Neurological manifestations of acute SARS-CoV-2 infection in pediatric patients: a 3-year study (preprint)

Purpose This study analyzed the neurological manifestation profiles of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection across pandemic waves in pediatric patients.Methods This retrospective study analyzed the data of patients aged 0–18 years who were diagnosed with acute SARS-CoV-2 infection and admitted to a pediatric tertiary hospital between March 1, 2020, and February 28, 2023. The presence of neurological manifestations was established based on the symptoms noted in each patient chart. The relationships between neurological manifestations and pandemic waves or age groups were assessed using the chi-square test.Results This study included 1677 patients. Neurological manifestations were noted in 10% (n = 168) of patients with a 3.2 years median age (interquartile range: 1–11.92). Neurological manifestations were significantly associated with the pandemic waves (p = 0.006) and age groups (p < 0.001). Seizures were noted in 4.2% of cases and reached an increasing frequency over time (p = 0.001), but were not associated with age groups. Febrile seizures accounted for the majority of seizures. Headache was reported in 2.6% of cases and had similar frequencies across the pandemic waves and age groups. Muscular involvement was noted in 2% of cases and reached a decreasing frequency over time (p < 0.001) and showed different frequencies among the age groups.Conclusions Neurological manifestations of acute SARS-CoV-2 infection exhibit distinct patterns, depending on the pandemic wave and patient age group. The Wuhan and Omicron waves involved the nervous system more often than the other waves; however, this was probably through different mechanisms.

Cardiac safety after AstraZeneca COVID-19 vaccination: A cohort observational study (preprint)

Background Vaccination is a well-established part of preventive and public health medicine but is not without risk. Most of the side effects related to COVID-19 vaccines are minor including local symptoms at the injection site and some systemic symptoms, such as fatigue, headache, and fever. Some preliminary reports mentioned a more serious side effect; myocarditis seen after certain COVID-19 vaccines. The purpose of this study was to reveal any decrease in left ventricular systolic function in patients receiving the AstraZeneca COVID-19 vaccine compared to healthy individuals who did not receive the vaccine.Methods This study included 150 people divided into two equal groups; the case group included individuals who received AstraZeneca COVID-19 vaccines, and the sex- and age-matched control group included healthy individuals who did not receive any of the COVID-19 vaccines. Echocardiographic parameters for assessment of systolic function were evaluated after full vaccination.Results By the end of the study, no difference was found between the case and control groups regarding the left ventricular ejection fraction (LVEF), the S' wave of the mitral valve, or the global longitudinal strain (GLS).Conclusions AstraZeneca COVID-19 vaccination was not associated with myocardial damage, as evaluated by 2D echocardiography, tissue Doppler, and speckle tracking echocardiography.

Tracking Persistent Symptoms in Scotland (TraPSS): A Longitudinal Prospective Cohort Study of COVID-19 Recovery After Mild Acute Infection (preprint)

Background: COVID-19 disease results in disparate responses between individuals and has led to the emergence of Long-COVID, characterized by persistent and cyclical symptomology. To understand the complexity of Long-COVID, the importance of symptom surveillance and prospective longitudinal studies is evident. Methods: A 9-month longitudinal prospective cohort study was conducted within Scotland (n=287), using a mobile app to determine the proportion of recovered individuals, those with persistent symptoms, common symptoms, and associations with gender and age. Results: 3.1% of participants experienced symptoms at month 9, meeting the criteria for Long-COVID, as defined by the NICE terminology. Fatigue, cough, and muscle pain were the most common symptoms at baseline, with fatigue persisting the longest, while symptoms like cough improved rapidly. Older age increased the likelihood of reporting pain and cognitive impairment. Female gender increased the likelihood of headaches and post-exertional malaise (PEM), and increased recovery time from fatigue and PEM. Conclusions: The majority of people fully recover from acute COVID-19, albeit often slowly. Age and gender play a role in symptom burden and recovery rates, emphasizing the need for tailored approaches to Long-COVID management. Further analysis is required to determine the characteristics of the individuals still reporting ongoing symptoms months after initial infection to identify risk factors and potential predictors for the development of Long-COVID.

