Post-acute sequelae of SARS-CoV-2 (PASC) impact quality of life at 6, 12 and 18 months post-infection

Little data exist on long COVID outcomes beyond one year. In a cohort enrolled with mild-moderate acute COVID-19, a wide range of symptoms manifest at 6, 12, and 18 months. Endorsing over 3 symptoms associates with poorer quality of life in 5 domains: physical, social, fatigue, pain, and general health.

Randomized controlled trial transfusing convalescent plasma as post-exposure prophylaxis against SARS-CoV-2 infection

BACKGROUNDThe efficacy of SARS-CoV-2 convalescent plasma (CCP) for preventing infection in exposed, uninfected individuals is unknown. We hypothesized that CCP might prevent infection when administered before symptoms or laboratory evidence of infection. METHODSThis double-blinded, phase 2 randomized, controlled trial (RCT) compared the efficacy and safety of prophylactic high titer ([≥]1:320) CCP with standard plasma. Asymptomatic participants aged [≥]18 years with close contact exposure to a person with confirmed COVID-19 in the previous 120 hours and negative SARS-CoV-2 test within 24 hours before transfusion were eligible. The primary outcome was development of SARS-CoV-2 infection. RESULTS180 participants were enrolled; 87 were assigned to CCP and 93 to control plasma, and 170 transfused at 19 sites across the United States from June 2020 to March 2021. Two were excluded for SARS-CoV-2 RT-PCR positivity at screening. Of the remaining 168 participants, 12/81 (14.8%) CCP and 13/87 (14.9%) control recipients developed SARS-CoV-2 infection; 6 (7.4%) CCP and 7 (8%) control recipients developed COVID-19 (infection with symptoms). There were no COVID-19-related hospitalizations in CCP and 2 in control recipients. There were 28 adverse events in CCP and 58 in control recipients. Efficacy by restricted mean infection free time (RMIFT) by 28 days for all SARS-CoV-2 infections (25.3 vs. 25.2 days; p=0.49) and COVID-19 (26.3 vs. 25.9 days; p=0.35) were similar for both groups. CONCLUSIONIn this trial, which enrolled persons with recent exposure to a person with confirmed COVID-19, high titer CCP as post-exposure prophylaxis appeared safe, but did not prevent SARS-CoV-2 infection. Trial RegistrationClinicaltrial.gov number NCT04323800.

Durability of SARS-CoV-2-specific IgG responses in saliva for up to 8 months after infection

We evaluated the durability of IgG responses specific to SARS-CoV-2 nucleocapsid (N), receptor binding domain (RBD), and spike (S) antigens in saliva up to 8 months after RT-PCR-confirmed COVID-19 using a multiplex salivary assay. We estimated a half-life of 64 days (d) (95% CI: 49, 80 d) for N, 100 d for RBD (95% CI: 58, 141 d), and 148 d (95% CI: 62, 238 d) for S IgG responses in saliva, consistent with half-life estimates previously reported in blood. Saliva can serve as an alternative to blood to monitor humoral immune responses on a large scale following SARS-CoV-2 infection and vaccination for surveillance and assessment of population immunity.

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.

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

Targeting the catecholamine-cytokine axis to prevent SARS-CoV-2 cytokine storm syndrome

In Coronavirus disease 2019 (COVID-19), the initial viral-replication phase is often followed by a hyperinflammatory reaction in the lungs and other organ systems that leads to acute respiratory distress syndrome (ARDS), the need for mechanical ventilation, and death despite maximal supportive care. As no antiviral treatments have yet proven effective, efforts to prevent progression to the severe stages of COVID-19 without inhibiting antiviral immune responses are desperately needed. We have previously demonstrated that a common, inexpensive, and well-tolerated class of drugs called alpha-1 adrenergic receptor (1-AR) antagonists can prevent hyperinflammation ("cytokine storm") and death in mice. We here present clinical data that supports the use of 1-AR antagonists in the prevention of severe complications of pneumonia, ARDS, and COVID-19.

Automated Brainstem Segmentation Detects Differential Involvement in Atypical Parkinsonian Syndromes

Objective@#Brainstem segmentation has been useful in identifying potential imaging biomarkers for diagnosis and progression in atypical parkinsonian syndromes (APS). However, the majority of work has been performed using manual segmentation, which is time consuming for large cohorts. @*Methods@#We investigated brainstem involvement in APS using an automated method. We measured the volume of the medulla, pons, superior cerebellar peduncle (SCP) and midbrain from T1-weighted MRIs in 67 patients and 42 controls. Diagnoses were corticobasal syndrome (CBS, n = 14), multiple system atrophy (MSA, n = 16: 8 with parkinsonian syndrome, MSA-P; 8 with cerebellar syndrome, MSA-C), progressive supranuclear palsy with a Richardson’s syndrome (PSP-RS, n = 12), variant PSP (n = 18), and APS not otherwise specified (APS-NOS, n = 7). @*Results@#All brainstem regions were smaller in MSA-C (19–42% volume difference, p < 0.0005) and in both PSP groups (18–33%, p < 0.0005) than in controls. MSA-P showed lower volumes in all regions except the SCP (15–26%, p < 0.0005). The most affected region in MSA-C and MSA-P was the pons (42% and 26%, respectively), while the most affected regions in both the PSP-RS and variant PSP groups were the SCP (33% and 23%, respectively) and midbrain (26% and 24%, respectively). The brainstem was less affected in CBS, but nonetheless, the pons (14%, p < 0.0005), midbrain (14%, p < 0.0005) and medulla (10%, p = 0.001) were significantly smaller in CBS than in controls. The brainstem was unaffected in APS-NOS. @*Conclusion@#Automated methods can accurately quantify the involvement of brainstem structures in APS. This will be important in future trials with large patient numbers where manual segmentation is unfeasible.