Persistent symptoms among post-COVID-19 survivors: A systematic review and meta-analysis.

BACKGROUND: Single studies support the presence of several post-COVID-19 symptoms; however, there is no evidence for the synthesis of symptoms. OBJECTIVE: We attempt to provide an overview of the persistent symptoms that post-COVID-19 patients encounter, as well as the duration of these symptoms to help them plan their rehabilitation. DESIGN: Systematic review and meta-analysis. PARTICIPANTS: A total of 16 studies involving 8756 patients post-COVID-19 were included. METHODS: The CINAHL, PubMed, EMBASE, Scopus, and Web of Science databases were searched from 2019 to August 2021. Observational studies that reported data on post-COVID-19 symptoms were included. The methodological quality of the studies was assessed using the Joanna Briggs Institute Critical Appraisal for Observational Studies. We included medium- to high-quality studies. We used a random-effects model for the meta-analytical pooled prevalence of each post-COVID-19 symptom, and I2 statistics for heterogeneity. RESULTS: From the 2481 studies identified, 16 met the inclusion criteria. The sample included 7623 hospitalised and 1133 non-hospitalised patients. We found the most prevalent symptoms were fatigue and dyspnea with a pooled prevalence ranging from 42% (27%-58%). Other post-COVID-19 symptoms included sleep disturbance 28% (14%-45%), cough 25% (10%-44%), anosmia/ageusia 24% (7%-47%), fever 21% (4%-47%), myalgia 17% (2%-41%), chest pain 11% (5%-20%), and headache 9% (2%-20%). In addition to physical symptoms, anxiety/depression was also prevalent 27% (8%-53%). CONCLUSIONS: Fatigue and dyspnea were the most prevalent post-COVID-19 symptoms and experienced up to 12 months. RELEVANCE TO CLINICAL PRACTICE: Multiple persistent symptoms are still experienced until 12 months of post-Covid 19. This meta-analysis should provide some awareness to nurses to highlights the unmet healthcare needs of post-COVID-19 patients. Long-term monitoring for the evaluation and treatment of symptoms and conditions and rehabilitation programs should be conducted.

A longitudinal SARS-CoV-2 biorepository for COVID-19 survivors with and without post-acute sequelae.

BACKGROUND: SARS-CoV-2 has swept across the globe, causing millions of deaths worldwide. Though most survive, many experience symptoms of COVID-19 for months after acute infection. Successful prevention and treatment of acute COVID-19 infection and its associated sequelae is dependent on in-depth knowledge of viral pathology across the spectrum of patient phenotypes and physiologic responses. Longitudinal biobanking provides a valuable resource of clinically integrated, easily accessed, and quality-controlled samples for researchers to study differential multi-organ system responses to SARS-CoV-2 infection, post-acute sequelae of COVID-19 (PASC), and vaccination. METHODS: Adults with a history of a positive SARS-CoV-2 nasopharyngeal PCR are actively recruited from the community or hospital settings to enroll in the Northern Colorado SARS-CoV-2 Biorepository (NoCo-COBIO). Blood, saliva, stool, nasopharyngeal specimens, and extensive clinical and demographic data are collected at 4 time points over 6 months. Patients are assessed for PASC during longitudinal follow-up by physician led symptom questionnaires and physical exams. This clinical trial registration is NCT04603677 . RESULTS: We have enrolled and collected samples from 119 adults since July 2020, with 66% follow-up rate. Forty-nine percent of participants assessed with a symptom surveillance questionnaire (N = 37 of 75) had PASC at any time during follow-up (up to 8 months post infection). Ninety-three percent of hospitalized participants developed PASC, while 23% of those not requiring hospitalization developed PASC. At 90-174 days post SARS-CoV-2 diagnosis, 67% of all participants had persistent symptoms (N = 37 of 55), and 85% percent of participants who required hospitalization during initial infection (N = 20) still had symptoms. The most common symptoms reported after 15 days of infection were fatigue, loss of smell, loss of taste, exercise intolerance, and cognitive dysfunction. CONCLUSIONS: Patients who were hospitalized for COVID-19 were significantly more likely to have PASC than those not requiring hospitalization, however 23% of patients who were not hospitalized also developed PASC. This patient-matched, multi-matrix, longitudinal biorepository from COVID-19 survivors with and without PASC will allow for current and future research to better understand the pathophysiology of disease and to identify targeted interventions to reduce risk for PASC. Registered 27 October 2020 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04603677 .

