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.

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/.

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.