Clinical and immunological factors that distinguish COVID-19 from pandemic influenza A(H1N1)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is a global health threat with the potential to cause severe disease manifestations in the lungs. Although COVID-19 has been extensively characterized clinically, the factors distinguishing SARS-CoV-2 from other respiratory viruses are unknown. Here, we compared the clinical, histopathological, and immunological characteristics of patients with COVID-19 and pandemic influenza A(H1N1). We observed a higher frequency of respiratory symptoms, increased tissue injury markers, and a histological pattern of alveolar pneumonia in pandemic influenza A(H1N1) patients. Conversely, dry cough, gastrointestinal symptoms and interstitial lung pathology were observed in COVID-19 cases. Pandemic influenza A(H1N1) was characterized by higher levels of IL-1RA, TNF-α, CCL3, G-CSF, APRIL, sTNF-R1, sTNF-R2, sCD30, and sCD163. Meanwhile, COVID-19 displayed an immune profile distinguished by increased Th1 (IL-12, IFN-γ) and Th2 (IL-4, IL-5, IL-10, IL-13) cytokine levels, along with IL-1β, IL-6, CCL11, VEGF, TWEAK, TSLP, MMP-1, and MMP-3. Our data suggest that SARS-CoV-2 induces a dysbalanced polyfunctional inflammatory response that is different from the immune response against pandemic influenza A(H1N1). Furthermore, we demonstrated the diagnostic potential of some clinical and immune factors to differentiate both diseases. These findings might be relevant for the ongoing and future influenza seasons in the Northern Hemisphere, which are historically unique due to their convergence with the COVID-19 pandemic

Mycobacterium tuberculosis infection drives a type I IFN signature in lung lymphocytes

Mycobacterium tuberculosis (Mtb) infects 25% of the world\u27s population and causes tuberculosis (TB), which is a leading cause of death globally. A clear understanding of the dynamics of immune response at the cellular level is crucial to design better strategies to control TB. We use the single-cell RNA sequencing approach on lung lymphocytes derived from healthy and Mtb-infected mice. Our results show the enrichment of the type I IFN signature among the lymphoid cell clusters, as well as heat shock responses in natural killer (NK) cells from Mtb-infected mice lungs. We identify Ly6A as a lymphoid cell activation marker and validate its upregulation in activated lymphoid cells following infection. The cross-analysis of the type I IFN signature in human TB-infected peripheral blood samples further validates our results. These findings contribute toward understanding and characterizing the transcriptional parameters at a single-cell depth in a highly relevant and reproducible mouse model of TB

Memory of Natural Killer Cells: A New Chance against Mycobacterium tuberculosis?

Natural killer (NK) cells are lymphocytes of the innate immune system, which play an important role in the initial defense against a wide variety of pathogens, including viruses and intracellular bacteria. NK cells produce cytokines that enhance immune responses directed toward pathogens and also exert cytotoxic activity against infected cells, thereby eliminating the reservoir of infection. Their role in defense against Mycobacterium tuberculosis (Mtb) has been recently studied, and there is increasing evidence that highlight the importance of NK cell function during pulmonary tuberculosis (PTB), especially in the absence of optimal T-cell responses. Additionally, in the last years, it has been observed that NK cells mediate secondary responses against antigens to which they were previously exposed, an ability classically attributed to lymphocytes of the adaptive branch of immunity. This phenomenon, called “innate memory,” could have important implications in the efforts to develop therapies and vaccines to improve the initial phases of immune reactions against different microorganisms, especially those to which there is not yet available vaccines to prevent infection, as is the case for tuberculosis. Therefore, the possibility of inducing memory-like NK cells ready to act prior to contact with Mtb or during the earliest stages of infection becomes quite interesting. However, our understanding of the mechanisms of innate memory remains incomplete. Here, we review recent literature about the mechanisms involved in the formation and maintenance of NK cell memory and the role of these cells in the immune response during tuberculosis. Finally, we discuss if the current evidence is sufficient to substantiate that NK cells exert more rapid and robust secondary responses after consecutive encounters with Mtb

