Symptom burden, viral load, and antibody response to ancestral SARS-CoV-2 strain D614G in an outpatient household cohort

Background Early in the SARS-CoV-2 pandemic, description of COVID-19 illness among non-hospitalized patients was limited. Data from household cohorts can help reveal the full spectrum of disease and the potential for long-term sequelae, even in non-severe disease. Methods Daily symptom diaries were collected in a US household cohort of SARS-CoV-2 infection from April to November 2020, during the pre-COVID vaccine period. SARS-CoV-2 nasal viral loads were measured at study entry and weekly until day 21; serologic testing was performed at study entry and day 28. A subset of volunteers underwent an additional assessment 8–10 months later. Participants who met the criteria for early infection—testing antibody-negative at study entry but PCR-positive either at baseline or during follow-up—were included in this analysis (n = 143). Results Daily symptoms were ascertained in 143 outpatients with acute COVID-19, including 60 index cases who sought testing and 83 of their household contacts. Asymptomatic cases comprised 16% (13/83) of SARS-CoV-2 infections detected among household contacts. Among 119 persons with mild or moderate illness, the number of symptoms peaked 3 or 4 days after symptom onset. Fever and anosmia occurred in nearly half of participants. Symptom severity was associated with increased age, viral load, and cardiovascular disease. Increased BMI was associated with a higher antibody level at day 28, independent of symptom severity. Those with a higher day 28 antibody level were more likely to develop symptoms consistent with post-acute sequelae of SARS-CoV-2 (PASC), also known as long COVID-19, 8–10 months later. Conclusions Fever, anosmia, as well as asymptomatic infection were common features of COVID-19 non-severe illness when the D614G variant circulated in the US, before the availability of vaccines or outpatient therapies. Antibody levels following acute infection were linked to the development of symptoms of PASC 8–10 months later.