Vaccination Against SARS-CoV-2 Is Associated With a Lower Viral Load and Likelihood of Systemic Symptoms

Abstract

Background: Data conflict on whether vaccination decreases severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load. The objective of this analysis was to compare baseline viral load and symptoms between vaccinated and unvaccinated adults enrolled in a randomized trial of outpatient coronavirus disease 2019 (COVID-19) treatment.

Methods: Baseline data from the first 433 sequential participants enrolling into the COVID-OUT trial were analyzed. Adults aged 30-85 with a body mass index (BMI) ≥25 kg/m² were eligible within 3 days of a positive SARS-CoV-2 test and <7 days of symptoms. Log₁₀ polymerase chain reaction viral loads were normalized to human RNase P by vaccination status, by time from vaccination, and by symptoms.

Results: Two hundred seventy-four participants with known vaccination status contributed optional nasal swabs for viral load measurement: median age, 46 years; median (interquartile range) BMI 31.2 (27.4-36.4) kg/m². Overall, 159 (58%) were women, and 217 (80%) were White. The mean relative log₁₀ viral load for those vaccinated <6 months from the date of enrollment was 0.11 (95% CI, -0.48 to 0.71), which was significantly lower than the unvaccinated group (P = .01). Those vaccinated ≥6 months before enrollment did not differ from the unvaccinated with respect to viral load (mean, 0.99; 95% CI, -0.41 to 2.40; P = .85). The vaccinated group had fewer moderate/severe symptoms of subjective fever, chills, myalgias, nausea, and diarrhea (all P < .05).

Conclusions: These data suggest that vaccination within 6 months of infection is associated with a lower viral load, and vaccination was associated with a lower likelihood of having systemic symptoms.

Keywords: SARS-CoV-2; symptoms; vaccines; viral load.

Figure 1.

Overview of the participants whose nasal swabs were included in the analysis. ^aSymptoms not required for participation. ^bMedication exclusion list: metformin, insulin, cimetidine, hydroxychloroquine, sulfonylurea, dolutegravir, dolutegravir, patiromir, ranalazine, tafenoquine, ivennectin, sodium picosulfate, lithium, valproate, fluvoxamine, rasagiline, selegiline, MAOis, linezolid, duloxetine, methylene blue, tizanidine, ramelteon, alosetron, agomelatine, bromopride, dapoxetine, tamsimelteon, thioridazine, urokinase, pimozide. Dose-dependent: SSRI, SNRI, tricyclic antidepressant, alprazolam, diazepam, theophylline, clozapine, olanzapine, NSAIDs, aspirin, warfarin, phenytoin, clopidrogrel, St. John’s wart, high-dose antipsychotic. Abbreviations: BMI, body mass index; CKD, chronic kidney disease; GFR, glomerular filtration rate; NSAIDs, nonsteroidal anti-inflammatory drugs; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; SNRI, serotonin and norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitors.

Figure 2.

COVID-19 symptoms by COVID-19 vaccination status. Proportions reflect the number of eligible patients with a moderate or severe symptom at baseline, as well as presence of symptoms for diarrhea in the last 24 hours, vomited in the last 24 hours, loss of smell, or loss of taste. Ninety-five percent Wilson score confidence intervals and P values for the differences in proportions are provided. Vaccinated participants had less frequent chills, diarrhea, subjective fever, myalgias, and nausea than unvaccinated participants. Abbreviation: COVID-19, coronavirus disease 2019.

Figure 3.

COVID-19 symptoms by log₁₀ viral load tertile. Proportions reflect the number of eligible patients with a moderate or severe symptom at baseline, as well as presence of symptoms for diarrhea in the last 24 hours, vomited in the last 24 hours, loss of smell, or loss of taste. Ninety-five percent Wilson score confidence intervals and P values for the differences in proportions are provided. Abbreviation: COVID-19, coronavirus disease 2019.

Figure 4.

SARS-CoV-2 log₁₀ viral load value by COVID-19 vaccination status. The beige dots reflect each observation in the study sample, whereas error bars reflect average log₁₀ viral load values and associated 95% confidence intervals. Random jittering was applied along the horizontal axis for visual clarity. Abbreviations: COVID-19, coronavirus disease 2019; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Figure 5.

SARS-CoV-2 log₁₀ viral load values by COVID-19 vaccination status and duration of antecedent vaccination. The beige dots reflect each observation in the study sample, whereas error bars reflect average log₁₀ viral load values and associated 95% confidence intervals. Random jittering was applied along the horizontal axis for visual clarity. Abbreviations: COVID-19, coronavirus disease 2019; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.