[Prospects and possibilities for the treatment of patients with long COVID-19 syndrome].

AIM: To study the efficacy and safety of a drug product based on the succinic acid complex with trimethylhydrazine used to treat patients with asthenic syndrome after a new coronavirus infection (COVID-19). MATERIALS AND METHODS: A prospective, multicenter, comparative, randomized, double-blind, placebo-controlled study of the safety and efficacy of sequential therapy with Brainmax® enrolled 160 patients 12-16 weeks after coronavirus infection (no more than 12 months). The study was conducted at 6 healthcare centers in different regions of the Russian Federation. At the enrollment, clinical and neurological examination and the following tests were performed: complete blood count, urinalysis, blood chemistry, coagulation test, pulse oximetry, electrocardiography, glomerular filtration rate calculation (according to Cockcroft-Gault formula) were performed. Also, the patients were assessed using the following tools: VAS headache rating scale, MFI-20 asthenia scale, PSQI index, FAS-10 fatigue assessment scale, Dizziness Handicap Inventory (DHI), MoCA-test for cognitive impairment assessment, Beck Anxiety Inventory, Kérdö Autonomic Index. RESULTS: The primary endpoint was the mean reduction in the MFI-20 asthenia scale score after the therapy (Visit 5, 41st day of therapy) compared to data from Visit 0 (beginning of therapy). A clinically significant advantage of the study drug versus the placebo was demonstrated, with a median absolute change in the MFI-20 score of -19.5 [-27; -11] points in the Brainmax® drug group and -3 [-7; 1] score in the placebo group (p<0.001). A significant sleep quality improvement according to the PSQI index was shown in the study group: by -2.5 [-4; -1] points versus no improvement in the placebo group (0 [-3; 0], p<0,001). Significant differences were also noted for the following secondary endpoints: PSQI sleep quality scale, FAS-10 fatigue assessment scale, DHI, and Beck Anxiety and Depression Inventory. There was also a decrease in patients' complaints of cognitive deterioration according to the CGI scale. CONCLUSION: Our study clearly demonstrated the efficacy and high safety profile of Brainmax® in a representative sample of patients with the post-COVID syndrome.

[Clinico-psychological profile and life quality of patients with post-COVID syndrome]. / Kliniko-psikhologicheskii profil' i kachestvo zhizni patsientov s postkovidnym sindromom.

OBJECTIVE: To study clinico-psychological profile and life quality of patients with post-COVID syndrome. MATERIAL AND METHODS: We examined 162 patients aged 24-60 years with confirmed SARS-CoV-2 infection which having symptoms that served as the basis for the diagnosis of post-COVID syndrome. Patients underwent general neurological and somatic examination with allocation of the corresponding neurological syndromes. The intensity and quality of pain were assessed using the McGill Pain questionnaire. The level of psychosocial stress was determined by the Holmes-Ray questionnaire, the identification and severity of asthenia - by the MFI-20 asthenia scale. The level of reactive and personal anxiety was studied according to the Spielberger-Khanin questionnaire, depression - according to the Beck scale. The assessment of life quality was carried out using the Russian version of SF-36 questionnaire. To correct the identified disorders, Mexidol was used according to the scheme: 500 mg once daily intravenously for 14 days, followed by Mexidol FORTE 250 750 mg per day orally (250 mg 3 times a day) for 2 months. RESULTS: The course of treatment with Mexidol in patients with post-COVID syndrome led to decrease in the severity of subjective and objective symptoms, asthenic, anxiety and depressive disorders, and improved the life quality of patients. CONCLUSION: The high efficacy and safety of sequential therapy with Mexidol (injections followed by tablets of Mexidol FORTE 250) has been shown.

[Asthenic post-COVID syndrome]. / Astenicheskii postkovidnyi sindrom.

