A Case Report: Co-presenting COVID-19 Infection and Acute Drug Intoxication.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has spread throughout the world since late 2019. Symptoms appear after a two-week incubation period and commonly include fever, cough, myalgia or fatigue, and shortness of breath. CASE REPORT: A 32-year-old male with a history of opiate abuse presented to the emergency department with altered mental status. The patient was lethargic and hypoxic with improvement from naloxone. Official chest radiograph was read as normal; however, the treating clinicians noted bilateral interstitial opacities, raising concern for underlying infectious etiology. Opiates and cocaine were positive on drug screen, and an arterial blood gas on room air showed hypoxemia with respiratory acidosis. The patient was intubated during the treatment course due to persistent hypoxemia and for airway protection after resuscitation. The COVID-19 test was positive on admission, and later computed tomography showed ground-glass opacities. The patient was extubated and discharged after one week on the ventilator. CONCLUSION: When screening patients at and during evaluation, physicans should consider a broad differential as patients with atypical presentations may be overlooked as candidates for COVID-19 testing. As screening and evaluation protocols evolve, we emphasize maintaining a high index of suspicion for COVID-19 in patients with atypical symptoms or presenting with other chief complaints in order to avoid spreading the disease.

Evidence for Ig Light Chain Isotype Exclusion in Shark B Lymphocytes Suggests Ordered Mechanisms.

Unlike most vertebrates, the shark IgL gene organization precludes secondary rearrangements that delete self-reactive VJ rearranged genes. Nurse sharks express four L chain isotypes, κ, λ, σ, and σ-2, encoded by 35 functional minigenes or clusters. The sequence of gene activation/expression and receptor editing of these isotypes have not been studied. We therefore investigated the extent of isotypic exclusion in separated B cell subpopulations. Surface Ig (sIg)κ-expressing cells, isolated with mAb LK14 that recognizes Cκ, carry predominantly nonproductive rearrangements of other L chain isotypes. Conversely, after depletion with LK14, sIgM+ cells contained largely nonproductive κ and enrichment for in-frame VJ of the others. Because some isotypic inclusion was observed at the mRNA level, expression in the BCR was examined. Functional λ mRNA was obtained, as expected, from the LK14-depleted population, but was also in sIgκ+ splenocytes. Whereas λ somatic mutants from the depleted sample displayed evidence of positive selection, the λ genes in sIgκ+ cells accumulated bystander mutations indicating a failure to express their products at the cell surface in association with the BCR H chain. In conclusion, a shark B cell expresses one L chain isotype at the surface and other isotypes as nonproductive VJ, sterile transcripts, or in-frame VJ whose products may not associate with the H chain. Based on the mRNA content found in the B cell subpopulations, an order of L chain gene activation is suggested as: σ-2 followed by κ, then σ and λ.

Biased Immunoglobulin Light Chain Gene Usage in the Shark.

This study of a large family of κ L chain clusters in nurse shark completes the characterization of its classical Ig gene content (two H chain isotypes, µ and ω, and four L chain isotypes, κ, λ, σ, and σ-2). The shark κ clusters are minigenes consisting of a simple VL-JL-CL array, where V to J recombination occurs over an ~500-bp interval, and functional clusters are widely separated by at least 100 kb. Six out of ~39 κ clusters are prerearranged in the germline (germline joined). Unlike the complex gene organization and multistep assembly process of Ig in mammals, each shark Ig rearrangement, somatic or in the germline, appears to be an independent event localized to the minigene. This study examined the expression of functional, nonproductive, and sterile transcripts of the κ clusters compared with the other three L chain isotypes. κ cluster usage was investigated in young sharks, and a skewed pattern of split gene expression was observed, one similar in functional and nonproductive rearrangements. These results show that the individual activation of the spatially distant κ clusters is nonrandom. Although both split and germline-joined κ genes are expressed, the latter are prominent in young animals and wane with age. We speculate that, in the shark, the differential activation of the multiple isotypes can be advantageously used in receptor editing.