Waning and boosting of functional humoral immunity to SARS-CoV-2

Since the emergence of the SARS-CoV-2 virus, we have witnessed a revolution in vaccine development with the rapid emergence and deployment of both traditional and novel vaccine platforms. The inactivated CoronaVac vaccine and the mRNA-based Pfizer/BNT162b2 vaccine are among the most widely distributed vaccines, both demonstrating high, albeit variable, vaccine effectiveness against severe COVID-19 over time. Beyond the ability of the vaccines to generate neutralizing antibodies, antibodies can attenuate disease via their ability to recruit the cytotoxic and opsinophagocytic functions of the immune response. However, whether Fc-effector functions are induced differentially, wane with different kinetics, and are boostable, remains unknown. Here, using systems serology, we profiled the Fc-effector profiles induced by the CoronaVac and BNT162b2 vaccines, over time. Despite the significantly higher antibody functional responses induced by the BNT162b2 vaccine, CoronaVac responses waned more slowly, albeit still found at levels below those present in the systemic circulation of BNT162b2 immunized individuals. However, mRNA boosting of the CoronaVac vaccine responses resulted in the induction of significantly higher peak antibody functional responses with increased humoral breadth, including to Omicron. Collectively, the data presented here point to striking differences in vaccine platform-induced functional humoral immune responses, that wane with different kinetics, and can be functionally rescued and expanded with boosting.

Preserved Omicron Spike specific antibody binding and Fc-recognition across COVID-19 vaccine platforms

Despite the dramatic spread of Omicron globally, even among highly vaccinated populations, death rates have not increased concomitantly. These data argue that alternative immune mechanisms, beyond neutralization, may continue to confer protection against severe disease. Beyond their ability to bind and block infection, antibodies contribute to control and clearance of multiple infections via their ability to direct antiviral immunity via Fc-effector mechanisms. Thus, here we probed the ability of vaccine induced antibodies, across three COVID-19 vaccines, to drive Fc-effector activity against Omicron. Despite the significant loss of IgM, IgA and IgG binding to the Omicron Receptor Binding Domain (RBD) across BNT162b2, mRNA-1273, and CoronaVac vaccines, stable isotype binding was observed across all of these vaccines to the Omicron Spike. Compromised RBD binding IgG was accompanied by a significant loss of cross RBD-specific antibody Fc{gamma}-receptor binding by the CoronaVac vaccine, but preservation of RBD-specific Fc{gamma}R2a and Fc{gamma}3a binding across the mRNA vaccines. Conversely, Spike-specific antibodies exhibited persistent binding to Fc{gamma}-receptors, across all three vaccines, albeit higher binding was observed with the mRNA vaccines, marked by a selective preservation of Fc{gamma}R2a and Fc{gamma}3a binding antibodies. Thus, despite the significant to near complete loss of Omicron neutralization across several vaccine platforms against Omicron, vaccine induced Spike-specific antibodies continue to recognize the virus and recruit Fc-receptors pointing to a persistent capacity for extra-neutralizing antibodies to contribute Omicron disease attenuation.

Long-lasting neutralizing antibody responses in SARS-CoV-2 seropositive individuals are robustly boosted by immunization with the CoronaVac and BNT162b2 vaccines

The durability of circulating neutralizing antibody (nAb) responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and their boosting by vaccination remains to be defined. We show that outpatient and hospitalized SARS-CoV-2 seropositive individuals mount a robust neutralizing antibody (nAb) response that peaks at days 23 and 27 post-symptom onset, respectively. Although nAb titers remained higher in hospitalized patients, both study groups showed long-lasting nAb responses that can persist for up to 12 months after natural infection. These nAb responses in previously seropositive individuals can be significantly boosted through immunization with two doses of the CoronaVac (Sinovac) or one dose of the BNT162b2 (BioNTech/Pfizer) vaccines, suggesting a substantial induction of B cell memory responses. Noteworthy, three obese previously seropositive individuals failed to mount a booster response upon vaccination, warranting further studies in this population. Immunization of naive individuals with two doses of the CoronaVac vaccine or one dose of the BNT162b2 vaccine elicited similar levels of nAbs compared to seropositive individuals 4.2 to 13.3 months post-infection with SARS-CoV-2. Thus, this preliminary evidence suggests that both, seropositive and naive individuals, require two doses of CoronaVac to ensure the induction of robust nAb titers.

