The risk of SARS-CoV-2 spread among COVID-19 patients to their close contacts was strongest in the 2 days before and 3 days after symptom onset and when index patients were mildly or moderately ill rather than asymptomatic, according to a US study of Chinese patients today in JAMA Internal Medicine.
The researchers wrote. “Infected contacts of asymptomatic index patients were less likely to present with COVID-19 symptoms, suggesting that quantity of exposure may be associated with clinical presentation in close contacts.”
Most secondary cases were mild, moderate
Researchers from the University of Georgia at Athens led the study, which included 730 COVID-19 index patients diagnosed as having COVID-19 from Jan 8 to Jul 30, 2020, and 8,852 close contacts evaluated until Aug 22 in Zhejiang Province, China. Close contacts included household members, coworkers, and those exposed at a hospital or after sharing a ride.
Index patients were identified through the provincial Center for Disease Control and Prevention, and all patients were quarantined, tested regularly, and screened daily for fever, cough, and shortness of breath. They were also surveyed about their demographic, clinical, and exposure-related characteristics.
Among index patients, median age was 46 years, and 51.2% were male. Of contacts, median age was 41 years, and 52.9% were male.
Of 8,852 close contacts, 3.6% tested positive for COVID-19. The median number of positive cases among contacts per index patient was 0.4, of whom 9.5% were critical. Most cases, however, were mild (30.0%) or moderate (41.9%), and 18.7% were asymptomatic.
Median time from index patient symptom onset to isolation was 5 days, and median time from first to last exposure between index patients and contacts was 3 days. The greatest risk of transmission was 2 days before and 3 days after the index patient became ill, peaking on the day of symptom onset (adjusted relative risk [aRR], 1.3). This link was consistent, regardless of other factors such as exposure setting and duration or age and sex of the contact.
Index, contact case severity linked
Relative to being exposed to an index patient without symptoms, the risk to close contacts was higher when the index patient had mild (aRR, 4.0) or moderate (aRR, 4.3) illness. Close contacts diagnosed as having COVID-19 were more likely to be asymptomatic if the index patient was also asymptomatic. As index case severity rose, infected contacts were increasingly less likely to be asymptomatic (aRR for mild or moderate illness, 0.3).
The most common types of contact were conversational (29.9%), household (16.7%), and being in an enclosed space with no direct contact (15.6%). Among index patients, most cases were either mild (46.0%) or moderate (42.9%), and 11.1% had no symptoms.
Contacts were at higher risk of infection the longer they were exposed to the index patient. For example, if contact occurred 2 days before index patient symptom onset and the exposure lasted for 13 days, the aRR of infection among contacts was 4.7. But at 5 or 6 days before index patient symptom onset, the aRR after a short exposure (eg, less than a week) was 0.4 to 0.8. SARS-CoV-2 attack rates were highest among household members of index patients (10.1%) and those exposed to the same index patient in multiple settings (6.8%).
In multivariable modeling, household contacts had an aRR of 8.1, while the aRR of contacts exposed to the same patient in multiple settings was 6.0, compared with those exposed during shared transportation, in an enclosed space without direct contact, and during conversation. Relative to contacts exposed to one index patient, contacts were at higher risk when exposed to two or three index patients (aRR, 1.8 and 10.2, respectively).
The results, if confirmed by other studies, may suggest that reducing illness severity with vaccination or prompt diagnosis and treatment have additional benefits, the authors wrote. “Alternatively, strain congruencies between close contacts and their index patients may explain our findings if particular COVID-19 strains are more likely to cause severe disease than others,” they wrote. “Further studies are needed to explore underlying mechanisms for this association.”