CD4+ T Cell Regulatory Network Underlies the Decrease in Th1 and the Increase in Anergic and Th17 Subsets in Severe COVID-19

In this model we use a dynamic and multistable Boolean regulatory network to provide a mechanistic explanation of the lymphopenia and dysregulation of CD4+ T cell subsets in COVID-19 and provide therapeutic targets. Using a previous model, the cytokine micro-environments found in mild, moderate, and severe COVID-19 with and without TGF-β and IL-10 was we simulated. It shows that as the severity of the disease increases, the number of antiviral Th1 cells decreases, while the the number of Th1-like regulatory and exhausted cells and the proportion between Th1 and Th1R cells increases. The addition of the regulatory cytokines TFG-β and IL-10 makes the Th1 attractor unstable and favors the Th17 and regulatory subsets. This is associated with the contradictory signals in the micro-environment that activate SOCS proteins that block the signaling pathways. Furthermore, it determined four possible therapeutic targets that increase the Th1 compartment in severe COVID-19: the activation of the IFN-γ pathway, or the inhibition of TGF-β or IL-10 pathways or SOCS1 protein; from these, inhibiting SOCS1 has the lowest number of predicted collateral effects. Finally, a tool is provided that allows simulations of specific cytokine environments and predictions of CD4 T cell subsets and possible interventions, as well as associated secondary effects

Leukocytes from Patients with Drug-Sensitive and Multidrug-Resistant Tuberculosis Exhibit Distinctive Profiles of Chemokine Receptor Expression and Migration Capacity

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains as a leading infectious cause of death worldwide. The increasing number of multidrug-resistant TB (MDR-TB) cases contributes to the poor control of the TB epidemic. Currently, little is known about the immunological requirements of protective responses against MDR-TB. This is of major relevance to identify immune markers for treatment monitoring and targets for adjuvant immunotherapies. Here, we hypothesized that MDR-TB patients display unique immunophenotypical features and immune cell migration dynamics compared to drug-sensitive TB (DS-TB). Hence, we prospectively conducted an extensive characterization of the immune profile of MDR-TB patients at different time points before and after pharmacological therapy. For this purpose, we focused on the leukocyte expression of chemokine receptors, distribution of different monocyte and lymphocyte subsets, plasma levels of chemotactic factors, and in vitro migration capacity of immune cells. Our comparative cohort consisted of DS-TB patients and healthy volunteer donors (HD). Our results demonstrate some unique features of leukocyte migration dynamics during MDR-TB. These include increased and prolonged circulation of CD3+ monocytes, CCR4+ monocytes, EM CD4+ T cells, EM/CM CD8+ T cells, and CXCR1+CXCR3+ T cells that is sustained even after the administration of anti-TB drugs. We also observed shared characteristics of both MDR-TB and DS-TB that include CCR2+ monocyte depletion in the blood; high plasma levels of MPC-1, CCL-7, and IP-10; and increased responsiveness of leukocytes to chemotactic signals in vitro. Our study contributes to a better understanding of the MDR-TB pathobiology and uncovers immunological readouts of treatment efficacy

A modified supraclavicular approach to scalenotomy without first rib resection for the treatment of neurogenic thoracic outlet syndrome

