What is the genomic diversity of SARS-CoV-2 infections in households?

In a recent study posted to the medRxiv* preprint server, researchers assessed the genomic diversity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in households.

Study: SARS-CoV-2 genomic diversity in households highlights the challenges of sequence-based transmission inference. Image Credit: Oqvector/Shutterstock
Study: SARS-CoV-2 genomic diversity in households highlights the challenges of sequence-based transmission inference. Image Credit: Oqvector/Shutterstock


Ribonucleic acid (RNA) viruses usually evolve and accumulate mutations with the growing magnitudes of an outbreak. This results in an evolutionary relationship between sequenced cases that holds essential data on the mechanisms that drive the epidemic forward. Similarly, sequential data on SARS-CoV-2 can be utilized to infer transmission linkages among coronavirus disease 2019 (COVID-19) patients in hospitals and other similar settings.

About the study

In the present study, researchers used whole genome sequencing (WGS) of SARS-CoV-2 populations to infer transmission linkages within households having a minimum of two SARS-CoV-2-infected individuals.

The Coronavirus Household Evaluation and Respiratory Testing (C-HEaRT) study included households from Utah and New York between August 2020 and February 2021 and monitored them for SARS-CoV-2 infections from September 2020 and August 2021.

Additionally, the Communities Organized for the Prevention of Arboviruses (COPA) assessed COVID-19 epidemiology leading to the creation of the COCOVID study that enrolled households from ponce, Puerto Rico.

The households eligible for the C-HEaRT study had more than one child aged between zero and 17 years, while the individuals eligible were household residents for three or more consecutive months and were willing to complete study surveys and report symptoms every week and self-collect respiratory samples.

The participants were required to self-collect mid-turbinate nasal samples every week, irrespective of illness symptoms, and place the swabs in a viral transport medium. The team contacted the participants via email or text message every week to enquire if they experienced any COVID-19-like (CLI) or other illness symptoms. Furthermore, the participants were asked to self-collect additional nasal swabs after CLI symptom onset. The study defined CLI as one or more of the following symptoms: fever, cough, sore throat, shortness of breath, diarrhea, chills, muscle aches, or alterations in smell or taste. Respiratory samples were shipped and analyzed. COVID-19 positive samples from the sample household that were detected within 14 days of each other were considered to be epidemiologically linked.

SARS-CoV-2 genomic sequencing was performed on all samples with a reverse transcription-polymerase chain reaction (RT-PCR) cycle threshold of 30 or less on either SARS-CoV-2 nucleocapsid protein 1 or 2 targets. RNA was extracted from the swab samples collected and reverse transcribed before amplification of SARS-CoV-2 complementary deoxyribonucleic acid (cDNA) was performed.     


The C-HEaRT and COCOVID studies actively monitored the participants for COVID-19 infections and CLI symptoms in 706 households housing 2,369 participants. During the study period, the cumulative incidence of COVID-19 was 11% in Utah, 7% in New York, and 5% in Puerto Rico.

Among the 706 households, 56 included two or fewer participants who tested COVID-19 positive within a 14-day period, which indicated a within-household transmission. Moreover, 26 of the households displayed a high quality of sequential data on two or more of the contemporaneous cases. Notably, the SARS-CoV-2 clades and lineages detected were the same among the individuals residing in the same household and reflected the viruses that were predominant in the US in the corresponding periods.

Almost 15 of the 26 households studied had indistinguishable consensus sequences grouped on their corresponding phylogenetic trees. Since these cases were epidemiologically linked, these could be deemed sequence-confirmed transmission events. The team also found several tree structures with monophyletic grouping with indistinguishable and contemporaneous sequences derived from non-household members from the same locality. Two of the households from New York exhibited several such sequences when the SARS-CoV-2 B.1.526 (Iota) variant was prevalent in the US. This indicated that even modest sampling levels showed indistinguishable viral sequences from infected individuals residing in the same area with a presumed absence of any epidemiological link.

Eleven households displayed consensus viral sequences from one or more household members that differed at only one to two positions. Furthermore, the trees corresponding to all the cases from such households had ancestor/descendant relationships and/or linkages for the viral sequences.

Some of the household lineages were also phylogenetically different from contemporaneous local sequences. These tree structures indicated transmission linkages; however, low sampling numbers of cases raise doubts regarding any missed linkages among household members and the larger community.   


The study findings highlighted that the integration of SARS-CoV-2 epidemiological and sequential data could prove as a powerful tool in studying COVID-19 transmission. The researchers believe that future studies of viral transmission in hospitals, households, and similar congregate settings could utilize Bayesian methods that integrate epidemiological and sequential information for improved inference. 

*Important notice

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.

Journal reference:
Bhavana Kunkalikar

Written by

Bhavana Kunkalikar

Bhavana Kunkalikar is a medical writer based in Goa, India. Her academic background is in Pharmaceutical sciences and she holds a Bachelor's degree in Pharmacy. Her educational background allowed her to foster an interest in anatomical and physiological sciences. Her college project work based on ‘The manifestations and causes of sickle cell anemia’ formed the stepping stone to a life-long fascination with human pathophysiology.


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