Associations between physical activity prior to infection and COVID-19 disease severity and symptoms: results from the prospective Predi-COVID cohort study.

OBJECTIVE: To investigate if the physical activity (PA) prior to infection is associated with the severity of the disease in patients positively tested for COVID-19, as well as with the most common symptoms. DESIGN: A cross-sectional study using baseline data from a prospective, hybrid cohort study (Predi-COVID) in Luxembourg. Data were collected from May 2020 to June 2021. SETTING: Real-life setting (at home) and hospitalised patients. PARTICIPANTS: All volunteers aged >18 years with confirmed SARS-CoV-2 infection, as determined by reverse transcription-PCR, and having completed the PA questionnaire (n=452). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was disease severity (asymptomatic, mild illness and moderate illness). The secondary outcomes were self-reported symptoms. RESULTS: From the 452 patients included, 216 (48%) were female, the median (IQR) age was 42 (31-51) years, 59 (13%) were classified as asymptomatic, 287 (63%) as mild illness and 106 (24%) as moderate illness. The most prevalent symptoms were fatigue (n=294; 65%), headache (n=281; 62%) and dry cough (n=241; 53%). After adjustment, the highest PA level was associated with a lower risk of moderate illness (OR 0.37; 95% CI 0.14 to 0.98, p=0.045), fatigue (OR 0.54; 95% CI 0.30 to 0.97, p=0.040), dry cough (OR 0.55; 95% CI 0.32 to 0.96, p=0.034) and chest pain (OR 0.32; 95% CI 0.14 to 0.77, p=0.010). CONCLUSIONS: PA before COVID-19 infection was associated with a reduced risk of moderate illness severity and a reduced risk of experiencing fatigue, dry cough and chest pain, suggesting that engaging in PA may be an effective approach to minimise the severity of COVID-19. TRIAL REGISTRATION NUMBER: NCT04380987.

Postacute/Long COVID in Pediatrics: Development of a Multidisciplinary Rehabilitation Clinic and Preliminary Case Series.

ABSTRACT: The long-term sequelae after SARS-CoV-2 infections in children is unknown. Guidance is needed on helpful models of care for an emerging subset of pediatric patients with postacute/long COVID who continue to experience persistent symptoms after initial COVID-19 diagnosis. Here, we describe a pediatric multidisciplinary post-COVID-19 rehabilitation clinic model as well as a case series of the initial cohort of patients who presented to this clinic. A consecutive sample of nine patients (pediatric patients <21 yrs of age) who presented to our clinic are included. The most common presenting symptoms were fatigue (8 of 9 patients), headaches (6 of 9), difficulty with schoolwork (6 of 8), "brain fog" (4 of 9), and dizziness/lightheadedness (4 of 9). Most patients had decreased scores on self-reported quality-of-life measures compared with healthy controls. In the patients who participated in neuropsychological testing, a subset demonstrated difficulties with sustained auditory attention and divided attention; however, most of these patients had preexisting attention and/or mood concerns. There were also some who self-reported elevated depression and anxiety symptoms. Pediatric patients with postacute/long COVID may present with a variety of physical, cognitive, and mood symptoms. We present a model of care to address these symptoms through a multidisciplinary rehabilitation approach.

High prevalence of post COVID-19 fatigue in patients with type 2 diabetes: A case-control study.