OBJECTIVE: To evaluate the efficacy and safety of combination therapy for post-COVID asthenic syndrome with multicomponent bioregulatory drugs Traumeel S, Ubichinon compositum and Coenzyme compositum. MATERIAL AND METHODS: The study included 104 patients (averaged age 39.5 [30.8; 48] years) after COVID-19, clinically recovered from an acute infectious process, with asthenic syndrome lasting from 2 weeks to 6 months; the severity of asthenic syndrome on the asthenia VAS scale was at least 30 points. Before the start of the study, in addition to a physical examination, the patient's condition was assessed using the following questionnaires and scales: VAS for asthenia, subjective scale for assessing asthenia (MFI-20), L.D. Malkova, a questionnaire for the quality of life (EQ-5D), a questionnaire for identifying signs of autonomic disorders (Vayne A.M.). The patient's condition was monitored during follow-up visits 2 weeks, 1 month after the start of treatment and 1 month after the end of treatment. Patients of the main group received combination therapy, which included Traumeel S 1 tablet x 3 times a day, Ubichinone compositum and Coenzyme compositum 2.2 ml intramuscularly, alternating every other day, for 1 month (15 injections of each drug per course of treatment). Patients of the comparison group received eleutherococcus extract 100 mg during 30 days, 2 tablets x 2 times a day before mealsand vitamins B. The effectiveness of therapy was assessed by analysis of the asthenia severity (VAS scale), quality of life (EQ-5D questionnaire), patient satisfaction with treatment on a 5-point scale, which was carried out 1 month after the end of the course of treatment. RESULTS: As a result of the treatment was positive. The general asthenia severity, low activity and motivation significantly decreased in patients of both groups without significant differences. At the same time, in patients of the comparison group, there was no correlation between the quality of life and physical and mental asthenia, while in the main group there was an inverse correlation with the asthenia severity, which indicates an increase in the quality of life with a decrease in the severity of asthenia. One of the significant differences was the regression of headache and musculoskeletal pain in patients of the main group. CONCLUSION: The advantage of combined therapy of post-COVID asthenic syndrome with bioregulation therapy Traumeel S, Ubichinone compositum and Coenzyme compositum was shown in comparison with one of the common treatment regimens, including eleutherococcus extract and combined preparations of B vitamins.

[Possibilities of optimizing therapy in COVID-19 survivors with focal epilepsy]. / Vozmozhnosti optimizatsii terapii u patsientov s fokal'noi epilepsiei, perenesshikh COVID-19.

OBJECTIVE: To study the effect of phenosanoic acid therapy on the frequency of seizures, asthenia and quality of life of adult patients with focal epilepsy who had a new coronavirus infection caused by SARS-CoV-2. MATERIAL AND METHODS: The data of 20 patients with focal epilepsy who suffered COVID-19 and received therapy with phenosanic acid (Dibufelon) were studied. The frequency of epileptic seizures, the severity of asthenia and the quality of life were evaluated according to clinical scales. RESULTS: Significant decrease in the frequency of bilateral tonic-clonic seizures and focal seizures with loss of consciousness was recorded. There was a significant improvement in the quality of life. There was no significant dynamics of asthenia against the background of taking the drug phenosanic acid in patients. CONCLUSION: The preparation of phenosanic acid can be an effective means of add-on therapy in patients with epilepsy who have undergone COVID-19.

Benign Acute Children Myositis: Five Years’ Experience in a Tertiary Care Pediatric Hospital (preprint)

Purpose: Benign acute childhood myositis (BACM) is a self-limited childhood illness, and it is mainly caused by viral infections. Clinical and laboratory alterations usually normalize rapidly; generally, the only medical intervention required is supportive (hydration, analgesic medication). The low awareness about BACM often led to delayed diagnosis and unneeded ancillary investigations. This study aims to better characterize the clinical and laboratory features of BACM to improve the diagnostic process and inpatient and outpatient management.  Materials and methods: We conducted a retrospective study selecting all children admitted to Meyer's Children's Hospital-IRCCS (Florence, Italy) with a diagnosis of BACM over the last 5 years. Clinical, laboratory, and instrumental data were collected from electronic clinical records and analyzed.  Results: Sixteen patients were enrolled. The median age was 7.68 years (IQR 5.7-12.9). Male gender (62.5%) and Caucasian ethnicity (68.75%) were prevalent. Most of the patients were admitted during winter, and a second peak has been found in summer. All patients had bilateral calf pain at admission (87.5%), associated with asthenia, and refuse to walk (93.7%). Prodromal symptoms were fever (81.25%), cough (37.5%), coryza (43.5%), sore throat (50%), and vomiting (31.25%). The median value of CPK was 2,183.5 U/L (IQR 1,395.5-7,156.25) at peak. CPK median time to normalization was 7 days (IQR 7-8.5) from the nadir. Influenza B was the virus most frequently BACM associated, followed by influenza A; a novel association with Sars-CoV-2 has been detected. Two patients had pathogenic variants at the Next Generation Sequencing myopathies panel.  Conclusions: School-aged children admitted to the hospital with walking difficulty and myalgia generally after an upper respiratory tract infection with a moderate CPK elevation should remind at first of BACM. Rapid complaint resolution and biochemical markers normalization will prevent unnecessary tests and inappropriate therapies.