Predictors of moderate-to-severe side-effects following COVID-19 mRNA booster vaccination: A prospective cohort study among primary health care providers in Belgium. (preprint)

Background COVID-19 vaccine effectiveness declines months after vaccination. Therefore, it is likely that during the next few years, people may be repeatedly offered a booster vaccine to enhance humoral immunity levels. A growing number of people are questioning whether the benefits of a booster vaccine outweigh the side-effects.Objective This study aims (1) to identify the most frequently reported side-effects after different doses of COVID-19 mRNA vaccines, (2) and the longest lasting symptoms; and (3) to predict the likelihood of having moderate-to-severe side-effects after a booster COVID-19 mRNA vaccine given individual- and vaccine-specific characteristics.Design, setting, and participants : Secondary analysis of a prospective cohort study in primary health care providers (PHCPs) in Belgium conducted between December 2020 and December 2021, and in February-March 2023.Methods In nine subsequent surveys over a period of 2 years vaccine dose-number and side-effects after COVID-19 vaccines were collected. A Generalized Estimation Equations approach on the data of the first and second booster dose was used to investigate the probability of having moderate-to-severe side-effects after mRNA booster vaccination. Predictive performance of a binary classifier was assessed by looking at discrimination (i.e., quantified in terms of the area under the receiver operating characteristic curve). The final prediction model was validated using data with regard to the third booster by assessing misclassification rate, sensitivity and specificity.Results In total, 11% of the PHCPs had moderate-to-severe side-effects after their booster COVID-19 mRNA vaccine. The most common side-effects of COVID-19 mRNA doses included fatigue, local pain at the injection site, general pains, and headache. These side-effects typically lasted for a median of 1 to 2 days. The final model included five predictors: sex, alcohol consumption, history of moderate-to-severe side-effects after any previous dose, recent COVID-19 infection, and the booster dose-number (first, second). Having experienced moderate-to-severe side-effects after any previous dose was the strongest predictor of moderate-to-severe side-effects following an mRNA vaccine booster, with an odds ratio (OR) of 3.64 (95% CI: 2.80–4.75). The OR for female sex was 1.49 (95% CI: 1.21–1.84) implying that females have a higher odds of moderate-to-severe side-effects following booster vaccination. The differences in effect for booster dose-number, alcohol consumption and recent COVID-19 infection was not significant.Conclusion and Relevance: COVID-19 mRNA booster vaccination implies a low prevalence of moderate-to-severe side-effects among PHCPs, with a short median duration of symptoms if any. The strongest predictors are a history of moderate-to-severe side-effects after any previous dose and being female. These reassuring findings can help addressing concerns about booster vaccination and encourage their uptake.Trial Registration: NCT04779424

Neurosyphilis with Concomitant Cryptococcal Meningitis in a Patient with AIDS after COVID-19: a case report (preprint)

Background The common infections agents causing meningitis in patients with human immunodeficiency virus (HIV) include Cryptococcus neoformans and Treponema pallidum. Furthermore, there is an elevated risk of meningitis in patients with HIV concomitantly infected with SARS-CoV-2.Case presentation: A 38-year-old male presented with headache and dizziness. After hospitalization, polymerase chain reaction test for SARS-CoV-2 in nasopharyngeal swab was positive, and lumbar puncture revealed neurosyphilis with concomitant cryptococcal meningitis. He underwent Paxlovid, penicillin, antifungal and antiretroviral treatment. The patient had no other neurological symptoms and was stable during the 6-month follow-up period.Conclusions During the COVID-19 pandemic, patients with HIV, particularly those not underwent antiretroviral therapy, are at higher risk for severe infections, including central nervous system complications, due to their compromised immune systems.

