Clinical Spectrum of Severe Acute Respiratory Syndrome Coronavirus 2 Infection and Protection From Symptomatic Reinfection

Abstract

Background: There are few data on the full spectrum of disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection across the lifespan from community-based or nonclinical settings.

Methods: We followed 2338 people in Managua, Nicaragua, aged <94 years from March 2020 through March 2021. SARS-CoV-2 infection was identified through real-time reverse transcription polymerase chain reaction (RT-PCR) or through enzyme-linked immunosorbent assay. Disease presentation was assessed at the time of infection or retrospectively by survey at the time of blood collection.

Results: There was a large epidemic that peaked between March and August 2020. In total, 129 RT-PCR-positive infections were detected, for an overall incidence rate of 5.3 infections per 100 person-years (95% confidence interval [CI], 4.4-6.3). Seroprevalence was 56.7% (95% CI, 53.5%-60.1%) and was consistent from age 11 through adulthood but was lower in children aged ≤10 years. Overall, 31.0% of the infections were symptomatic, with 54.7% mild, 41.6% moderate, and 3.7% severe. There were 2 deaths that were likely due to SARS-CoV-2 infection, yielding an infection fatality rate of 0.2%. Antibody titers exhibited a J-shaped curve with respect to age, with the lowest titers observed among older children and young adults and the highest among older adults. When compared to SARS-CoV-2-seronegative individuals, SARS-CoV-2 seropositivity at the midyear sample was associated with 93.6% protection from symptomatic reinfection (95% CI, 51.1%-99.2%).

Conclusions: This population exhibited a very high SARS-CoV-2 seropositivity with lower-than-expected severity, and immunity from natural infection was protective against symptomatic reinfection.

Keywords: 2; CoV; SARS; based; cohort; community; reinfection; seropositive.

Figure 1.

Epidemic timing and reverse-transcription polymerase chain reaction (RT-PCR) positivity. Gray-shaded regions indicate the timing of annual and midyear blood sample collections. A, Illness onsets among enzyme-linked immunosorbent assay (ELISA)–positive cases. B, Dates of individuals’ first severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–positive RT-PCR. C, Incidence per 100 person-years of SARS-CoV-2 infection outcomes over time. Outcomes are indicated by color: ELISA-positive cases of all severities are pink, moderate cases are magenta, severe cases purple; RT-PCR–confirmed infections are orange. Peak incidence rates for infection during May 2020 with 95% confidence intervals and the number of observations for each outcome are printed to the right of the peak. D, SARS-CoV-2 RT-PCR positivity by age.

Figure 2.

Enzyme-linked immunosorbent assay (ELISA)–confirmed infections and severity, by age. A, ELISA-confirmed infections, by age. B, Percentage of ELISA-confirmed infections that were subclinical. C, Percentage of ELISA-confirmed infections that were cases. The proportions of cases of each severity level are shown on the right: mild [pink, (D)], moderate [magenta, (E)], and severe [purple, (F)]. Error bars represent 95% confidence intervals.

Figure 3.

Coronavirus disease 2019 (COVID-19) severity measures among enzyme-linked immunosorbent assay (ELISA)–confirmed cases, by age. A, Percentage of participants who thought they had COVID-19. B, Number of symptoms. C, Percentage who had recovery times of ≥28 days.

Figure 4.

Midyear immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) antibody titers to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), by age. Titers are also shown by sex (A), symptoms (B), and severity (C). Midyear samples were collected in October–November 2020. Locally estimated scatterplot smoothing lines were fit to the log₂-transformed data and shaded regions show 95% confidence intervals (A and B). Boxplots show the 25th and 75th percentiles and median; diamonds represent mean titer values, and P values shown are for trends, from linear models (C).