SCS trial should be performed before a definitive SCS implant except in anginal pain (grade B). All patients must be screened with an objective validated instrument for psychosocial factors, and this must include depression (grade B). Despite some limitations, a trial helps patient selection and provides patients with an opportunity to experience the therapy. These recommendations are expected to guide practicing physicians and other stakeholders and should not be mistaken as practice standards. Physicians should continue to make their best judgment based on individual patient considerations and preferences.

Assessment of the Frequency, Phenotypes, and Outcomes of Acute Liver Injury Associated with Amoxicillin/Clavulanate in 1.4 Million Patients in the Veterans Health Administration.

INTRODUCTION: Drug-induced liver injury is a significant health issue, yet the exposure-based incidence remains to be characterized. OBJECTIVE: We aimed to assess the frequency, phenotypes, and outcomes of acute liver injury associated with amoxicillin/clavulanate using a large electronic health record system. METHODS: Using the Veterans Health Administration electronic health record system, we developed the framework to identify unexplained acute liver injury, defined by alanine aminotransferase and/or alkaline phosphatase elevation temporally linked to prescription records of amoxicillin/clavulanate, a major culprit of clinically significant drug-induced liver injury, excluding other competing causes. The population was subcategorized by pre-existing liver conditions and inpatient status at the time of exposure for the analysis. RESULTS: Among 1,445,171 amoxicillin/clavulanate first exposures in unique individuals [92% men; mean age (standard deviation): 59 (15) years], 6476 (incidence: 0.448%) acute liver injuries were identified. Of these, 4427 (65%) had alternative causes, yielding 2249 (incidence: 0.156%) with unexplained acute liver injuries. The incidence of unexplained acute liver injury was lowest in outpatients without underlying liver disease (0.067%) and highest in inpatients with pre-existing liver conditions (0.719%). Older age, male sex, and American Indian or Alaska Native (vs White) were associated with a higher incidence of unexplained acute liver injury. Cholestatic injury affected 74%, exhibiting a higher frequency with advanced age, inpatient exposure, and pre-existing liver conditions. Hepatocellular injury with bilirubin elevation affected 0.003%, with a higher risk at age >45 years. During a 12-month follow-up, patients with unexplained acute liver injury had a higher adjusted overall mortality risk than those without evident acute liver injury. CONCLUSIONS: This framework identifies unexplained acute liver injury following drug exposure in large electronic health record datasets. After validating in other systems, this framework can aid in deducing drug-induced liver injury in the general patient population and regulatory decision making to promote drug safety and public health.

Ultrasound-guided percutaneous peripheral nerve stimulation for chronic refractory neuropathic pain: a unique series.

During the last two decades, with the advent of recent technology, peripheral nerve stimulation has become an appealing modality at the forefront of pain management. In this case series, we document the clinical rationale and technical considerations on three of the most challenging cases, refractory to previous interventions, that were treated by our team with an ultrasound-guided percutaneous peripheral nerve stimulator targeting the musculocutaneous, bilateral greater occipital and subcostal nerves. At the 6-month follow-up, all patients experienced greater than 50% relief of baseline pain, with a near-complete resolution of pain exacerbations. Furthermore, to our knowledge, this is the first report of an ultrasound-guided percutaneous technique of a peripheral nerve stimulator targeting the musculocutaneous and subcostal nerves.

Peripheral nerve stimulation is a new tool used in the treatment of peripheral nerve pain. In this study, we share our experience using this technology in three unusual, difficult-to-treat chronic nerve pain presentations, targeting the musculocutaneous, bilateral greater occipital and subcostal nerves. All patients were asked about how pain levels had changed since the peripheral nerve stimulation device had been implanted. In every case, patients reported a decline in their pain level from day one. After 6 months of peripheral nerve stimulator use, all patients reported a greater than 50% pain relief.

Chemogenetic and Optogenetic Manipulations of Microglia in Chronic Pain.

Chronic pain relief remains an unmet medical need. Current research points to a substantial contribution of glia-neuron interaction in its pathogenesis. Particularly, microglia play a crucial role in the development of chronic pain. To better understand the microglial contribution to chronic pain, specific regional and temporal manipulations of microglia are necessary. Recently, two new approaches have emerged that meet these demands. Chemogenetic tools allow the expression of designer receptors exclusively activated by designer drugs (DREADDs) specifically in microglia. Similarly, optogenetic tools allow for microglial manipulation via the activation of artificially expressed, light-sensitive proteins. Chemo- and optogenetic manipulations of microglia in vivo are powerful in interrogating microglial function in chronic pain. This review summarizes these emerging tools in studying the role of microglia in chronic pain and highlights their potential applications in microglia-related neurological disorders.