Effectiveness and Safety of COVID-19 Vaccines, including Vaccination Issues in Trinidad and Tobago: A Systematic Review (preprint)

Vaccination against the SARS-CoV2 virus has shown great promise in managing the spread and severity of Covid-19. While these vaccines were able to provide a favourable response in controlling the SARS-CoV2 infection, its use came with accompanying side effects. This systematic review aimed to determine the effectiveness of the different Covid-19 vaccine subtypes and discover the side effects associated with each vaccine elsewhere but specially in Trinidad and Tobago. For this systematic review, the keywords “Pfizer-BioNTech OR Moderna OR Oxford-AstraZeneca OR Janssen OR Sinopharm OR Novavax AND Covid-19 vaccine efficacy” and “Covid-19 vaccines AND Trinidad and Tobago” were researched under PubMed, MEDLINE and other internet sources through which other notable journals, and documents were discovered and searched similarly as outlined previously. In doing so, 65 relevant articles were included as part of this review. Of the studies examined, overall the vaccine with the greatest VE was found to be Pfizer-BioNTech (95%), followed by Moderna (94.1%), Novavax (89.7%), AstraZeneca (70.4%), Sinopharm (67%) and finally Janssen (66.9%). The use of Pfizer-BioNTech or Moderna was most efficacious in response to the different Covid-19 variants. Some side effects were common for all vaccine types however adverse effects were more commonly seen with vaccination by mRNA vaccines, Pfizer-BioNTech and Oxford-Astrazeneca. Researchers targeted individuals aged 18 and above residing in various geographical areas of TT, specifically focusing on those who had not received the COVID-19 vaccine and expressed hesitancy towards it. Convenience sampling was used to select the study participants, and formal in-depth virtual interviews were conducted on a one-to-one basis, employing a semi-structured questionnaire to guide the discussions. The interviews were meticulously recorded and transcribed, following the principles of reflexive thematic analysis, to distill key insights from the participants' responses. The study's findings, derived from the perspectives of 25 participants, illuminated a complex tapestry of reasons underlying vaccine hesitancy in Trinidad and Tobago. Notably, prominent themes emerged, including fear, doubts regarding vaccine efficacy, a perceived inadequacy of information, a sense of susceptibility to the virus, deep-seated mistrust, alternative herbal remedies, and religious reservations. Interestingly, the motivations expressed by these vaccine-hesitant individuals for potentially receiving the vaccine in the future were rooted in notions of necessity, an increased sense of susceptibility to the virus, a desire to reach a certain health benchmark, and a need for assurance regarding the vaccine's safety and effectiveness. This comprehensive exploration of vaccine hesitancy in TT provides valuable insights for public health officials and policymakers in crafting targeted strategies to address this critical issue within the local context. Conclusion: The findings of this study determined that vaccination against the SARS-CoV2 virus provided beneficial outcomes against infection, Covid-19 related hospitalizations, ICU admissions and mortality. While vaccination was deemed highly appropriate in managing the spread of the SARS-CoV2 virus and enhancing the outcomes in infected persons, the effectiveness of the different vaccine platforms indicated that certain vaccine platforms are preferential to others in different populations. In terms of vaccine efficacy, nucleic acid vaccines such as Pfizer-BioNTech and Moderna showed the greatest effectiveness while inactivated whole virus vaccines such as Sinopharm and viral vectors like Janssen had the least effectiveness. The side effects, joint/muscle soreness, pain at the injection site, shoulder pain, headaches, fever, chills, weakness, epistaxis, renal and certain cardiovascular events were common for all vaccine types. Adverse effects were more frequent and severe with the mRNA vaccines by Pfizer-BioNTech and Oxford-Astrazeneca than inactivated whole virus vaccines. The data collected in this research can be very useful to help individuals make a decision on which vaccine would be appropriate for them. More long-term studies are needed to better gauge the scope of side effects for each vaccine type.