Recognizing the Clinical Sequelae of COVID-19 in Adults: COVID-19 Long-Haulers.

As the numbers of acute severe acute respiratory syndrome coronavirus 2 infections continue to rise, we are learning that symptoms do not resolve quickly in all patients. Although why some patients experience persistent symptoms is not clear, these individuals suffer. Long-hauler is the term that is associated with these persistent symptoms, and this review of the literature provides information to nurse practitioners working in primary care about symptoms, risk factors, and resources for disease management.

Post-COVID postural orthostatic tachycardia syndrome (POTS): a new phenomenon.

Background: The impact of COVID-19 has been far-reaching, and the field of neurology is no exception. Due to the long-hauler effect, a variety of chronic health consequences have occurred for some post-COVID patients. A subset of these long-hauler patients experienced symptoms of autonomic dysfunction and tested positive for postural orthostatic tachycardia syndrome (POTS) via autonomic testing. Methods: We conducted a chart review of a convenience sample from patients seen by neurologists at our tertiary care center for suspicion of post-COVID POTS. Patients included in our study had clearly defined POTS based on clinical criteria and positive tilt table test, were 81.25% female, and had an average age of approximately 36. Out of 16 patients, 12 had a confirmed positive COVID test result, with the remaining 4 having strong clinical suspicion for COVID infection. Our analysis examined the most bothersome 3 symptoms affecting each patient per the neurologist's note at their initial visit for post-COVID POTS, clinical presentation, comorbidities, neurological exam findings, autonomic testing results, and COMPASS-31 autonomic questionnaire and PROMIS fatigue survey results. Results: Palpitations (68.75%) and fatigue (62.5%) were the most common of the impactful symptoms reported by patients in their initial Cleveland Clinic neurology visit. The most frequent comorbidities in our sample were chronic migraines (37.5%), irritable bowel syndrome (IBS) (18.75%), and Raynaud's (18.75%). Neurological exam findings and autonomic testing results other than tilt table yielded variable findings without clear trends. Survey results showed substantial autonomic symptom burden (COMPASS-31 autonomic questionnaire average score 44.45) and high levels of fatigue (PROMIS fatigue survey average score 64.64) in post-COVID POTS patients. Conclusion: Our sample of post-COVID POTS patients are similar to the diagnosed POTS general population including in comorbidities and autonomic testing. Fatigue was identified by patients as a common and debilitating symptom. We hope that our study will be an early step toward further investigation of post-COVID POTS with focus on the trends identified in this chart review.

Giving a Voice to Patients With Smell Disorders Associated With COVID-19: Cross-Sectional Longitudinal Analysis Using Natural Language Processing of Self-Reports.