Clinical Pattern of Tolvaptan-Associated Liver Injury in Trial Participants With Autosomal Dominant Polycystic Kidney Disease (ADPKD): An Analysis of Pivotal Clinical Trials.

RATIONALE & OBJECTIVE: Tolvaptan is associated with risk of drug-induced liver injury when used to treat autosomal dominant polycystic kidney disease (ADPKD). After this risk was described based on the clinical trials TEMPO 3:4 and TEMPO 4:4, additional data from the REPRISE trial and a long-term extension of TEMPO 4:4, REPRISE, and other tolvaptan trials in ADPKD have become available. To further characterize the hepatic safety profile of tolvaptan, an analysis of the expanded dataset was conducted. STUDY DESIGN: Analysis of safety data from prospective clinical trials of tolvaptan. SETTING & PARTICIPANTS: Multicenter clinical trials including more than 2,900 tolvaptan-treated participants, more than 2,300 with at least 18 months of drug exposure. INTERVENTION: Tolvaptan administered twice daily in split-dose regimens. OUTCOMES: Frequency of liver enzyme level increases detected by regular laboratory monitoring. RESULTS: In the placebo-controlled REPRISE trial, more tolvaptan- than placebo-treated participants (38 of 681 [5.6%] vs 8 of 685 [1.2%]) experienced alanine aminotransferase level increases to >3× the upper limit of normal (ULN), similar to TEMPO 3:4 (40 of 957 [4.4%] vs 5 of 484 [1.0%]). No participant in REPRISE or the long-term extension experienced concurrent alanine aminotransferase level increases to >3× ULN and total bilirubin increases to >2× ULN ("Hy's Law" laboratory criteria). Based on the expanded dataset, liver enzyme increases most often occurred within 18 months after tolvaptan initiation and were less frequent thereafter. Increased levels returned to normal or near normal after treatment interruption or discontinuation. Thirty-eight patients were rechallenged with tolvaptan after the initial drug-induced liver injury episode, with return of liver enzyme level increases in 30; 1 additional participant showed a clinical "adaptation" after the initial episode, with resolution of the enzyme level increases despite continuation of tolvaptan. LIMITATIONS: Retrospective analysis. CONCLUSIONS: The absence of Hy's Law cases in REPRISE and the long-term extension trial support monthly liver enzyme monitoring during the first 18 months of tolvaptan exposure and every 3 months thereafter to detect and manage enzyme level increases, as is recommended on the drug label. FUNDING: Otsuka Pharmaceutical Development & Commercialization, Inc. TRIAL REGISTRATION: Trials included in the dataset were registered at ClinicalTrials.gov with study numbers NCT00428948 (TEMPO 3:4), NCT01214421 (TEMPO 4:4), NCT02160145 (REPRISE), and NCT02251275 (long-term extension).

Spinal microglia contribute to sustained inflammatory pain via amplifying neuronal activity.

Microglia are highly dynamic immune cells of the central nervous system (CNS). Microglial processes interact with neuronal elements constantly on the order of minutes. The functional significance of this acute microglia-neuron interaction and its potential role in the context of pain is still largely unknown. Here, we found that spinal microglia increased their process motility and electrophysiological reactivity within an hour after the insult in a mouse model of formalin-induced acute, sustained, inflammatory pain. Using an ablation strategy to specifically deplete resident microglia in the CNS, we demonstrate that microglia participate in formalin-induced acute sustained pain behaviors by amplifying neuronal activity in the spinal dorsal horn. Moreover, we identified that the P2Y12 receptor, which is specifically expressed in microglia in the CNS, was required for microglial function in formalin-induced pain. Taken together, our study provides a novel insight into the contribution of microglia and the P2Y12 receptor in inflammatory pain that could be used for potential therapeutic strategies.

Rescue therapy with novel waveform spinal cord stimulation for patients with failed back surgery syndrome refractory to conventional stimulation: a systematic review and meta-analysis.