Headache or Disturbed Smell and Taste During Acute COVID-19 as Predictors of Long COVID at One Year (preprint)

Purpose: Long coronavirus disease (COVID) poses a significant health concern for a substantial proportion of COVID-19 patients. Viral pathogenesis studies suggest the potential of central nervous system (CNS) affection in the acute phase of COVID-19 predicting long COVID. This study investigates whether acute COVID-19 symptoms, particularly headache and disturbed smell and taste, predict manifestations of long COVID. Methods: This prospective cohort study included COVID-19 patients hospitalized between March 2020, and May 2021. One year after discharge, patients responded to a symptom questionnaire. Logistic regression analysis was used to determine the odds ratio (OR) for these outcomes. Results: Of 288 eligible patients, 111 responded to the follow-up questionnaire. At 1 year follow-up, disturbed smell and taste during acute COVID-19 did not elevate the risk of long COVID. However, patients with acute headache demonstrated a tendency towards an elevated risk of CNS-related long COVID. Notably, this risk significantly increased in patients reporting dizziness (adjusted OR=4.20; 95% confidence interval (CI) 1.19 - 14.85). Neither disturbed smell and taste nor headache during acute COVID-19 indicated a statistically significant risk of worsening in fatigue, health, or total symptom score at 1-year follow-up. Conclusion: Headache, and not disturbed smell and taste, predicted CNS-related long COVID. Further research is warranted to clarify pathways connecting CNS-related symptoms during acute COVID-19 with long COVID, aiding the efforts of addressing the range of symptoms observed among long COVID patients and developing effective interventions.

IMPACT OF PANDEMIC ON COVID-19 QUALITY OF LIFE AND EFFECTING FACTORS AMONG ADULTS WITH LONG COVID: FAMILY HEALTH CENTERS BASED STUDY (preprint)

Aim: The aim of the study was to evaluate impact of pandemic on COVD-19 quality of life and effecting factors among adults wıth long COVID. Methods: The study included 440 individuals applying at family health centers for any reason. Participants were asked to complete a survey after their written consent was received. The survey consisted of two parts: the first related to socio-demographic information; the second including “COVID-19 Quality of Life Scale” and the “Perception Health Scale” . Mean, median, Kruskal Wallis and Mann-Whitney U tests and Sperman Correlation analysis were used in analysis. Results: Of the participants, 40.9% were male, 59.1% were female as well as 33.2% had at least one long COVID symptoms, 44.5% were reported that symptoms continued for 1-3 months. In addition, the median age was 41 years, the body mass index was 24.6 kg/m2. The median time since first infected was 7 month. The median COV19-QoL and Perception of Health Scale scores were 3.0 and 40.0 respectively. Among the prolonged COVID symptoms, fatigue/tiredness was shown with 53.2%. Other common symptoms were muscle pain (27.1%), headache/dizziness (24.1%), difficulty thinking or concentrating (20.9%), difficulty in breathing and heart palpitation (20.0%). The COV19-QoL median score significantly differed by education level, existing chronic conditions, COVID-19 treatment type, number of experienced long COVID symptoms and continuation of the symptoms p<0.05. There was significant correlation between COV19-QoL and age, time since first infected and perceived health score (p<0.05) . Conclusion: Aging, low education, existing chronic conditions, hospitalization, number of long symptoms, continuation of symptoms, and perception of health were risky factors for impact of the pandemic on COVID-19 quality of life. Specific rehabilitation services and programmes seems to be urgent need in overcoming this issue and to improve health. Key words: Long COVID, COVID-19, quality of life, adults, family health

IMPACT OF COVID-19 PANDEMIC ON QUALITY OF LIFE AND EFFECTING FACTORS AMONG ADULTS WITH LONG COVID: FAMILY HEALTH CENTERS BASED STUDY (preprint)

Background: Long COVID are the uninterpretable symptoms of COVID-19. However, quality of life and other factors among COVID-19 survivors remain less clear. Objectives: The aim of the study was to evaluate impact of COVID-19 pandemic on quality of life and effecting factors among adults with long COVID. Design and Setting: This cross-sectional study included 440 individuals applying at family health centers for any reason. Methods: The survey consisted of two parts: the first related to socio-demographic information; the second including “COVID-19 Quality of Life Scale”and the “Perception Health Scale”. Results: Of the participants, 40.9% were male, 59.1% were female as well as 33.2% had at least one long COVID symptoms. The median COV19-QoLand Perception of Health Scale scores were 3.0 and 40.0 respectively. Among the prolonged COVID symptoms, fatigue/tiredness was shown with 53.2%. Other common symptoms were muscle pain (27.1%), headache/dizziness (24.1%), difficulty thinking or concentrating (20.9%), difficulty in breathing and heart palpitation (20.0%). The COV19-QoL median score significantly differed by education level, existing chronic conditions, COVID-19 treatment type, number of experienced long COVID symptoms and continuation of the symptoms p<0.05. There was significant correlation between COV19-QoL and age, time since first infected and perceived health score (p<0.05). Conclusion: Aging, low education, existing chronic conditions, hospitalization, number of long symptoms, continuation of symptoms, and perception of health were risky factors for impact of the pandemic on quality of life. Specific rehabilitation services and programmes seems to be urgent need in overcoming this issue and to improve health. Key Words (MeSH Terms): Long COVID; COVID-19; quality of life; adults; family health

