Search Results (124)

The COVID-19 pandemic has demonstrated that its effects go far beyond the initial respiratory illness, with many survivors experiencing lasting neurological problems. Some patients develop a condition known as Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), which includes current issues such as reduced cognitive function, chronic headaches, depression, neuropathic pain, and sensory disturbances. These symptoms can severely disrupt daily life and overall well-being. In this narrative review, we provide an overview of current understanding regarding the neurological effects of COVID-19, with a focus on Long COVID. We discuss possible underlying mechanisms, including direct viral invasion of the nervous system, immune-related damage, and vascular complications. We also summarize findings from cohort studies and meta-analyses that explore the causes, symptom patterns, and frequency of these neurological issues. Approximately one-third of people who have had COVID-19 report neurological symptoms, especially those who experienced severe illness or were infected with pre-Omicron variants. Emerging research has identified potential biomarkers such as neurofilament light chain (NFL) and glial fibrillary acidic protein (GFAP) that may help in diagnosis. Treatment approaches under investigation include antiviral medications, nutraceuticals, and comprehensive rehabilitation programs. Factors like older age, existing health conditions, and genetic differences in ACE2 and TMPRSS2 genes may affect an individual’s risk. To effectively address these challenges, current research is essential to improve diagnostic methods, develop targeted treatments, and enhance rehabilitation strategies. Ultimately, a coordinated, multidisciplinary effort is crucial to reduce the neurological impact of Long COVID and support better recovery for patients. Full article

Long COVID is frequently accompanied by enduring neurocognitive and physical symptoms that substantially affect quality of life. Cognitive complaints—including difficulties in memory, attention, and executive functioning—often co-occur with physical manifestations such as fatigue, dyspnea, and headache. Despite growing research, openly available datasets integrating demographic, cognitive, and physical symptom profiles assessed during chronic phases of Long COVID remain scarce. Here, we present two complementary self-report datasets collected ≥6 months after the most recent COVID-19 infection. The first dataset (“Neuro–Long COVID-212”) includes demographic information, binary neurocognitive symptom indicators, and a 14-item Post-COVID Cognitive Impairment Scale assessing memory and attention complaints. The second dataset (“Neuro–Long COVID–210”) provides a broad range of physical symptoms—operationally defined as somatic and neurological complaints (e.g., fatigue, pain, sleep disturbance, anosmia/ageusia)—recorded as binary indicators (present/absent). Data were collected online via the Porsline platform using individualized links, with remote researcher support to ensure accuracy. Quality assurance procedures included duplicate-response removal, consistency checks, and transparent handling of missing values. The datasets are released in Excel (.xlsx) format, fully de-identified and accompanied by a detailed data dictionary to facilitate reuse. These datasets enable reproducibility, secondary analyses, and meta-analyses on cognitive and physical outcomes in Long COVID, and may inform future cross-disciplinary rehabilitation research. Full article

Background: Headache is a common symptom during acute viral infections, and its pathophysiology has been linked with the immune response to the virus. Headache is one of the most frequent symptoms of coronavirus disease 2019 (COVID-19), and it has been associated with a more efficient immune response and a better prognosis. The aim of this article is to evaluate whether vaccination could modify the clinical phenotype and the probability of developing persistent headache after acute COVID-19. Methods: A case–control study comparing the duration of the headache and the clinical phenotype between fully vaccinated individuals and non-vaccinated controls was conducted. Each case was matched with two controls that were paired by age, sex, and prior history of headache. Patients were evaluated by a physician that administered a structured questionnaire and were followed up for at least three months. Results: The sample included 103 cases and 206 controls, with a median age of 42 (inter-quartile range (IQR) 33–51); 68% were female; and 26% had a prior history of headache. Headache had a shorter duration for vaccinated patients (4 (IQR 2–8) vs. 8 (IQR 4–16.5) days, p < 0.001). Vaccinated patients had a higher frequency of holocranial topography, pressing quality, phonophobia, and cranial autonomic symptoms. Conclusions: Our results suggest that full vaccination modifies the clinical phenotype of COVID-19 onset-associated headache and might lead to a shorter duration. These findings could represent an additional benefit of COVID-19 vaccines, which could extend to the post-COVID-19 phase and decrease the probability of a persistent disabling symptom such as headache. Full article

