Researchers from the University of Padua and Imperial College London tested more than 85% of the 3,000 residents of Vo’, Italy, in February/March 2020 for infection with SARS-CoV-2, the virus that causes COVID-19, and tested them again in May and November 2020 for antibodies against the virus, reports MedicalBrief.
According to Hayley Dunning, writing for Imperial College, London, the team found that 98.8% of people infected in February/March showed detectable levels of antibodies in November, and there was no difference between people who had suffered symptoms of COVID-19 and those who had been symptom-free.
Antibody levels were tracked using three ‘assays’ – tests that detect different types of antibodies that respond to different parts of the virus. The results showed that while all antibody types showed some decline between May and November, the rate of decay was different depending on the assay.
The team also found cases of antibody levels increasing in some people, suggesting potential re-infections with the virus, providing a boost to the immune system.
Antibody levels
Lead author Dr Ilaria Dorigatti, from the MRC Centre for Global Infectious Disease Analysis and the Abdul Latif Jameel Institute for Disease and Emergency Analytics (J-IDEA) at Imperial, said: “We found no evidence that antibody levels between symptomatic and asymptomatic infections differ significantly, suggesting that the strength of the immune response does not depend on the symptoms and the severity of the infection.
“However, our study does show that antibody levels vary, sometimes markedly, depending on the test used. This means that caution is needed when comparing estimates of infection levels in a population obtained in different parts of the world with different tests and at different times.”
Professor Enrico Lavezzo, from the University of Padua, said: “The May testing demonstrated that 3.5% of the Vo’ population had been exposed to the virus, even though not all of these subjects were aware of their exposure, given the large fraction of asymptomatic infections. However, at the follow-up, performed roughly nine months after the outbreak, we found that antibodies were less abundant, so we need to continue to monitor antibody persistence for longer time spans.”
The team also investigated the infection status of household members, to estimate how likely an infected member is to pass on the infection within the household. Their modelling suggests a probability of about 1 in 4 that a person infected with SARS-CoV-2 passes the infection to a relative and that most transmission (79%) is caused by 20% of infections.
This finding confirms there are large differences in the number of secondary cases generated by infected people, with the majority of infections generating no further infections and a minority of the infections generating a large number of infections. The large differences in how one infected person may infect others in the population suggests that behavioural factors are key for epidemic control, and physical distancing, as well as limiting the number of contacts and mask wearing, continue to be important to reduce the risk of transmitting the disease, even in highly vaccinated populations.
Control measures
The team’s dataset, which includes the results of the two mass PCR testing campaigns conducted in February and March and the antibody survey conducted in May and then again in November, also allowed them to tease apart the impact of various control measures.
They showed that, in the absence of case isolation and short lockdowns, manual contact tracing alone would not have been enough to suppress the epidemic.
Project lead Professor Andrea Crisanti, from the Department of Life Sciences at Imperial and the Department of Molecular Medicine at the University of Padua, said: “Our study also shows that manual contact tracing – the search for positive individuals on the basis of known and declared contacts – would have had a limited impact on the containment of the epidemic, had it not been accompanied by a mass screening.”
And Dorigatti added: “It is clear the epidemic is not over, neither in Italy nor abroad. Moving forward, I think it is of fundamental importance to continue administering first and second vaccine doses as well as to strengthen surveillance, including contact tracing. Encouraging caution and limiting the risk of acquiring SARS-CoV-2 will continue to be essential.”
Study details
ARS-CoV-2 antibody dynamics and transmission from community-wide serological testing in the Italian municipality of Vo’
Ilaria Dorigatti, Enrico Lavezzo and Andrea Crisanti
Author affiliations: Imperial College London and University of Padova and Italy
Published in Nature Communications 19 July 2021. Volume 12, Article number: 4383 (2021)
Abstract
In February and March 2020, two mass swab testing campaigns were conducted in Vo’, Italy. In May 2020, we tested 86% of the Vo’ population with three immuno-assays detecting antibodies against the spike and nucleocapsid antigens, a neutralisation assay and Polymerase Chain Reaction (PCR). Subjects testing positive to PCR in February/March or a serological assay in May were tested again in November.
Here we report on the results of the analysis of the May and November surveys. We estimate a seroprevalence of 3.5% (95% Credible Interval (CrI): 2.8–4.3%) in May. In November, 98.8% (95% Confidence Interval (CI): 93.7–100.0%) of sera which tested positive in May still reacted against at least one antigen; 18.6% (95% CI: 11.0–28.5%) showed an increase of antibody or neutralisation reactivity from May. Analysis of the serostatus of the members of 1,118 households indicates a 26.0% (95% CrI: 17.2–36.9%) Susceptible-Infectious Transmission Probability. Contact tracing had limited impact on epidemic suppression.