WHAT THE COVID-19 PANDEMIC TAUGHT US IN CHILDREN (preprint)

Objective: The COVID-19 pandemic is an important cause of morbidity and mortality, which has had a negative impact worldwide. We aimed to contribute to the medical literature by sharing the knowledge and experience of pediatric patients who were diagnosed as having COVID-19 in a one-year period. Method: Patients aged 1 month to 18 years who were diagnosed as having COVID-19 in our clinic, between March 2020 and April 2020, from when COVID-19 was declared as a pandemic, were included in the study. Results: Four hundred sixty-seven children were included in the study. There were 34 (7.3%) patients under one year of age, 111 (23.8%) between 1-5 years, 98 (30.4%) between 5-10 years, 142 (30.4%) between 11-15 years, and 82 (17.6%) age over 15 years. Fever (88.2%), vomiting (32.4%), and diarrhea (29.4%) in patients aged under 1 year, sore throat (36.6%) in patients aged 11-15 years, and dysgeusia (11%), anosmia (14.6%), headache (18.3%), malaise (40.8%), myalgia (28%), and dyspnea (17.1%) in those aged over 15 years of age were found significantly more common compared with the other age groups. Thirty-five (7.5%) patients were asymptomatic, 365 (78.1%) had mild disease, 35 (7.5%) were moderate, 27 (5.8%) were severe, and five (1.07%) were critical. Leukocyte count, erythrocyte sedimentation rate, ferritin, and C-reactive protein values were significantly higher in hospitalized patients. Four patients died during the study period (0.8%, 4/494). Conclusion: Although COVID-19 has an asymptomatic and mild course in children, it should be kept in mind that it may have a severe course.

Rhinoviruses restored while fighting the COVID-19 Pandemic in Guangzhou, China (preprint)

Background: To analyze the epidemic characteristics of the human rhinovirus (HRV) outbreaks in Guangzhou, China, in 2020. Method Descriptive epidemiological methods were used to analysis the HRV related outbreaks of Guangzhou, 2020. Results 17 outbreaks were reported in 2020 during the COVID-19 pandemic in Guangzhou, a total of 465 patients (290 males and 175 females) were enrolled, with a median age of 10. 223(47.96%) had been tested for HRV, 89 (39.91%) of which were positive. 344/465 (73.98%) had fever, 138/465 (29.68%) had runny nose, 139/465 (29.89%) had sore throat, 86/465 (18.49%) had cough, 41/465 (8.82%) had headache, 37/465 (7.96%) had sneeze. Patients at age of 13 to 15 had the highest rate of sore throat and runny nose, patients at the age of 11 to 12 had the highest rate of sneeze, and patients at age of 12 to 14 had the highest rate of positive rate. Patients tested positive had a higher rate of fever (2=11.271, P=0.001), cough (2=6.987, P=0.008), runny nose (2=7.980, P=0.005) and sneeze (2=4.676, P=0.031). Conclusion The HRV was restored during the fighting the COVID-19 Pandemic. The conventional COVID-19 control measures were not effective enough in preventing rhinovirus. More appropriate control measures should be used to control HRV.