BACKGROUND: Smell disorders are commonly reported with COVID-19 infection. The smell-related issues associated with COVID-19 may be prolonged, even after the respiratory symptoms are resolved. These smell dysfunctions can range from anosmia (complete loss of smell) or hyposmia (reduced sense of smell) to parosmia (smells perceived differently) or phantosmia (smells perceived without an odor source being present). Similar to the difficulty that people experience when talking about their smell experiences, patients find it difficult to express or label the symptoms they experience, thereby complicating diagnosis. The complexity of these symptoms can be an additional burden for patients and health care providers and thus needs further investigation. OBJECTIVE: This study aims to explore the smell disorder concerns of patients and to provide an overview for each specific smell disorder by using the longitudinal survey conducted in 2020 by the Global Consortium for Chemosensory Research, an international research group that has been created ad hoc for studying chemosensory dysfunctions. We aimed to extend the existing knowledge on smell disorders related to COVID-19 by analyzing a large data set of self-reported descriptive comments by using methods from natural language processing. METHODS: We included self-reported data on the description of changes in smell provided by 1560 participants at 2 timepoints (second survey completed between 23 and 291 days). Text data from participants who still had smell disorders at the second timepoint (long-haulers) were compared with the text data of those who did not (non-long-haulers). Specifically, 3 aims were pursued in this study. The first aim was to classify smell disorders based on the participants' self-reports. The second aim was to classify the sentiment of each self-report by using a machine learning approach, and the third aim was to find particular food and nonfood keywords that were more salient among long-haulers than those among non-long-haulers. RESULTS: We found that parosmia (odds ratio [OR] 1.78, 95% CI 1.35-2.37; P<.001) as well as hyposmia (OR 1.74, 95% CI 1.34-2.26; P<.001) were more frequently reported in long-haulers than in non-long-haulers. Furthermore, a significant relationship was found between long-hauler status and sentiment of self-report (P<.001). Finally, we found specific keywords that were more typical for long-haulers than those for non-long-haulers, for example, fire, gas, wine, and vinegar. CONCLUSIONS: Our work shows consistent findings with those of previous studies, which indicate that self-reports, which can easily be extracted online, may offer valuable information to health care and understanding of smell disorders. At the same time, our study on self-reports provides new insights for future studies investigating smell disorders.

The Impact of Post-COVID-19 Syndrome in Adolescents: A Pilot Study.

BACKGROUND:  Post-COVID-19 syndrome has emerged as a long-term complication in adults and children; its effect on adolescents' performance in school is not well studied. OBJECTIVES: To study the physical/psychological impact of prolonged post-COVID-19 symptoms on school performance. METHODS:  This is a cross-sectional study using Google Forms, a web-based fully anonymized survey of children in grades 10-12. RESULTS:  The study included 54 students with a mean age of 16 years of whom 32 had COVID-19. Two were hospitalized and 10 had symptoms lasting more than four weeks. Commonly reported chronic symptoms were fatigue and cough. Seven students quit sports; eight had a decrease in their academic performance. Adolescents being infected more than once or not being fully vaccinated were more likely to develop prolonged symptoms and quit sports while academic performance in school was not affected. Three out of 10 (30%) students who had COVID-19 and responded to the questionnaire reported not seeking help. CONCLUSION: Post-COVID-19 syndrome is associated with a decline in physical but not mental performance in school. Being infected more than once with SARS-CoV-2 seems to play an important role in the persistence of post-COVID-19 symptoms despite the fact that some adolescents are hesitant to seek medical or psychological care.

"Healing Can Be a Very Jagged Line": Reflections on Life as a COVID-19 Long Hauler.

"Long COVID" - a term referring to COVID-19-associated symptoms and conditions (ie, sequelae) that remain or emerge after resolution of a SARS-CoV-2 infection - is a multifaceted condition about which little is known. As part of formalized patient-engaged research at a large Midwestern health system, patient stakeholders with long COVID (N=5) wrote stories based on their lived experience, as this was their preferred format for detailing their experience with the condition. These patient stakeholders reviewed one another's stories, identified relevant quotes, and provided opportunities for elaboration. Independently, a trained researcher extracted quotes from the stories, identified themes, and wove the quotes together to share the independent, yet similar, stories. Emergent themes were that of uncertainty about the symptomatology of long COVID and its effects on patients' mental health, physical functioning, family unit, self-identity, and future outlook. Further patient-engaged research on understanding the lived experience of long COVID may serve to advance knowledge and treatment. Health care providers caring for those with long COVID can benefit from listening and validating the stories of individuals suffering from this condition.

Post-COVID-19 Syndrome Mechanisms, Prevention and Management.

