The Aftermath of COVID-19: Exploring Long-Term Effects on the Organ Systems (preprint)

Background: Post-acute sequelae of SARS-CoV-2 infection (PASC) is a complicated disease that affects millions of people all over the world. Previous studies have shown that PASC impacts 10% of SARS-CoV-2 infected patients of which 50-70% are hospitalized. It has also been shown that 10-12% of those vaccinated against COVID-19 were affected with PASC and its complications. The severity and the later development of PASC symptoms is positively associated with the early intensity of the infection. Results: The generated health complications caused by PASC involve a vast variety of organ systems. Patients affected by PASC have been diagnosed with neuropsychiatric and neurological symptoms. Cardiovascular system also has been involved and several diseases such as myocarditis, pericarditis, and coronary artery diseases were reported. Chronic hematological problems such as thrombotic endothelialitis and hypercoagulability were described as a condition that could increase the risk of clotting disorders and coagulopathy in PASC patients. Chest pain, breathlessness, and cough in PASC patients were associated with respiratory system in long COVID-19 causing respiratory distress syndrome. The observed immune complications were notable, involving several diseases. Renal system also was impacted and result in raising the risk of diseases such as thrombotic issues, fibrosis, and sepsis. Endocrine gland malfunction can lead to diabetes, thyroiditis, and male infertility. Symptoms such as diarrhea, nausea, loss of appetite and taste were also among reported observations due to several gastrointestinal disorders. Skin abnormalities might be an indication of infection and long-term implications such as persistent cutaneous complaints were linked to PASC. Conclusions: Long COVID is a multidimensional syndrome with considerable public health implications, affecting several physiological systems and demanding thorough medical therapy as well as more study to address its underlying causes and long-term effects.

Evaluating Nirmatrelvir-Ritonavir (Paxlovid®) in Outpatient COVID-19 Treatment: Safety, Tolerability, and Adherence Insights from Primary Healthcare Clinics (preprint)

Objective: This study aims to fill this gap by evaluating the safety, tolerability, and adherence of patients prescribed Paxlovid® in outpatient settings, focusing on its use in managing category 2 COVID-19 patients across three primary healthcare clinics in Selangor, Malaysia. Design: Retrospective cross-sectional study Setting: Data were collected from the Paxlovid® pharmacy registry and medical records at Klinik Kesihatan Seksyen 7, Klinik Kesihatan Seksyen 19, and Klinik Kesihatan Kelana Jaya between April 1, 2022, and November 30, 2022. Participants: This study analysed data from 415 category 2 COVID-19 patients aged ≥18 years old. Primary and secondary outcomes: Parameters assessed included patient demographics, dosing, current medication, changes in drug regimen, adherence, and ADR. Pharmacists follow-ups were conducted on days 3 and 5 post-medication initiation. Results: The majority (79.5%) of the cohort experienced ADR, predominantly dysgeusia, diarrhoea, body ache, vomiting, and nausea. Despite these, the ADR were generally well-tolerated, with no severe impacts reported. High adherence was observed, with 96.9% of patients completing the 5-day regimen. The primary reasons for non-adherence included adverse effect intolerability, dosing ambiguity, forgetfulness, concerns about ADR, and perceived health improvement. Notable medications interacting with Paxlovid® were simvastatin, amlodipine, and atorvastatin, and 21.7% of 23 concurrent medications were found not complying to the recommended interventions by the University of Liverpool COVID-19 Drug Interaction database. Conclusion: Nirmatrelvir-ritonavir (Paxlovid®) demonstrates a high level of safety and tolerability in outpatient COVID-19 patients, with optimal adherence observed. This study underscores the vital role of healthcare professionals in managing Paxlovid® within primary healthcare and highlights the need for broader research and direct patient involvement to enhance treatment strategies against COVID-19.

