High secondary attack rate and persistence of SARS-CoV-2 antibodies in household transmission study participants, Finland 2020

Background Household transmission studies offer the opportunity to assess both secondary attack rate and persistence of SARS-CoV-2 antibodies over time. Methods We invited confirmed COVID-19 cases and their household members to attend up to four household visits with collection of nasopharyngeal and serum samples over 28 days after index case onset. We calculated secondary attack rates (SAR) based on the presence of SARS-CoV-2 nucleoprotein IgG antibodies (IgG Ab) and/or neutralizing antibodies (NAb) overall and per households. Three and six months later, we assessed the persistence of SARS-CoV-2 antibodies. Findings We recruited 39 index cases and 90 household members. Among 87 household members evaluated, SAR was 48% (n=42), including 37 symptomatic secondary cases. In total, 80/129 (62%) participants developed both IgG Ab and NAb, while three participants only developed IgG Ab. Among participants who had both IgG Ab and NAb during the initial follow-up, 68/69 (99%) and 63/70 (90%) had IgG Ab and NAb at 3 months, while at 6 months, 59/75 (79%) and 63/75 (84%) had IgG Ab and NAb, respectively. Participants who required hospital care had initially 5-fold IgG Ab concentrations compared to cases with mild symptoms and 8-fold compared to asymptomatic cases. Interpretation Following detection of a COVID-19 case in a household, other members had a high risk of becoming infected. Follow-up of participants showed strong persistence of antibodies in most cases. Funding This study was supported by THL coordinated funding for COVID-19 research (Finnish Government’s supplementary budget) and by the Academy of Finland (Decision number 336431). Evidence before this study Household transmission studies are pivotal to the characterization of transmission dynamics of emerging infectious diseases in a closed setting with homogenous exposure, including proportion of asymptomatic cases using serologic assessment of infection. Additionally, data on long-term persistence of immune response, including neutralizing antibodies following COVID-19 remains scarce. Our search on PubMed for articles published between January 1st 2020, and June 1st, 2021 using the search terms “household” AND “transmission” AND (“COVID-19” OR “SARS-CoV-2”) retrieved 381 results including 35 relevant articles: 21 original household transmission studies, 5 reviews and 9 statistical transmission, modelling or register linkage studies. Depending on the diagnosis method and the duration of follow-up, secondary attack rates (SAR) ranged from 4.6% when household contacts were followed for 14 days and tested only in case of symptoms to close to 90%. None of the household transmission studies involved long-term convalescent follow-up. Added value of this study This extensive (one month) active follow-up, using RT-PCR diagnosis and serological testing for SARS-CoV-2 nucleoprotein IgG antibodies (IgG Ab) and neutralizing antibodies (NAb) showed that household transmission was high, with a 48% (42/87) SAR overall and 50% [IQR: 0-100%] at the level of the household. All but one out of 64 RT-PCR confirmed participants had developed both IgG Ab and NAb after immediate convalescence. Six months after inclusion, majority of previously seropositive (IgG and/or NAb) participants still had IgG Ab (59/75) or NAb (63/75) showing long-term persistence of humoral immunity to SARS-CoV-2. Implications of all the available evidence The risk of transmission of SARS-CoV-2 infections within households is considerable. Isolation of the primary case, especially from household contacts with a high risk of severe disease, e.g. due to age or comorbidities, should be considered even though viral shedding might occur before confirmed diagnosis in household contacts. Long-term persistence of antibodies following infection, even in asymptomatic and mild cases, suggests enduring natural immunity and possibly protection from severe COVID-19. ### Competing Interest Statement THL has received research funding for studies not related to COVID-19 from GlaxoSmithKline Vaccines (NE, CV, AAP and MM as investigators), Pfizer (AAP) and Sanofi Pasteur (AAP). ### Funding Statement This study was supported by THL coordinated funding for COVID-19 research (Finnish Government's supplementary budget) and by the Academy of Finland (Decision number 336431). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: A waiver of ethical approval was received from Professor Mika Salminen (Director of the Department for Health Security of the Finnish Institute for Health and Welfare) and allowed the implementation of the initial household transmission study and 3 months convalescent sample collection The protocol for the follow-up visits at 6 months was reviewed and approved by the HUS ethical committee and registered under the Development of seroprevalence in Finland during the new coronavirus (SARS-CoV-2) epidemic serological population study protocol HUS/1137/2020. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Individual data remains the sole property of the Finnish institute for Health and Welfare and will not be shared. Additional analyses can be requested to the corresponding author.