As the population of patients recovering from COVID-19 grows, post COVID-19 challenges are recognizing by ongoing evidences at once. Long COVID is defined as a syndrome with a range of persistent symptoms that remain long after (beyond 12 weeks) the acute SARS-CoV-2 infection. Studies have shown that long COVID can cause multi-organ damages with a wide spectrum of manifestations. Many systems, but not limited to, including respiratory, cardiovascular, nervous, gastrointestinal, and musculoskeletal systems, are involved in long COVID. Fatigue and dyspnea are the most common symptoms of long COVID. Long COVID-19 may be driven by tissue damage caused by virus-specific pathophysiologic changes or secondary to pathological long-lasting inflammatory response because of viral persistence, immune dysregulation, and autoimmune reactions. Some risk factors like sex and age, more than five early symptoms, and specific biomarkers have been revealed as a probable long COVID predicator discussed in this review. It seems that vaccination is the only way for prevention of long COVID and it can also help patients who had already long COVID. Managing long COVID survivors recommended being in a multidisciplinary approach, and a framework for identifying those at high risk for post-acute COVID-19 must be proposed. Possible therapeutic options and useful investigation tools for follow-up are suggested in this review. In sum, as evidence and researches are regularly updated, we provide the current understanding of the epidemiology, clinical manifestation, suspected pathophysiology, associated risk factors, and treatment options of long COVID in this review.

Nutritional Modulation of Gut Microbiota Alleviates Severe Gastrointestinal Symptoms in a Patient with Post-Acute COVID-19 Syndrome.

With the increase in total coronavirus disease 2019 (COVID-19) infection cases, post-acute COVID-19 syndrome, defined as experiencing ongoing health problems 4 or more weeks after the first severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has become a new arising public health concern. As part of post-acute COVID-19 syndrome, gastrointestinal symptoms might be associated with dysbiosis of the gut microbiota, which has the potential to become a target for intervention. In this study, a patient with post-acute COVID-19 syndrome with long-lasting severe gastrointestinal symptoms was provided 2-month expanded access to a high-fiber formula with investigational new drug (IND) status developed to alleviate COVID-19-related symptoms by modulating the gut microbiota. Symptoms including severe "loss of appetite," palpitation, and anxiety were significantly alleviated by the end of the intervention. The medication dosage for controlling nausea decreased during the intervention. The serum lipid profile, insulin level, and leptin level were improved compared to the baseline values. Significant structural changes of the patient's gut microbiota and reduced microbial fermentation activity in the small intestine were found during the intervention. Eighteen amplicon sequence variants (ASVs) of the V4 region of the 16S rRNA gene significantly responded to this nutritional intervention. Six out of the 18 ASVs were also found to be negatively correlated with symptom severity/medication dosage. Five of the six ASVs (ASV0AKS_Oscillibacter, ASV009F_Anaerofustis, ASV02YT_Blautia, ASV07LA_Blautia, and ASV0AM6_Eubacterium hallii) were potential short-chain fatty acid (SCFA)-producing bacteria, which might be associated with the alleviation of symptoms. Our study indicates the feasibility of alleviating gastrointestinal symptoms in patients with post-acute COVID-19 syndrome by way of nutritional modulation of their gut microbiota. IMPORTANCE It has become evident that the care of patients with COVID-19 does not end at the time of negative SARS-CoV-2 detection, as the number of patients with post-acute COVID-19 syndrome increases with an ever-increasing total infected patient population. This case report shows the possibility of alleviating the gastrointestinal symptoms of post-acute COVID-19 syndrome via microbiota-targeted nutritional intervention. As a promising strategy, it might not only improve the quality of life of patients but also reduce the burden to the public health system when the end of the COVID-19 pandemic is not in sight.

A Single-Blind, Randomized, Placebo Controlled Study to Evaluate the Benefits and Safety of Endourage Targeted Wellness Formula C Sublingual +Drops in People with Post-Acute Coronavirus Disease 2019 Syndrome.

