key: cord-0846751-qanuwvfc
authors: Sachdev, Darpun D; Chew Ng, Rilene; Sankaran, Madeline; Ernst, Alexandra; Hernandez, Katherine T; Servellita, Venice; Sotomayor-Gonzalez, Alicia; Stoltey, Juliet; Cohen, Stephanie E; Nguyen, Trang Quyen; Chiu, Charles; Philip, Susan
title: Contact tracing outcomes among household contacts of fully vaccinated COVID-19 patients — San Francisco, California, January 29-July 2, 2021
date: 2021-12-20
journal: Clin Infect Dis
DOI: 10.1093/cid/ciab1042
sha: 4567840d05f08ce02b16f04b5ddc969aec2bb854
doc_id: 846751
cord_uid: qanuwvfc

BACKGROUND: The extent to which vaccinated persons diagnosed with COVID-19 can transmit to other vaccinated and unvaccinated persons is unclear. METHODS: Using data from the San Francisco Department of Public Health (SFDPH), this report describes outcomes of household contact tracing during January 29–July 2, 2021, where fully vaccinated COVID-19 patients were the index case in the household. RESULTS: Among 248 fully vaccinated patients with breakthrough infections, 203 (82%) were symptomatic and 105 were identified as the index patient within their household. Among 179 named household contacts, 71 (40%) contacts tested, over half (56%) were fully vaccinated and the secondary attack rate was 28%. Overall transmission from a symptomatic fully vaccinated patient with breakthrough infection to household contacts was suspected in 14 of 105 (13%) of households. Viral genomic sequencing of samples from 44% of fully vaccinated patients showed that 82% of those sequenced were infected by a variant of concern or interest, and 77% by a variant carrying mutation(s) associated with resistance to neutralizing antibodies. CONCLUSIONS: Transmission from fully vaccinated symptomatic index patients to vaccinated and unvaccinated household contacts can occur. Indoor face masking and timely testing of all household contacts should be considered when a household member receives a positive test result in order to identify and interrupt transmission chains.

Real-world data demonstrate that vaccines are effective at preventing asymptomatic and symptomatic SARS-CoV-2 infection, the virus that causes COVID-19, however breakthrough infections can occur [1, 2] . While early studies suggested that vaccinated persons with breakthrough infections have a lower viral load and were less likely to transmit disease to household contacts compared with infected unvaccinated persons, data collected in the era of the delta variant (B.1.617.2) suggest no difference in viral loads for vaccinated and unvaccinated persons diagnosed with SARS-CoV-2 [3] [4] [5] [6] [7] . More data are needed to assess whether fully vaccinated persons who become infected can transmit SARS-CoV-2 to others, particularly in high-risk household settings where people are generally unmasked and transmission is common.

By July 2, 2021, nearly 75% of San Franciscans age ≥12 years were fully vaccinated with an authorized COVID-19 vaccine (60% Pfizer, 32% Moderna, and 8% Johnson & Johnson) and over half of household contacts identified through contact tracing were fully vaccinated. In order to better understand COVID-19 transmission from fully vaccinated persons to their contacts, the San Francisco Department of Public Health used contact tracing data to analyze attack rates among household contacts of fully vaccinated patients with breakthrough infections. This study includes data collected several months prior to and immediately after the delta variant became predominant in California.

During January 29-July 2, 2021, patients with laboratory-confirmed COVID-19 (positive reverse transcription-polymerase chain reaction [RT-PCR], loop-mediated amplification A c c e p t e d M a n u s c r i p t 4 [LAMP], or detected antigen) reported within 10 days of specimen collection to SFDPH were assigned for case investigation and contact tracing [8] . Persons reported as COVID-19 patients were interviewed to collect demographic, clinical, exposure, and vaccination data and to ask about close contacts during their infectious period (two days before either symptom onset [or specimen collection date if the patient was asymptomatic] until the patient was isolated). COVID-19 symptoms were reviewed during the interview; asymptomatic patients denied any symptoms in the two weeks prior to testing. Maskwearing was not assessed. Vaccination status was self-reported; missing or unknown vaccination dates were obtained from the California Immunization Registry. Fully vaccinated patients with breakthrough infections (COVID-19 patients) were those who received a positive SARS-CoV-2 test result ≥2 weeks after receiving the single-dose Johnson & Johnson vaccine or the second of either of the two-dose series mRNA vaccines.

