Coronavirus COVID-19 Update for March 26, 2021

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Clinical Reports

Aspirin Use Is Associated With Decreased Mechanical Ventilation, Intensive Care Unit Admission, and In-Hospital Mortality in Hospitalized Patients With Coronavirus Disease 2019
A retrospective, observational cohort study of adult patients admitted with COVID-19 to multiple hospitals in the United States between March 2020 and July 2020 was performed. The primary outcome was the need for mechanical ventilation. Secondary outcomes were ICU admission and in-hospital mortality. Adjusted hazard ratios (HRs) for study outcomes were calculated using Cox-proportional hazards models after adjustment for the effects of demographics and comorbid conditions. Four hundred twelve patients were included in the study. Three hundred fourteen patients (76.3%) did not receive aspirin, while 98 patients (23.7%) received aspirin within 24 hours of admission or 7 days before admission. Aspirin use had a crude association with less mechanical ventilation (35.7% aspirin versus 48.4% nonaspirin, P = .03) and ICU admission (38.8% aspirin versus 51.0% nonaspirin, P = .04), but no crude association with in-hospital mortality (26.5% aspirin versus 23.2% nonaspirin, P = .51). After adjusting for 8 confounding variables, aspirin use was independently associated with decreased risk of mechanical ventilation (adjusted HR, 0.56, 95% confidence interval [CI], 0.37-0.85, P = .007), ICU admission (adjusted HR, 0.57, 95% CI, 0.38-0.85, P = .005), and in-hospital mortality (adjusted HR, 0.53, 95% CI, 0.31-0.90, P = .02). There were no differences in major bleeding (P = .69) or overt thrombosis (P = .82) between aspirin users and nonaspirin users. Aspirin use may be associated with improved outcomes in hospitalized COVID-19 patients. However, a sufficiently powered randomized controlled trial is needed to assess whether a causal relationship exists between aspirin use and reduced lung injury and mortality in COVID-19 patients.
Post-acute COVID-19 syndrome
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the coronavirus disease 2019 (COVID-19) pandemic, which has resulted in global healthcare crises and strained health resources. As the population of patients recovering from COVID-19 grows, it is paramount to establish an understanding of the healthcare issues surrounding them. COVID-19 is now recognized as a multi-organ disease with a broad spectrum of manifestations. Similarly to post-acute viral syndromes described in survivors of other virulent coronavirus epidemics, there are increasing reports of persistent and prolonged effects after acute COVID-19. Patient advocacy groups, many members of which identify themselves as long haulers, have helped contribute to the recognition of post-acute COVID-19, a syndrome characterized by persistent symptoms and/or delayed or long-term complications beyond 4 weeks from the onset of symptoms. Authors provide a comprehensive review of the current literature on post-acute COVID-19, its pathophysiology and its organ-specific sequelae. Relevant considerations for the multidisciplinary care of COVID-19 survivors are discussed with a framework for the identification of those at high risk for post-acute COVID-19 and their coordinated management through dedicated COVID-19 clinics.
COVID-19 Survivors’ Reports of the Timing, Duration, and Health Impacts of Post-Acute Sequelae of SARS-CoV-2 (PASC) Infection