Introduction: Coronavirus Disease 2019 (COVID-19) causes a wide range of symptoms, including death. As persons recover, some continue to experience symptoms described as Post-Acute COVID-19 Syndrome (PACS). The objectives of this study were to measure the efficacy of Formula C™, a cannabidiol (CBD)-rich, whole-flower terpene-rich preparation in managing PACS symptoms. Materials and Methods: This randomized, placebo-controlled, single-blind, open-label crossover study was conducted in 2021. Informed consent was obtained from participants, and they were randomized to two treatment groups. Group 1 (n=15) received blinded active product for 28 days, and Group 2 (n=16) received blinded placebo for 28 days (Treatment Period 1). Both groups crossed over to open-label active product for 28 days (Treatment Period 2) with a safety assessment at day 70. Patient-Reported Outcomes Measurement Information System (PROMIS®) scores and the Patient Global Impression of Change (PGIC) score were used to assess primary and secondary objectives. Safety assessments were also done at each visit. Results: Twenty-four participants completed study, with 8 withdrawals, none related to study product. PGIC and PROMIS scores improved across both groups at day 28. This raised questions about the placebo. A reanalysis of the placebo confirmed absence of CBD and unexpected medical concentration of terpenes. The study continued despite no longer having a true placebo. The improved scores on outcome measures were maintained across the open label treatment period. There were no safety events reported throughout the study. Discussion: For persons with PACS who are nonresponsive to conventional therapies, this study demonstrated symptom improvement for participants utilizing Formula C. In addition, the benefits seen in Group 2 suggest the possibility that non-CBD formulations rich in antioxidants, omega-3, and omega-6 fatty acids, gamma-linoleic acid, and terpenes may also have contributed to the overall improvement of the partial active group through the study. Conclusion: Given that both groups demonstrated improvement, both formulations may be contributing to these findings. Limitations include the small number of participants, the lack of a true placebo, and limited time on study products. Additional studies are warranted to explore both CBD-rich hemp products and hempseed oil as treatment options for PACS. Trial Registration ClinicalTrials.gov Identifier: NCT04828668.

Demographic and social determinants of cognitive dysfunction following hospitalization for COVID-19.

BACKGROUND: Persistent cognitive symptoms have been reported following COVID-19 hospitalization. We investigated the relationship between demographics, social determinants of health (SDOH) and cognitive outcomes 6-months after hospitalization for COVID-19. METHODS: We analyzed 6-month follow-up data collected from a multi-center, prospective study of hospitalized COVID-19 patients. Demographic and SDOH variables (age, race/ethnicity, education, employment, health insurance status, median income, primary language, living arrangements, and pre-COVID disability) were compared between patients with normal versus abnormal telephone Montreal Cognitive Assessments (t-MOCA; scores<18/22). Multivariable logistic regression models were constructed to evaluate predictors of t-MoCA. RESULTS: Of 382 patients available for 6-month follow-up, 215 (56%) completed the t-MoCA (n = 109/215 [51%] had normal and n = 106/215 [49%] abnormal results). 14/215 (7%) patients had a prior history of dementia/cognitive impairment. Significant univariate predictors of abnormal t-MoCA included older age, ≤12 years of education, unemployment pre-COVID, Black race, and a pre-COVID history of cognitive impairment (all p < 0.05). In multivariable analyses, education ≤12 years (adjusted OR 5.21, 95%CI 2.25-12.09), Black race (aOR 5.54, 95%CI 2.25-13.66), and the interaction of baseline functional status and unemployment prior to hospitalization (aOR 3.98, 95%CI 1.23-12.92) were significantly associated with abnormal t-MoCA scores after adjusting for age, history of dementia, language, neurological complications, income and discharge disposition. CONCLUSIONS: Fewer years of education, Black race and unemployment with baseline disability were associated with abnormal t-MoCA scores 6-months post-hospitalization for COVID-19. These associations may be due to undiagnosed baseline cognitive dysfunction, implicit biases of the t-MoCA, other unmeasured SDOH or biological effects of SARS-CoV-2.

School Nurses on the Front Lines of Health Care: Clinical Presentations Associated With COVID-19 Infection.

Over the past 2 years, COVID-19 has swept through the United States and our world, infecting millions of people. Due to the high transmissibility of this communicable disease, school-age children are at a unique risk because of close contact with others throughout the day. Many children who contract COVID-19 will go on to have asymptomatic or mild noncomplicated symptomatic infections. However, some children will develop severe or persistent symptoms. Given the unique position of school nurses in seeing a large volume of children and adolescents, it is important that they are familiar with the variable presentations and complications of COVID-19. Throughout this article, we discuss three cases of students presenting to the school nurse's office with signs and symptoms associated with COVID-19 infection.