BACKGROUND: Post COVID-19 syndrome (PCS) has emerged as a major roadblock in the recovery of patients infected with SARS-CoV-2. Amongst many symptoms like myalgia, headache, cough, breathlessness; fatigue is is most prevalent and makes the patient severely debilitated. Research on PCS, in particular fatigue, in patients with diabetes has not been done. METHODOLOGY: In this prospective study, we included patients with type 2 diabetes (T2D) who had COVID-19 (mild to moderate severity), and matched T2D patients who did not suffer from COVID-19. Demography, anthropometry, glycemic measures, treatment, and details of COVID-19 were recorded. Symptoms were scored using Chalder Fatigue Scale (reported as fatigue score, FS) and handgrip strength (in kg) was recorded by Jamar Hydraulic Hand Dynamometer. RESULTS: A total of 108 patients were included (cases, 52, controls, 56). Both groups were matched for age, duration of diabetes, BMI, TSH, serum albumin and vitamin D levels. T2D patients who had COVID-19 showed significantly more fatigue when compared with patients who did not have COVID-19 but both groups had comparable handgrip strength. Furthermore, patients with T2D with previous COVID-19 infection and who had FS > 4 have had significant higher inflammation markers during acute illness, and post COVID-19, had increased post prandial blood glucose levels, lost more weight, had reduced physical activity and showed significantly lower handgrip strength as compared to those with FS < 4. CONCLUSION: Patients with T2D who had COVID-19 infection as compared to those without had significantly more fatigue after the acute illness, and those with higher FS had reduced handgrip strength indicating sarcopenia, even after careful matching for common contributory factors to fatigue at baseline. Rehabilitation of those with FS>4 after acute infection would require careful attention to nutrition, glycemic control and graduated physical activity protocol.

Fatigue and Dyspnoea as Main Persistent Post-COVID-19 Symptoms in Previously Hospitalized Patients: Related Functional Limitations and Disability.

BACKGROUND: Multicentre studies focussing on specific long-term post-COVID-19 symptoms are scarce. OBJECTIVE: The aim of this study was to determine the levels of fatigue and dyspnoea, repercussions on daily life activities, and risk factors associated with fatigue or dyspnoea in COVID-19 survivors at long term after hospital discharge. METHODS: Age, gender, height, weight, symptoms at hospitalization, pre-existing medical comorbidity, intensive care unit admission, and the presence of cardio-respiratory symptoms developed after severe acute respiratory syndrome coronavirus 2 infection were collected from patients who recovered from COVID-19 at 4 hospitals in Madrid (Spain) from March 1 to May 31, 2020 (first COVID-19 wave). The Functional Impairment Checklist was used for evaluating fatigue/dyspnoea levels and functional limitations. RESULTS: A total of 1,142 patients (48% women, age: 61, standard deviation [SD]: 17 years) were assessed 7.0 months (SD 0.6) after hospitalization. Fatigue was present in 61% patients, dyspnoea with activity in 55%, and dyspnoea at rest in 23.5%. Only 355 (31.1%) patients did not exhibit fatigue and/or dyspnoea 7 months after hospitalization. Forty-five per cent reported functional limitations with daily living activities. Risk factors associated with fatigue and dyspnoea included female gender, number of pre-existing comorbidities, and number of symptoms at hospitalization. The number of days at hospital was a risk factor just for dyspnoea. CONCLUSIONS: Fatigue and/or dyspnoea were present in 70% of hospitalized COVID-19 survivors 7 months after discharge. In addition, 45% patients exhibited limitations on daily living activities. Being female, higher number of pre-existing medical comorbidities and number of symptoms at hospitalization were risk factors associated to fatigue/dyspnoea in COVID-19 survivors 7 months after hospitalization.

Prevalence of Symptoms More Than Seven Months After Diagnosis of Symptomatic COVID-19 in an Outpatient Setting.

BACKGROUND: With millions of SARS-CoV-2 infections worldwide, increasing numbers of patients are coming forward with long-term clinical effects of the disease lasting several weeks to months. OBJECTIVE: To characterize symptoms 7 to 9 months after diagnosis of COVID-19. DESIGN: Self-reported surveys and semistructured telephone interviews at enrollment and 30 to 45 days and 7 to 9 months from diagnosis. SETTING: From 18 March to 15 May 2020, symptomatic persons who tested positive for SARS-CoV-2 at the Geneva University Hospitals were followed by CoviCare, a virtual, clinical, outpatient follow-up program. Persons were contacted again at 30 to 45 days and 7 to 9 months from diagnosis. PARTICIPANTS: Persons who were a part of the CoviCare program from 18 March to 15 May 2020. MEASUREMENTS: A standardized interview of symptoms consistent with COVID-19, with grading of intensity. RESULTS: Of the 629 participants in the study who completed the baseline interviews, 410 completed follow-up at 7 to 9 months after COVID-19 diagnosis; 39.0% reported residual symptoms. Fatigue (20.7%) was the most common symptom reported, followed by loss of taste or smell (16.8%), dyspnea (11.7%), and headache (10.0%). LIMITATION: Limitations include generalizability and missing data for 34.8% of participants. CONCLUSION: Residual symptoms after SARS-CoV-2 infection are common among otherwise young and healthy persons followed in an outpatient setting. These findings contribute to the recognition of long-term effects in a disease mostly counted by its death toll to date by promoting communication on postacute sequelae of SARS-CoV-2 and encouraging physicians to continue long-term monitoring of their patients. PRIMARY FUNDING SOURCE: None.

