Background Coccidioidomycosis (CM) is a common cause of community acquired pneumonia (CAP) where CM is endemic. Manifestations include self-limited pulmonary infection, chronic fibrocavitary pulmonary disease, and disseminated coccidioidomycosis (DCM). Most infections are identified by serological assays including enzyme-linked immunoassay (EIA), complement fixation (CF) and immunodiffusion (IMDF). These are time-consuming and take days to result, impeding early diagnosis. A new lateral flow assay (LFA, Sōna, IMMY, Norman OK) improves time-to-result to one hour. Methods We prospectively enrolled 392 suspected CM patients, compared the LFA to standard EIA and included procalcitonin evaluation. Results Compared to standard EIA, LFA demonstrates 31% sensitivity (95% CI of 20%-44%) and 92% specificity (95% CI of 88%-95%). Acute pulmonary disease (74%) was the most common clinical syndrome. Hospitalized patients constituted 75% of subjects, and compared to outpatients, they more frequently had ≥ 3 previous healthcare facility visits (p = 0.05), received antibacterials (p & 0.01) and had > 3 antibacterial courses (p & 0.01). Procalcitonin (PCT) was &0.25 ng/ml in 52 (83%) EIA+ patients, suggesting infection was not bacterial. Conclusions When CM is a possible diagnosis, LFA identified nearly a third of EIA+ infections. Combined with PCT &0.25 ng/ml, LFA could reduce unnecessary antibacterial use by 77%.

ImportanceData on the epidemiology of mild to moderately severe COVID-19 are needed to inform public health guidance.ObjectiveTo evaluate associations between 2 or 3 doses of mRNA COVID-19 vaccine and attenuation of symptoms and viral RNA load across SARS-CoV-2 viral lineages.Design, Setting, and ParticipantsA prospective cohort study of essential and frontline workers in Arizona, Florida, Minnesota, Oregon, Texas, and Utah with COVID-19 infection confirmed by reverse transcriptase–polymerase chain reaction testing and lineage classified by whole genome sequencing of specimens self-collected weekly and at COVID-19 illness symptom onset. This analysis was conducted among 1199 participants with SARS-CoV-2 from December 14, 2020, to April 19, 2022, with follow-up until May 9, 2022, reported.ExposuresSARS-CoV-2 lineage (origin strain, Delta variant, Omicron variant) and COVID-19 vaccination status.Main Outcomes and MeasuresClinical outcomes included presence of symptoms, specific symptoms (including fever or chills), illness duration, and medical care seeking. Virologic outcomes included viral load by quantitative reverse transcriptase–polymerase chain reaction testing along with viral viability.ResultsAmong 1199 participants with COVID-19 infection (714 [59.5%] women; median age, 41 years), 14.0% were infected with the origin strain, 24.0% with the Delta variant, and 62.0% with the Omicron variant. Participants vaccinated with the second vaccine dose 14 to 149 days before Delta infection were significantly less likely to be symptomatic compared with unvaccinated participants (21/27 [77.8%] vs 74/77 [96.1%]; OR, 0.13 [95% CI, 0-0.6]) and, when symptomatic, those vaccinated with the third dose 7 to 149 days before infection were significantly less likely to report fever or chills (5/13 [38.5%] vs 62/73 [84.9%]; OR, 0.07 [95% CI, 0.0-0.3]) and reported significantly fewer days of symptoms (10.2 vs 16.4; difference, −6.1 [95% CI, −11.8 to −0.4] days). Among those with Omicron infection, the risk of symptomatic infection did not differ significantly for the 2-dose vaccination status vs unvaccinated status and was significantly higher for the 3-dose recipients vs those who were unvaccinated (327/370 [88.4%] vs 85/107 [79.4%]; OR, 2.0 [95% CI, 1.1-3.5]). Among symptomatic Omicron infections, those vaccinated with the third dose 7 to 149 days before infection compared with those who were unvaccinated were significantly less likely to report fever or chills (160/311 [51.5%] vs 64/81 [79.0%]; OR, 0.25 [95% CI, 0.1-0.5]) or seek medical care (45/308 [14.6%] vs 20/81 [24.7%]; OR, 0.45 [95% CI, 0.2-0.9]). Participants with Delta and Omicron infections who received the second dose 14 to 149 days before infection had a significantly lower mean viral load compared with unvaccinated participants (3 vs 4.1 log10 copies/μL; difference, −1.0 [95% CI, −1.7 to −0.2] for Delta and 2.8 vs 3.5 log10 copies/μL, difference, −1.0 [95% CI, −1.7 to −0.3] for Omicron).Conclusions and RelevanceIn a cohort of US essential and frontline workers with SARS-CoV-2 infections, recent vaccination with 2 or 3 mRNA vaccine doses less than 150 days before infection with Delta or Omicron variants, compared with being unvaccinated, was associated with attenuated symptoms, duration of illness, medical care seeking, or viral load for some comparisons, although the precision and statistical significance of specific estimates varied.

Background The risk of coccidioidomycosis (CM) as a life-threatening respiratory illness or disseminated CM (DCM) increases as much as 150-fold in immunosuppressed patients. The safety of biologic response modifiers (BRMs) as treatment for patients with autoimmune disease (AI) in CM-endemic regions is not well defined. We sought to determine that risk in the Tucson and Phoenix areas. Methods We conducted a retrospective study reviewing demographics, Arizona residency length, clinical presentations, specific AI diagnoses, CM test results, and BRM treatments in electronic medical records (EMR) of patients >18 years old with International Classification of Diseases (ICD-10) codes for CM and AI from 10/01/2017 to 12/31/2019. Results We reviewed 944 charts with overlapping ICD-10 codes for CM and AI, of which 138 were confirmed to have both diagnoses. Male gender was associated with more CM (p=0.003), and African ancestry was three times more likely than European to develop DCM (p<0.001). Comparing CM+/AI+ (138) with CM+/AI- (449) patients, there were no significant differences in CM clinical presentations. Patients receiving BRMs had 2.4 times more DCM compared to Pulmonary CM (PCM). Conclusions AI does not increase the risk of any specific CM clinical presentation, and BRM treatment of most AI patients does not lead to severe CM. However, BRMs significantly increase the risk of DCM, and prospective studies are needed to identify the immunogenetic subset that permits BRM-associated DCM.

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Objective: This analysis assessed the putative causal association between genetically predicted percent body fat and areal bone mineral density (aBMD) and, more specifically, the association between genetically predicted metabolically "favorable adiposity" (MFA) and aBMD at clinically relevant bone sites.Methods: Mendelian randomization was used to assess the relationship of MFA and percent body fat with whole-body, lumbar spine, femoral neck, and forearm aBMD.Sex-stratified and age-stratified exploratory analyses were conducted.Results: In all MR analyses, genetically predicted MFA was inversely associated with aBMD for the whole body (β = À0.053, p = 0.0002), lumbar spine (β = À0.075; p = 0.0001), femoral neck (β = À0.045; p = 0.008), and forearm (β = À0.115; p = 0.001). This negative relationship was strongest in older individuals and did not differ by sex. The relationship between genetically predicted percent body fat and aBMD was nonsignificant across all Mendelian randomization analyses. Several loci that were associated at a genome-wide significance level (p < 5 Â 10 À8 ) in opposite directions with body fat and aBMD measures were also identified.Conclusions: This study did not support the hypothesis that MFA protects against low aBMD. Instead, it showed that MFA may result in lower aBMD. Further research is needed to understand how MFA affects aBMD and other components of bone health such as bone turnover, bone architecture, and osteoporotic fractures.