Symptoms of SARS-CoV-2 infection and vaccine status of sixty-seven adult patients affected by inherited metabolic diseases: a phone survey. (preprint)

Background: The Covid pandemic seems to have had several detrimental effects on managing patients affected by inherited metabolic diseases (IMD), although published data about the impact of COVID-19 on patients suffering from IMD are very scarce. The scope of our work was to evaluate adherence to the vaccination plan, the side effects experienced by our adult IMD patients, and the symptoms of the SARS-CoV-2 infection. Results: sixty-seven patients agreed to respond to a phone interview. The mean age was 36.5 (±11,6 SD). Regarding the vaccination campaign, fifty-five patients (82%) joined it, of whom ten have received two doses and the remaining forty-five, three. Forty-two patients (76%) reported adverse events following vaccination, the most frequent being local reaction, fever, and asthenia, which lasted an average of two days and resolved without sequelae. Regarding SARS-CoV-2 infection, twenty-seven out of sixty-seven patients (40%) have tested positive for the virus; seven of them were not vaccinated at the time of infection; on the other hand, twenty had already had at least two doses. Regarding the prevalence of long-Covid, as many as 12 patients (44%) reported symptoms that persisted after the nasopharyngeal swab tested negative and lasted an average of 81 (±74 SD) days. There were no statistically significant differences in BMI of patients who contracted the infection and patients who did not (25.15 vs 25.20, p=.861), between those who had adverse reactions to the vaccine and those who did not (24.40 vs 25.75, p=.223), between those who had long Covid and those who did not (25.9 vs 27.7, p=.183). No relation was observed between metabolic inherited disease, SARS-CoV-2 infection symptoms and adverse vaccine reactions. Conclusions: The data indicate that IMD patients adhered to the vaccination plan comparably to the general Italian population. Adverse events to the vaccine were negligible. SARS-CoV-2 infection, which occurred in most cases after receiving at least two doses of the vaccine, did not cause serious symptoms and never required hospitalisation. A non-negligible share of patients suffered from long Covid symptoms.

Long COVID prevalence, follow-up and use of resources in Primary Care: a confirmed case series study (preprint)

Background SARS-CoV-2 infection may produce symptoms for longer than 4 weeks (long COVID). Its duration, causes and consequences are still not well known. The objective of this study is to estimate the prevalence of long COVID, its signs and symptoms and the use of resources in adult patients in Primary Care (PC). Methods Observational, descriptive, retrospective case series study performed in PC. Patients older than 18 years who had a positive polymerase chain reaction test for SARS-CoV-2 from February 29th until April 15th, 2020 were included. Variables related to clinical symptoms and use of resources were registered from 4 weeks after the confirmed COVID-19 case notification, up to 39 weeks. Results Mean age of the 267 patients analyzed was 57 years old (16.0 SD) and 55.8% were women. In the acute phase, 61.8% of the patients required hospitalization and 43.8% suffered bilateral pneumonia. Long COVID prevalence found was 45.7% (CI 95% 39.6–51.9), and 53.3% of them had symptoms longer than 12 weeks. Most common symptoms were dyspnea (45.1%, CI 95% 36.1–54.3), asthenia (42.6%, CI 95% 33.7–51.9), cough (24.6%, CI 95% 17.2–33.2), and neuropsychiatric disorders (18%, CI 95% 11.7–26). 98.4% of long COVID patients required contact with PC during follow-up, with an average of 6.7 (5.0 SD) contacts. At least 45.1% had a lab test, 34.4% a chest x-ray and 41.8% required work leave. Factors associated with a higher number of contacts with PC included developing ARDS (IRR 1.7, CI 95% 1.2–2.2), long COVID (IRR 2.9, CI 95% 2.5–3.4), requiring a work leave (IRR 2.4, CI 95% 2.1–2.9), and the need of hospitalization (IRR 1.5, CI 95% 1.2–1.9). Conclusion Almost half of the patients of this study developed long COVID, similar to preceding works. Most frequent persistent symptoms were dyspnea, asthenia, and cough. Use of resources such as lab tests, chest x-rays, work leaves, PC appointments and hospital referrals, was two to six times greater among long COVID patients, in contrast with those who did not develop long COVID. Requiring hospitalization and having a severe disease at onset was associated to a higher number of PC contacts.

