Coronavirus disease 2019 (COVID-19) exhibits variable symptom severity ranging from asymptomatic to life-threatening, yet the relationship between severity and the humoral immune response is poorly ...understood. We examined antibody responses in 113 COVID-19 patients and found that severe cases resulting in intubation or death exhibited increased inflammatory markers, lymphopenia, pro-inflammatory cytokines, and high anti-receptor binding domain (RBD) antibody levels. Although anti-RBD immunoglobulin G (IgG) levels generally correlated with neutralization titer, quantitation of neutralization potency revealed that high potency was a predictor of survival. In addition to neutralization of wild-type SARS-CoV-2, patient sera were also able to neutralize the recently emerged SARS-CoV-2 mutant D614G, suggesting cross-protection from reinfection by either strain. However, SARS-CoV-2 sera generally lacked cross-neutralization to a highly homologous pre-emergent bat coronavirus, WIV1-CoV, which has not yet crossed the species barrier. These results highlight the importance of neutralizing humoral immunity on disease progression and the need to develop broadly protective interventions to prevent future coronavirus pandemics.
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•Severe COVID-19 associates with higher antibody production and neutralization titers•Neutralization potency of anti-RBD antibodies predicts disease severity and survival•Immunomodulatory COVID-19-directed therapies modulate antibody responses•COVID-19 sera neutralize D614 and G614 variants, but not pre-emergent WIV1-CoV
Garcia-Beltran et al. show that the development of more potent neutralizing antibodies during SARS-CoV-2 infection predicts COVID-19 survival. Protective antibody responses exhibit potent neutralization against the currently circulating SARS-CoV-2 D614G spike variant but lack significant activity against pre-emergent WIV1-CoV spike, suggesting that convalescent patients are likely to remain susceptible to future pandemics.
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by pathogenic autoantibodies against nucleoproteins and DNA. Here we show that DNA-containing immune complexes (ICs) within ...lupus serum (SLE-ICs), but not protein-containing ICs from other autoimmune rheumatic diseases, stimulates plasmacytoid DCs (PDCs) to produce cytokines and chemokines via a cooperative interaction between Toll-like receptor 9 (TLR9) and FcgammaRIIa (CD32). SLE-ICs transiently colocalized to a subcellular compartment containing CD32 and TLR9, and CD32+, but not CD32-, PDCs internalized and responded to SLE-ICs. Our findings demonstrate a novel functional interaction between Fc receptors and TLRs, defining a pathway in which CD32 delivers SLE-ICs to intracellular lysosomes containing TLR9, inducing a signaling cascade leading to PDC activation. These data demonstrate that endogenous DNA-containing autoantibody complexes found in the serum of patients with SLE activate the innate immune system and suggest a novel mechanism whereby these ICs contribute to the pathogenesis of this autoimmune disease.
SARS-CoV-2-specific ELISA development Roy, Vicky; Fischinger, Stephanie; Atyeo, Caroline ...
Journal of immunological methods,
09/2020, Volume:
484-485
Journal Article
Peer reviewed
Open access
Critical to managing the spread of COVID-19 is the ability to diagnose infection and define the acquired immune response across the population. While genomic tests for the novel Several Acute ...Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) detect the presence of viral RNA for a limited time frame, when the virus is shed in the upper respiratory tract, tests able to define exposure and infection beyond this short window of detectable viral replication are urgently needed. Following infection, antibodies are generated within days, providing a durable read-out and archive of exposure and infection. Several antibody tests have emerged to diagnose SARS-CoV-2. Here we report on a qualified quantitative ELISA assay that displays all the necessary characteristics for high-throughput sample analysis. Collectively, this test offers a quantitative opportunity to define both exposure and levels of immunity to SARS-CoV-2.
A 54-year-old woman was evaluated in the emergency department because of abdominal pain, nausea, and vomiting. Computed tomography of the abdomen and pelvis revealed circumferential jejunal-wall ...thickening. Medical history was notable for episodic swelling of the arms, hands, and feet. Diagnostic tests were performed, and treatment decisions were made.
There is considerable variation in ordering practices for the initial laboratory evaluation of monoclonal gammopathies (MGs) despite clear society guidelines to include serum free light chain (sFLC) ...testing. We assessed the ability of a clinical decision support (CDS) alert to improve guideline compliance and analyzed its clinical impact.
We designed and deployed a targeted CDS alert to educate and prompt providers to order an sFLC assay when ordering serum protein electrophoresis (SPEP) testing.
The alert was highly effective at increasing the co-ordering of SPEP and sFLC testing. Preimplementation, 62.8% of all SPEP evaluations included sFLC testing, while nearly 90% of evaluations included an sFLC assay postimplementation. In patients with no prior sFLC testing, analysis of sFLC orders prompted by the alert led to the determination that 28.9% (800/2,769) of these patients had an abnormal κ/λ ratio. In 452 of these patients, the sFLC assay provided the only laboratory evidence of a monoclonal protein. Moreover, within this population, there were numerous instances of new diagnoses of multiple myeloma and other MGs.
The CDS alert increased compliance with society guidelines and improved the diagnostic evaluation of patients with suspected MGs.
An 82-year-old woman was admitted because of difficulty walking, falls, and cognitive decline. Light touch of the right hand, right knee, and both feet caused pain. A diagnosis was made.
Case 17-2022: A 17-Year-Old Boy with Chest Pain Arya, Puneeta; Westra, Sjirk J.; Benavidez, Oscar J. ...
The New England journal of medicine,
06/2022, Volume:
386, Issue:
23
Journal Article
Peer reviewed
A 17-year-old boy was admitted to the pediatric ICU with chest pain, syncope, electrocardiographic abnormalities, and elevated creatine kinase and troponin T. He had been well until 5 days earlier, ...when fever, nausea, diarrhea, muscle aches, and chest pain developed.
A 68-year-old woman was admitted because of confusion and abnormal movements of the face, arms, and legs. MRI of the head showed multiple strokes. A diagnosis was made.
Genetic characterization of myeloma at diagnosis by interphase fluorescence in situ hybridization and next-generation sequencing (NGS) can assist with risk stratification and treatment planning. ...Measurable residual disease (MRD) status after treatment, as evaluated by next-generation flow cytometry or NGS on bone marrow aspirate material, is one of the most important predictors of prognosis. Less-invasive tools for MRD assessment such as liquid biopsy approaches have also recently emerged as potential alternatives.
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