Background: Current approaches to scalenectomy for brachial plexus decompression can cause nerve injuries in patients with neurogenic thoracic outlet syndrome (nTOS), especially when first rib resection (FRR) is performed. We describe a modified supraclavicular approach for scalenotomy that reduces the postoperative morbidity of nTOS patients. Methods: The patient is placed in supine position with the neck slightly extended and turned to the opposite side of the procedure. The modified incision begins above the clavicle 2.5 cm lateral to its first third, extends in medial direction, and turns upwards along the lateral edge of the sternocleidomastoid muscle (SCM) 2.5 cm from the clavicle. Skin flaps are elevated. The external jugular vein is dissected and retracted. The supraclavicular nerves and omohyoid muscle are conserved if found. The phrenic nerve is identified, dissected, and retracted. The anterior scalene muscle is divided, and the brachial plexus is freed. The clinical data and postoperative outcomes of patients that underwent surgery over the last three years were retrieved. The functionality of the arm after surgery was evaluated using the Disabilities of the Arm, Shoulder, and Hand questionnaire in Spanish (DASHe). Results: Sixteen nTOS patients received surgery with one bilateral procedure (17 procedures). Seventy-five percent were females with a median age of 53 years. Obesity and smoking were observed in 43.75% and 37.5% of patients, respectively. No postoperative complications occurred, except for one partial phrenic nerve palsy. All patients reduced their DASHe scores after surgery (mean reduction 41.09 ± 18.37). Conclusion: Our modified supraclavicular approach for scalenotomy is safe and improves outcomes in patients with nTOS, reducing the need for FRR

Management of complex brain lesions arising at sellar, petroclival, and interpeduncular regions via the pretemporal approach: Technical note

Background: Lesions of sellar, interpeduncular, and petroclival regions represent surgical challenges due to the spatial limitations imposed by the temporal lobe. The pretemporal approach is rarely advocated for this kind of lesions even when it offers a wider operative field than other traditional techniques. Case presentation: Here, we share our experience with the use of the pretemporal approach in a small case series: a giant meningioma of the tentorial notch (case 1), an aneurysm of the left posterior cerebral artery (case 2), and a giant pituitary adenoma (case 3). A frontotemporal incision was made with patients in supine position, their heads turned to the opposite side, and the malar eminence as their upper point. The skin flap and the temporal muscle were retracted anteriorly and inferiorly, respectively. The frontotemporosphenoidal craniotomy was performed and the lesser sphenoid wing removed. For cases 2 and 3, an orbitozygomatic craniotomy was added. After an S-shaped dura matter opening, the access to the interpeduncular fossa was through the sylvian fissure by careful dissection of adhesions between frontal and temporal lobes. Conclusions: On experienced hands, the pretemporal approach is a safe procedure for the management of lesions located in deep brain areas with low postoperative morbidity

A retrospective comparison of simultaneous and staged surgery for degenerative cervico-lumbar tandem spinal stenosis

Background: Cervical and lumbar tandem spinal stenosis (CLTSS) is a major cause of morbidity secondary to compressive degeneration of the spine. Currently, there is a paucity of studies objectively addressing the best management for this condition in terms of efficacy and cost-effectiveness. Hence, we aimed to conduct a side-by-side retrospective analysis of surgical outcomes, clinical improvement, and cost of care in non-Caucasian Hispanic patients with moderate-to-severe CLTSS subjected to simultaneous or staged cervical and lumbar spine surgery. Methods: Retrospective review of clinical records and postoperative outcomes of adult patients subjected to cervical and lumbar spine surgery either simultaneously or in stages. The surgical pattern was selected based on clinical studies, physical examination, and radiological findings, with monthly follow-up through objective clinical scores for at least six months after the last surgery. Results: Twelve patients received simultaneous cervical and lumbar spine surgery and six staged operations, both groups with comparable baseline comorbidities, manifestations, radiological findings, and receiving similar surgical procedures and postoperative management. Anterior cervical discectomy and fusion and transforaminal lumbar interbody fusion were the standard procedures performed in the cohort. Three patients in the staged-operation group received cervical decompression first. There were no differences between the groups' surgical outcomes, functional recovery, and complication rates. Nonetheless, the total cost of care was significantly lower in patients receiving simultaneous operation, while the clinical improvement was equivalent in both groups. Conclusions: Simultaneous and staged decompression offer similar outcomes for patients with CLTSS, but the one-staged combined surgery has a better cost- effectiveness profile