OBJECTIVE: Conventional spinal cord stimulators (SCSs) have demonstrated efficacy in individuals with failed back surgery syndrome (FBSS). However, a subgroup of patients may become refractory to the effects of conventional waveforms over time. The objective of this study was to systematically review and evaluate the current literature on the use of novel waveform spinal cord stimulation for the management of FBSS refractory to conventional SCSs. METHODS: A comprehensive electronic search of the literature published in electronic databases, including Ovid MEDLINE and Epub Ahead of Print, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus, was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The outcomes of interest were reduction in back pain and/or leg pain after conversion from conventional to novel SCSs. Risk of bias was assessed with the Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) tool. The strength of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) criteria. RESULTS: A total of 6 studies with 137 patients with FBSS were identified. Studies were published between 2013 and 2021. The mean ± SD age of the pooled patient sample was 55 ± 10.5 years. All patients who underwent treatment with conventional SCSs were identified. Two studies evaluated the efficacy of high-density spinal cord stimulation, 3 studies evaluated burst spinal cord stimulation, and 1 study assessed multimodal waveforms. The mean difference in back pain scores after conversion from a standard SCS to a novel waveform SCS was 2.55 (95% CI 1.59-4.08), demonstrating a significant reduction in back pain after conversion to novel stimulation. The authors also performed a subgroup analysis to compare burst stimulation to tonic waveforms. In this analysis, the authors found no significant difference in the average reductions in back pain between the 2 groups (p = 0.534).The authors found an I2 statistic equivalent to 98.47% in the meta-regression model used to assess the effect of follow-up duration on study outcome; this value implied that the variability in the data can be attributed to the remaining between-study heterogeneity. The overall certainty was moderate, with a high risk of bias across studies. CONCLUSIONS: Rescue therapy with novel waveform spinal cord stimulation is a potential option for pain reduction in patients who become refractory to conventional SCSs. Conversion to novel waveform SCSs may potentially mitigate expenses and complications.

A case for ultrasound-guided peripheral nerve stimulation in intractable anterior cutaneous nerve entrapment syndrome.

Aim: This case report documents the use of peripheral nerve stimulation in the setting of entrapment of the anterior cutaneous branches of the intercostal nerves, with pain rated by the patient as severe during exacerbation episodes. Materials & methods: Under ultrasound guidance, two permanent leads were implanted caudad to cephalad, along and superficial to the lateral aspect of the rectus abdominis, distal to the umbilicus (1 lead per side). Results: At the 6 month follow-up, the patient reported near complete resolution of baseline pain, as well as fewer, sporadic pain exacerbation episodes, rated as mild-to-moderate. Conclusion: This case report suggests that peripheral nerve stimulation might be a valuable treatment option for previously intractable abdominal pain due to entrapment of the anterior cutaneous branches.

Anterior cutaneous nerve entrapment syndrome is a peculiar, a largely disregarded pain condition. Current management algorithms rely mostly on local injections followed by surgical anterior neurectomy. This case report presents a case of longstanding, anterior cutaneous nerve entrapment syndrome, unresponsive to first-line treatment, that was successfully treated with peripheral nerve stimulation technology targeting the anterior cutaneous branches.

Associations Between Gastrointestinal Symptoms and COVID-19 Severity Outcomes Based on a Propensity Score-Weighted Analysis of a Nationwide Cohort.

Background and Aims: Gastrointestinal (GI) symptoms are well-recognized manifestations of coronavirus disease 2019 (COVID-19). Our primary objective was to evaluate the association between GI symptoms and COVID-19 severity. Methods: In this nationwide cohort of US veterans, we evaluated GI symptoms (nausea/vomiting/diarrhea) reported 30 days before and including the date of positive SARS-CoV-2 testing (March 1, 2020, to February 20, 2021). All patients had ≥1 year of prior baseline data and ≥60 days follow-up relative to the test date. We used propensity score (PS)-weighting to balance covariates in patients with vs without GI symptoms. The primary composite outcome was severe COVID-19, defined as hospital admission, intensive care unit admission, mechanical ventilation, or death within 60 days of positive testing. Results: Of 218,045 SARS-CoV-2 positive patients, 29,257 (13.4%) had GI symptoms. After PS weighting, all covariates were balanced. In the PS-weighted cohort, patients with vs without GI symptoms had severe COVID-19 more often (29.0% vs 17.1%; P < .001). When restricted to hospitalized patients (14.9%; n=32,430), patients with GI symptoms had similar frequencies of intensive care unit admission and mechanical ventilation compared with patients without symptoms. There was a significant age interaction; among hospitalized patients aged ≥70 years, lower COVID-19-associated mortality was observed in patients with vs without GI symptoms, even after accounting for COVID-19-specific medical treatments. Conclusion: In the largest integrated US health care system, SARS-CoV-2-positive patients with GI symptoms experienced severe COVID-19 outcomes more often than those without symptoms. Additional research on COVID-19-associated GI symptoms may inform preventive efforts and interventions to reduce severe COVID-19.