Background: Numerous studies have proved the efficacy of vaccination in reducing Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) transmission and the coronavirus disease (COVID-19) burden. However, even though the COVID-19 vaccination coverage is high for primary doses, a booster dose is needed to sustain protection. Continuing our previous research, this study evaluates the immunogenicity and safety of full and half doses of two COVID-19 booster vaccines, ChAdOx1-S (AstraZeneca) and BNT162b2 (Pfizer-BioNTech), in individuals primed with ChAdOx1-S. Methods: This study was an observer-blind randomized controlled trial to evaluate the immunogenicity and safety of half and full doses of two COVID-19 booster vaccine types, BNT162b2 and ChAdOx1-S, among fully vaccinated, ChAdOx1-S-primed individuals in Jakarta, Indonesia. A total of 329 participants were randomized to receive either full or half doses of the booster vaccines, namely the ChAdOx1-S and BNT162b2 COVID-19 vaccines. Immunogenicity was assessed through SARS-CoV-2 antibody titers and neutralizing antibodies (NAbs) at 28 days post-booster, while safety was monitored via adverse event reporting. Results: The results showed that both vaccines demonstrated increased geometric mean titers (GMTs) post-booster. In the ChAdOx1-S booster group, at the baseline visit (day 0) and third visit (day 28), no statistically significant differences in GMT between the half- and full-dose groups were observed (p = 0.970 and 0.539, respectively). In the BNT162b2 group, no statistically significant difference was noted at the baseline visit, while the full dose was higher than the half dose at 28 days (Day 28, p = 0.011). Surrogate virus neutralization tests (sVNTs) and NAbs assays also revealed no significant differences between the half and full dose groups for both the Wuhan strain and the Delta variant. The BNT162b2 group compared to the ChAdOx1-S group revealed a statistically significant increase in IgG levels compared to ChAdOx1-S, with p-values of <0.001 and <0.001 for the half dose and full dose, respectively. This was also reflected in the NAbs test results, where BNT162b2 showed significantly higher levels against both the Wuhan strain and Delta variant. Adverse events were predominantly mild: 79.6% (n = 86/108) in the ChAdOx1-S full-dose group, 75.4% (n = 43/57) in the ChAdOx1-S half-dose group, 84.2% (n = 101/120) in the BNT162b2 full-dose group, and 92.6% (n = 88/95) in the BNT162b2 half-dose group, with pain at the injection site being the most common local reaction and myalgia and headache the most frequent systemic reactions. One serious adverse event was reported, assessed as unrelated to the vaccine. Conclusions: This study confirms that half doses of ChAdOx1-S and BNT162b2 are as immunogenic and safe as full doses, and a heterologous booster is more immunogenic than a homologous booster. Full article

Background: During the global fight against the COVID-19 pandemic, vaccinations have been widely recognized as the most effective and generally safe method for preventing the spread of COVID-19. However, it has been reported that children may experience post-vaccination serious adverse drug reactions (SADRs). Thus, we aimed to analyze the risk of SADRs to COVID-19 vaccines in the pediatric population. Methods: In this retrospective, cross-sectional study, 5422 cases of SADRs (n = 5018 for Pfizer BioNTech, Comirnaty and n = 494 for Moderna, Spikevax) were analyzed after 37,344,343 doses of COVID-19 vaccines were administered. This study covered the European Economic Area. The analysis period for both vaccinations and SADRs spanned from 7 December 2020 to 5 October 2023. The analysis encompassed 207 types of SADRs grouped into 12 categories. All estimated real-world reporting rates were reported as normalized per million ADR reports and adjusted using real-world trial-based scaling (APMR). Results: The total estimated real-world reporting rates of SADRs were 5792 APMR for Comirnaty and 5671 for Spikevax. The most commonly reported clinical categories of suspected SADRs for both vaccines were neuropsychiatric, cardiovascular and gastroenterological disorders. The most often reported SADRs encompassed headaches, myocarditis, episodes of syncope, dizziness and dyspnea. Conclusions: According to the data from this study, several SADRs were reported in children following COVID-19 vaccination. The estimated real-world reporting rates of SADRs related to COVID-19 vaccines seem to be rare among children. Additionally, the data suggest that Comirnaty (Pfizer-BioNTech) may have a similar risk profile compared to Spikevax (Moderna). Full article