[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.

Clinical and laboratory factors associated with coronavirus disease 2019 (Covid-19): A systematic review and meta-analysis.

SARS Coronavirus-2 is one of the most widespread viruses globally during the 21st century, whose severity and ability to cause severe pneumonia and death vary. We performed a comprehensive systematic review of all studies that met our standardised criteria and then extracted data on the age, symptoms, and different treatments of Covid-19 patients and the prognosis of this disease during follow-up. Cases in this study were divided according to severity and death status and meta-analysed separately using raw mean and single proportion methods. We included 171 complete studies including 62,909 confirmed cases of Covid-19, of which 148 studies were meta-analysed. Symptoms clearly emerged in an escalating manner from mild-moderate symptoms, pneumonia, severe-critical to the group of non-survivors. Hypertension (Pooled proportion (PP): 0.48 [95% Confident interval (CI): 0.35-0.61]), diabetes (PP: 0.23 [95% CI: 0.16-0.33]) and smoking (PP: 0.12 [95% CI: 0.03-0.38]) were highest regarding pre-infection comorbidities in the non-survivor group. While acute respiratory distress syndrome (PP: 0.49 [95% CI: 0.29-0.78]), (PP: 0.63 [95% CI: 0.34-0.97]) remained one of the most common complications in the severe and death group respectively. Bilateral ground-glass opacification (PP: 0.68 [95% CI: 0.59-0.75]) was the most visible radiological image. The mortality rates estimated (PP: 0.11 [95% CI: 0.06-0.19]), (PP: 0.03 [95% CI: 0.01-0.05]), and (PP: 0.01 [95% CI: 0-0.3]) in severe-critical, pneumonia and mild-moderate groups respectively. This study can serve as a high evidence guideline for different clinical presentations of Covid-19, graded from mild to severe, and for special forms like pneumonia and death groups.

Neurological symptoms and axonal damage in COVID-19 survivors: are there sequelae?

The persistence of neurological symptoms after SARS-CoV-2 infection, as well as the presence of late axonal damage, is still unknown. We performed extensive systemic and neurological follow-up evaluations in 107 out of 193 consecutive patients admitted to the COVID-19 medical unit, University Hospital of Verona, Italy between March and June 2020. We analysed serum neurofilament light chain (NfL) levels in all cases including a subgroup (n = 29) of patients with available onset samples. Comparisons between clinical and biomarker data were then performed. Neurological symptoms were still present in a significant number (n = 49) of patients over the follow-up. The most common reported symptoms were hyposmia (n = 11), fatigue (n = 28), myalgia (n = 14), and impaired memory (n = 11) and were more common in cases with severe acute COVID-19. Follow-up serum NfL values (15.2 pg/mL, range 2.4-62.4) were within normal range in all except 5 patients and did not differentiate patients with vs without persistent neurological symptoms. In patients with available onset and follow-up samples, a significant (p < 0.001) decrease of NfL levels was observed and was more evident in patients with a severe acute disease. Despite the common persistence of neurological symptoms, COVID-19 survivors do not show active axonal damage, which seems a peculiar feature of acute SARS-CoV-2 infection.

Long COVID in a prospective cohort of home-isolated patients.