Life stressors significantly impact long-term outcomes and post-acute symptoms 12-months after COVID-19 hospitalization.

BACKGROUND: Limited data exists evaluating predictors of long-term outcomes after hospitalization for COVID-19. METHODS: We conducted a prospective, longitudinal cohort study of patients hospitalized for COVID-19. The following outcomes were collected at 6 and 12-months post-diagnosis: disability using the modified Rankin Scale (mRS), activities of daily living assessed with the Barthel Index, cognition assessed with the telephone Montreal Cognitive Assessment (t-MoCA), Neuro-QoL batteries for anxiety, depression, fatigue and sleep, and post-acute symptoms of COVID-19. Predictors of these outcomes, including demographics, pre-COVID-19 comorbidities, index COVID-19 hospitalization metrics, and life stressors, were evaluated using multivariable logistic regression. RESULTS: Of 790 COVID-19 patients who survived hospitalization, 451(57%) completed 6-month (N = 383) and/or 12-month (N = 242) follow-up, and 77/451 (17%) died between discharge and 12-month follow-up. Significant life stressors were reported in 121/239 (51%) at 12-months. In multivariable analyses, life stressors including financial insecurity, food insecurity, death of a close contact and new disability were the strongest independent predictors of worse mRS, Barthel Index, depression, fatigue, and sleep scores, and prolonged symptoms, with adjusted odds ratios ranging from 2.5 to 20.8. Other predictors of poor outcome included older age (associated with worse mRS, Barthel, t-MoCA, depression scores), baseline disability (associated with worse mRS, fatigue, Barthel scores), female sex (associated with worse Barthel, anxiety scores) and index COVID-19 severity (associated with worse Barthel index, prolonged symptoms). CONCLUSIONS: Life stressors contribute substantially to worse functional, cognitive and neuropsychiatric outcomes 12-months after COVID-19 hospitalization. Other predictors of poor outcome include older age, female sex, baseline disability and severity of index COVID-19.

Post-COVID-19 Syndrome: Involvement and Interactions between Respiratory, Cardiovascular and Nervous Systems.

Though the acute effects of SARS-CoV-2 infection have been extensively reported, the long-term effects are less well described. Specifically, while clinicians endure to battle COVID-19, we also need to develop broad strategies to manage post-COVID-19 symptoms and encourage those affected to seek suitable care. This review addresses the possible involvement of the lung, heart and brain in post-viral syndromes and describes suggested management of post-COVID-19 syndrome. Post-COVID-19 respiratory manifestations comprise coughing and shortness of breath. Furthermore, arrhythmias, palpitations, hypotension, increased heart rate, venous thromboembolic diseases, myocarditis and acute heart failure are usual cardiovascular events. Among neurological manifestations, headache, peripheral neuropathy symptoms, memory issues, lack of concentration and sleep disorders are most commonly observed with varying frequencies. Finally, mental health issues affecting mental abilities and mood fluctuations, namely anxiety and depression, are frequently seen. Finally, long COVID is a complex syndrome with protracted heterogeneous symptoms, and patients who experience post-COVID-19 sequelae require personalized treatment as well as ongoing support.

Treatment of a COVID-19 long hauler with an amniotic fluid-derived extracellular vesicle biologic.

Post-COVID-19 infection symptoms such as mental fog, tachycardia, and extreme fatigue are just a few of the symptoms wreaking havoc on patients' lives. Patients with long-term symptoms following COVID-19 are being called long haulers. To date, long haulers are receiving little to no guidance from physicians on their lingering COVID-19 symptoms with limited treatment options available. Zofin is an acellular biologic that contains the extracellular vesicle (EV) fraction of human amniotic fluid and is under investigation for use as a COVID-19 therapeutic. We obtained FDA and IRB approval to investigate the therapeutic use of Zofin in a single long hauler patient case experiencing prolonged shortness of breath and respiratory impairment. Administration of the EV product was shown to be safe. Furthermore, demonstrated respiratory improvements through chest X ray images and oxygen saturation measurement. The single patient IND studies were completed without any reported adverse events or safety concerns. Furthermore, these completed studies demonstrate the feasibility and a therapeutic potential of amniotic fluid-derived EVs for COVID-19 long hauler intervention.