Extended Duration and Intense Manifestations of COVID-19-Linked Cytotoxic Lesions of the Corpus Callosum: Case Reports and Literature Review (preprint)

While clinical instances of cytotoxic lesions of the corpus callosum (CLOCCs) are well-documented, international reports specific to COVID-19-related cases remain limited. This paper presents the case of a 40-year-old female patient admitted due to "sudden dizziness and poor limb coordination for 7 weeks following fever." She tested positive for COVID-19 and experienced symptoms like dizziness, temporary confusion, nausea, vomiting, cerebellar speech issues, and ataxia after fever onset. Later, she developed pyramidal tract symptoms and behavioral abnormalities. Head MRI revealed abnormal high signal in the splenium of the corpus callosum and abnormal signals in the left cerebellar peduncle on DWI. With no significant medical history and exclusion of other causes during treatment (including steroid therapy and two doses of intravenous immunoglobulin), a follow-up MRI after one month showed the lesions had disappeared. However, clinical recovery was slow, with residual symptoms persisting for almost a year, including involuntary tremors in the upper limbs and head. Phenytoin, gabapentin, and pregabalin showed limited effectiveness in treatment, but Arotinolol and donepezil led to slight improvement in involuntary tremors. This case suggests that COVID-19-associated CLOCCs might have a protracted course and severe symptoms, demanding differentiation from ischemic cerebrovascular diseases, particularly in early stages.

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.

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.

Safety and efficacy of rimegepant orally disintegrating tablet for the acute treatment of migraine in China and South Korea: a phase 3, double-blind, randomised, placebo-controlled trial.

BACKGROUND: No acute treatments targeting calcitonin gene-related peptide (CGRP) have been approved for use in China or South Korea. We aimed to compare the efficacy and safety of rimegepant-an orally administered small molecule CGRP antagonist-with placebo in the acute treatment of migraine among adults in these countries. METHODS: This double-blind, randomised, placebo-controlled, multicentre phase 3 trial was done at 86 outpatient clinics at hospitals and academic medical centres (73 in China and 13 in South Korea). Participants were adults (≥18 years) with at least a 1-year history of migraine who had two to eight moderate or severe attacks per month and fewer than 15 headache days per month within the 3 months before the screening visit. Participants were randomly assigned (1:1) to 75 mg rimegepant or placebo to treat a single migraine attack of moderate or severe pain intensity. Randomisation was stratified by the use of preventive medication and by country. The allocation sequence was generated and implemented by study personnel using an interactive web-response system accessed online from each study centre. All participants, investigators, and the sponsor were masked to treatment assignment. The coprimary endpoints of freedom from pain and freedom from the most bothersome symptom (nausea, phonophobia, or photophobia) 2 h after dosing were assessed in the modified intention-to-treat (mITT) population (randomly assigned participants who took study medication for a migraine attack of moderate or severe pain intensity, and provided at least one efficacy datapoint after treatment) using Cochran-Mantel Haenszel tests. Safety was assessed in all participants who received rimegepant or placebo. The study is registered with ClinicalTrials.gov, number NCT04574362, and is completed. FINDINGS: 1431 participants were randomly assigned (716 [50%] to rimegepant and 715 [50%] to placebo). 668 (93%) participants in the rimegepant group and 674 (94%) participants in the placebo group received treatment. 1340 participants were included in the mITT analysis (666 [93%] in the rimegepant group and 674 [94%] in the placebo group). 2 h after dosing, rimegepant was superior to placebo for pain freedom (132 [20%] of 666 vs 72 [11%] of 674, risk difference 9·2, 95% CI 5·4-13·0; p<0·0001) and freedom from the most bothersome symptom (336 [50%] of 666 participants vs 241 [36%] of 674 participants, 14·8, 9·6-20·0; p<0·0001). The most common (≥1%) adverse events were protein in urine (8 [1%] of 668 participants in the rimepegant group vs 7 [1%] of 674 participants in the placebo group), nausea (7 [1%] of 668 vs 18 [3%] of 674), and urinary tract infection (5 [1%] of 668 vs 8 [1%] of 674). There were no rimegepant-related serious adverse events. INTERPRETATION: Among adults living in China or South Korea, a single dose of 75 mg rimegepant was effective for the acute treatment of migraine. Safety and tolerability were similar to placebo. Our findings suggest that rimegepant might be a useful new addition to the range of medications for the acute treatment of migraine in China and South Korea, but further studies are needed to support long-term efficacy and safety and to compare rimegepant with other medications for the acute treatment of migraine in this population. FUNDING: BioShin Limited. TRANSLATIONS: For the Chinese and Korean translations of the abstract see Supplementary Materials section.