Prevalence of physical and psychological impacts of wearing personal protective equipment (PPE) on health care workers during COVID-19; a systematic review and meta-analysis. (preprint)

Background: The COVID-19 pandemic has necessitated the use of personal protective equipment (PPE) among the frontline health care workers (HCWs). Although PPE offers a great deal of help in preventing infection, it poses significant physical and psychological impacts at varying levels. Correspondingly, multiple independent studies have brought out the PPE associated problems. However, there exists a lacuna on comprehensive information of global prevalence related to the same. Aims: To estimate the prevalence and risk factors of PPE among HCWs during COVID-19 across the globe. Design: Systematic review and Meta-analysis. Method: The review was undertaken as per the protocol registered in PROSPERO xxxxxx following PRISMA guidelines. Two independent reviewers have undertaken the search strategy, study selection and methodological quality assessment. Discrepancies were addressed by the third reviewer. Heterogeneity was addressed through I2 statistics and forest plots generated by open meta-software. Results: A total of 16 articles conducted across 6 different countries among 10,182 HCWs were included in the review. The pooled prevalence of skin lesions, headache, sweating, breathing difficulty, vision difficulty, thirst/dry mouth, fatigue and communication difficulty, anxiety, fear were 57(47-66%),51(37-64%),75(56-90%),44(23-68%),61(21-94%),54%(30-77%),67(58-76%),74%(47-94%),28(24-33%),14(10-17%) respectively. Moreover, the various risk factors included; the use of PPE greater than 6 Hrs. and young females. In addition, the medical management of new-onset problems created an additional burden on the frontline HCWs. Conclusion: The front-line HCWs encountered physical and psychological problems at varying levels as a result of wearing PPE which needs to be addressed to prevent the inadequate use of PPE leading to infections. Relevance to clinical practice: The review sheds light on the need to address the physical and psychological morbidity due to PPE use for ensuring the working morale and optimum health status of frontline HCWs to combat ongoing and future pandemics.

A case of adverse reaction to booster dose of COVID-19 vaccination: could D-dimer elevation suggest increased clotting risk? (preprint)

we here report the clinical case of a serious adverse reaction to booster dose COVID-19 vaccination in a 40-year-old woman, who soon ,developed severe headache, high fever, and musculoskeletal pains, with very important elevation of D-dimer levels and clear reduction of White Blood Count.

Symptoms of children and adolescents infected with SARS-CoV-2 variants alpha, delta or omicron (preprint)

Symptoms experienced by children and adolescents with SARS-CoV-2 infections in the alpha, delta and omicron variant dominated phases were investigated using an online survey, and the frequencies of reported symptoms and changes over time were analyzed. The most prevalent symptoms were fever above 38 {degrees}C, tiredness, headache, runny or blocked nose, sneezing and dry cough. Lethargy and nausea were reported significantly more frequently in the omicron variant dominated phase than in the earlier phases of the pandemic. Compared to symptoms reported by adults, fever and gastrointestinal symptoms were reported more frequently for children, especially in the omicron variant dominated phase, whereas the frequency of loss of smell and loss of taste was significantly lower in children than in adults.

The prevalence and influencing factors of COVID-19 in pregnant women in Hunan Province, China, immediately following the relaxation of epidemic control measures (preprint)

Objective: To investigate the prevalence and influencing factors of COVID-19 in pregnant women in Hunan Province immediately following the relaxation of epidemic control measures. Methods: This was a cross-sectional study with a multistage stratified sampling method. The questionnaire collected basic maternal information, data on COVID-19 infection status, and pregnancy-related information. The survey was conducted by trained investigators, and data quality checks were carried out twice per week. Results: Among the 7761 included pregnant women, 5191 (66.9%) had a positive SARS-CoV-2 test result or related symptoms. The majority of maternal infections were mild (90.0%), and very few were severe and critical (0.4% and 0.1%), and headache and body aches (65.3%) were the most common symptoms. A total of 2711 (52.2%) women gave birth, and 449 (16.6%) newborns had infections. Logistic multivariable regression analysis showedthatpregnant women with an education level of junior college and above (OR=1.392, 95% CI: 1.182, 1.639), those with a monthly household income ≥3000 yuan and above (OR=1.175, 95% CI: 1.027, 1.344), those who lived with their family during family member infection (OR=1.476, 95% CI: 1.316, 1.655), and those with pulmonary (OR=1.408, 95% CI: 1.070, 1.854) or other (OR=1.398, 95% CI: 1.188, 1.645) underlying diseases were more likely to have COVID-19. A farmer/worker occupation type (OR=0.617, 95% CI: 0.484, 0.786) was a protective factor. Conclusions: Many pregnantwomen had COVID-19 immediately following the relaxation of epidemic control measures, but most had mild cases, and few effects on newborns were observed. Mobility is the most critical factor influencing infection. The continued utilization of masks and adherence to social distancing measures remain crucial in mitigating COVID-19 transmission.