Introduction
In Europe, the successful implementation of non-pharmaceutical interventions (NPIs) in the first wave of SARS-CoV-2 transmission was followed by a resurgence in transmission in the autumn 2020, requiring the implementation of a new tier-based system in several countries and most recently, stay-at-home orders. The development of rapid diagnostic tests and the approval of new, effective vaccines provide hope for the future, though fundamental knowledge gaps must be addressed to fully exploit these new tools. There are still several uncertainties around the routes and settings where transmission occurs.
Within-household transmission has been suggested to play an important role in SARS-CoV-2 transmission based on the reported within-household secondary attack rates, quantifying the proportion of household members of an infected subject also infected by SARS-CoV-2. However, infection occurs in multiple settings, and it is important to discern the likelihood of acquiring the infection within or outside the household. An accurate measure of the extent of within-household transmission is provided by the probability that a household member acquires the infection from an infectious household member, which can be estimated using mathematical modelling.
The great majority of SARS-CoV-2 infections, irrespective of symptom onset, develop antibodies against different viral antigens and mount a significant T-cell mediated response, as documented by recent analyses of the T-cell antigen receptor repertoire. This immune response seems to confer some level of protection against re-infection, as supported by the observation that re-infections are rare amongst individuals previously exposed to SARS-CoV-2, but there are still key questions concerning the duration of immune-mediated protection and its capability to block virus replication upon re-exposure.
Over the past year, while waiting for vaccine development and production, substantial resources have been invested in contact tracing aiming to systematically isolate cases and contacts and thereby interrupt transmission chains. This approach has generated disappointing results in Europe and most of the Western world, as it proved to be unable to achieve SARS-CoV-2 control. A better understanding of the different routes and settings where infection occurs, along with quantitative estimates of the impact of interventions and of the persistence of the immune response in SARS-CoV-2 exposed individuals can be used to improve both vaccination and non-pharmaceutical interventions.
We show here the results of two sequential serological and oro-nasopharyngeal swab surveys conducted in the Italian municipality of Vo’ in May and November 2020 using three different assays quantifying IgG antibodies targeting the spike (S) and nucleocapsid (N) as well as the total (IgM and IgG) antibodies against the N antigen. These surveys follow two previous oro-nasopharyngeal swab surveys conducted in the same population in February and March 2020.
We estimated the population-level seroprevalence, quantified the magnitude of the antibody response and its persistence, investigated their association with severity, health, and demographic indicators and report on the association between infection and co-morbidities as well as medication history. We also used information on the serological status of 2,566 household members to estimate the Susceptible Infectious Transmission Probability (SITP), which is the probability of SARS-CoV-2 transmission occurring between each susceptible-infectious pair of individuals, measured over the whole period of infectiousness of the infectious individual and in the case when the susceptible individual is not infected by a third party during that period, and is an alternative, more nuanced measure of within-household transmission intensity than the within-household secondary attack rate.
We estimated the sensitivity of contact tracing by combining the results of the large-scale PCR surveys conducted in Vo’ with the records of the intensive contact tracing efforts implemented at the start of the pandemic by the local health authorities. In a counterfactual analysis, we explore the impact that contact tracing alone, in the absence of the mass testing campaigns and lockdown implemented in February and March 2020, would have had on the epidemic dynamics.
Results
Investigating serum reactivity to viral antigens
The May survey involved 2,602 participants, most living in Vo’ or in nearby countryside settlements, collectively defined as Vo’ cluster using three distinct immunological assays detecting antibodies against the S and N antigen. In total 88.5% of the participants (2,303 subjects) also took part in at least one of the surveys conducted in February and March 2020. Out of the 2,602 tested participants, 162 (6.2%) showed the presence of virus specific antibodies in at least one of the three assays, and 27.2% of these sera had neutralising antibody titres > 1:40 (1/dil). A total of 2,303 (88.5%) sera did not show the presence of antibodies in any of the three assays (2 had an equivocal DiaSorin result).
A further 137 sera (5.3%) were tested only with one of the three assays, because of lack of material, and all of them gave a negative result (1 gave an equivocal DiaSorin result). Out of the 2,602 tested subjects, 2,443 (93.9%) showed a clear reactivity profile to all three assays (i.e., a negative or positive test result, excluding the equivocal DiaSorin results).
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