Epidemiological and clinical characteristics of survivors of SARS-COV-2 infection: A descriptive study. / Características epidemiológicas y clínicas de sobrevivientes a infección por SARS-CoV-2: estudio descriptivo.

Introduction: In March 2020, the World Health Organization (WHO) declared a pandemic for coronavirus 19. Typical symptoms were fever, cough, asthenia, dyspnea, and muscle pain. Pulmonary and central nervous system compromise presented challenging characteristics for healthcare physicians. The objectives of this study were to identify epidemiological and clinical characteristics of SARS-COV-2 infection survivors in a region of Argentina and to determine differences between gender, age groups, year of infection, and evolution time since diagnosis. Methods: A descriptive and analytical cross-sectional observational study was carried out. A self-administered questionnaire was applied, which was available between August and December 2021. Results: Among 1868 individuals included, the mean age was 39.4 ± 13.9 years, and 72.8% were female. Arterial hypertension was the most frequent comorbidity (11.7%). The majority were outpatients (81.9%). The most frequent presentation symptoms at all ages were asthenia (83.7%), fever (54.9%), headache (60.8%), anosmia (64.8%), ageusia (53.2%), cough (54.4%) and myalgias (53.7%). For the 18 to 29 years old age group, the most prevalent presentation symptoms were: headache (69.4%), anosmia (69.1%), ageusia (60.2%), odynophagia (45%), and rhinitis/nasal congestion (46.9%). In the 30 to 64 years old age group, there was a higher prevalence of myalgias (55.8%), arthralgias (41%), and concentration/memory disorder (28.3%). Male showed higher prevalence of fever (64.9% versus 51.1%; p < 0.001) and pneumonia (23.5% versus 13.4%; p < 0.001). After 12 weeks from diagnosis, 38.1% of patients persisted with asthenia, 23.6% with anosmia/dysosmia, and 21.2% with concentration/memory disorders. Conclusions: Systemic symptoms were common to all age groups with coronavirus 19 disease; however, younger, and intermediate age groups presented a higher prevalence of central nervous system symptoms such as anosmia and cognitive disorders, respectively. Symptoms beyond 12 weeks of diagnosis reached slightly more than 10% of the participants.

Introducción: En marzo de 2020 la enfermedad por coronavirus 19 fue declarada pandemia por la Organización Mundial de la Salud. Los síntomas más comunes fueron fiebre, tos, astenia, disnea y dolor muscular. Los compromisos pulmonar y del sistema nervioso central presentaron características desafiantes para los médicos asistenciales. Los objetivos del estudio fueron conocer las características epidemiológicas y clínicas de sobrevivientes a infección por SARS-CoV-2 en una región de Argentina, y determinar las diferencias entre género, grupos etarias, año de contagio, tiempo de evolución desde el diagnóstico. Métodos: Se realizó un estudio observacional descriptivo y analítico de corte transversal. Se aplicó un cuestionario auto administrado, que estuvo disponible entre agosto y diciembre de 2021. Resultados: La media de edad fue de 39,4 ± 13,9 años, el 72,8% fueron mujeres. La comorbilidad más frecuente fue hipertensión arterial (11,7%). La mayoría de los pacientes fueron ambulatorios (81,9%). Los síntomas de presentación más frecuentes a cualquier edad, fueron astenia (83,7%), fiebre (54,9%), cefalea (60,8%), anosmia (64,8%), ageusia (53,2%), tos (54,4%) y mialgias (53,7%). Para el grupo de 18 a 29 años los síntomas de presentación más prevalentes fueron cefalea (69,4%), anosmia 69,1%), ageusia (60,2%), odinofagia (45%) y rinitis/congestión nasal (46,9%). En el grupo de 30 a 64 años se observó mayor prevalencia de mialgias (55,8%), artralgias (41%), falta de concentración/memoria (28,3%). Los hombres mostraron más prevalencia de fiebre (64,9% versus 51,1%; p < 0,001) y neumonía (23,5% versus 13,4%; p < 0,001). Luego de las 12 semanas del diagnóstico 38,1% de los pacientes persistían con astenia, 23,6% con anosmia/disosmia y 21,2% con trastornos de concentración/memoria. Conclusiones: La enfermedad por coronavirus 19 presenta un patrón de síntomas sistémicos común a todos los grupos etarios. No obstante, los grupos más jóvenes presentan más prevalencia de síntomas de afección del sistema nervioso central como la anosmia y los grupos intermedios, mayor prevalencia de trastornos cognitivos. Los síntomas más allá de las 12 semanas del diagnóstico alcanzaron a algo más del 10% de los participantes.