Background: This cross-sectional study was conducted among adult Omani patients with a confirmed laboratory diagnosis of COVID-19 to determine the prevalence of dizziness, tinnitus and headache in the pre-, during and post-COVID-19 recovery phases. Methodology: The characteristics and severity of symptoms of dizziness, tinnitus and headache in the above three phases were determined by telephone interviews. The severity of symptoms was recorded using the visual analog score. Results: The total number of patients selected was n = 102 (M/F 50/50%; overall mean age = 33.52 ± 3.6 years). The pre-COVID-19 prevalence of dizziness was 16%, tinnitus 13% and headache 53%. During COVID, the prevalence of dizziness increased to 41%; for tinnitus, it remained the same; and for headache, it increased to 73%. Compared to the lower age group category (30–32 years); the pre-COVID-19 prevalence of dizziness was significantly higher in the 33–40 years age group. The severity of symptoms showed a significant correlation in different phases, pre- and post-COVID-19, for dizziness (r = 0.556), tinnitus (r = 0.714) and headache (r = 0.696), and tinnitus during and post-COVID-19 (r = 0.570). Conclusion: The prevalence of dizziness, tinnitus and headaches was high in COVID-19 patients. All symptoms pre-COVID-19 and during COVID-19 persisted post-COVID-19. Full article

Background and Aims: The majority of individuals with COVID-19 developed acute symptoms. Post-COVID-19 syndrome refers to the signs and symptoms of COVID-19 that persist for more than 12 weeks. The present study was conducted to estimate the prevalence and risk factors for post-COVID-19 syndrome in the Omani population. Methods: This is a cross-sectional study that was conducted at the University Hospital Center (UHC). All patients diagnosed with COVID-19 (through polymerase chain reaction PCR testing) between March 2020 and March 2022 were included. Eligible participants were interviewed through a phone call, informed about the study procedure, and invited to participate in the study. Results: The study enrolled 265 COVID-19 patients, of whom 156 (59.2%) were females and 204 (77.3%) had been vaccinated. The overall prevalence of post-COVID-19 syndrome was 48.5%. The most common symptom was fatigue (71, 26.9%), followed by joint pain (44, 16.7%). The other symptoms included loss of taste/smell (34, 12.9%), cough (32, 12.1%), palpitation (25, 9.5%), and hair loss (27, 10.2%). Unvaccinated patients showed a higher incidence of fatigue (p = 0.03) and loss of smell/taste (p = 0.01) on univariate analysis. Females were at high risk for the development of various symptoms, including fatigue, muscular pain, breathing difficulty, cough, chest pain, palpitation, headache, and hair loss. Multivariate analysis showed that female gender is a significant independent predictor (odds ratio: 3.1; p = 0.00) for the development of post-COVID-19 syndrome. Conclusions: The prevalence of post-COVID-19 syndrome among the Omani population was high, highlighting the need for targeted interventions to manage long-term symptoms in vulnerable groups. Full article