SARS-CoV-2 induces acute neurological signs while Calcitonin Gene-Related Peptide (CGRP) signaling blockade reduces interleukin 6 (IL-6) release and weight loss in mouse models (preprint)

COVID-19 can result in neurological symptoms such as fever, headache, dizziness, and nausea. We evaluated whether the Calcitonin Gene-Related Peptide (CGRP) receptor antagonist, olcegepant, used in migraine treatment could mitigate acute neuroinflammatory and neurological responses to SARS-COV-2 infection. We infected wildtype C57BL/6J and 129/SvEv mice, and a 129 CGRP-null mouse line with a mouse-adapted SARS-CoV-2 virus, and evaluated the effect of CGRP receptor antagonism on the outcome of that infection. We determined that CGRP receptor antagonism provided protection from permanent weight loss in older (>12 m) C57BL/6J and 129 SvEv mice. We also observed acute fever and motion-induced dizziness in all older mice, regardless of treatment. However, in both wildtype mouse lines, CGRP antagonism reduced acute interleukin 6 (IL-6) levels by half, with virtually no IL-6 release in mice lacking CGRP. These findings suggest that blockage of CGRP signaling protects against acute IL-6 release and subsequent inflammatory events after SARS-CoV-2 infection.

The more symptoms the better? Covid-19 vaccine side effects and long-term neutralizing antibody response (preprint)

Protection against SARS-CoV-2 wanes over time, and booster uptake has been low. This study explores the link between post-vaccination symptoms, biometric changes, and neutralizing antibodies (nAB) after mRNA vaccination. Data were collected from adults (n = 363) who received two doses of either BNT162b2 or mRNA-1273, with serum nAB concentration measured at 1 and 6 months post-vaccination. Daily symptom surveys were completed for six days starting on the day of each dose. Concurrently, objective biometric measurements, including skin temperature, heart rate, heart rate variability, and respiratory rate, were collected. We found that certain symptoms (chills, tiredness, feeling unwell, and headache) after the second dose were associated with increases in nAB at 1 and 6 months post-vaccination, to roughly 140-160% the level of individuals without each symptom. Each additional symptom predicted a 1.1-fold nAB increase. Greater changes in skin temperature and heart rate after the second dose predicted higher nAB levels. Skin temperature had a stronger predictive relationship for 6-month than 1-month nAB level. In the context of low ongoing vaccine uptake, our findings suggest that public health messaging could seek to reframe systemic symptoms after vaccination as desirable.

Navigating the Neurological Aftermath of COVID-19: An In-Depth Exploration (preprint)

Background: The COVID-19 pandemic caused by SARS-CoV-2 has affected millions of people and can result in both immediate and prolonged neurological effects, including severe complications. While numerous studies have explored the occurrence and consequences of neurological issues in COVID-19, they have often involved limited sample sizes. Purpose: This paper aims to determine the overall occurrence of neurological complications in COVID-19, examine their links with patient demographics, and assess their impact on patient outcomes. Additionally, it seeks to provide an overview of the current understanding of the underlying mechanisms. Methodology: Two systematic reviews were conducted to investigate acute and chronic neurological complications associated with COVID-19. A comprehensive search of medical databases was performed, and relevant studies were evaluated following PRISMA guidelines. Meta-analysis was carried out using the Mantel-Haenszel method, with subgroup analysis and meta-regression used to assess heterogeneity. Results: The analysis of acute complications included 20,011 patients with an average age of 58.1 years and a slight male predominance (55.2%). Common neurological symptoms included loss of taste and smell, headaches, acute encephalopathy, and stroke. For the analysis of long-term complications, 2,094 patients were included. Survivors of COVID-19 experienced ongoing neurological issues ranging from sensory impairments to fatigue, headaches, strokes, and even cognitive and psychiatric problems. Conclusion: By examining various neurological symptoms, this study found a significant association between these manifestations and worse overall outcomes, especially in patients over 60 years old. Identifying high-risk individuals and maintaining a high level of suspicion are crucial for enhancing our understanding of the underlying mechanisms, validating biomarkers, and improving the management of these neurological issues.

