ABSTRACT
BackgroundLong COVID contributes to the global burden of disease. Proposed root cause hypotheses include the persistence of SARS-CoV-2 viral reservoir, autoimmunity, and reactivation of latent herpesviruses. Patients have reported various changes in Long COVID symptoms after COVID-19 vaccinations, leaving uncertainty about whether vaccine-induced immune responses may alleviate or worsen disease pathology. MethodsIn this prospective study, we evaluated changes in symptoms and immune responses after COVID-19 vaccination in 16 vaccine-naive individuals with Long COVID. Surveys were administered before vaccination and then at 2, 6, and 12 weeks after receiving the first vaccine dose of the primary series. Simultaneously, SARS-CoV-2-reactive TCR enrichment, SARS-CoV-2-specific antibody responses, antibody responses to other viral and self-antigens, and circulating cytokines were quantified before vaccination and at 6 and 12 weeks after vaccination. ResultsSelf-report at 12 weeks post-vaccination indicated 10 out of 16 participants had improved health, 3 had no change, 1 had worse health, and 2 reported marginal changes. Significant elevation in SARS-CoV-2-specific TCRs and Spike protein-specific IgG were observed 6 and 12 weeks after vaccination. No changes in reactivities were observed against herpes viruses and self-antigens. Within this dataset, higher baseline sIL-6R was associated with symptom improvement, and the two top features associated with non-improvement were high IFN-{beta} and CNTF, among soluble analytes. ConclusionsOur study showed that in this small sample, vaccination improved the health or resulted in no change to the health of most participants, though few experienced worsening. Vaccination was associated with increased SARS-CoV-2 Spike protein-specific IgG and T cell expansion in most individuals with Long COVID. Symptom improvement was observed in those with baseline elevated sIL-6R, while elevated interferon and neuropeptide levels were associated with a lack of improvement. Plain language summaryThe impact of the COVID-19 vaccine on vaccine-naive individuals suffering from Long COVID is uncertain. This study assessed the experience and immune signatures of 16 unvaccinated participants with Long COVID. A total of 10 participants had improved health status after vaccination, and one person reported only worsening health. As expected, vaccination increased immune cells and antibodies against the viral spike protein. Immune signatures may prove to be predictors of health status after vaccination. However, given the small number of participants, these initial findings need further validation.
Subject(s)
COVID-19 , Severe Acute Respiratory SyndromeABSTRACT
IntroductionA chronic post-vaccination syndrome (PVS) after covid-19 vaccination has been reported but has yet to be well characterized. MethodsWe included 241 individuals aged 18 and older who self-reported PVS after covid-19 vaccination and who joined the online Yale Listen to Immune, Symptom and Treatment Experiences Now (LISTEN) Study from May 2022 to July 2023. We summarized their demographics, health status, symptoms, treatments tried, and overall experience. ResultsThe median age of participants was 46 years (interquartile range [IQR]: 38 to 56), with 192 (80%) identifying as female, 209 (87%) as non-Hispanic White, and 211 (88%) from the United States. Among these participants with PVS, 127 (55%) had received the BNT162b2 [Pfizer-BioNTech] vaccine, and 86 (37%) received the mRNA-1273 [Moderna] vaccine. The median time from the day of index vaccination to symptom onset was three days (IQR: 1 day to 8 days). The time from vaccination to symptom survey completion was 595 days (IQR: 417 to 661 days). The median Euro-QoL visual analogue scale score was 50 (IQR: 39 to 70). The five most common symptoms were exercise intolerance (71%), excessive fatigue (69%), numbness (63%), brain fog (63%), and neuropathy (63%). In the week before survey completion, participants reported feeling unease (93%), fearfulness (82%), and overwhelmed by worries (81%), as well as feelings of helplessness (80%), anxiety (76%), depression (76%), hopelessness (72%), and worthlessness (49%) at least once. Participants reported a median of 20 (IQR: 13 to 30) interventions to treat their condition. ConclusionsIn this study, individuals who reported PVS after covid-19 vaccination had low health status, high symptom burden, and high psychosocial stress despite trying many treatments. There is a need for continued investigation to understand and treat this condition.