Background and Aim: PASC is a potentially debilitating clinical condition consisting of different general symptoms experienced by about 10% of patients with previous SARS-CoV-2 infection. Our study analyses a cohort of patients with a history of hospitalization for COVID-19 and aims to evaluate prognostic factors for experiencing PASC and to investigate the characteristics of patients experiencing PASC symptoms. Methods: This is an observational, monocentric retrospective study including all adult patients admitted to our COVID unit from 28 February 2020 to 30 April 2022, discharged alive, and having performed at least one follow-up visit at our post-COVID outpatient clinic after a minimum of three months from discharge. Patients who experienced persistent clinical manifestations or the development of new symptoms three months after the initial SARS-CoV-2 infection, with these symptoms lasting for at least two months with no other explanation, were defined as having PASC. Results: A total of 429 patients were discharged alive from our COVID Unit and 244 patients performed at least one follow-up visit in our outpatient clinic. Of these, 134 patients did not experience PASC, while 110 patients experienced PASC. Long-COVID patients were more frequently female (43.6% vs. 31.3%, p = 0.048), more frequently presented throat pain and headache at hospital admission (respectively 8.9% vs. 2.5%, p = 0.041 and 15.8% vs. 5%, p = 0.007), and were more likely to have a history of type 2 diabetes mellitus (25.5% vs. 13%, p =0.013). At the multivariable analysis, female gender, type 2 diabetes, and headache at admission were factors associated with PASC. All 46 patients who performed at least two different admissions in our outpatient clinic were divided in two groups: the first including the 16 patients who experienced a reduction or a resolution of symptoms related to COVID-19, the second comprising the 30 patients who experienced clinical worsening or persisting symptoms. Smoking habit was more represented among patients with stable or worsening symptoms (42.3% vs. 7.7%, p = 0.042); myalgias at admission were more frequent in the clinical worsening group (27.6% vs. 0%, p= 0.039); and a larger amount of patients who reported neuropsychiatric symptoms and respiratory symptoms were in the stable or worsening PASC symptoms group. Discussion: In conclusion, this study underscores the complexity of PASC, identifying female sex, Type 2 diabetes, and certain acute COVID-19 symptoms as potential predisposing factors for its development. PASC still represents a substantial public health challenge, and ongoing efforts are essential to better understand its underlying mechanisms and improve patient outcomes. Full article

Background/Objectives: The present study aimed to analyze changes in symptom intensity during the recovery period of COVID-19 survivors and patients with post-COVID syndrome. Methods: Initially, we described a new remote patient monitoring system to track the intensity of specific symptoms in individuals’ home environments. Remote patient monitoring (RPM) was implemented over 15 days in a cohort of 133 individuals aged 20 to 78 years, divided into four groups: mild (MG, n = 40), Hospital Discharge Without Invasive Mechanical Ventilation (WIMV, n = 40), Hospital Discharge With Invasive Mechanical Ventilation (IMV, n = 13), and reinfected (RG, n = 40). Results: The most prevalent symptoms reported across all groups, based on average intensity, were shortness of breath, fatigue, cough, headache, and body pain. The WIMV group exhibited the highest average intensities in six symptoms (p < 0.01), while the IMV group reported the highest averages in four symptoms (p < 0.05). Fatigue was the symptom with the highest overall intensity, followed by memory lapses. The hospitalized groups demonstrated the highest intensities and most persistent symptoms (p < 0.05). Blood pressure was significantly higher in the MG group compared to the RG group (p < 0.0001), although all values remained within the normal range. Conclusions: These results provide novel insights, revealing distinct differences in the symptom profiles among the studied groups. These findings hold significant implications for developing more personalized care strategies and informing future pandemic preparedness and response efforts. Full article

Background: The COVID-19 pandemic highlighted the need for innovative vaccine platforms that elicit durable immunity. Self-amplifying RNA (saRNA) vaccines offer rapid production and dose-sparing advantages over traditional mRNA platforms. In Uganda’s first SARS-CoV-2 vaccine trial (NCT04934111), we assessed the safety and immunogenicity of a saRNA vaccine encoding the SARS-CoV-2 spike (S) glycoprotein in seronegative and seropositive adults. Methods: This non-randomised phase 1 trial (December 2021–April 2022) enrolled 42 healthy adults (18–45 years), including 12 seronegative and 30 seropositive for SARS-CoV-2. Participants received two 5 μg doses of saRNA vaccine, four weeks apart. Reactogenicity was assessed using diary cards for seven days post-vaccination, and adverse events were monitored throughout the 24-week study. Binding and neutralising antibody levels were quantified using ELISA and pseudovirus neutralisation assays. Findings: The vaccine was well tolerated, with only mild-to-moderate adverse events, including fatigue, headache, and chills. No serious vaccine-related events occurred. Among seronegative participants, 91.6% seroconverted after two doses (median S-IgG: 3695 ng/mL, p < 0.001). In the seropositive participants, S-IgG rose modestly from 7496 to 11,028 ng/mL after the second dose. Neutralising titres increased modestly across WT, BA.2, and A.23.1 variants, with no significant differences between groups. Conclusion: The saRNA SARS-CoV-2 vaccine was safe and immunogenic, inducing robust spike glycoprotein-specific antibody responses, particularly in seronegative participants. This trial demonstrates the potential of saRNA vaccines for broader use. Full article

