Antibody avidity maturation favors SARS-CoV-2 convalescents over vaccinated individuals granting breadth in neutralizability and tolerance against variants

BackgroundThe durability and cross-neutralizability of protective antibodies against evolving SARS-CoV-2 variants are primary concerns in mitigating (re-)exposures. The role of antibody maturation, the process whereby selection of higher avidity antibodies augments host immunity, to determine SARS-CoV-2 neutralizability was investigated. MethodsSera collected from SARS-CoV-2 convalescent individuals at 2- or 10-months after recovery, and BNT162b2 vaccine recipients at 3 or 25 weeks post-vaccination, were analyzed. Anti-spike IgG avidity was measured on a urea-treated ELISA platform. Neutralizing ability of antibodies was assessed by surrogate virus neutralization. Fold change between variant and wild-type antigen neutralizability was calculated to infer breadth of neutralizability. ResultsCompared with early-convalescence, the avidity index of late-convalescent sera was significantly higher (median 37.7 (interquartile range 28.4-45.1) vs. 64.9 (57.5-71.5), p < 0.0001), indicative of progressive antibody maturation extending months beyond acute-phase illness. The urea-resistant, high-avidity fraction of IgG was best predictive of neutralizability (Spearmans r = 0.49 vs. 0.67 for wild-type; 0.18-0.52 vs. 0.48-0.83 for variants). Higher-avidity convalescent sera showed greater cross-neutralizability against SARS-CoV-2 variants (p < 0.001 for Alpha; p < 0.01 for Delta and Omicron). Vaccinees experienced delayed maturation kinetics, translating to limited breadth of neutralizability at week-25 post-vaccination which was only comparable to that of early-convalescence. ConclusionsAvidity maturation grants broader neutralizability that is resilient against emerging SARS-CoV-2 variants. With immunopotentiation through repeat vaccinations becoming a pivotal strategy to accomplish herd immunity, understanding the variable longitudinal evolutions of the two building blocks of hybrid immunity is crucial.

Serological testing reveals the hidden COVID-19 burden among healthcare workers experiencing a SARS-CoV-2 nosocomial outbreak.

We describe the results of testing healthcare workers from a tertiary care hospital in Japan, which had experienced a COVID-19 outbreak during the first peak of the pandemic, for SARS-CoV-2 specific antibody seroconversion. Using two chemiluminescent immunoassays and a confirmatory surrogate virus neutralization test, serological testing unveiled that a surprising 42.2% (27/64) of overlooked COVID-19 diagnoses had occurred when case detection had relied solely on SARS-CoV-2 nucleic acid amplification testing. This undetected portion of the COVID-19 iceberg beneath the surface may potentially have led to silent transmissions and triggered the spread. A questionnaire-based risk assessment was further indicative of exposures to specific aerosol-generating procedures, i.e. non-invasive ventilation, having had conveyed the highest transmission risks and served as the origin of outbreak. Our observations are supportive of a multi-tiered testing approach, including the use of serological diagnostics, in order to accomplish exhaustive case detection along the whole COVID-19 spectrum.

Spontaneous Low Cerebrospinal Fluid Pressure Headache Initially Misdiagnosed as a Tension-type Headache / General Medicine

We report the case of a 34-year-old man who was initially diagnosed with a tension-type headache after complaining of a headache and nausea. His headache worsened in severity and it was exacerbated on standing in the upright position. The patient was admitted to the hospital on suspicion of spontaneous low cerebrospinal fluid (CSF) pressure headache. Gadolinium-enhanced brain magnetic resonance imaging (MRI) revealed diffuse pachymeningeal enhancement, brain sagging, cerebellar tonsillar herniation, brainstem descent and a subdural hematoma. Successful emergency surgery was undertaken.<br>Spontaneous low CSF pressure headache syndrome is characterized by orthostatic headache, and if such a headache worsens, clinicians should consider a subdural hematoma, a life-threatening complication of this unusual disorder.

General Remarks: Effective Strategies for Preventing and Controlling SARS Infection-Prevention from the Point of View of Epidemiology- / 日本農村医学会雑誌

For severe acute respiratory syndrome (SARS), methodologies are yet to be established for prompt diagnostic testing, treatment and prevention by means of vaccination. Such being the situation, it is necessary to implement stringent measures in preventing the transmission of this infectious disease based on a correct understanding of its epidemiological characteristics. The pathways of transmission are by droplet and by contact. Risk factors include social contacts with SARS cases within a radius of 2 meters or household contacts, badly ventilated rooms, touching contaminated objects and surfaces, exposure to body fluids. The major clinical symptoms of the acute respiratory disease include, like influenza, fever, chill, tiredness (malaise), muscle aches, trepidation, nausea and headache. Compared with patients who contract influenza, SARS patients often had dyspnea and diarrhea, but rarely complain of pharyngalgia and pituita. A close correlation has been noted between the stage of SARS and its infectivity, capability. During the incubation period, which lasts 2 to 10 days, the disease is asymptomatic and reportedly almost no infectious. But there is general agreement among experts that SARS becomes highly infectious when it enters the lower airway infection period and begins to produce such symptoms as fever and dry cough, dyspnea.<BR>As the main points of the measures to prevent SARS from spreading, we would like to refer to triage and prevention of cross infection. A triage system should be adopted as the need arises. Under the system, patients suspected to have SARS are separated from other patients and given priority in medical treatment. Standard precautions should not be forgotten. The use of alcohol-based hand rubs and the wearig of surgical masks are effective means to cut off the route of infection. These efforts would make it possible to effectively prevent the infectious diseases like SARS from being spread form person to person and thus protect the public from the pandemic.

General Remarks : Effective Strategies for Preventing and Controlling SARS Infection / 日本農村医学会雑誌

For severe acute respiratory syndrome (SARS), methodologies are yet to be established for prompt diagnostic testing, treatment and prevention by means of vaccination. Such being the situation, it is necessary to implement stringent measures in preventing the transmission of this infectious disease based on a correct understanding of its epidemiological characteristics. The pathways of transmission are by droplet and by contact. Risk factors include social contacts with SARS cases within a radius of 2 meters or household contacts, badly ventilated rooms, touching contaminated objects and surfaces, exposure to body fluids. The major clinical symptoms of the acute respiratory disease include, like influenza, fever, chill, tiredness (malaise), muscle aches, trepidation, nausea and headache. Compared with patients who contract influenza, SARS patients often had dyspnea and diarrhea, but rarely complain of pharyngalgia and pituita. A close correlation has been noted between the stage of SARS and its infectivity, capability. During the incubation period, which lasts 2 to 10 days, the disease is asymptomatic and reportedly almost no infectious. But there is general agreement among experts that SARS becomes highly infectious when it enters the lower airway infection period and begins to produce such symptoms as fever and dry cough, dyspnea.As the main points of the measures to prevent SARS from spreading, we would like to refer to triage and prevention of cross infection. A triage system should be adopted as the need arises. Under the system, patients suspected to have SARS are separated from other patients and given priority in medical treatment. Standard precautions should not be forgotten. The use of alcohol-based hand rubs and the wearig of surgical masks are effective means to cut off the route of infection. These efforts would make it possible to effectively prevent the infectious diseases like SARS from being spread form person to person and thus protect the public from the pandemic.