Persistent Dyspnea after Recovery from COVID-19: Two Case Reports from Bangladesh

Globally, millions of documented SARS-CoV-2 infections with hundreds of thousands of deaths already reported. The majority of the fatal events have been reported in adults older than 70 years and those who have multiple co-morbidities. Despite the misery fatality of the virus, a significant number of peoples recovered from critical conditions also. Mild cases improved significantly with symptomatic management with strict maintenance of isolation. Therefore, many people believed that COVID-19 is a short-term illness, mild cases recovered completely within 2 weeks and severe or critical illness may require 3-6 weeks for complete recovery. However, the latest issue coming forward is delayed recovery in the surviving patients from severe or moderate COVID presenting with multisystem complications. We reported two cases of post COVID complications, newly named as "long COVID syndrome”. We described the common symptoms two patients experienced following recovery from acute phase of COVID-19 and how they were managed. We also discussed on the pathogenesis and management plan of common symptoms persisting after recovery of COVID-19.

What's So Funny About COVID-19? How Some Comic Strip Artists Have Approached or Avoided a Sensitive Subject

Newspaper comic strip artists in the "funny pages” have approached the subject of the COVID-19 pandemic in a number of ways. There was a delayed reaction to the pandemic because of the significant lead times preceding when the strip appeared in the paper. Some artists chose never to address the pandemic;other strips are "classic” in that they had appeared previously before the pandemic (e.g., Classic Peanuts, For Better or Worse) or were firmly grounded in a different time period (e.g., Prince Valiant) and would not be expected to broach the subject. A variety of aspects of the pandemic were fodder for the strips and panels such as: shortages and rationing, quarantine behavior, hand washing and mask wearing, escapism, family togetherness and its opposite, loneliness, social distancing, virtual meetings and telecommuting. Some of these subjects are exaggerated in an attempt to highlight their humorous, even ludicrous, aspects. Others are especially poignant and pay tribute to health care workers, delivery persons, grocery store employees, teachers, and other unsung heroes helping people get through the worst of the pandemic. Special attention is paid to the themes discussed in the following three comics: Dr. Rex Morgan, MD, Frank and Ernest, and Pearls Before Swine. Thirty-seven comic strips and panels appearing in the daily and Sunday editions of two different Kentucky newspapers to which the author subscribes;they form the basis for the study. These nationally syndicated strips were analyzed from the time of the first stay at home order in mid-March 2020 until the end of February 2021. This examination is exploratory in nature. Trends in the number of cartoons addressing aspects of COVID-19 are analyzed, but more importantly an attempt is made to interpret the themes of the comic strips or panels. © The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

The association between the number of symptoms and the severity of Post-COVID-Fatigue after SARS-CoV-2 infection treated in an outpatient setting.

BACKGROUND: Post-COVID-Fatigue (PCF) is one of the most reported symptoms following SARS-CoV-2 infection. Currently, research on persistent symptoms focuses mainly on severe infections, while outpatients are rarely included in observations. OBJECTIVE: To investigate whether the severity of PCF is related to the number of acute and persistent symptoms due to mild-to-moderate COVID-19 and to compare the most common symptoms during acute infection with the persistent symptoms in PCF patients. METHODS: A total of 425 participants were examined after COVID-19 treated as an outpatient (median 249 days [IQR: 135; 322] after acute disease) at the site of University Hospital Augsburg, Germany. The Fatigue Assessment Scale (FAS) was used to quantify the severity of PCF. The number of symptoms (maximum 41) during acute infection and persistent symptoms (during the last 14 days before examination) were added up to sum scores. Multivariable linear regression models were used to show the association between the number of symptoms and PCF. RESULTS: Of the 425 participants, 37% (n = 157) developed PCF; most were women (70%). The median number of symptoms was significantly higher in the PCF group than in the non-PCF group at both time points. In multivariable linear regression models, both sum scores were associated with PCF (acute symptoms: ß-estimate per additional symptom [95%-CI]: 0.48 [0.39; 0.57], p < 0.0001); persistent symptoms: ß-estimate per additional symptom [95%-CI]: 1.18 [1.02; 1.34], p < 0.0001). The acute symptoms strongest associated with PCF severity were difficulty concentrating, memory problems, dyspnea or shortness of breath on exertion, palpitations, and problems with movement coordination. CONCLUSION: Each additional symptom that occurs in COVID-19 increases the likelihood of suffering a higher severity of PCF. Further research is needed to identify the aetiology of PCF. TRIAL REGISTRATION: Nr. NCT04615026. Date of registration: November 4, 2020.