Viral shedding dynamics reveals sputum as a reliable and cost-saving specimen for SARS-CoV-2 diagnosis within the first 10 days since symptom onset: A prospective cohort study

BackgroundCoronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome virus (SARS-CoV-2) is challenging global public health, due to an increasing demand for testing and the shortage of diagnostic supplies. Nasopharyngeal swab (NPS) is considered the optimal sample for SARS-CoV2 diagnosis and sputum (SPT) has been proposed as an economic alternative. However, the temporal concordance of diagnosis in NPS and SPT has not been addressed. MethodsThrough a longitudinal study we compared the shedding dynamics of SARS-CoV-2 RNA evaluated by RT-qPCR in serially collected SPT and NPS obtained from 82 ambulatory and hospitalized patients during acute infection and convalescence. The concordance during the follow-up and cost analysis between both collected specimens was evaluated. FindingsWe analyzed 379 samples, 177 NPS and 202 SPT. The highest proportion of positive samples was detected within the first 15 days after the symptoms onset. The median time of positivity was higher for NPS (median= 25 days) than SPT (median= 21 days). There was no significant difference in the median RT-qPCR CT values between both sample types. The temporal categorization of matched-paired samples indicated substantial correlation (r=0{middle dot}6023) and substantial agreement (87{middle dot}23%) during the first ten days since symptoms onset (kappa = 0{middle dot}697). A cost analysis demonstrated a significant saving when the SPT specimen was used. InterpretationSputum is a feasible and cost-saving alternative to NPS, providing an equivalent value for the detection and follow-up of SARS-CoV-2 RNA. FundingAgencia Nacional de Investigacion y Desarrollo (ANID) of Chile, NIH-NIAID USA.

Evaluación de la carga laboral en residentes Chilenos de especialidades y subespecialidades médicas / Workload assessment in Chilean residents of specialties and medical subspecialties

Introducción: La sobrecarga laboral horaria es un importante problema en los programas de especialización médica. Se asocia a mayor prevalencia de depresión, burnout, deserción, e impacta en la calidad de vida de los residentes. Nuestro objetivo fue cuantificar las horas semanales de carga laboral horaria en residentes de especialidad y subespecialidad de la Pontificia Universidad Católica de Chile (PUC). Métodos: Se realizó una encuesta electrónica a los residentes de especialidad y subespecialidad de la Pontificia Universidad Católica de Chile (2013). Esta incluyó autorreporte de horas semanales trabajadas (jornada habitual, turnos presenciales y turnos de llamada). Para el análisis se consideraron solo las horas presenciales (jornada habitual y turnos presenciales Resultados: se obtuvieron 415 respuestas (tasa de respuesta 86%). Los residentes de especialidad reportaron una jornada de 52,8 ± 20,3 horas semanales más un promedio de 22,6 ± 22,5 horas de turnos presenciales semanales. Los residentes de programas de subespecialidad reportaron una jornada de 55,9 ± 22,2 horas semanales más un promedio de 23 ± 3,9 horas de turnos presenciales semanales. De los 53 programas evaluados, el 22,6 por ciento sobrepasó el límite recomendado por la Dirección de Postgrado PUC (80 horas semanales). Cinco programas reportaron 90-100 horas semanales (todas especialidades o subespecialidades quirúrgicas) y 7 programas reportaron 80-90 horas semanales (3 subespecialidades médicas, 1 subespecialidad quirúrgica, 2 especialidades médicas y 1 especialidad quirúrgica). Conclusión: los residentes de especialidades y subespecialidades médicas en la Pontificia Universidad Católica de Chile están sometidos a una carga horaria significativa. Los programas quirúrgicos presentaron la mayor sobrecarga horaria presencial, con un promedio mayor al recomendado a nivel internacional. (AU)

Introduction: Residents work hours' overload constitutes an important problem in medical postgraduate residency programs. It has been associated to an increased prevalence of depression, burnout, attrition and affects quality of life of residents. The aim of our study was to quantify the duty hours in residents of specialty and subspecialty at the Pontificia Universidad Católica de Chile (PUC). Methods: An electronic survey was performed to residents of specialty and subspecialty at PUC (2013). It included an auto report of the duty hours worked in a week (regular working day, night shifts and on call shifts). We only included for analysis the face hours (regular working day and night shifts). Results: 415 surveys were answered (response rate 86percent). Specialty residents reported 52.8 ± 20.3 regular working hours per week plus an average of 22.6 ± 22.5 hours of night shifts. Subspecialty residents reported 55.9 ± 22.2 regular working hours per week plus an average of 23 ± 3.9 hours of night shifts. From the 53 evaluated programs, 22.6 percent exceeded the limit recommended in the PUC Postgraduate Office (80 hours per week). Five programs reported 90-100 hours per week (all were surgical specialties and subspecialties) and 7 programs reported 80-90 hours per week (3 medical subspecialties, 1 surgical subspecialty, 2 medical specialties and 1 surgical specialty). Conclusion: The residents of specialty and subspecialty from medical postgraduate programs at PUC are subject to a significant workload. The surgical programs present the highest time workload, with a greater average than the internationally recommended.(AU)