A survey of 5,163 COVID-19 survivors reporting symptoms for more than 21 days following SARS-CoV-2 infection was conducted to evaluate the timing, duration, and health impacts of PASC reported by a large group of primarily non-hospitalized COVID-19 survivors.. Participants were recruited from Survivor Corps and other online COVID-19 survivor support groups. Participants reported demographic information, as well as the timing, duration, health impacts, and other attributes of PASC. The temporal distribution of symptoms, including average time of onset and duration of symptoms were determined, as well as the perceived distress and impact on ability to work. On average, participants reported 21.4 symptoms and the number of symptoms ranged from 1 to 93. The most common symptoms were fatigue (79.0%), headache (55.3%), shortness of breath (55.3%), difficulty concentrating (53.6%), cough (49.0%), changed sense of taste (44.9%), diarrhea (43.9%), and muscle or body aches (43.5%). The timing of symptom onset varied and was best described as happening in waves. The longest lasting symptoms on average for all participants (in days) were “frequently changing” symptoms (112.0), inability to exercise (106.5), fatigue (101.7), difficulty concentrating (101.1), memory problems (100.8), sadness (99.2), hormone imbalance (99.1), and shortness of breath (96.9). The symptoms that affected ability to work included the relapsing/remitting nature of illness (described by survivors as “changing symptoms”), inability to concentrate, fatigue, and memory problems, among others. Symptoms causing the greatest level of distress (on scale of 1 “none” to 5 “a great deal”) were extreme pressure at the base of the head (4.4), syncope (4.3), sharp or sudden chest pain (4.2), brain pressure (4.2), headache (4.2), persistent chest pain or pressure (4.1), and bone pain in extremities (4.1). PASC is an emerging public health priority characterized by a wide range of changing symptoms, which hinder survivors’ ability to work. PASC has not been fully characterized and the trajectory of symptoms and long-term outcomes are unknown. There is no treatment for PASC, and survivors report distress in addition to a host of ongoing symptoms. Capturing patient reports of symptoms through open-ended inquiry is a critical first step in accurately and comprehensively characterizing PASC to ensure that medical treatments and management strategies best meet the needs of individual patients and help mitigate health impacts of this new disease.
Persistent neurologic symptoms and cognitive dysfunction in non‐hospitalized Covid‐19 “long haulers”
Most SARS‐CoV‐2‐infected individuals never require hospitalization. However, some develop prolonged symptoms. In this study authors sought to characterize the spectrum of neurologic manifestations in non‐hospitalized Covid‐19 “long haulers”. This is a prospective study of the first 100 consecutive patients (50 SARS‐CoV‐2 laboratory‐positive and 50 laboratory‐negative individuals) presenting to the Neuro‐Covid‐19 clinic between May and November 2020. Due to early pandemic testing limitations, patients were included if they met Infectious Diseases Society of America symptoms of Covid‐19, were never hospitalized for pneumonia or hypoxemia and had neurologic symptoms lasting over 6 weeks. Frequency of neurologic symptoms were recorded and patient‐reported quality of life measures and standardized cognitive assessments were analyzed. Mean age was 43.2±11.3 years, 70% were female and 48% were evaluated in televisits. The most frequent comorbidities were depression/anxiety (42%) and autoimmune disease (16%). The main neurologic manifestations were: “brain fog” (81%), headache (68%), numbness/tingling (60%), dysgeusia (59%), anosmia (55%), myalgias (55%), with only anosmia being more frequent in SARS‐CoV‐2+ than SARS‐CoV‐2‐ patients (37/50 [74%] vs (18/50 [36%]; p <0.001). Moreover, 85% also experienced fatigue. There was no correlation between time from disease onset and subjective impression of recovery. Both groups exhibited impaired quality of life in cognitive and fatigue domains. SARS‐CoV‐2+patients performed worse in attention and working memory cognitive tasks compared to a demographic‐matched US population (T‐score 41.5 [37, 48.25] and 43 [37.5, 48.75], respectively; both p<0.01). Non‐hospitalized Covid‐19 “long haulers” experience prominent and persistent “brain fog” and fatigue that affect their cognition and quality of life.