[Clinical and immunological correlates in endogenous psychoses developed after COVID-19]. / Kliniko-immunologicheskie korrelyaty pri endogennykh psikhozakh, razvivshikhsya posle perenesennogo COVID-19.

OBJECTIVE: The clinical and immunological study of the potential impact of coronavirus infection on the course of endogenous psychosis. MATERIAL AND METHODS: Thirty-three female patients, aged 16 to 48 years, with depressive-delusional conditions (ICD-10 F20.01, F21, F31) developed after coronavirus infection, of whom 15 people (group 1) had depressive-delusional states 1-2 months after COVID-19 and 18 people (group 2), who developed similar psychoses in later periods (2-6 months). The severity of the psychopathologic symptoms was evaluated with PANSS and HDRS-21 scales. The activity of inflammatory markers - leukocyte elastase (LE) and α1-proteinase inhibitor (α1-PI) in the blood was determined. The absolute neutrophil count, the absolute lymphocyte count and the neutrophil/lymphocyte ratio were calculated. As a control, we used standard values of indicators of age - and sex-matched healthy donors. RESULTS: The endogenous psychosis that developed later after a coronavirus infection (group 2) is associated with a "typical" inflammatory reaction with an increase in the activity of acute phase proteins (according to α1-PI) and degranulation activity of neutrophils (according to LE), which is associated with the development of depressive-delusional states in patients with the dominance of manifestations of positive affectivity (anxiety, melancholy) and the extended nature of delusional disorders, which were predominantly incongruent to affect. On the contrary, the development of endogenous psychosis during the first two months after COVID-19 (group 1) is characterized by a spectrum of inflammatory biomarkers with a decrease in the number of neutrophils and low activity of LE. This immunological profile is associated with the predominance of manifestations of negative affectivity (apathy, asthenia, adynamia) in the structure of depressive-delusional states and the relatively undeveloped nature of delusional disorders, which were predominantly congruent to affect. CONCLUSION: The clinical and biological correlates presumably indicate the modulating effect of the coronavirus infection (COVID-19) on neuroinflammation and the structure of endogenous psychosis.

[Factors associated with an unfavorable evolution in patients diagnosed with COVID-19 and followed up in primary care in 2020]. / Factores asociados con una evolución desfavorable en pacientes diagnosticados de COVID-19 y seguidos en atención primaria en 2020.

AIM: To know the factors associated with an unfavorable evolution (UE) of patients diagnosed with COVID-19 with total or partial follow-up in primary care. DESIGN: A case series. SETTING: Urban health center. PARTICIPANTS: By systematic sampling, patients ≥18 years, diagnosed with COVID-19, with analytical confirmation, in 2020 and followed up by their family doctors, were selected. MAIN MEASUREMENTS: Dependent variable: hospital admission or death due to COVID-19. INDEPENDENT VARIABLES: age, sex, medical background, clinical data and treatments related to the disease. Statistical analysis, with SPSS 25.0: descriptive analysis, comparison of proportions (chi square) and medians (Mann-Whitney U). The analysis is completed with logistic regression. RESULTS: 610 patients were included in the study. The median age was 49 years (interquartile range: 35-61); 51.8% were women; 14.9% presented UE (95% CI: 12.0-17.8). The sociodemographic variables or the variables related to medical background that showed an independent association with UE were age (OR: 1.066; 95% CI: 1.038-1.095), sex (OR for men: 3.277; 95% CI: 1.304-8.235) and being a smoker or former smoker (OR: 2.565; 95% CI: 1.135-5.800). Regarding the clinical variables of the disease, an association was found for altered consciousness (OR: 62.829; 95% CI: 9.177-430.149), dyspnea (OR: 14.339; 95% CI: 6.046-34.009), expectoration (OR: 4.764; 95% CI: 1.858-12.213)) and asthenia (OR: 3.993; 95% CI: 1.705-9.351). CONCLUSIONS: 14.9% of the patients diagnosed with COVID-19 presented an UE. Older age, male sex and being a smoker or former smoker increased the probability of it. Altered consciousness, dyspnea, expectoration, and asthenia were the clinical data that best predicted UE.