Clinical and Epidemiological Risk Factors Associated with Hospitalization and Mortality Rate of COVID-19 Patients in Banja Luka County: Retrospective Observational Cohort Study on 40,000 patients (preprint)

Background and Objectives: Since the beginning of COVID-19 pandemic, the infection primarily affected patients with following chronic conditions: cardiovascular disease, hypertension, chronic obstructive pulmonary disease, diabetes mellitus, obesity and cancer. The aim of this study was to explore clinical and epidemiological characteristics associated with COVID-19 outcomes in patients at the primary health care centre from March 2020 to September 2022. Materials and Methods: The study included 40,692 citizens of Banja Luka County, Bosnia and Herzegovina, who were confirmed and registered as RT-PCR positive on COVID-19. Differences regarding the distributions of patients between groups were analysed using Pearson chi square test and Mantel-Haenszel chi square test for trends, while differences in mean values were compared using independent samples t test. Relationship between mortality and independent variables were examined using logistic regression. Results: Out of 40,692 COVID-19 positive patients, 7.76% were hospitalized. The average age of hospitalized patients was significantly higher than the age of non-hospitalized patients (64.2±16.1 vs. 45.4±18.7; p<0.001). The average age of patients with lethal outcome was nearly twice higher compared to patients with non-lethal outcome (74.6±11.5 vs. 45.7±18.6; p<0.001). Male patients had higher hospitalization and mortality rate, compared to females (9.8% vs. 5.9%, p<0.001; 4.8% vs. 3%, p<0.001, respectively). The highest hospitalization rate was in patients with chronic renal failure, diabetes and cardiovascular diseases, while the death rate was the highest among patients with CRF and hearth comorbidities. Fever, cough, fatigue, nausea and vomiting, chest pain, shortness of breath and appetite loss favoured hospitalization. Patients with fatigue and appetite loss had higher percentage of lethal outcome. Vaccinated patients had significantly lower rate of lethal outcome. Conclusions: Clinical symptoms, signs and outcomes, are posing as predictive parameters for further management of COVID-19. Vaccination has an important role in clinical outcomes of COVID-19.

Menstrual-Related Disturbances Following SARS-CoV-2 Vaccination: A Spanish Retrospective Observational Study in Formerly Menstruating Women (preprint)

To date, the impact of COVID-19 vaccination on formerly menstruating women remains unknown. For this reason, a retrospective observational cross-sectional study was conducted (N= 548) using an online survey. General characteristics, medical history, and adverse events following COVID-19 vaccination were recorded. In comparison with the first dose, significantly higher percentages of respondents experienced menstrual-related disturbances (dose 1: 38.5% vs. dose 2: 44.8%; McNemar=9.15; mid P-value=0.002), as well as the simultaneous occurrence of two or more of these symptoms (dose 1: 11.2% vs. dose 2: 15.3%; McNemar=13.53; mid P-value=0.044) after receiving the second one. Among them, those related with the length and flow stand out, being of long-term nature in about 17-20% of cases. Interindividual factors influencing this unexpected event after receiving the dose 1 may include weight (AOR 1.02, CI 95% 1.01–1.03, P<.001), perimenopause (AOR 2.28, CI 95% 1.37–3.77, P=.001), pre-existing diagnoses of non-autoimmune rheumatic/articular conditions (AOR 0.31, CI 95% 0.10–1.00, P=0.05), hormonal contraceptive use (AOR 0.25, CI 95% 0.07-0.82, P=0.02), suffering from other vaccine side effects − such as arm pain (AOR 0.61, CI 95% 0.39–0.95, P=0.03), headache (AOR 0.53, CI 95% 0.35 – 0.80, P=.003), swollen glands (AOR 0.29, CI 95% 0.15 – 0.60, P=.001) and nauseas (AOR 0.35, CI 95% 0.14 – 0.86, P=0.02) – and the number of previous pregnancies (AOR 2.70, CI 95% 1.54 – 4.76, P=.001). Formerly menstruating women may experience long-term menstrual-related disturbances following COVID-19 vaccination.

