Asymptomatic COVID-19 in the elderly: Dementia and viral clearance as risk factors for disease progression

Rationale SARS-CoV-2 infected individuals elders have the highest hospitalization rates and represent >80% fatalities. However, most infected seniors remain asymptomatic and never progress to experience severe disease. Among those without symptoms, the rate of pre-symptomatic illness is unclear and potential predictors of progression are unknown. Our objective was to delineate the natural evolution of asymptomatic SARS-CoV-2 infection and identify determinants of progression to symptomatic illness. Methods We established a medical surveillance team monitoring 63 geriatric institutions in Buenos Aires between June and July 2020. When an index COVID-19 case emerged in one of these residencies, we tested all other eligible participants for SARS-CoV-2. Participating seniors were asymptomatic individuals ≥75 years of age, or between 65-74 years with ≥1 comorbidity. SARS-CoV-2 infected, asymptomatic elders were followed daily for 28 days by a medical team using pre-designed questionnaires. Disease was diagnosed when any COVID-19 manifestation occurred within 14 days of SARS-CoV-2 detection. SARS-CoV-2 load at enrollment and shedding on day 15, and antibody responses at the end of study participation were also studied. Results 113 asymptomatic SARS-CoV-2-infected elderly participated in the study. After 28 days of follow up, 75(66%) elders remained asymptomatic. In 38(34%) presymptomatic patients, median time to onset of symptoms was 3 days(IQR 5). 20/38(56%) pre-symptomatic patients developed hypoxemia, a presenting sign in 10/20(50%). Ten pre-symptomatic patients [26%;10/113(9%)] died(median day 14, IQR 12). Dementia was the only clinical risk factor associated with disease (OR 2.36(95%CI 1.05 to 5.29);P=.036;Table 1). PCR mean cycle threshold was similar in both groups at the time of enrollment. SARS-CoV-2 RT-PCR re-testing on day 15(IQR 1) was detectable in 61% of pre-symptomatic vs. 30% asymptomatic subjects(P=.012). Anti-S SARS-CoV-2 IgM and IgG assays on day 28 detected similar rates of antibody seropositivity in both groups (Table 1). Conclusion Our findings suggest that disease inception and disease progression may be driven by different pathogenic pathways. Dementia was the sole baseline difference potentially predicting progression to symptomatic disease in our study. Other comorbidities associated with progression from mild to severe symptoms did not affect the odds of experiencing pre-symptomatic illness. Evolution to symptomatic disease associated with longer viral shedding, suggesting that control of viral replication may influence symptom inception. In summary, dementia and persistent SARS-CoV-2 shedding associated with progression from asymptomatic to symptomatic infection in elders. These observations suggest that the mechanistic pathway to experiencing disease symptoms differs from the pathways determining severity in COVID-19.