Subject(s)
COVID-19ABSTRACT
Background: Internal tremors and vibrations symptoms have been described as part of neurologic disorders but have not been fully described as a part of long COVID. We compared demographics, socioeconomic characteristics, pre-pandemic comorbidities, and new-onset conditions between people with internal tremors and vibrations as part of their long COVID symptoms and people with long COVID but without these symptoms. Methods: A cross-sectional study, Listen to Immune, Symptom and Treatment Experiences Now (LISTEN), collected data from adults with long COVID. The study sample included 423 participants enrolled between May 2022 and June 2023. Results: The 423 participants had a median age of 46 years (interquartile range, 38-56), 74% were female, 87% were Non-Hispanic White, and 158 (37%) reported "internal tremors, or buzzing/vibration" as a long COVID symptom. Before long COVID, the groups had similar comorbidities. Post-COVID, participants with internal tremors and vibrations had significantly worse health as measured by the Euro-QoL visual analogue scale (median: 40 vs. 50 points, P = 0.007), higher rates of financial difficulties caused by the pandemic and housing insecurity (P < 0.001 for each), and were significantly more likely to have new-onset conditions of mast cell disorders (11% vs. 2.6%), neurologic conditions (22% vs. 8.3%), anxiety (20% vs. 8.7%), and trauma- or stress-related mental health disorders (12% vs. 3.4%) compared with those without internal tremors (Bonferroni-adjusted P < 0.05 for each). Participants with internal tremors also reported significantly higher rates of cardiovascular, gastrointestinal, integumentary, and neurologic long COVID symptoms compared with those without internal tremors (Bonferroni-adjusted P < 0.05 for each). Conclusions and Relevance: Among people with long COVID, those with internal tremors and vibrations have more associated symptoms and worse health status, suggesting it may be associated with a severe phenotype of the condition.
Subject(s)
Anxiety Disorders , Wounds and Injuries , Tremor , Nervous System Diseases , MastocytosisABSTRACT
To introduce the perspective of patients who have PASC with vibrations and tremors as a prominent component, we leveraged the efforts by Survivor Corps, a grassroots COVID-19 patient advocacy group, to gather information from people in their Facebook group suffering from vibrations and tremors. Survivor Corps collected 140 emails and 450 Facebook comments from members. From the emails, we identified 22 themes and 7 broader domains based on common coding techniques for qualitative data and the constant comparative method of qualitative data analysis. Facebook comments were analyzed using Word Clouds to visualize frequency of terms. The respondent emails reflected 7 domains that formed the basis of characterizing their experience with vibrations and tremors. These domains were: (1) symptom experience, description, and anatomic location; (2) initial symptom onset; (3) symptom timing; (4) symptom triggers or alleviators; (5) change from baseline health status; (6) experience with medical establishment; and (7) impact on lives and livelihood. There were 22 themes total, each corresponding to one of the broader domains. The Facebook comments Word Cloud revealed that the 10 most common words used in comments were: tremors (64), covid (55), pain (51), vibrations (43), months (36), burning (29), feet (24), hands (22), legs (21), back (20). Overall, these patient narratives described intense suffering, and there is still no diagnosis or treatment available.
Subject(s)
COVID-19 , Tremor , PainABSTRACT
ABSTRACT Nationwide public health restrictions due to the coronavirus disease 2019 (COVID-19) pandemic have disrupted people’s routine physical activities, yet little objective information is available on the extent to which physical activity has changed among patients with pre-existing cardiac diseases. Using remote monitoring data of 9,924 patients with pacemakers and implantable cardiac defibrillators (ICDs) living in New York City and Minneapolis/Saint Paul, we assessed physical activity patterns among these patients in 2019 and 2020 from January through October. We found marked declines in physical activity among patients with implantable cardiac devices during COVID-19-related restrictions and the reduction was consistent across age and sex subgroups. Moreover, physical activity among these vulnerable patients did not return to pre-restrictions levels several months after COVID-19 restrictions were eased. Our findings highlight the need to consider the unintended consequences of mitigation strategies and develop approaches to encourage safe physical activity during the pandemic.