Long-term complications after coronavirus disease 2019 (COVID-19) are common in hospitalized patients, but the spectrum of symptoms in milder cases needs further investigation. We conducted a long-term follow-up in a prospective cohort study of 312 patients-247 home-isolated and 65 hospitalized-comprising 82% of total cases in Bergen during the first pandemic wave in Norway. At 6 months, 61% (189/312) of all patients had persistent symptoms, which were independently associated with severity of initial illness, increased convalescent antibody titers and pre-existing chronic lung disease. We found that 52% (32/61) of home-isolated young adults, aged 16-30 years, had symptoms at 6 months, including loss of taste and/or smell (28%, 17/61), fatigue (21%, 13/61), dyspnea (13%, 8/61), impaired concentration (13%, 8/61) and memory problems (11%, 7/61). Our findings that young, home-isolated adults with mild COVID-19 are at risk of long-lasting dyspnea and cognitive symptoms highlight the importance of infection control measures, such as vaccination.

Prevalence of Post-COVID-19 Cough One Year After SARS-CoV-2 Infection: A Multicenter Study.

This multicenter study presents prevalence data and associated risk factors of post-COVID-19 cough one year after hospital discharge in COVID-19 survivors. Individuals recovered from COVID-19 at three public hospitals in Madrid (Spain) were scheduled for a telephonic interview. They were systematically asked about the presence of respiratory symptoms, e.g., fatigue, dyspnea, chest pain, and cough after hospital discharge. Clinical and hospitalization data were collected from hospital records. Overall, 1,950 patients (47% women, mean age:61, SD:16 years) were assessed at 11.2 months (SD 0.5) after hospital discharge. Just 367 (18.8%) were completely free of any respiratory post-COVID -19 symptom. The prevalence of long-term cough, chest pain, dyspnea, and fatigue was 2.5%, 6.5%, 23.3%, and 61.2%, respectively. Clinical and hospitalization factors were not associated with long-term post-COVID-19 cough. In conclusion, the prevalence of post-COVID-19 cough one year after SARS-CoV-2 infection was 2.5% in subjects who had survived hospitalization for COVID-19. No clear risk factor associated to long-term post-COVID-19 cough was identified.

Epidemiological and clinical characteristics of imported cases of COVID-19: a multicenter study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic continues to expand. Herein, we report the epidemiological and clinical features of 478 patients with confirmed COVID-19 from a multicenter study conducted in four cities in China excluding Wuhan. METHODS: A total of 478 patients transferred by emergency medical services to designated hospitals in four major cities in China (Beijing, Chongqing, Jinan, and Nanning) were enrolled. We compared the characteristics of imported and indigenous cases and calculated the frequencies of fatal, severe, mild, and asymptomatic disease. The results were used to generate a pyramid of COVID-19 severity. RESULTS: The mean age of patients with COVID-19 was 46.9 years and 49.8% were male. The most common symptoms at onset were fever (69.7%), cough (47.5%), fatigue (24.5%), dyspnea (8.4%), and headache (7.9%). Most cases (313, 65.5%) were indigenous, while 165 (34.5%) were imported. Imported cases dominated during the early stages of the pandemic, but decreased from 1 February 2020 as indigenous cases rose sharply. Compared with indigenous cases, imported cases differed significantly in terms of sex (P = 0.002), severity of disease (P = 0.006), occurrence of fever (P < 0.001), family clustering (P < 0.001), history of contact (P < 0.001), and primary outcome (P < 0.001). CONCLUSIONS: Within the population studied, imported cases had distinct characteristics from those of indigenous cases, with lower fatality rates and higher discharge rates. New infections shifted from imported cases to local infection gradually, and overall infections have declined to a low level. We suggest that preventing import of cases and controlling spread within local areas can help prevent SARS-CoV-2 infection spread.

Newly detected rapid eye movement associated sleep apnea after coronavirus disease 2019 as a possible cause for chronic fatigue: two case reports.

