Delayed rise of oral fluid antibodies, elevated BMI, and absence of early fever correlate with longer time to SARS-CoV-2 RNA clearance in an longitudinally sampled cohort of COVID-19 outpatients

BackgroundSustained molecular detection of SARS-CoV-2 RNA in the upper respiratory tract (URT) in mild to moderate COVID-19 is common. We sought to identify host and immune determinants of prolonged SARS-CoV-2 RNA detection. MethodsNinety-five outpatients self-collected mid-turbinate nasal, oropharyngeal (OP), and gingival crevicular fluid (oral fluid) samples at home and in a research clinic a median of 6 times over 1-3 months. Samples were tested for viral RNA, virus culture, and SARS-CoV-2 and other human coronavirus antibodies, and associations were estimated using Cox proportional hazards models. ResultsViral RNA clearance, as measured by SARS-CoV-2 RT-PCR, in 507 URT samples occurred a median (IQR) 33.5 (17-63.5) days post-symptom onset. Sixteen nasal-OP samples collected 2-11 days post-symptom onset were virus culture positive out of 183 RT-PCR positive samples tested. All participants but one with positive virus culture were negative for concomitant oral fluid anti-SARS-CoV-2 antibodies. The mean time to first antibody detection in oral fluid was 8-13 days post-symptom onset. A longer time to first detection of oral fluid anti-SARS-CoV-2 S antibodies (aHR 0.96, 95% CI 0.92-0.99, p=0.020) and BMI [≥] 25kg/m2 (aHR 0.37, 95% CI 0.18-0.78, p=0.009) were independently associated with a longer time to SARS-CoV-2 viral RNA clearance. Fever as one of first three COVID-19 symptoms correlated with shorter time to viral RNA clearance (aHR 2.06, 95% CI 1.02-4.18, p=0.044). ConclusionsWe demonstrate that delayed rise of oral fluid SARS-CoV-2-specific antibodies, elevated BMI, and absence of early fever are independently associated with delayed URT viral RNA clearance.

Dysregulated immunity in SARS-CoV-2 infected pregnant women

ImportanceThe effects of SARS-CoV-2 infection on immune responses during pregnancy have not been systematically evaluated. ObjectiveTo assess the impact of SARS-CoV-2 infection during pregnancy on inflammatory and humoral responses in maternal and fetal samples and compare antibody responses to SARS-CoV-2 among pregnant and non-pregnant women. DesignImmune responses to SARS-CoV-2 were analyzed using samples from pregnant and non-pregnant women who had either tested positive or negative for SARS-CoV-2. We measured, proinflammatory and placental cytokine mRNAs, neonatal Fc receptor (FcRn) receptor expression, and tetanus antibody transfer in maternal and cord blood samples. Additionally, we measured anti-spike (S) IgG, anti-S-receptor binding domain (RBD) IgG, and neutralizing antibody (nAb) responses to SARS-CoV-2 in serum or plasma collected from non-pregnant women, pregnant women, and cord blood. SettingJohns Hopkins Hospital (JHH) ParticipantsPregnant women were recruited through JHH outpatient obstetric clinics and the JHH Labor & Delivery unit. Non-pregnant women were recruited after receiving outpatient SARS-CoV-2 testing within Johns Hopkins Health System, USA. Adult non-pregnant women with positive RT-PCR results for SARS-CoV-2, within the age range of 18-48 years, were included in the study. ExposuresSARS-CoV-2 Main Outcomes and MeasuresParticipant demographic characteristics, antibody titers, cytokine mRNA expression, and FcRn receptor expression. ResultsSARS-COV-2 positive pregnant women expressed more IL1{beta}, but not IL6, in blood samples collected within 14 days versus > 14 days after a confirmed SARS-CoV-2 test, with similar patterns observed in the fetal side of placentas, particularly among asymptomatic pregnant women. Pregnant women with confirmed SARS-CoV-2 infection also had reduced anti-S-RBD IgG titers and were less likely to have detectable nAb as compared with non-pregnant women. Although SARS-CoV-2 infection did not disrupt FcRn expression in the placenta, maternal transfer of nAb was inhibited by SARS-CoV-2 infection during pregnancy. Conclusions and RelevanceSARS-CoV-2 infection during pregnancy was characterized by placental inflammation and reduced antiviral antibody responses, which may impact the efficacy of COVID-19 therapeutics in pregnancy. The long-term implications of placental inflammation for neonatal health also requires greater consideration.

Variability of Salivary and Nasal Specimens for SARS-CoV-2 Detection

In a large cohort of ambulatory confirmed COVID-19 patients with multiple self-collected sample time points, we compared 202 matched nasal-oropharyngeal swabs and oral salivary fluid sample pairs by RT-PCR. Nasal-oropharyngeal swabs were more sensitive than this salivary sample type (oral crevicular fluid) suggesting that not all saliva sample types have equivalent sensitivity. However, all samples that were Vero E6-TMPRSS2 cell culture positive (e.g., infectious virus) were also oral fluid RT-PCR positive suggesting that oral fluid may find the patients most likely to transmit disease to others.

The clinical course of COVID-19 in the outpatient setting: a prospective cohort study

BackgroundOutpatient COVID-19 has been insufficiently characterized. ObjectiveTo determine the progression of disease and subsequent determinants of hospitalization. DesignA prospective outpatient cohort. SettingOutpatients were recruited by phone between April 21 to June 23, 2020 after receiving outpatient or emergency department testing within a large health network in Maryland, USA. ParticipantsOutpatient adults with positive RT-PCR results for SARS-CoV-2. MeasurementsSymptoms, portable pulse oximeter oxygen saturation (SaO2), heart rate, and temperature were collected by participants on days 0, 3, 7, 14, 21, and 28 after enrollment. Baseline demographics, comorbid conditions were evaluated for risk of subsequent hospitalization using negative binomial, logistic, and random effects logistic regression. ResultsAmong 118 SARS-CoV-2 infected outpatients, the median age was 56.0 years (IQR, 50.0 to 63.0) and 50 (42.4%) were male. Among those reporting active symptoms, the most common symptoms during the first week since symptom onset included weakness/fatigue (67.3%), cough (58.0%), headache (43.8%), and sore throat (34.8%). Participants returned to their usual health a median of 20 days (IQR, 13 to 38) from the symptom onset, and only 65.5% of respondents were at their usual health during the fourth week of illness. Over 28 days, 10.9% presented to the emergency department and 7.6% required hospitalization. Individuals at the same duration of illness had a 6.1 times increased adjusted odds of subsequent hospitalization per every percent decrease in home SaO2 (95% confidence interval [CI]: 1.41 to 31.23, p=0.02). LimitationsSeverity and duration of illness may differ in a younger population. ConclusionSymptoms often persisted but uncommonly progressed to hospitalization. Home SaO2 might be an important adjunctive tool to identify progression of COVID-19. RegistrationClinicaltrials.gov NCT number: NCT04496466 Funding SourceThe Sherrilyn and Ken Fisher Center for Environmental Infectious Diseases Discovery Program and the Johns Hopkins University School of Medicine