How and why patients made Long Covid.

Patients collectively made Long Covid - and cognate term 'Long-haul Covid' - in the first months of the pandemic. Patients, many with initially 'mild' illness, used various kinds of evidence and advocacy to demonstrate a longer, more complex course of illness than laid out in initial reports from Wuhan. Long Covid has a strong claim to be the first illness created through patients finding one another on Twitter: it moved from patients, through various media, to formal clinical and policy channels in just a few months. This initial mapping of Long Covid - by two patients with this illness - focuses on actors in the UK and USA and demonstrates how patients marshalled epistemic authority. Patient knowledge needs to be incorporated into how COVID-19 is conceptualised, researched, and treated.

Prevalence and Predictors of Prolonged Cognitive and Psychological Symptoms Following COVID-19 in the United States.

BACKGROUND/OBJECTIVES: Little is known regarding the prevalence and predictors of prolonged cognitive and psychological symptoms of COVID-19 among community-dwellers. We aimed to quantitatively measure self-reported metrics of fatigue, cognitive dysfunction, anxiety, depression, and sleep and identify factors associated with these metrics among United States residents with or without COVID-19. METHODS: We solicited 1000 adult United States residents for an online survey conducted February 3-5, 2021 utilizing a commercial crowdsourcing community research platform. The platform curates eligible participants to approximate United States demographics by age, sex, and race proportions. COVID-19 was diagnosed by laboratory testing and/or by exposure to a known positive contact with subsequent typical symptoms. Prolonged COVID-19 was self-reported and coded for those with symptoms ≥ 1 month following initial diagnosis. The primary outcomes were NIH PROMIS/Neuro-QoL short-form T-scores for fatigue, cognitive dysfunction, anxiety, depression, and sleep compared among those with prolonged COVID-19 symptoms, COVID-19 without prolonged symptoms and COVID-19 negative subjects. Multivariable backwards step-wise logistic regression models were constructed to predict abnormal Neuro-QoL metrics. RESULTS: Among 999 respondents, the average age was 45 years (range 18-84), 49% were male, 76 (7.6%) had a history of COVID-19 and 19/76 (25%) COVID-19 positive participants reported prolonged symptoms lasting a median of 4 months (range 1-13). Prolonged COVID-19 participants were more often younger, female, Hispanic, and had a history of depression/mood/thought disorder (all P < 0.05). They experienced significantly higher rates of unemployment and financial insecurity, and their symptoms created greater interference with work and household activities compared to other COVID-19 status groups (all P < 0.05). After adjusting for demographics, past medical history and stressor covariates in multivariable logistic regression analysis, COVID-19 status was independently predictive of worse Neuro-QoL cognitive dysfunction scores (adjusted OR 11.52, 95% CI 1.01-2.28, P = 0.047), but there were no significant differences in quantitative measures of anxiety, depression, fatigue, or sleep. CONCLUSION: Prolonged symptoms occurred in 25% of COVID-19 positive participants, and NeuroQoL cognitive dysfunction scores were significantly worse among COVID-19 positive subjects, even after accounting for demographic and stressor covariates. Fatigue, anxiety, depression, and sleep scores did not differ between COVID-19 positive and negative respondents.

Recommendations for the recognition, diagnosis, and management of long COVID: a Delphi study.