Clinical manifestations, treatment options, and comorbidities in COVID-19 relapse patients: A systematic review.

INTRODUCTION: Interest revolving around coronavirus disease 2019 (COVID-19) reinfection is escalating rapidly. By definition, reinfection denotes severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), PCR redetection, and COVID-19 recurrence within three months of the initial symptoms. The main aim of the current systematic review was to evaluate the features of COVID-19 relapse patients. MATERIALS AND METHODS: For this study, we used a string of terms developed by a skilled librarian and through a systematical search in PubMed, Web of Science, and Embase for eligible studies. Clinical surveys of any type were included from January 2019 to March 2021. Eligible studies consisted of two positive assessments separated by a negative result via RT-PCR. RESULTS: Fifty-four studies included 207 cases of COVID-19 reinfection. Children were less likely to have COVID-19 relapse. However, the most patients were in the age group of 20-40 years. Asthenia (66.6%), headache (66.6%), and cough (54.7%) were prevalent symptoms in the first SARS-CoV-2 infection. Asthenia (62.9%), myalgia (62.9%), and headache (61.1%) were most frequent in the second one. The most common treatment options used in first COVID-19 infection were lopinavir/ritonavir (80%), oxygen support (69.2%), and oseltamivir (66.6). However, for the treatment of second infection, mostly antibiotics (100%), dexamethasone (100%), and remdesivir (80%) were used. In addition, obesity (32.5%), kidney failure (30.7%), and hypertension (30.1%) were the most common comorbidities. Unfortunately, approximately 4.5% of patients died. CONCLUSION: We found the potency of COVID-19 recurrence as an outstanding issue. This feature should be regarded in the COVID-19 management. Furthermore, the first and second COVID-19 are similar in clinical features. For clinically practical comparison of the symptoms severity between two epochs of infection, uniform data of both are required. We suggest that future studies undertake a homogenous approach to establish the clinical patterns of the reinfection phenomena.

[The use of neurotropic therapy in young patients with postcovid syndrome]. / Primenenie neirotropnoi terapii u molodykh patsientov s postkovidnym sindromom.

OBJECTIVE: The aim of the present study was to identify postcovid asthenic syndrome and cognitive disorders in young patients on an outpatient basis, and to evaluate the experience of using combined neurotropic therapy in this category of patients. MATERIAL AND METHODS: Included 87 young patients who underwent COVID-19 and applied for an outpatient appointment with a neurologist. All patients underwent a scale assessment of the severity of asthenia on the MFI-20 scale, cognitive functions - on the MMSE scale, the 5-word test and the Schulte test. The severity of the anxiety syndrome - according to the Spielberger Anxiety Scale. All patients in the study group were treated with a combination of Cortexin and Recognan, and a repeat study was conducted 4 weeks after treatment. RESULTS: The study revealed the predominance in the observation group of patients with a comorbid background, as well as pronounced anxiety disorders. After the complex treatment, there was a significant decrease in the indicators of common, physical, mental asthenia, as well as an increase in motivational activity, there was a decrease in situational anxiety, and to a lesser extent personal anxiety. According to cognitive tests, there was an improvement in indicators on the MMSE scale, direct reproduction of the 5-word test, significant changes in the evaluation of work efficiency when performing the Schulte test. CONCLUSION: It should be noted that the positive results of this study can be considered a decrease in the severity and severity of asthenia symptoms, a decrease in anxiety manifestations, and an improvement in cognitive functions against the background of complex neurotropic therapy with Cortexin and Recognan. Preference in this situation should be given to drugs with a multimodal mechanism of action, as well as creating optimal combinations of drugs that potentiate each other's action.