Post-COVID-19 Syndrome: A Novel Diagnosis.

Patients with post-COVID-19 syndrome have reported a wide array of symptoms that include autonomic dysfunction. It is hypothesized that this may be secondary to interruption of baroreflex pathways in the carotid arteries or nucleus tractus solitarius, however, confirming studies have yet to be performed. A limited number of studies have highlighted the presence of an exaggerated baroreflex response in patients with a post-COVID-19 syndrome that mirror other chronic autonomic dysfunction-related conditions.

Post-COVID-19 fatigue: A systematic review.

Fatigue is recognized as one of the most commonly presented long-term complaints in individuals previously infected with SARS-CoV-2. This systematic review was performed to describe symptoms, etiology, possible risk factors related to post-COVID-19 fatigue and the therapeutic approaches used for the treatment of post-COVID-19 fatigue. For the systematic literature search the databases PubMed, Web of Science, Cochrane Library, and PsycInfo were used. All articles that met the inclusion criteria were analyzed for demographics, clinical data and treatment. Included were studies which focused on an adult population (18-65 years old); elderly patients and patients with chronic somatic diseases which can also cause fatigue were excluded. We identified 2,851, screened 2,193 and finally included 20 studies with moderate to high methodological quality, encompassing 5,629 participants. Potential risk factors for post-COVID-19 fatigue were old age, female sex, severe clinical status in the acute phase of infection, a high number of comorbidities, and a prediagnosis of depression/anxiety. Lastly, a possible autoimmune etiology was suspected. Several treatment approaches have been tested mostly in small and uncontrolled studies so far: a Chinese herbal formulation improved breathlessness and fatigue. Moreover, molecular hydrogen (H2) inhalation had beneficial health effects in terms of improved physical (6-min walking test) and respiratory function in patients with post-COVID-19. Patients also noticed improvement in fatigue after undergoing hyperbaric oxygen therapy (HBOT) and enhanced external counterpulsation (EECP). Lastly. muscle strength and physical function were improved after undergoing an 8-weeks biweekly physical therapy course including aerobic training, strengthening exercises, diaphragmatic breathing techniques, and mindfulness training. However, larger and controlled studies e.g., investigating the effect of physical and / or psychotherapy for patients with post-COVID-19 fatigue are urgently warranted. Systematic Review Registration: Unique Identifier: CRD42022320676, https://www.crd.york.ac.uk/PROSPERO/.

Longitudinal changes in COVID-19 concern and stress: Pandemic fatigue overrides individual differences in caution.

Background: Pandemic fatigue describes a phenomenon whereby individuals experience a decrease in COVID-19 concern over time, despite their risk for infection remaining stable, or even increasing. Individual differences in the experience of pandemic fatigue may have important implications for people's adherence to public health recommendations. Design and methods: Using data collected from a large community cohort in McLennan County, TX, longitudinal changes in COVID-19-related concern, stress, and affect across three appointments separated by approximately 4 weeks (July-November 2020) were examined. About 495, 349, and 286 participants completed one, two, and three appointments, respectively. Changes to stress physiology and local travel over time were also analyzed. Results: Results of a latent class growth analysis revealed four distinct classes of individuals: (a) low concern, low stress, (b) moderate concern, moderate stress, (c) moderate concern, low stress, and (d) high concern, high stress. Despite differences between latent classes in initial levels of concern, stress, and negative affect, levels of each variable decreased over time for all groups. While this reduction of concern did not coincide with changes in local travel, it was reflected in heart rate and blood pressure. Conclusions: Together, these results suggest a general trend of pandemic fatigue in the sample, even for those with moderate-to-high levels of initial COVID-19 stress and concern. Such findings may provide insights into the expected challenges of promoting compliance with public health recommendations as the pandemic continues.