Background/Objectives: Headache is one of the most common neurological symptoms associated with COVID-19, affecting approximately 25% of patients. While most headaches resolve within weeks, some persist for months, suggesting underlying structural brain changes. This study aimed to identify brain MRI abnormalities associated with chronic headaches in patients with a history of COVID-19 infection. Methods: This retrospective study included 30 patients with post-COVID-19 headaches and 30 control patients with no history of COVID-19. Demographic characteristics were analyzed using t-tests and chi-square tests. MRI findings were categorized into six types: cortical atrophy, white matter lesions, vascular lesions, lacunar lesions, vascular encephalopathy, and sinusitis. Differences in MRI findings between the two groups were evaluated using chi-square tests. Secondary outcomes included the analysis of symptoms accompanying headaches, diagnoses following MRI, and treatments applied. Results: White matter lesions were significantly more frequent in the post-COVID-19 group (50%) compared to controls (20%) (p = 0.015). Conversely, sinusitis was more prevalent in the control group (36.7%) than in the post-COVID-19 group (6.7%) (p = 0.005). Other MRI abnormalities showed no significant differences. Cognitive dysfunction (30%) and dizziness (33.3%) were the most common associated symptoms. The most frequent diagnoses after MRI in the post-COVID-19 group were headaches/migraines (23.3%), post-COVID-19 headache (20%), and vestibular syndrome (13.3%). Conclusions: Persistent post-COVID-19 headaches may be linked to structural white matter changes observed in MRI. Further research, ideally including pre-infection imaging data, is needed to determine the causal relationship between these lesions and chronic headache symptoms. Trial Registration: This study was registered in ClinicalTrials with the trial registration number NCT06825741 on 13 February 2025. Full article

This study aimed to evaluate the type, frequency, onset, and recovery duration of neurological symptoms caused by COVID-19, including newly emerging post-COVID-19 neurological findings, to contribute to improved prognosis and follow-up strategies. A total of 110 COVID-19 patients hospitalized with positive SARS-CoV-2 PCR tests (24 December 2021–10 March 2022) were prospectively assessed. Neurological symptoms during hospitalization and at 1, 3, and 6 months post-discharge were documented, with all findings confirmed by a neurologist. The time of symptom onset was recorded for each patient. Fatigue (75.5%) was the most common symptom, lasting 10.43 weeks on average, followed by myalgia (57.3%, 4.29 weeks) and headache (56.4%, 3.35 weeks). Forgetfulness persisted the longest (22.03 weeks). Headache and myalgia were more frequent in women, while symptoms like dizziness, insomnia, and nausea/vomiting were more common in patients aged ≤50. No significant differences in symptom duration were observed based on age or gender. Neurological symptoms, such as fatigue, headache, myalgia, and forgetfulness, were prevalent in both the acute and post-COVID-19 phases. The study underscores the importance of systematic neurological monitoring and the development of individualized follow-up strategies to manage long-term neurological effects and improve patient outcomes. Full article

(1) Background: Persistent post-COVID-19 headaches are emerging as a significant post-infection symptom. This study investigates the clinical characteristics of persistent post-COVID-19 headaches and the potential role of pro-inflammatory cytokines. (2) Methods: We conducted a pilot case–control study involving 84 participants divided into three groups: post-COVID with headache (n = 28), post-COVID without headache (n = 28), and healthy controls (n = 28). The detailed headache characteristics, including pain intensity, were assessed using the Visual Analog Scale (VAS). The serum levels of inflammatory cytokines (IL-6 and TNF-α) were measured. (3) Results: Post-COVID headaches predominantly presented as bilateral (53.6%) and throbbing (60.7%) in nature, with a median of 12 headache days per month and high pain intensity (median VAS score = 80). The associated symptoms were phonophobia (85.7%), fatigue (78.6%), and photophobia (75%). The serum levels of IL-6 and TNF-α were significantly higher in post-COVID headache patients than in the post-COVID without headache and healthy control groups (p < 0.001). A Receiver Operating Characteristic analysis showed that the circulating levels of IL-6 and TNF-α could discriminate our study groups at cutoffs with variable sensitivity and specificity. (4) Conclusions: Persistent post-COVID-19 headaches have diverse clinical characteristics and are associated with elevated circulating levels of pro-inflammatory cytokines, suggesting a potential underlying neuroinflammation. Full article