Antiviral Therapeutics and Vaccines

Impact of the COVID-19 Vaccine on Asymptomatic Infection Among Patients Undergoing Pre-Procedural COVID-19 Molecular Screening
A retrospective cohort study was conducted of consecutive, asymptomatic adult patients (n = 39,156) within a large United States healthcare system who underwent 48,333 pre-procedural SARS-CoV-2 molecular screening tests between December 17, 2020 and February 8, 2021. The primary exposure of interest was vaccination with at least one dose of an mRNA COVID-19 vaccine. The primary outcome was relative risk of a positive SARS-CoV-2 molecular test among those asymptomatic persons who had received at least one dose of vaccine, as compared to persons who had not received vaccine during the same time period. Relative risk was adjusted for age, sex, race/ethnicity, patient residence relative to the hospital (local vs. non-local), healthcare system regions, and repeated screenings among patients using mixed effects log-binomial regression. Positive molecular tests in asymptomatic individuals were reported in 42 (1.4%) of 3,006 tests performed on vaccinated patients and 1,436 (3.2%) of 45,327 tests performed on unvaccinated patients (RR=0.44 95% CI: 0.33-0.60; p<.0001). Compared to unvaccinated patients, the risk of asymptomatic SARS-CoV-2 infection was lower among those >10 days after 1 st dose (RR=0.21; 95% CI: 0.12-0.37; p<.0001) and >0 days after 2 nd dose (RR=0.20; 95% CI: 0.09-0.44; p<.0001) in the adjusted analysis. COVID-19 vaccination with an mRNA-based vaccine showed a significant association with a reduced risk of asymptomatic SARS-CoV-2 infection as measured during pre-procedural molecular screening. The results of this study demonstrate the impact of the vaccines on reduction in asymptomatic infections supplementing the randomized trial results on symptomatic patients.
Are vaccines safe in patients with Long COVID? A prospective observational study
Although the efficacy of SARS-CoV-2 vaccination to prevent symptomatic COVID-19 is well established, there are no published studies on the impact on symptoms in patients with Long Covid. Anecdotal reports have suggested both a potential benefit and worsening of symptoms post vaccination with the uncertainty leading to some vaccine hesitancy amongst affected individuals. Patients initially hospitalised with COVID-19 were prospectively recruited to an observational study with clinical follow-up at 3 months (June-July 2020) and 8 months (Dec 2020-Jan 2021) post-admission. Participants who received the Pfizer-BioNTech (BNT162b2) or Oxford-AstraZeneca (ChAdOx1 nCoV-19) vaccine between January to February 2021 were identified and matched 2:1 (in terms of 8-month symptoms) with participants from the same cohort who were unvaccinated. All were re-assessed at 1 month post vaccination (or matched timepoint for unvaccinated cohort). Validated quality of life (SF-36), mental wellbeing (WEMWBS) and ongoing symptoms were assessed at all timepoints. Formal statistical analysis compared the effect of vaccination on recent quality of life using baseline symptoms, age, and gender in linear regression. Forty-four vaccinated participants were assessed at a median of 32 days (IQR 20-41) post vaccination with 22 matched unvaccinated participants. Most were highly symptomatic of Long Covid at 8 months (82% in both groups had at least 1 persistent symptom), with fatigue (61%), breathlessness (50%) and insomnia (38%) predominating. There was no significant worsening in quality-of-life or mental wellbeing metrics pre versus post vaccination. Nearly two-thirds (n=27) reported transient (<72hr duration) systemic effects (including fever, myalgia and headache). When compared to matched unvaccinated participants from the same cohort, those who had receive a vaccine had a small overall improvement in Long Covid symptoms, with a decrease in worsening symptoms (5.6% vaccinated vs 14.2% unvaccinated) and increase in symptom resolution (23.2% vaccinated vs 15.4% unvaccinated) (p=0.035). No difference in response was identified between Pfizer-BioNTech or Oxford-AstraZeneca vaccines. Receipt of vaccination with either an mRNA or adenoviral vector vaccine was not associated with a worsening of Long Covid symptoms, quality of life, or mental wellbeing. Individuals with prolonged COVID-19 symptoms should receive vaccinations as suggested by national guidance.

Epidemiology

COVID-19 in Primary and Secondary School Settings During the First Semester of School Reopening — Florida, August–December 2020
Limited U.S. data have been reported regarding COVID-19 in students and school staff members as kindergarten through grade 12 (K–12) schools have reopened. COVID-19 school-related disease incidence among Florida students was correlated with community incidence in the counties observed and was highest in smaller counties, districts without mask requirements, and those that reopened earliest after closure in March 2020. Incidence increased with the proportion of students receiving in-person instruction. Fewer than 1% of registered students were identified as having school-related COVID-19. Both community-level and school-based mitigation measures are important in limiting transmission of COVID-19; school reopening can likely be achieved without widespread student illness in K–12 settings.
Low SARS-CoV-2 Transmission in Elementary Schools — Salt Lake County, Utah, December 3, 2020–January 31, 2021
Data suggest that school-associated SARS-CoV-2 transmission is low. SARS-CoV-2 testing was offered to 1,041 school contacts of 51 index patients across 20 elementary schools in Salt Lake County, Utah. In a high community transmission setting, low school-associated transmission was observed with a 0.7% secondary attack rate. Mask adherence was high, but students’ classroom seats were <6 ft apart and a median of 3 ft apart. These findings add to evidence that in-person elementary schools can be opened safely with minimal in-school transmission when critical prevention strategies including mask use are implemented, even though maintaining ≥6 ft between students’ seats might not be possible.