Oxaloacetate Treatment For Mental And Physical Fatigue In Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long-COVID fatigue patients: a non-randomized controlled clinical trial.

BACKGROUND: There is no approved pharmaceutical intervention for Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS). Fatigue in these patients can last for decades. Long COVID may continue to ME/CFS, and currently, it is estimated that up to 20 million Americans have significant symptoms after COVID, and the most common symptom is fatigue. Anhydrous Enol-Oxaloacetate, (AEO) a nutritional supplement, has been anecdotally reported to relieve physical and mental fatigue and is dimished in ME/CFS patients. Here, we examine the use of higher dosage AEO as a medical food to relieve pathological fatigue. METHODS: ME/CFS and Long-COVID patients were enrolled in an open label dose escalating "Proof of Concept" non-randomized controlled clinical trial with 500 mg AEO capsules. Control was provided by a historical ME/CFS fatigue trial and supporting meta-analysis study, which showed average improvement with oral placebo using the Chalder Scale of 5.9% improvement from baseline. At baseline, 73.7% of the ME/CFS patients were women, average age was 47 and length of ME/CFS from diagnosis was 8.9 years. The Long-COVID patients were a random group that responded to social media advertising (Face Book) with symptoms for at least 6 months. ME/CFS patients were given separate doses of 500 mg BID (N = 23), 1,000 mg BID (N = 29) and 1000 mg TID (N = 24) AEO for six weeks. Long COVID patients were given 500 mg AEO BID (N = 22) and 1000 mg AEO (N = 21), again over a six-week period. The main outcome measure was to compare baseline scoring with results at 6 weeks with the Chalder Fatigue Score (Likert Scoring) versus historical placebo. The hypothesis being tested was formulated prior to data collection. RESULTS: 76 ME/CFS patients (73.7% women, median age of 47) showed an average reduction in fatigue at 6 weeks as measured by the "Chalder Fatigue Questionnaire" of 22.5% to 27.9% from baseline (P < 0.005) (Likert scoring). Both physical and mental fatigue were significantly improved over baseline and historical placebo. Fatigue amelioration in ME/CFS patients increased in a dose dependent manner from 21.7% for 500 mg BID to 27.6% for 1000 mg Oxaloacetate BID to 33.3% for 1000 mg TID. Long COVID patients' fatigue was significantly reduced by up to 46.8% in 6-weeks. CONCLUSIONS: Significant reductions in physical and metal fatigue for ME/CFS and Long-COVID patients were seen after 6 weeks of treatment. As there has been little progress in providing fatigue relief for the millions of ME/CFS and Long COVID patients, anhydrous enol oxaloacetate may bridge this important medical need. Further study of oxaloacetate supplementation for the treatment of ME/CFS and Long COVID is warranted. Trial Registration https://clinicaltrials.gov/ct2/show/NCT04592354 Registered October 19, 2020. 1,000 mg BID Normalized Fatigue Data for Baseline, 2-weeks and 6-weeks evaluated by 3 Validated Fatigue Scoring Questionnaires.

Assessment of Physical Disability After Three Months in Patients Recovered From COVID-19: A Cross-Sectional Study.

PURPOSE: This study was done to assess the extent of disability in coronavirus disease 2019 (COVID-19) survivors using the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0). MATERIAL AND METHODS: This was a cross-sectional study with convenient sampling. Institutional ethical clearance was taken. Informed consent was taken from all patients. Disability assessment was done using WHODAS 2.0. All patients were initial reverse transcriptase-polymerase chain reaction (RT-PCR) positive for COVID-19. Patients with neuromuscular deficits or who were taking medication for psychiatric illness before getting infected with COVID-19 were excluded from the study. RESULTS: Fatigue followed by dyspnea was the most common reported symptom after three months of COVID-19 infection. COVID-19 survivors with fatigue or dyspnea had a more significant disability as compared to other patients. Females had a more significant disability when compared to males. We did not find any significant disability in COVID-19 survivors after three months of disease based on body mass index, hospitalization, diabetes, and oxygen requirements. CONCLUSION: COVID-19 survivors suffered from significant disability after three months of disease especially females and survivors with fatigue or dyspnea. Recognizing post-COVID-19 sequelae and the availability of rehabilitation services will be critical in preventing another public health crisis after acute COVID-19 infection.