Brain infection by wild-type SARS-CoV-2 and the B.1.617.2 and B.1.1.529 variants of concern is a severe outcome in K18-hACE2 transgenic mice (preprint)

Background: SARS-CoV-2 is a respiratory virus with neurological complications including loss of smell and taste, headache, and confusion that can persist for months or longer. Severe neuronal cell damage has also been reported in some cases. The objective of this study was to compare the infectivity of Wild-type, Delta, and Omicron variants in transgenic mice that express the human angiotensin-converting enzyme 2 (hACE2) receptor under the control of the keratin 18 promoter (K18) and characterize the progression of infection and inflammatory response in the lung and brain of these animals. Methods: K18-hACE2 female mice were intranasally infected with Wild-type, Delta, or Omicron variants and euthanized either at 3 days post-infection (dpi) or at the humane endpoint. None of the animals infected with the Omicron variant reached the humane endpoint and were euthanized at day 8 dpi. Virological and immunological analyses were performed in the lungs, olfactory bulbs, medulla oblongata, and brains. Results: We established that Wild-type, Delta, and Omicron infect the lung and brain of K18-hACE2 mice. At 3 dpi, mice infected with the Omicron variant show lower levels of viral RNA than those infected with Wild-type or Delta in the lung and brain. However, they still demonstrate upregulation of cytokines and chemokines, indicating that the Omicron variant can induce pulmonary and neuronal inflammation despite reduced viral proliferation after infection. At the humane endpoint/8dpi, there is a significant increase in viral RNA in mice infected with the Wild-type or Delta variant brains. However, viral RNA levels in Omicron-infected mice did not increase significantly as compared to 3dpi, and the expression of cytokines and chemokines in the brain, olfactory bulb, and medulla oblongata was downregulated, suggesting that infection by the Omicron variant results in attenuated neuroinflammation as compared with Wild-type and Delta.

Prevalence and pattern of Post Covid-19 symptoms in recovered patients of Delhi: A Population-Based study (preprint)

Background: Post-coronavirus disease (COVID) is widely reported but the data of Post COVID-19 after infection with the Omicron variant is limited. This prospective study was conducted to determine the prevalence, pattern, and duration of symptoms related to Covid-19 recovered patients. Methods: Adults (>18 years old) in 11 districts of Delhi who had recovered from Covid-19 were followed up at 3 months and 6 months post-recovery. Results: The study found that the participants had a mean age of 42.07 years, with a standard deviation of 14.89. Additionally, a significant proportion of the participants (79.7%) experienced post-Covid symptoms. The participants elicited a history of Joint Pain (36%), Persistent dry cough (35.7%), anxiousness (28.4%) and shortness of breath (27.1%). The other symptoms reported were persistent fatigue (21.6%), persistent headache (20%), forgetfulness (19.7%) and weakness in limbs (18.6%). The longest duration of symptom was observed in participants reporting anxiousness (138.75 +54.14) followed by fatigue (137.57+48.33), shortness of breath (131.89+60.21) and joint pain/swelling (131.59+58.76). During the first follow-up, 2.2% of participants had an abnormal ECG reading, while no abnormalities were reported during the second follow-up. Additionally, 4.06% of participants had abnormal chest X-ray findings during the first follow-up, with this number decreasing to 2.16% during the second follow-up. Conclusion: Our study concluded that the clinical symptoms persist in participants until 6 months and a multi-system involvement is seen in the post-COVID period. Thus, the findings necessitate long-term, regular follow-ups.