Subject(s)
COVID-19 , Heart DiseasesABSTRACT
Hospitalizations for acute cardiac conditions have markedly declined during the coronavirus disease 2019 (COVID-19) pandemic, yet the cause of this decline is not clear. Using remote monitoring data of 4,029 patients with implantable cardiac defibrillators (ICDs) living in New York City and Minneapolis/Saint Paul, we assessed changes in markers of cardiac status among these patients and compared thoracic impedance and arrhythmia burden in 2019 and 2020 from January through August. We found no change in several key disease decompensation markers among patients with implanted ICD devices during the first phase of COVID-19 pandemic, suggesting that the decrease in cardiovascular hospitalizations in this period is not reflective of a true population-level improvement in cardiovascular health.
Subject(s)
COVID-19 , Arrhythmias, Cardiac , Heart DiseasesABSTRACT
BackgroundThe coronavirus disease 2019 (COVID-19) has continued to spread in the US and globally. Closely monitoring public engagement and perception of COVID-19 and preventive measures using social media data could provide important information for understanding the progress of current interventions and planning future programs. ObjectiveTo measure the publics behaviors and perceptions regarding COVID-19 and its daily life effects during the recent 5 months of the pandemic. MethodsNatural language processing (NLP) algorithms were used to identify COVID-19 related and unrelated topics in over 300 million online data sources from June 15 to November 15, 2020. Posts in the sample were geotagged, and sensitivity and specificity were both calculated to validate the classification of posts. The prevalence of discussion regarding these topics was measured over this time period and compared to daily case rates in the US. ResultsThe final sample size included 9,065,733 posts, 70% of which were sourced from the US. In October and November, discussion including mentions of COVID-19 and related health behaviors did not increase as it had from June to September, despite an increase in COVID-19 daily cases in the US beginning in October. Additionally, counter to reports from March and April, discussion was more focused on daily life topics (69%), compared with COVID-19 in general (37%) and COVID-19 public health measures (20%). ConclusionsThere was a decline in COVID-19-related social media discussion sourced mainly from the US, even as COVID-19 cases in the US have increased to the highest rate since the beginning of the pandemic. Targeted public health messaging may be needed to ensure engagement in public health prevention measures until a vaccine is widely available to the public.
Subject(s)
COVID-19ABSTRACT
ImportanceCOVID-19 case fatality and hospitalization rates, calculated using the number of confirmed cases of COVID-19, have been described widely in the literature. However, the number of infections confirmed by testing underestimates the total infections as it is biased based on the availability of testing and because asymptomatic individuals may remain untested. The infection fatality rate (IFR) and infection hospitalization rate (IHR), calculated using the estimated total infections based on a representative sample of a population, is a better metric to assess the actual toll of the disease. ObjectiveTo determine the IHR and IFR for COVID-19 using the statewide SARS-CoV-2 seroprevalence estimates for the non-congregate population in Connecticut. DesignCross-sectional. SettingAdults residing in a non-congregate setting in Connecticut between March 1 and June 1, 2020. ParticipantsIndividuals aged 18 years or above. ExposureEstimated number of adults with SARS-CoV-2 antibodies. Main Outcome and MeasuresCOVID-19-related hospitalizations and deaths among adults residing in a non-congregate setting in Connecticut between March 1 and June 1, 2020. ResultsOf the 2.8 million individuals residing in the non-congregate settings in Connecticut through June 2020, 113,515 (90% CI 56,758-170,273) individuals had SARS-CoV-2 antibodies. There were a total of 9425 COVID-19-related hospitalizations and 4071 COVID-19-related deaths in Connecticut between March 1 and June 1, 2020, of which 7792 hospitalizations and 1079 deaths occurred among the non-congregate population. The overall COVID-19 IHR and IFR was 6.86% (90% CI, 4.58%-13.72%) and 0.95% (90% CI, 0.63%-1.90%) among the non-congregate population. Older individuals, men, non-Hispanic Black individuals and those belonging to New Haven and Litchfield counties had a higher burden of hospitalization and deaths, compared with younger individuals, women, non-Hispanic White or Hispanic individuals, and those belonging to New London county, respectively. Conclusion and RelevanceUsing representative seroprevalence estimates, the overall COVID-19 IHR and IFR were estimated to be 6.86% and 0.95% among the non-congregate population in Connecticut. Accurate estimation of IHR and IFR among community residents is important to guide public health strategies during an infectious disease outbreak.