Long COVID, also known as post-acute sequelae of SARS-CoV-2 infection (PASC), is increasingly recognized as a condition affecting not only adults but also children and adolescents. While children often experience milder acute COVID-19 symptoms compared to adults, some develop persistent physical, psychological, and neurological symptoms lasting for weeks or months after initial infection. The most commonly reported symptoms include debilitating fatigue, respiratory issues, headaches, muscle pain, gastrointestinal disturbances, and cognitive difficulties, which significantly impact daily activities, schooling, and social interactions. Additionally, many children with long COVID experience psychological symptoms, such as anxiety, depression, mood swings, and irritability, likely exacerbated by prolonged illness and lifestyle disruptions. Risk factors for long COVID in children include pre-existing health conditions such as asthma, obesity, and neurological disorders, with adolescents and females seemingly more affected. Hypothesized mechanisms underlying long COVID include chronic immune dysregulation, persistent viral particles stimulating inflammation, autonomic nervous system dysfunction, and mitochondrial impairment, which may collectively contribute to the variety of observed symptoms. Long-term outcomes remain uncertain; however, long COVID can lead to school absenteeism, social withdrawal, and psychological distress, potentially affecting cognitive development. Severe cases may develop chronic conditions such as postural orthostatic tachycardia syndrome (POTS) and reduced exercise tolerance. This review synthesizes the existing literature on long COVID in children, examining its prevalence, symptomatology, risk factors, and potential mechanisms, with an emphasis on the need for further clinical studies. While existing research largely relies on surveys and self-reported data, clinical assessments are essential to accurately characterize long COVID in pediatric populations and to guide effective management strategies. Full article

Background/Objectives: Millions of individuals worldwide continue to experience symptoms following SARS-CoV-2 infection. This study aimed to assess the prevalence and phenotype of multi-system symptoms attributed to Long COVID—including fatigue, pain, cognitive-emotional disturbances, headache, cardiopulmonary issues, and alterations in taste and smell—that have persisted for at least two years after acute infection, which we define as “persistent Long COVID”. Additionally, the study aimed to identify clinical features and blood biomarkers associated with persistent Long COVID symptoms. Methods: We sent a detailed long COVID symptoms questionnaire to an existing cohort of 1258 vaccinated adults (age 18–79 years) who had mild infection (e.g., non-hospitalized) SARS-CoV-2 Delta variant 2 years earlier. These individuals had comprehensive datasets, including blood samples, available for further analysis. We estimated prevalence of persistent long COVID two years post-infection using weighted adjustment (Horvitz–Thompson estimator) to overcome reporting bias. Multivariable logistic regression models were used to determine association of clinical features and blood biomarkers (pre-infection SARS-CoV-2 RBD-IgG, SARS-CoV-2 neutralizing antibodies, and pre-infection and post-infection neurofilament light) with prevalence of persistent long COVID. Results: N = 323 participants responded to the survey, of whom N = 74 (23%) reported at least one long COVID symptom that had persisted for two years after the acute infection. Weighted prevalence of persistent long COVID symptoms was 21.5% (95% CI = 16.7–26.3%). Female gender, smoking, and severity of acute COVID-19 infection were significantly associated with persistent Long COVID. The blood biomarkers assessed were not significantly associated with persistent Long COVID. Conclusions: Among vaccinated adults two years after mild infection with Delta variant SARS-CoV-2, persistent symptoms attributed to Long COVID are extremely common, certain subgroups are at higher risk, and further research into biological mechanisms and potential treatment targets is needed. Full article