Vaccinated index patients were persons who lived with at least one other person and who were the first household member to receive a positive test result for SARS-CoV-2 or to experience COVID-19 symptoms. Household contacts were persons living in the same residence as the index patient during their infectious period. Secondary cases were infected household contacts suspected to have acquired infection following exposure to the fully vaccinated index patient during the infectious period. Co-primary index patients (two household members who received positive test results or developed symptoms within one day of each other and were suspected to have acquired infection from a shared exposure outside the household), were not counted as secondary cases. Vaccinated persons who developed symptoms <2 weeks after receipt of their most recent vaccine dose were A c c e p t e d M a n u s c r i p t 5 considered not fully vaccinated for this analysis, and asymptomatic fully vaccinated persons with laboratory-confirmed COVID-19 in the 180 days before specimen collection were excluded. Fully vaccinated contacts were persons with an exposure ≥2 weeks after receiving the final dose of either a one-or two-dose vaccination series. Partially vaccinated contacts were persons who received at least one dose of vaccine but were not fully vaccinated. The median number of days between last vaccine dose and the test date was calculated. When a breakthrough case was identified, public health investigators contacted laboratories where specimens were originally analyzed and requested that specimens be sent for whole genome sequencing. Sequencing results were reported to the health department as part of mandatory public health reporting requirements. Cycle threshold values were not reportable and not collected by the health department.

Based on the CDC recommendations at the time, unvaccinated (irrespective of symptoms) and symptomatic vaccinated household contacts were referred for SARS-CoV-2 testing; as well, some asymptomatic fully vaccinated contacts opted to test [9] . Pearson Chi-square tests were performed to assess the independence of testing and vaccination status among household contacts and the independence of testing and symptom status among fully vaccinated household contacts. Contact and testing databases were matched to ascertain testing results. The proportions of tested contacts who received a positive SARS-CoV-2 test result (secondary attack rate) and households with any secondary infections were calculated. Assuming a reasonably representative contact testing rate by symptom status, a secondary attack rate conditioned on contact symptom status (symptomatic, asymptomatic, unknown symptom status) was also calculated among all fully vaccinated contacts, to A c c e p t e d M a n u s c r i p t 6 address the higher likelihood of testing symptomatic household contacts. The positivity rate among those tested was applied to the total number of fully vaccinated contacts per symptom status group (e.g., 11 symptomatic contacts multiplied by 0.44 positivity among tested = 4.8 new secondary cases) to quantify the number of cases that may have been identified if all contacts had been tested; these products were summed and divided by the total number of fully vaccinated contacts (n=101).

COVID-19 patient and contact characteristics and attack rates were stratified by demographic and clinical covariates, as well as variant exposure type. In households where positive contacts were identified, public health investigators assessed epidemiologic linkages to determine the likelihood of household transmission from the index case [10, 11] .

This work was conducted as part of San Francisco Department of Public Health COVID-19 surveillance; institutional review board approval and informed consent were not required. 

Among 248 fully vaccinated patients with breakthrough infection, 105 (42%) were identified as the index patients. These patients named 179 household contacts. Overall, 101 (56%) contacts were fully vaccinated, 27 (15%) were partially vaccinated, and 51 (29%) were unvaccinated/unknown ( Figure 1 ). Seventy-one household contacts (40%) were tested for SARS-CoV-2. There was not a significant association found between vaccination status and whether a contact was tested (p=.18), with 38% of fully vaccinated, 56% of partially vaccinated, and 35% of unvaccinated/unknown contacts undergoing testing for SARS-CoV-2.

There was a significant association found between symptom status and whether a fully vaccinated contact was tested (p<0.00001). Among 101 fully vaccinated contacts, 11 (11%) reported symptoms, 9 (82%) of whom were tested, 51 (50%) reported being asymptomatic, A c c e p t e d M a n u s c r i p t 8 26 (51%) of whom were tested, and 39 (39%) had unknown symptom status, 3 (8%) of whom were tested.

Overall, of 71 tested contacts, 20 tested positive for SARS-CoV-2, resulting in a secondary attack rate of 28%. Among the positive contacts, 12 (32%) were fully vaccinated, 2 (13%) were partially vaccinated, and 6 (33%) were unvaccinated or unknown. Among the 12 fully vaccinated positive contacts, four (44%) were symptomatic, 6 (23%) were asymptomatic, and 2 (67%) were unknown.