Severe Fatigue and Memory Impairment Are Associated with Lower Serum Level of Anti-SARS-CoV-2 Antibodies in Patients with Post-COVID Symptoms.

BACKGROUND: Post-COVID manifestation is defined as persistent symptoms or long-term complications beyond 4 weeks from disease onset. Fatigue and memory impairment are common post-COVID symptoms. We aimed to explore associations between the timeline and severity of post-COVID fatigue and anti-SARS-CoV-2 antibodies. METHODS: Fatigue and memory impairment were assessed in a total of 101 post-COVID subjects using the Chalder fatigue scale (CFQ-11) and a visual analogue scale. Using the bimodal scoring system generated from CFQ-11, a score ≥4 was defined as severe fatigue. Serum anti-SARS-CoV-2 spike (anti-S-Ig) and nucleocapsid (anti-NC-Ig) antibodies were examined at two time points: 4-12 weeks after onset of symptoms, and beyond 12 weeks. RESULTS: The serum level of anti-S-Ig was significantly higher in patients with non-severe fatigue compared to those with severe fatigue at 4-12 weeks (p = 0.006) and beyond 12 weeks (p = 0.016). The serum level of anti-NC-Ig remained high in patients with non-severe fatigue at both time points. In contrast, anti-NC-Ig decreased significantly in severe fatigue cases regardless of the elapsed time (4-12 weeks: p = 0.024; beyond 12 weeks: p = 0.005). The incidence of memory impairment was significantly correlated with lower anti-S-Ig levels (-0.359, p < 0.001). CONCLUSION: The systemic immune response reflected by antibodies to SARS-CoV-2 is strongly correlated with the severity of post-COVID fatigue.

[Correction of mitochondrial dysfunction in the complex rehabilitation of COVID-19]. / Korrektsiya mitokhondrial'noi disfunktsii v kompleksnoi reabilitatsii patsientov, perenesshikh COVID-19.

OBJECTIVE: To study the effectiveness of a course of intravenous administration of cytoflavin in combination with a standard rehabilitation program for post-COVID fatigue syndrome caused by mitochondrial dysfunction. MATERIAL AND METHODS: The dynamic examination of 45 patients with post-COVID syndrome at the second stage of rehabilitation was carried out. The patients were subdivided into 2 groups comparable in gender and age. The volume of lung damage in patients of both groups was also comparable at range of 25-80%. Twenty-four patients of the control group were treated with the standard post-COVID rehabilitation protocol: pulse magnetic therapy, inhalation therapy, aeroion therapy, infrared laser therapy, course aerobic training, psychotherapy, and standard drug therapy. Twenty-one patients of the main group additionally received intravenous administration of cytoflavin daily for 10 days. The dynamics of the scores on the Rehabilitation Routing Scale, HDRS, the Asthenic Status Scale, and the 6-minute walk test was analyzed. RESULTS AND CONCLUSION: The additional intravenous administration of cytoflavin at the complex rehabilitation of post-COVID syndrome can significantly improve the therapeutic results: it significantly improves the overall functional state, reduces depression and fatigue level and increases tolerance to physical exertion.

A Paradigm for Post-Covid-19 Fatigue Syndrome Analogous to ME/CFS.

