ABSTRACT
Importance: Pregnant women are at increased risk of severe COVID-19, but the contribution of viral RNA load, the presence of infectious virus, and mucosal antibody responses remain understudied. Objective: To evaluate the association of COVID-19 outcomes following confirmed infection with vaccination status, mucosal antibody responses, infectious virus recovery and viral RNA levels in pregnant compared with non-pregnant women. Design: A retrospective observational cohort study of remnant clinical specimens from SARS-CoV-2 infected patients between October 2020-May 2022. Setting: Five acute care hospitals within the Johns Hopkins Health System (JHHS) in the Baltimore, MD-Washington, DC area. Participants: Participants included confirmed SARS-CoV-2 infected pregnant women and matched non-pregnant women (matching criteria included age, race/ethnicity, and vaccination status). Exposure: SARS-CoV-2 infection, with documentation of SARS-CoV-2 mRNA vaccination. Main Outcome(s): The primary dependent measures were clinical COVID-19 outcomes, infectious virus recovery, viral RNA levels, and mucosal anti-spike (S) IgG titers from upper respiratory tract samples. Clinical outcomes were compared using odds ratios (OR), and measures of virus and antibody were compared using either Fisher's exact test, two-way ANOVA, or regression analyses. Results were stratified according to pregnancy, vaccination status, maternal age, trimester of pregnancy, and infecting SARS-CoV-2 variant. Results(s): A total of 452 individuals (117 pregnant and 335 non-pregnant) were included in the study, with both vaccinated and unvaccinated individuals represented. Pregnant women were at increased risk of hospitalization (OR = 4.2; CI = 2.0-8.6), ICU admittance, (OR = 4.5; CI = 1.2-14.2), and of being placed on supplemental oxygen therapy (OR = 3.1; CI =1.3-6.9). An age-associated decrease in anti-S IgG titer and corresponding increase in viral RNA levels (P< 0.001) was observed in vaccinated pregnant, but not non-pregnant, women. Individuals in their 3rd trimester had higher anti-S IgG titers and lower viral RNA levels (P< 0.05) than those in their 1st or 2nd trimesters. Pregnant individuals experiencing breakthrough infections due to the omicron variant had reduced anti-S IgG compared to non-pregnant women (P< 0.05). Conclusions and Relevance: In this cohort study, vaccination status, maternal age, trimester of pregnancy, and infecting SARS-CoV-2 variant were each identified as drivers of differences in mucosal anti-S IgG responses in pregnant compared with non-pregnant women. Observed increased severity of COVID-19 and reduced mucosal antibody responses particularly among pregnant participants infected with the Omicron variant suggest that maintaining high levels of SARS-CoV-2 immunity may be important for protection of this at-risk population.
Subject(s)
Severe Acute Respiratory Syndrome , Breakthrough Pain , COVID-19 , Neural Tube DefectsABSTRACT
Increased reinfection rates with SARS-CoV-2 have recently been reported, with some locations basing reinfection on a second positive PCR test at least 90 days after initial infection. We investigated sequencing and clinical data on the 750 patients (920 samples) we identified with these criteria. The median time between tests was 377 days, and 724 (79%) of the post 90-day positives were collected after the emergence of the Omicron variant in November 2021. Successful sequencing occurred in 127 of 231 attempted samples, spiked during the Omicron surge and showed higher median days from initial infection compared to failed sequences (median 398 days compared to 276 days, p<0.0005). A total of 122 (98%) patients showed evidence of reinfection, 45 of which had sequence proven reinfection and 77 had inferred reinfections (later sequence showed a clade that was not circulating when the patient was initially infected). Children accounted for only 4% of reinfections. 43 (96%) of 45 infections with sequence proven reinfection were caused by the Omicron variant, 41 (91%) were symptomatic, 32 (71%), were vaccinated prior to the second infection, and 6 (13%) were Immunosuppressed. Only 2 (4%) were hospitalized, and both had underlying conditions.
ABSTRACT
Background: Prior observation has shown differences in COVID-19 hospitalization rates between SARS-CoV-2 variants, but limited information describes differences in hospitalization outcomes. Methods: Patients admitted to 5 hospitals with COVID-19 were included if they had hypoxia, tachypnea, tachycardia, or fever, and data to describe SARS-CoV-2 variant, either from whole genome sequencing, or inference when local surveillance showed [≥]95% dominance of a single variant. The average effect of SARS-CoV-2 variant on 14-day risk of severe disease, defined by need for advanced respiratory support, or death was evaluated using models weighted on propensity scores derived from baseline clinical features. Results: Severe disease or death within 14 days occurred for 950 of 3,365 (28%) unvaccinated patients and 178 of 808 (22%) patients with history of vaccination or prior COVID-19. Among unvaccinated patients, the relative risk of 14-day severe disease or death for Delta variant compared to ancestral lineages was 1.34 (95% confidence interval [CI] 1.13-1.55). Compared to Delta variant, this risk for Omicron patients was 0.78 (95% CI 0.62-0.97) and compared to ancestral lineages was 1.04 (95% CI 0.84-1.24). Among Omicron and Delta infections, patients with history of vaccination or prior COVID-19 had one-half the 14-day risk of severe disease or death (adjusted hazard ratio 0.46, IQR 0.34-0.62) but no significant outcome difference between Delta and Omicron infections. Conclusions: Although the risk of severe disease or death for unvaccinated patients with Omicron was lower than Delta, it was similar to ancestral lineages. Severe outcomes were less common in vaccinated patients, but there was no difference between Delta and Omicron infections.