In a recent study posted to the medRxiv* preprint server, researchers compared the transmissibility of novel and emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants.
Currently, the majority of reporting of secondary attack rates (SAR) in coronavirus disease 2019 (COVID-19) have defined secondary infection as recent polymerase chain reaction (PCR) positivity in a contact who is displaying symptoms. By only including those who are symptomatic while having detectable viral ribonucleic acid (RNA) during sampling, this method undercounts the total number of infected individuals.
Serological testing can detect prior infections, whether or not they are symptomatic, and potentially missed transmission events where the contact has already tested PCR-negative. Serological responses should therefore be included in SAR comparisons between environments or virus variations to know the true transmissibility.
About the study
In the present study, researchers determined the frequencies of household secondary attacks using serology to assess the relative transmissibility of the SARS-CoV-2 Alpha variant of concern (VOC) to non-VOC SARS-CoV-2.
Between 9 November 2020 and 31 January 2021, the team conducted a cross-sectional seroprevalence investigation of household contacts (HHC) from individuals who were SARS-CoV-2-positive and whose virus had successfully undergone whole genome sequencing (WGS). This time frame was chosen since there was a simultaneous spread of Alpha and non-VOC SARS-CoV-2 within the community.
Patients with symptomatic index diagnoses from two hospitals in North London were invited to join with all of their HHC. Potential participants were those who sent samples from the Emergency Department, occupational health services, out-of-hours general practitioners (GP) services, and hospitalized patients to either laboratory where PCR identified SARS-CoV-2.
For the first hospital index cases, the team started hiring on 26 March 2021, and for the second hospital, the hiring started on 11 May 2021. The hiring process was finished by 11 July 2021. The questionnaire included information on the index case's age, sex, ethnicity, and COVID-19 disease severity, as well as information on each contact's length of time living with the index patient while they displayed symptoms, the intensity of their contact, any additional SARS-CoV-2 exposures, their vaccination status, and any prior diagnoses of COVID-19 or SARS-CoV-2 detection. Using a multiplex chemiluminescence immunoassay, samples were examined for the presence of immunoglobulin (Ig)-G in the SARS-CoV-2 spike (S) protein and nucleocapsid (N) protein for both non-VOC and SARS-CoV-2 alpha VOC.
The study results showed that 1366 individuals in total, across the two study locations, tested SARS-CoV-2 positive and had viral genotyping information available. Of these, 354 index people agreed to participate, and in the end, 238 index participants, including 188 SARS-CoV-2 alpha-infected and 50 non-VOC-infected patients. Approximately 454 household contacts provided a blood sample and completed the questionnaires provided. Blood samples were obtained from 102 HHC who were exposed to an index infected with a non-VOC and 352 HHC who were exposed to an index infected with SARS-CoV-2 alpha VOC.
Index case Alpha/non-VOC assignment revealed index case characteristics. Almost 76% of index cases reported having respiratory symptoms, with 95% of cases reported being symptomatic, while 67% needed hospitalization for an average of nine days. SARS-CoV-2 alpha infection and non-VOC index cases did not differ statistically. HHC of Alpha index patients reported a longer average duration of exposure to their infected index case than contacts from non-VOC index homes. They also reported receiving a diagnosis of symptomatic COVID-19 when their index case was diagnosed.
SARS-CoV-2 diagnosis simultaneous to the index cases was reported by 47% of contacts exposed to non-VOC-infected index and 67% of those exposed to Alpha-infected index cases. Not all contacts diagnosed with COVID-19 were experiencing symptoms at the time. Nonetheless, contacts of an Alpha index case reported COVID-19 symptoms or a SARS-CoV-2 diagnosis more frequently and had higher anti-nucleocapsid IgG titers.
In comparison to 82.1% of SARS-CoV-2 Alpha-exposed HHC, 61.8% of non-VOC SARS-CoV-2-exposed HHC reported seropositivity. When household clustering was considered, household contacts exposed to an index infected with the Alpha variant had a 3.5-fold higher chance of having nucleocapsid seropositivity. In non-VOC and Alpha-affected houses, 6% and 0.5% of households with no contacts had detectable SARS-CoV-2 anti-nucleocapsid antibodies, respectively, indicating a complete absence of household transmission.
The study findings showed that 61.8% of contacts exposed to non-VOCs and 82.1% of contacts exposed to the SARS-CoV-2 Alpha variant were seropositive. With exposure to an index with an Alpha diagnosis, the likelihood of infection doubled. In practically every home, there was evidence of transmission-related events. The present study firmly establishes the need for serological data to be included in SAR estimates to increase precision and comprehension.
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
- Katherine M Gaskell, Natalie El Kheir, Mariyam Mirfenderesky, Tommy Rampling, Michael Marks, Catherine Houlihan, Norbert Lemonge, Henrietta Bristowe, Suhail Aslam, Demetra Kyprianou, Eleni Nastouli, David Goldblatt, Katherine Fielding, David Moore, CONTACT study team. (2022). Comparison Of New and emerging SARS-CoV-2 variant Transmissibility through Active Contact Testing. A comparative cross-sectional household seroprevalence study. medRxiv. doi: https://doi.org/10.1101/2022.09.27.22280419 https://www.medrxiv.org/content/10.1101/2022.09.27.22280419v1