BACKGROUND: Coronavirus disease 2019 has become a health problem spreading worldwide with pandemic characteristics since March 2020. Post coronavirus disease 2019 symptoms are more frequent than initially expected, with fatigue as an often-mentioned issue. CASE PRESENTATIONS: We describe a 32-year-old white male and a 55-year-old white female who suffered from post coronavirus disease 2019 fatigue syndrome. On polysomnography, rapid eye movement associated sleep apnea with an increased hypopnea index during rapid eye movement phases of 36.8 and 19.5 events per hour was found. Based on the patients' burdensome fatigue symptoms, we initiated automatic positive airway pressure therapy, which diminished sleep apnea (rapid eye movement index: 0.0 in both patients) and, consequently, also the fatigue symptoms. CONCLUSIONS: Since sleep apnea and coronavirus disease 2019 are both associated with fatigue, a screening for sleep apnea might be considered in coronavirus disease 2019 patients with fatigue syndrome.

'Long COVID' syndrome.

SARS-CoV-2 has resulted in a global pandemic and an unprecedented public health crisis. Recent literature suggests the emergence of a novel syndrome known as 'long COVID', a term used to describe a diverse set of symptoms that persist after a minimum of 4 weeks from the onset of a diagnosed COVID-19 infection. Common symptoms include persistent breathlessness, fatigue and cough. Other symptoms reported include chest pain, palpitations, neurological and cognitive deficits, rashes, and gastrointestinal dysfunction. We present a complex case of a previously well 28-year-old woman who was diagnosed with COVID-19. After resolution of her acute symptoms, she continued to experience retrosternal discomfort, shortness of breath, poor memory and severe myalgia. Investigations yielded no significant findings. Given no alternative diagnosis, she was diagnosed with 'long COVID'.

Long-COVID syndrome-associated brain fog and chemofog: Luteolin to the rescue.

COVID-19 leads to severe respiratory problems, but also to long-COVID syndrome associated primarily with cognitive dysfunction and fatigue. Long-COVID syndrome symptoms, especially brain fog, are similar to those experienced by patients undertaking or following chemotherapy for cancer (chemofog or chemobrain), as well in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) or mast cell activation syndrome (MCAS). The pathogenesis of brain fog in these illnesses is presently unknown but may involve neuroinflammation via mast cells stimulated by pathogenic and stress stimuli to release mediators that activate microglia and lead to inflammation in the hypothalamus. These processes could be mitigated by phytosomal formulation (in olive pomace oil) of the natural flavonoid luteolin.

'Long COVID': persistent COVID-19 symptoms in survivors managed in Lagos State, Nigeria.

BACKGROUND: Coronavirus disease once thought to be a respiratory infection is now recognised as a multi-system disease affecting the respiratory, cardiovascular, gastrointestinal, neurological, immune, and hematopoietic systems. An emerging body of evidence suggests the persistence of COVID-19 symptoms of varying patterns among some survivors. This study aimed to describe persistent symptoms in COVID-19 survivors and investigate possible risk factors for these persistent symptoms. METHODS: The study used a retrospective study design. The study population comprised of discharged COVID-19 patients. Demographic information, days since discharge, comorbidities, and persistent COVID-19 like symptoms were assessed in patients attending the COVID-19 outpatient clinic in Lagos State. Statistical analysis was done using STATA 15.0 software (StataCorp Texas) with significance placed at p-value < 0.05. RESULTS: A total of 274 patients were enrolled in the study. A majority were within the age group > 35 to ≤49 years (38.3%), and male (66.1%). More than one-third (40.9%) had persistent COVID-19 symptoms after discharge, and 19.7% had more than three persistent COVID-like symptoms. The most persistent COVID-like symptoms experienced were easy fatigability (12.8%), headaches (12.8%), and chest pain (9.8%). Symptomatic COVID-19 disease with moderate severity compared to mild severity was a predictor of persistent COVID-like symptoms after discharge (p < 0.05). CONCLUSION: Findings from this study suggests that patients who recovered from COVID-19 disease may still experience COVID-19 like symptoms, particularly fatigue and headaches. Therefore, careful monitoring should be in place after discharge to help mitigate the effects of these symptoms and improve the quality of life of COVID-19 survivors.