When conditioned on contact symptom status, the estimated number of new cases among fully vaccinated contacts was 4.9 among symptomatic, 11.8 among asymptomatic, and 26 among unknown status, resulting in a secondary attack rate of 42.3%. Secondary attack rates stratified by demographic and clinical covariates of contacts, as well as variant type exposure, are summarized in the Table. In summary, 20 secondary cases were diagnosed among household contacts of 14 fully 

These findings indicate that symptomatic fully vaccinated patients with breakthrough infections can transmit the virus to others in their household. Among the 20 secondary cases identified, nine were fully vaccinated among whom six reported no symptoms. These data support updated CDC guidance from July 27, 2021 recommending that vaccinated persons who have a known exposure to someone with suspected or confirmed COVID-19 test 3-5 days after exposure and wear a mask in indoor settings for 14 days or until they receive a negative test result *9+. In addition, while only 29% of contacts were A c c e p t e d M a n u s c r i p t 10 unvaccinated, 33 of 51 (65%) unvaccinated household contacts did not test, underscoring the importance of ongoing messaging and resources to facilitate timely testing for those who are exposed to disease. Viral genomic sequencing of samples from 44% of fully vaccinated patients showed that 82% were associated with infection by VOCs/VOIs. Although the frequency of VOC/VOI infections was similar to that in California (89%) during April-May 2021, the prevalence of B.1.1.7 among fully vaccinated patients (17%) was lower than state estimates (59%) [12] . In contrast, from June and July 2021 the prevalence of delta among fully vaccinated patients reflected contemporaneous state estimates (55% and 86%, respectively) [12] . Unlike delta, B.1.1.7 is the only VOC/VOI identified that does not contain the E484Q, E484K, or L452R mutations potentially associated with viral escape from vaccine-induced immunity [13, 14] . Results showed a much higher secondary attack rate among fully vaccinated contacts when taking into account that asymptomatic persons were less likely to be tested. Third, in some households the fully vaccinated COVID-19 patient might not have been the initial index patient in the household, particularly if the primary patient was asymptomatic or if household members had a shared exposure outside the household that was not identified by the public health investigators. Fourth, it is not possible to meaningfully compare secondary attack rates between vaccinated and unvaccinated contacts since a larger proportion of vaccinated contacts compared with unvaccinated contacts was tested. Fifth, although statistical tests were performed to assess for selection bias in testing of contacts, we were unable to fully account for differential testing recommendations of contacts based on both vaccination and symptom status due to a small A c c e p t e d M a n u s c r i p t 12 sample size and missing symptom data for 37% of contacts. Finally, interviewed patients might have inaccurately reported symptom or vaccination history.

Despite these limitations, these data provide a comprehensive, population-level description of breakthrough infections and secondary transmission in the era before and immediately after the resurgence of COVID-19 due to delta variant in the United States. Breakthrough infections made up less than 5% of all cases identified in San Francisco during this study period, however, by July 2021, nearly half of new infections in San Francisco were among fully vaccinated persons. Given the rapid speed of transmission of delta to contacts and return to pre-pandemic levels of activity, conducting timely contact tracing in order to halt transmission chains will be increasingly challenging [8, 19, 22] . This report found that transmission of SARS-CoV-2 can occur from symptomatic fully vaccinated index patients to both unvaccinated and vaccinated household contacts. These findings reinforce the importance of mitigation measures such as wearing face masks in shared spaces when a member of the household is infected or symptomatic and awaiting test results and timely testing if exposed to disease, regardless of vaccination status. As 

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A c c e p t e d M a n u s c r i p t 15 A c c e p t e d M a n u s c r i p t * The 105 index patients are a subset of 248 fully vaccinated patients with breakthrough infection. Households were identified by index patient and confirmed during contact tracing interviews. Index patients were identified as the patient with the earliest positive SARS-CoV-2 specimen collection date or symptom onset date for each household. † Secondary attack rate based on characteristic of contact. § Persons aged 0-17 years would not have been able to be fully vaccinated during this time frame. ¶ Number of persons in household. ** Household size data for contacts is not available. † † Interviewers asked about medical conditions including chronic lung, liver, immune, neurodevelopmental, renal, cardiovascular conditions, diabetes, and smoking. Information about childhood obesity and oral health was not collected. Condition -specific data are not shown because of small numbers. § § Interviewers asked about signs and symptoms including chills, headache, muscle ache, rhinorrhea, vomiting, abdominal pain, cough, diarrhea, fever, shortness of breath, altered sense of smell or taste, and sore throat. ¶ ¶ Partially vaccinated patients were defined as patients who received at least 1 dose of vaccine but were not fully vaccinated. Fully vaccinated patients were defined as patients who had received a second mRNA vaccine dose or a single-dose viral vector vaccine ≥14 days from symptom onset or collection of a positive specimen. *** Classified by Pangolin (https://pangolin.cog-uk.io) identification of lineage. Whole genome sequencing of specimens was performed by multiple laboratories. † † † Sequencing data not available for contacts. Lineages listed for household contacts are based on the lineage identified for th e associated index patient. § § § CDC classification as a variant of concern or variant of interest as of August 3, 2021. https://www.cdc.gov/coronavirus/2019ncov/variants/variant-info.html ¶ ¶ ¶ Five variants each with (n=1) not shown.