A significant proportion of COVID-19 patients are suffering from prolonged Post-COVID-19 Fatigue Syndrome, with characteristics typically found in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). However, no clear pathophysiological explanation, as yet, has been provided. A novel paradigm for a Post-COVID-19 Fatigue Syndrome is developed here from a recent unifying model for ME/CFS. Central to its rationale, SARS-CoV-2, in common with the triggers (viral and non-viral) of ME/CFS, is proposed to be a physiologically severe stressor, which could be targeting a stress-integrator, within the brain: the hypothalamic paraventricular nucleus (PVN). It is proposed that inflammatory mediators, released at the site of COVID-19 infection, would be transmitted as stress-signals, via humoral and neural pathways, which overwhelm this stress-center. In genetically susceptible people, an intrinsic stress-threshold is suggested to be exceeded causing ongoing dysfunction to the hypothalamic PVN's complex neurological circuitry. In this compromised state, the hypothalamic PVN might then be hyper-sensitive to a wide range of life's ongoing physiological stressors. This could result in the reported post-exertional malaise episodes and more severe relapses, in common with ME/CFS, that perpetuate an ongoing disease state. When a certain stress-tolerance-level is exceeded, the hypothalamic PVN can become an epicenter for microglia-induced activation and neuroinflammation, affecting the hypothalamus and its proximal limbic system, which would account for the range of reported ME/CFS-like symptoms. A model for Post-COVID-19 Fatigue Syndrome is provided to stimulate discussion and critical evaluation. Brain-scanning studies, incorporating increasingly sophisticated imaging technology should enable chronic neuroinflammation to be detected, even at a low level, in the finite detail required, thus helping to test this model, while advancing our understanding of Post-COVID-19 Fatigue Syndrome pathophysiology.

Post COVID fatigue: Can we really ignore it?

Long-COVID, also referred to as post-acute COVID-19, chronic COVID-19, post-COVID syndrome, or post-acute sequelae of SARS-CoV-2 infection (PASC), generally refers to symptoms that develop during or after acute COVID-19 illness, continue for ≥12 weeks, and are not explained by an alternative diagnosis. It is not yet known whether "long-COVID" represents a new syndrome unique to COVID-19 or overlaps with recovery from similar illnesses. It's difficult for physicians to predict when symptoms will improve as it varies differently in different people. Patient's recovery depends on various factors including age, associated comorbidities, severity of COVID-19 infection. Some symptoms, like fatigue, might continue even while others improve or go away. This review addresses the pathogenesis, presentation of post covid fatigue, its severity and its management.

Mental Health and Behavior of College Students During the COVID-19 Pandemic: Longitudinal Mobile Smartphone and Ecological Momentary Assessment Study, Part II.

BACKGROUND: Since late 2019, the lives of people across the globe have been disrupted by COVID-19. Millions of people have become infected with the disease, while billions of people have been continually asked or required by local and national governments to change their behavioral patterns. Previous research on the COVID-19 pandemic suggests that it is associated with large-scale behavioral and mental health changes; however, few studies have been able to track these changes with frequent, near real-time sampling or compare these changes to previous years of data for the same individuals. OBJECTIVE: By combining mobile phone sensing and self-reported mental health data in a cohort of college-aged students enrolled in a longitudinal study, we seek to understand the behavioral and mental health impacts associated with the COVID-19 pandemic, measured by interest across the United States in the search terms coronavirus and COVID fatigue. METHODS: Behaviors such as the number of locations visited, distance traveled, duration of phone use, number of phone unlocks, sleep duration, and sedentary time were measured using the StudentLife mobile smartphone sensing app. Depression and anxiety were assessed using weekly self-reported ecological momentary assessments, including the Patient Health Questionnaire-4. The participants were 217 undergraduate students. Differences in behaviors and self-reported mental health collected during the Spring 2020 term, as compared to previous terms in the same cohort, were modeled using mixed linear models. RESULTS: Linear mixed models demonstrated differences in phone use, sleep, sedentary time and number of locations visited associated with the COVID-19 pandemic. In further models, these behaviors were strongly associated with increased interest in COVID fatigue. When mental health metrics (eg, depression and anxiety) were added to the previous measures (week of term, number of locations visited, phone use, sedentary time), both anxiety and depression (P<.001) were significantly associated with interest in COVID fatigue. Notably, these behavioral and mental health changes are consistent with those observed around the initial implementation of COVID-19 lockdowns in the spring of 2020. CONCLUSIONS: In the initial lockdown phase of the COVID-19 pandemic, people spent more time on their phones, were more sedentary, visited fewer locations, and exhibited increased symptoms of anxiety and depression. As the pandemic persisted through the spring, people continued to exhibit very similar changes in both mental health and behaviors. Although these large-scale shifts in mental health and behaviors are unsurprising, understanding them is critical in disrupting the negative consequences to mental health during the ongoing pandemic.