Lipase Elevation in Patients With COVID-19.

INTRODUCTION: Although coronavirus disease (COVID-19) has been associated with gastrointestinal manifestations, its effect on the pancreas remains unclear. We aimed to assess the frequency and characteristics of hyperlipasemia in patients with COVID-19. METHODS: A retrospective cohort study of hospitalized patients across 6 US centers with COVID-19. RESULTS: Of 71 patients, 9 (12.1%) developed hyperlipasemia, with 2 (2.8%) greater than 3 times upper limit of normal. No patient developed acute pancreatitis. Hyperlipasemia was not associated with poor outcomes or symptoms. DISCUSSION: Although a mild elevation in serum lipase was observed in some patients with COVID-19, clinical acute pancreatitis was not seen.

Gastrointestinal Symptoms of Monkeypox Infection: A systematic review and meta-analysis.

Since early May 2022, outbreaks of Monkeypox (Mpox) cases have emerged and become a global concern. Studies exploring the gastrointestinal symptoms and/or liver injury of Mpox are still very limited. This systematic review and meta-analysis is the first to summarize the gastrointestinal symptoms reported by Mpox patients. We searched for Mpox studies published until October 21, 2022, in MEDLINE, EMBASE, SCOPUS, and organization websites. Mpox studies were observational studies that reported at least one of either gastrointestinal symptoms and/or liver injury in Mpox patients. Meta-analysis was done to obtain the pooled prevalence of gastrointestinal symptoms in Mpox patients. Subgroup analyses were done based on the study location, age groups, and Mpox Clades. The quality of included studies was assessed using the NIH Quality Assessment Tool. Overall, 31 studies that reported gastrointestinal symptoms and/or liver injury in Mpox patients were included. The reported gastrointestinal symptoms were abdominal pain, anorexia, diarrhea, nausea, and vomiting. There is a lack of reporting for liver injury. The most prevalent gastrointestinal symptoms in Mpox patients were anorexia (47%; 95% confidence interval [CI] 41%-53%), followed by vomiting (12%; 95% CI 11%-13%), nausea (10%; 95% CI 9%-11%), abdominal pain (9%; 95% CI 8%-10%), and diarrhea (5%; 95% CI 4%-6%). Additionally, the prevalence of proctitis, rectal/anal pain, and rectal bleeding were 11% (95% CI 11%-12%), 25% (95% CI 24%-27%), and 12% (95% CI 11%-13%), respectively. Anorexia was the most frequently reported gastrointestinal symptom in Mpox patients, followed by vomiting, nausea, abdominal pain, and diarrhea. Proctitis is a novel presentation of Mpox in the 2022 outbreak.

Neurological Manifestations in COVID-19 Infection: A Systematic Review and Meta-Analysis.

BACKGROUND: Growing evidence showed that coronavirus disease 2019 (COVID-19) infection may present with neurological manifestations. This review aimed to determine the neurological manifestations and complications in COVID-19. METHODS: We conducted a systematic review and meta-analysis that included cohort and case series/reports involving a population of patients confirmed with COVID-19 infection and their neurologic manifestations. We searched the following electronic databases until April 18, 2020: PubMed, Embase, Scopus, and World Health Organization database (PROSPERO registration number: CRD42020180658). RESULTS: From 403 articles identified, 49 studies involving a total of 6,335 confirmed COVID-19 cases were included. The random-effects modeling analysis for each neurological symptom showed the following proportional point estimates with 95% confidence intervals: "headache" (0.12; 0.10-0.14; I2 = 77%), "dizziness" (0.08; 0.05-0.12; I2 = 82%), "headache and dizziness" (0.09; 0.06-0.13; I2 = 0%), "nausea" (0.07; 0.04-0.11; I2 = 79%), "vomiting" (0.05; 0.03-0.08; I2 = 74%), "nausea and vomiting" (0.06; 0.03-0.11; I2 = 83%), "confusion" (0.05; 0.02-0.14; I2 = 86%), and "myalgia" (0.21; 0.18-0.25; I2 = 85%). The most common neurological complication associated with COVID-19 infection was vascular disorders (n = 23); other associated conditions were encephalopathy (n = 3), encephalitis (n = 1), oculomotor nerve palsy (n = 1), isolated sudden-onset anosmia (n = 1), Guillain-Barré syndrome (n = 1), and Miller-Fisher syndrome (n = 2). Most patients with neurological complications survived (n = 14); a considerable number of patients died (n = 7); and the rest had unclear outcomes (n = 12). CONCLUSION: This review revealed that neurologic involvement may manifest in COVID-19 infection. What has initially been thought of as a primarily respiratory illness has evolved into a wide-ranging multi-organ disease.