Long COVID-19 symptoms: Clinical characteristics and recovery rate among non-severe outpatients over a six-month follow-up.

BACKGROUND: To describe persistent symptoms in long COVID-19 non-severe outpatients and report the 6-month clinical recovery (CR) rate. METHODS: Observational study enrolling outpatients (≥ 18 years) with confirmed non-severe COVID-19 (positive nasopharyngeal RT-PCR or presence of SARS-CoV-2 antibodies) who consulted for persistent symptoms after the first pandemic wave (March-May 2020). CR was assessed at the 6-month visit and defined as complete (no symptom), partial (persistent symptoms of lower intensity) or lack of recovery (no improvement). RESULTS: Sixty-three patients (79% women, mean age: 48 years) enrolled; main symptoms (mean 81 days after acute infection): asthenia/myalgia (77%), dyspnea (51%), headaches (35%), cough (33%). At 6 months (n=56), 30% had complete, 57% partial, and 13% lack of recovery. The proportion of patients with>2 persistent symptoms was 26% at 6 months (main symptoms: dyspnea [54%] and asthenia/myalgia [46%]). CONCLUSION: We observed a slow but high recovery rate at 6 months among these outpatients.

Erythema nodosum induced by Covid-19 Pfizer-BioNTech mRNA Vaccine (preprint)

Erythema nodosum (EN), the most form of panniculitis, is mainly caused by numerous infective (especially Beta-hemolytic streptococcal infections) and non-infective (especially sarcoidosis) diseases and drugs. EN associated with vaccines has been rarely reported. We describe herein, an original clinical observation of EN induced by BNT162b2, an mRNA vaccine. A 75-year-old woman presented with diffuse erythematous painful rounded nodular lesions, located symmetrically over her legs. Six days before, she had received the second dose of Covid-19 vaccine (BNT162b2 (Pfizer–BioNTech)), followed by a sudden asthenia, polyarthralgia, throbbing and edema over her lower limbs. She had been given the first dose of the same Covid-19 vaccine 29 days prior to the second without incident. General physical examination was normal. Skin examination showed multiple, erythematous tender, nodules, 10–30 mm in diameter, over the tibial area. Complete blood count, renal and hepatic tests, antistreptolysin O titer, antinuclear antibody, thyroid test and chest radiograph and PCR, were carried out, and found to be normal. Histopathology revealed infiltration of deep dermal vessels and subcutaneous fat with lymphomononuclear cells and neutrophils, consistent with erythema nodosum. Treatment with analgesics led to complete resolution of the lesion after three months. The patient has shown no relapse after follow-up for three months. In conclusion, to our knowledge, this is the first case of EN induced by the second dose of BNT162b2 (Pfizer–BioNTech) Covid-19 vaccine. It is important for clinicians to be aware of this rare, yet potential, adverse effect to this vaccine.

Study of Prevalence and Characteristics of Long Covid in Spanish Children (preprint)

Objectives: Prolonged symptoms after acute COVID-19 have been described in the pediatric population. Our objective was to know the prevalence of prolonged symptoms in children with confirmed SARS-CoV-2 infection, and to describe their clinical characteristics and possible risk factors.Patients & methodsMulticentre retrospective study carried by telephone questionnaire of all children under 18 years old diagnosed of symptomatic COVID-19, both hospitalized and outpatient attended in three hospitals in Spain between March and December 2020. Long-COVID was defined as the presence of symptoms longer than 12 weeks. A control group of children attended by other causes was also contacted and compared.Results451 children met criteria and agreed to participate; 370/451 (82%) presented mild outpatient infection, and 23 required admission in PICU (5.1%). The mean age was 5.9 years old (SD 5.3). A control group of 98 children was included.In 66 cases (14.6%) at least one symptom lasted longer than 12 weeks. Insomnia, concentration problems, apathy or sadness and anxiety were the longest (median >90 days). Age above 5 years (48/66; 72.7%, OR: 3, CI 95% (1.8-5)); admission (OR 3.9 CI 95% (2.2-6.8)), the need for PICU (OR 4.3 CI 95% (1.8-10.4)), and to have a relative with prolonged symptoms (OR 2.8 CI 95% (1.5-5.2)) were significantly associated with Long-COVID. When comparing with controls age above 5 years old, myalgia, asthenia, and loss of appetite were significantly associated with Long-COVID.ConclusionsOur study shows that children also suffer prolonged symptoms after COVID-19 infection, and require specific attention.