BACKGROUND: In the absence of research into therapies and care pathways for long COVID, guidance based on 'emerging experience' is needed. AIM: To provide a rapid expert guide for GPs and long COVID clinical services. DESIGN AND SETTING: A Delphi study was conducted with a panel of primary and secondary care doctors. METHOD: Recommendations were generated relating to the investigation and management of long COVID. These were distributed online to a panel of UK doctors (any specialty) with an interest in, lived experience of, and/or experience treating long COVID. Over two rounds of Delphi testing, panellists indicated their agreement with each recommendation (using a five-point Likert scale) and provided comments. Recommendations eliciting a response of 'strongly agree', 'agree', or 'neither agree nor disagree' from 90% or more of responders were taken as showing consensus. RESULTS: Thirty-three clinicians representing 14 specialties reached consensus on 35 recommendations. Chiefly, GPs should consider long COVID in the presence of a wide range of presenting features (not limited to fatigue and breathlessness) and exclude differential diagnoses where appropriate. Detailed history and examination with baseline investigations should be conducted in primary care. Indications for further investigation and specific therapies (for myocarditis, postural tachycardia syndrome, mast cell disorder) include hypoxia/desaturation, chest pain, palpitations, and histamine-related symptoms. Rehabilitation should be individualised, with careful activity pacing (to avoid relapse) and multidisciplinary support. CONCLUSION: Long COVID clinics should operate as part of an integrated care system, with GPs playing a key role in the multidisciplinary team. Holistic care pathways, investigation of specific complications, management of potential symptom clusters, and tailored rehabilitation are needed.

A prospective study of long-term outcomes among hospitalized COVID-19 patients with and without neurological complications.

BACKGROUND: Little is known regarding long-term outcomes of patients hospitalized with COVID-19. METHODS: We conducted a prospective study of 6-month outcomes of hospitalized COVID-19 patients. Patients with new neurological complications during hospitalization who survived were propensity score-matched to COVID-19 survivors without neurological complications hospitalized during the same period. The primary 6-month outcome was multivariable ordinal analysis of the modified Rankin Scale(mRS) comparing patients with or without neurological complications. Secondary outcomes included: activities of daily living (ADLs;Barthel Index), telephone Montreal Cognitive Assessment and Neuro-QoL batteries for anxiety, depression, fatigue and sleep. RESULTS: Of 606 COVID-19 patients with neurological complications, 395 survived hospitalization and were matched to 395 controls; N = 196 neurological patients and N = 186 controls completed follow-up. Overall, 346/382 (91%) patients had at least one abnormal outcome: 56% had limited ADLs, 50% impaired cognition, 47% could not return to work and 62% scored worse than average on ≥1 Neuro-QoL scale (worse anxiety 46%, sleep 38%, fatigue 36%, and depression 25%). In multivariable analysis, patients with neurological complications had worse 6-month mRS (median 4 vs. 3 among controls, adjusted OR 1.98, 95%CI 1.23-3.48, P = 0.02), worse ADLs (aOR 0.38, 95%CI 0.29-0.74, P = 0.01) and were less likely to return to work than controls (41% versus 64%, P = 0.04). Cognitive and Neuro-QOL metrics were similar between groups. CONCLUSIONS: Abnormalities in functional outcomes, ADLs, anxiety, depression and sleep occurred in over 90% of patients 6-months after hospitalization for COVID-19. In multivariable analysis, patients with neurological complications during index hospitalization had significantly worse 6-month functional outcomes than those without.

Implications of Innate Immunity in Post-Acute Sequelae of Non-Persistent Viral Infections.

Non-persistent viruses classically cause transient, acute infections triggering immune responses aimed at the elimination of the pathogen. Successful viruses evolved strategies to manipulate and evade these anti-viral defenses. Symptoms during the acute phase are often linked to dysregulated immune responses that disappear once the patient recovers. In some patients, however, symptoms persist or new symptoms emerge beyond the acute phase. Conditions resulting from previous transient infection are termed post-acute sequelae (PAS) and were reported for a wide range of non-persistent viruses such as rota-, influenza- or polioviruses. Here we provide an overview of non-persistent viral pathogens reported to be associated with diverse PAS, among them chronic fatigue, auto-immune disorders, or neurological complications and highlight known mechanistic details. Recently, the emergence of post-acute sequelae of COVID-19 (PASC) or long COVID highlighted the impact of PAS. Notably, PAS of non-persistent infections often resemble symptoms of persistent viral infections, defined by chronic inflammation. Inflammation maintained after the acute phase may be a key driver of PAS of non-persistent viruses. Therefore, we explore current insights into aberrant activation of innate immune signaling pathways in the post-acute phase of non-persistent viruses. Finally, conclusions are drawn and future perspectives for treatment and prevention of PAS are discussed.