RESUMO
Diagnostic assays currently used to monitor the efficacy of COVID-19 vaccines measure levels of antibodies to the receptor-binding domain of ancestral SARS-CoV-2 (RBDwt). However, the predictive value for protection against new variants of concern (VOCs) has not been firmly established. Here, we used bead-based arrays and flow cytometry to measure binding of antibodies to spike proteins and receptor-binding domains (RBDs) from VOCs in 12,000 sera. Effects of sera on RBD-ACE2 interactions were measured as a proxy for neutralizing antibodies. The samples were obtained from healthy individuals or patients on immunosuppressive therapy who had received two to four doses of COVID-19 vaccines and from COVID-19 convalescents. The results show that anti-RBDwt titers correlate with the levels of binding- and neutralizing antibodies against the Alpha, Beta, Gamma, Delta, Epsilon and Omicron variants. The benefit of multiplexed analysis lies in the ability to measure a wide range of anti-RBD titers using a single dilution of serum for each assay. The reactivity patterns also yield an internal reference for neutralizing activity and binding antibody units per milliliter (BAU/ml). Results obtained with sera from vaccinated healthy individuals and patients confirmed and extended results from previous studies on time-dependent waning of antibody levels and effects of immunosuppressive agents. We conclude that anti-RBDwt titers correlate with levels of neutralizing antibodies against VOCs and propose that our method may be implemented to enhance the precision and throughput of immunomonitoring.
Assuntos
COVID-19RESUMO
Diagnostic assays currently used to monitor the efficacy of COVID-19 vaccines measure levels of antibodies to the receptor-binding domain of ancestral SARS-CoV-2 (RBDwt). However, the predictive value for protection against new variants of concern (VOCs) has not been firmly established. Here, we used bead-based arrays and flow cytometry to measure binding of antibodies to spike proteins and receptor-binding domains (RBDs) from VOCs in 12,000 sera. Effects of sera on RBD-ACE2 interactions were measured as a proxy for neutralizing antibodies. The samples were obtained from healthy individuals or patients on immunosuppressive therapy who had received two to four doses of COVID-19 vaccines and from COVID-19 convalescents. The results show that anti-RBDwt titers correlate with the levels of binding- and neutralizing antibodies against the Alpha, Beta, Gamma, Delta, Epsilon and Omicron variants. The benefit of multiplexed analysis lies in the ability to measure a wide range of anti-RBD titers using a single dilution of serum for each assay. The reactivity patterns also yield an internal reference for neutralizing activity and binding antibody units per milliliter (BAU/ml). Results obtained with sera from vaccinated healthy individuals and patients confirmed and extended results from previous studies on time-dependent waning of antibody levels and effects of immunosuppressive agents. We conclude that anti-RBDwt titers correlate with levels of neutralizing antibodies against VOCs and propose that our method may be implemented to enhance the precision and throughput of immunomonitoring.
Assuntos
COVID-19RESUMO
Long-term complications following COVID-19 are common in hospitalised patients, but the spectrum of symptoms in milder cases remains unclear. In a Norwegian prospective cohort study of 312 patients, 61% of COVID-19 patients (247 home-isolated and 65 hospitalised) had persistent symptoms at six months, most commonly fatigue (37%), impaired concentration (26%), disturbed smell and/or taste (25%), memory loss (24%) and dyspnoea (21%). In young home-isolated adults, aged 16–30, 52% had symptoms at six months, with fatigue (21%), dyspnoea (13%), impaired concentration (13%) and memory loss (11%) posing particular challenges. Pre-existing chronic lung disease and high convalescent antibody titres predicted persistent symptoms, particularly fatigue. Our finding that young, home-isolated adults with mild COVID-19 are at risk of long-lasting dyspnoea and cognitive symptoms highlights the importance of infection control measures, such as vaccination.
Assuntos
Transtornos da Memória , Doença Pulmonar Obstrutiva Crônica , Dispneia , COVID-19 , FadigaRESUMO
Background: Household attack rates of SARS-CoV-2 ranging from 7% to 38% have been reported, using reverse transcription polymerase chain reaction (RT-PCR) of respiratory samples. Lower attack rates were described in children, but the importance of age in household transmission dynamics remains to be clarified. Methods: During the first month of the outbreak, we enrolled 112 households (291 participants) in a prospective case-ascertained study, collecting demographic and clinical data from index cases and household members. Sera were collected 6-8 weeks after index case symptom onset, to measure SARS-CoV-2-specific antibodies. Findings: The overall household attack rate was 45% assessed by seroconversion, and 47% when also including RT-PCR positives. Serology identified a significantly higher number of infected household members than RT-PCR. Attack rates were equally high in children (43%) and young adults (46%), but highest among household members aged [≥]60 years (72%). The attack rate was 16% in asymptomatic household members, and 42% in RT-PCR negative household members. Older adults generally had higher antibody titres than younger adults. The risk of household transmission was higher when the index case had fever or dyspnoea during acute illness but not associated with cough. Interpretation: Serological assays provide more accurate estimates of household secondary attack rate than RT-PCR, especially among children who have a lower RT-PCR positivity rate. Children are equally susceptible to infection as adults, but elderly show higher attack rates. Negative RT-PCR or lack of symptoms are not sufficient to rule out infection in household members.