[NEUROLOGICAL COMPLICATIONS OF COVID-19: REVIEW OF LITERATURE AND OWN EXPERIENCE].

According to the literature, the main neurological complications of COVID-19 are hyposmia, hypogeia, headache, dizziness, myalgia, and severe neurological syndromes like encephalopathy, stroke, and coma. The mechanisms of neurological complications of the acute period are direct viral damage, hypoxic damage, and immune damage due to the activation of inflammation, including autoantibodies. After the end of the acute phase of the disease, neurological complications in the form of asthenic syndrome, vascular syndrome, exacerbation of chronic diseases (deterioration of cognitive and communication functions in patients with autism, schizophrenia, exacerbation of autoimmune neurological diseases, aggravation of the condition of patients with tics, increased frequency of epileptic seizures in adults and children, resumption of epileptic seizures in patients who were previously in stable remission, the debut of epileptic seizures). These disorders are based on the following mechanisms: neuroinflammation, activation of pro-inflammatory cytokines (IL-1, -2, -6, -8, -10, -17, -18, CXCL10, CCL2), formation of autoantibodies, increased permeability of the blood-brain barrier, mitochondrial dysfunction, adrenal and thyroid dysfunction, venous dyscirculation. In the treatment of neurological complications after a COVID-19 infection, it is advisable to use anti-inflammatory therapy, mitochondrial therapy (including the technique of intermittent hypoxic-hyperoxic therapy), detoxication, correction of hormonal status (primarily the state of the adrenal glands and thyroid gland), vasoactive therapy, and symptomatic therapy.

Long-term manifestations and modifiers of prevalence estimates of the post-COVID-19 syndrome: A systematic review and meta-analysis. (preprint)

Background: Post-acute COVID-19 syndrome (PACS) is a multi-system disease comprising persistent symptomatology after the acute phase of infection. Long-term PACS effects significantly impact patient outcomes, but their incidence remains uncharacterized due to high heterogeneity between studies. Therefore, we aimed to summarize published data on PACS, characterizing the clinical presentation, prevalence, and modifiers of prevalence estimates. Method: In this systematic review and meta-analysis, we research MEDLINE for original studies published from January 1st, 2020, to January 31st, 2021, that reported proportions of PACS manifestations. Studies were eligible for inclusion if they included patients aged [≥]18 years with confirmed COVID-19 by RT-PCR or antigen testing and a minimum follow-up of 21 days. The prevalence of individual manifestations across studies was pooled using random-effects meta-analysis. For evaluating determinants of heterogeneity, meta-regression analysis was performed. This study was registered in PROSPERO (CRD42019125025). Results: After screening 1,235 studies, we included 29 reports for analysis. Twenty-seven meta-analyses were performed, and 61 long-term manifestations were described. The pooled prevalence of PACS was 56% (95%CI 45-66%), with the most common manifestations being diminished health status, fatigue, asthenia, dyspnea, myalgias, hyposmia and dysgeusia. Most of the included studies presented high heterogeneity. After conducting the meta-regression analysis, we identified that age, gender, number of comorbidities, and reported symptoms significantly modify the prevalence estimation of PACS long-term manifestations. Conclusion: PACS is inconsistently reported between studies, and population characteristics influence the prevalence estimates due to high heterogeneity. A systematized approach for the study of PACS is needed to characterize its impact adequately.

[Asthenic disorders as a manifestation of chronic fatigue syndrome]. / Astenicheskie rasstroistva kak proyavlenie sindroma khronicheskoi ustalosti.

The article explains the changes in terminology and diagnostic criteria for asthenic disorders as manifestations of chronic fatigue syndrome CFS (myalgic encephalomyelitis). Chronic fatigue syndrome is defined as neuroimmune endocrine dysfunction with a purely clinical diagnosis. Probably, viral infections can play a leading role in the pathogenesis. Published diagnostic criteria reveal possible correlations between chronic fatigue syndrome and COVID-19 disease. A promising strategy for the therapy and rehabilitation of patients is the use of smart peptides, a representative of which is the drug cortexin.