Cross-reactive CD4 + T cells that recognize SARS-CoV-2 are more commonly detected in the peripheral blood of unexposed individuals compared to SARS-CoV-2-reactive CD8 + T cells. However, large numbers of memory CD8 + T cells reside in tissues, feasibly harboring localized SARS-CoV-2-specific immune responses. To test this idea, we performed a comprehensive functional and phenotypic analysis of virusspecific T cells in tonsils, a major lymphoid tissue site in the upper respiratory tract, and matched peripheral blood samples obtained from children and adults before the emergence of COVID-19. We found that SARS-CoV-2-specific memory CD4 + T cells could be found at similar frequencies in the tonsils and peripheral blood in unexposed individuals, whereas functional SARS-CoV-2-specific memory CD8 + T cells were almost only detectable in the tonsils. Tonsillar SARS-CoV-2-specific memory CD8 + T cells displayed a follicular homing and tissue-resident memory phenotype, similar to tonsillar Epstein-Barr virus-specific memory CD8 + T cells, but were functionally less potent than other virus-specific memory CD8 + T cell responses. The presence of pre-existing tissue-resident memory CD8 + T cells in unexposed individuals could potentially enable rapid sentinel immune responses against SARS-CoV-2.
BackgroundAcute appendicitis is one of the most common acute abdominal conditions. Among other parameters, the decision to perform surgical exploration in suspected appendicitis involves diagnostic accuracy, patient age and co-morbidity, patient’s own wishes, the surgeon’s core medical values, expected natural course of non-operative treatment and priority considerations regarding the use of limited resources. Do objective clinical findings, such as radiology and laboratory results, have greater impact on decision-making than “soft” clinical variables? In this study we investigate the parameters that surgeons consider significant in decision-making in cases of suspected appendicitis; specifically we describe the process leading to surgical intervention in real settings.The purpose of the study was to explore the process behind the decision to undertake surgery on a patient with suspected appendicitis as a model for decision-making in surgery.MethodsAll appendectomy procedures (n = 201) at the Department of Surgery at Karolinska University Hospital performed in 2009 were retrospectively evaluated. Every two consecutive patients seeking for abdominal pain after each case undergoing surgery were included as controls. Signs and symptoms documented in the medical records were registered according to a standardized protocol. The outcome of this retrospective review formed the basis of a prospective registration of patients undergoing appendectomy. During a three- month period in 2011, the surgeons who made the decision to perform acute appendectomy on 117 consecutive appendectomized patients at the Karolinska University Hospital, Huddinge, and Södersjukhuset, were asked to answer a questionnaire about symptoms, signs and diagnostic measures considered in their treatment decision. They were also asked which three symptoms, signs and diagnostic measures had the greatest impact on their decision to perform appendectomy.ResultsIn the retrospective review, tenderness in the right fossa had the greatest impact (OR 76) on treatment decision. In the prospective registration, the most frequent symptom present at treatment decision was pain in the right fossa (94 %). Tenderness in the right fossa (69 %) was also most important for the decision to perform surgery. Apart from local status, image diagnostics and blood sample results had the greatest impact.ConclusionLocal tenderness in the right fossa, lab results and the results of radiological investigations had the greatest impact on treatment decision.
ClinicalTrials.gov Identifier: NCT02315911.
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