Cardiopulmonary Exercise Testing to Assess Persistent Symptoms at 6 Months in People With COVID-19 Who Survived Hospitalization: A Pilot Study.

OBJECTIVE: The aim of this pilot study was to assess physical fitness and its relationship with functional dyspnea in survivors of COVID-19 6 months after their discharge from the hospital. METHODS: Data collected routinely from people referred for cardiopulmonary exercise testing (CPET) following hospitalization for COVID-19 were retrospectively analyzed. Persistent dyspnea was assessed using the modified Medical Research Council dyspnea scale. RESULTS: Twenty-three people with persistent symptoms were referred for CPET. Mean modified Medical Research Council dyspnea score was 1 (SD = 1) and was significantly associated with peak oxygen uptake (VO2peak; %) (rho = -0.49). At 6 months, those hospitalized in the general ward had a relatively preserved VO2peak (87% [SD = 20]), whereas those who had been in the intensive care unit had a moderately reduced VO2peak (77% [SD = 15]). Of note, the results of the CPET revealed that, in all individuals, respiratory equivalents were high, power-to-weight ratios were low, and those who had been in the intensive care unit had a relatively low ventilatory efficiency (mean VE/VCO2 slope = 34 [SD = 5]). Analysis of each individual showed that none had a breathing reserve <15% or 11 L/min, all had a normal exercise electrocardiogram, and 4 had a heart rate >90%. CONCLUSION: At 6 months, persistent dyspnea was associated with reduced physical fitness. This study offers initial insights into the mid-term physical fitness of people who required hospitalization for COVID-19. It also provides novel pathophysiological clues about the underlaying mechanism of the physical limitations associated with persistent dyspnea. Those with persistent dyspnea should be offered a tailored rehabilitation intervention, which should probably include muscle reconditioning, breathing retraining, and perhaps respiratory muscle training. IMPACT: This study is the first, to our knowledge, to show that a persistent breathing disorder (in addition to muscle deconditioning) can explain persistent symptoms 6 months after hospitalization for COVID-19 infection and suggests that a specific rehabilitation intervention is warranted.

Analysis of the primary presenting symptoms and hematological findings of COVID-19 patients in Bangladesh.

INTRODUCTION: SARS-Cov-2 infection or COVID-19 is a global pandemic. In this manuscript, we investigated the primary symptoms and basic hematological presentations of SARS-CoV-2 infection among the Bangladeshi patients. METHODOLOGY: This was a multicentre cross-sectional study done on COVID-19 patients tested positive by RT PCR in Bangladesh. Clinical features of mild to moderate degree of COVID-19 patients; hematological and biochemical admission day laboratory findings of moderate to severe degree hospitalized COVID-19 patients were analyzed. RESULTS: COVID-19 patients in Bangladesh commonly presented with fever, cough, fatigue, shortness of breath, and sore throat. But symptoms like myalgia, diarrhea, skin rash, headache, Abdominal pain/cramp, nausea, vomiting, restlessness, and a higher temperature of >100°F have a greater presentation rate and more frequent than other published studies. CRP and Prothrombin time was found to increase in all the patients. Serum ferritin, ESR, SGPT, and D-Dimer were increased among 53.85%, 80.43, 44%, and 25% patients. 17.39% of the patients had leucocytosis and neutrophilia, 28.26% presented with lymphocytopenia, and 62.52% had mild erythrocytopenia. The difference between the decrease hemoglobin count (higher in the male) and increased SGPT (higher in female) against gender was significant. CONCLUSIONS: Our study had evaluated a different expression in presenting symptoms of COVID-19 patients in Bangladesh. CRP, Prothrombin time, serum ferritin, ESR, SGPT, D-Dimer, erythrocytopenia, and lymphocytopenia can be assessments for diagnosis and prognosis of COVID-19 disease. Decrease hemoglobin count (higher in the male) and increased SGPT (higher in female) establish these two markers as a good candidate for diagnostic value against gender.