Subject(s)
COVID-19ABSTRACT
Current bottlenecks for improving accessibility and scalability of SARS-CoV-2 testing include diagnostic assay costs, complexity, and supply chain shortages. To resolve these issues, we developed SalivaDirect, which received Emergency Use Authorization (EUA) from the U.S. Food and Drug Administration on August 15th, 2020. The critical component of our approach is to use saliva instead of respiratory swabs, which enables non-invasive frequent sampling and reduces the need for trained healthcare professionals during collection. Furthermore, we simplified our diagnostic test by (1) not requiring nucleic acid preservatives at sample collection, (2) replacing nucleic acid extraction with a simple proteinase K and heat treatment step, and (3) testing specimens with a dualplex quantitative reverse transcription PCR (RT-qPCR) assay. We validated SalivaDirect with reagents and instruments from multiple vendors to minimize the risk for supply chain issues. Regardless of our tested combination of reagents and instruments from different vendors, we found that SalivaDirect is highly sensitive with a limit of detection of 6-12 SARS-CoV-2 copies/L. When comparing SalivaDirect to paired nasopharyngeal swabs using the authorized ThermoFisher Scientific TaqPath COVID-19 combo kit, we found high agreement in testing outcomes (>94%). In partnership with the National Basketball Association (NBA) and Players Association, we conducted a large-scale (n = 3,779) SalivaDirect usability study and comparison to standard nasal/oral tests for asymptomatic and presymptomatic SARS-CoV-2 detection. From this cohort of healthy NBA players, staff, and contractors, we found that 99.7% of samples were valid using our saliva collection techniques and a 89.5% positive and >99.9% negative test agreement to swabs, demonstrating that saliva is a valid and noninvasive alternative to swabs for large-scale SARS-CoV-2 testing. SalivaDirect is a flexible and inexpensive ($1.21-$4.39/sample in reagent costs) option to help improve SARS-CoV-2 testing capacity. Register to become a designated laboratory to use SalivaDirect under our FDA EUA on our website: publichealth.yale.edu/salivadirect/.
Subject(s)
COVID-19ABSTRACT
BackgroundPatients with comorbid conditions have a higher risk of mortality with SARS-CoV-2 (COVID-19) infection, but the impact on heart failure patients living near a disease hotspot is unknown. Therefore, we sought to characterize the prevalence and outcomes of COVID-19 in a live registry of heart failure patients across an integrated health care system in Connecticut. MethodsIn this retrospective analysis, the Yale Heart Failure Registry (NCT04237701) that includes 26,703 patients with heart failure across a 6-hospital integrated health care system in Connecticut was queried on April 16th, 2020 for all patients tested for COVID-19. Sociodemographic and geospatial data as well as, clinical management, respiratory failure, and patient mortality were obtained via the real-time registry. Data on COVID-19 specific care was extracted by retrospective chart review. ResultsCOVID-19 testing was performed on 900 symptomatic patients, comprising 3.4% of the Yale Heart Failure Registry (N=26,703). Overall, 206 (23%) were COVID-19+. As compared to COVID-19-, these patients were more likely to be older, black, have hypertension, coronary artery disease, and were less likely to be on renin angiotensin blockers (P<0.05, all). COVID-19- patients tended to be more diffusely spread across the state whereas COVID-19+ were largely clustered around urban centers. 20% of COVID-19+ patients died, and age was associated with increased risk of death [OR 1.92 95% CI (1.33-2.78); P<0.001]. Among COVID-19+ patients who were [≥]85 years of age rates of hospitalization were 87%, rates of death 36%, and continuing hospitalization 62% at time of manuscript preparation. ConclusionsIn this real-world snapshot of COVID-19 infection among a large cohort of heart failure patients, we found that a small proportion had undergone testing. Patients found to be COVID-19+ tended to be black with multiple comorbidities and clustered around lower socioeconomic status communities. Elderly COVID-19+ patients were very likely to be admitted to the hospital and experience high rates of mortality.