Early symptoms preceding post-infectious irritable bowel syndrome following COVID-19: a retrospective observational study incorporating daily gastrointestinal symptoms.

BACKGROUND: Intestinal microinflammation with immune dysfunction due to severe acute respiratory syndrome coronavirus 2 reportedly precipitates post-infectious irritable bowel syndrome. This study aimed to elucidate potential risk factors for subsequent development of irritable bowel syndrome, hypothesizing that it is associated with specific symptoms or patient backgrounds. METHODS: This single-center retrospective observational study (2020-2021) included adults with confirmed coronavirus disease requiring hospital admission and was conducted using real-world data retrieved from a hospital information system. Patient characteristics and detailed gastrointestinal symptoms were obtained and compared between patients with and without coronavirus disease-induced irritable bowel syndrome. Multivariate logistic models were used to validate the risk of developing irritable bowel syndrome. Moreover, daily gastrointestinal symptoms during hospitalization were examined in patients with irritable bowel syndrome. RESULTS: Among the 571 eligible patients, 12 (2.1%) were diagnosed with irritable bowel syndrome following coronavirus disease. While nausea and diarrhea during hospitalization, elevated white blood cell count on admission, and intensive care unit admission were associated with the development of irritable bowel syndrome, nausea and diarrhea were identified as risk factors for its development following coronavirus disease, as revealed by the adjusted analyses (odds ratio, 4.00 [1.01-15.84] and 5.64 [1.21-26.31], respectively). Half of the patients with irritable bowel syndrome had both diarrhea and constipation until discharge, and constipation was frequently followed by diarrhea. CONCLUSIONS: While irritable bowel syndrome was rarely diagnosed following coronavirus disease, nausea and diarrhea during hospitalization precede the early signs of irritable bowel syndrome following coronavirus disease.

Safety and tolerability results of atogepant for the preventive treatment of episodic migraine from a 40-week, open-label multicenter extension of the phase 3 ADVANCE trial.

BACKGROUND: Atogepant is a United States Food and Drug Administration-approved oral calcitonin gene-related peptide receptor antagonist for the preventive treatment of episodic migraine. The study objective was to evaluate the long-term safety and tolerability of atogepant in participants who completed the phase 3 ADVANCE trial (NCT03777059). METHODS: This 40-week, open-label extension trial (NCT03939312) monitored safety in participants receiving oral atogepant 60 mg once daily, followed by a four-week safety follow-up period. RESULTS: Of the 685 participants taking at least one dose of atogepant, the treatment period was completed by 74.6% of participants with a mean (standard deviation) treatment duration of 233.6 (89.3) days. Treatment-emergent adverse events occurred in 62.5% of participants, with upper respiratory tract infection (5.5%), urinary tract infection (5.3%), nasopharyngitis (4.8%), sinusitis (3.6%), constipation (3.4%), and nausea (3.4%) occurring at ≥3%. Serious adverse events were observed in 3.4% of participants (none were treatment-related), and there were no deaths. Adverse events leading to discontinuation occurring at >0.1% were nausea (0.4%) and abdominal pain, vomiting, weight decrease, dizziness, and migraine (0.3% each). CONCLUSION: These results are consistent with atogepant's known safety profile and support long-term use of atogepant 60 mg once daily dosing as safe and well tolerated.ClinicalTrials.gov Registration Number: NCT03939312.

The Effect of Acotiamide on Nausea as a Symptom of Chronic Nausea and Vomiting Syndrome after Coronavirus Disease 2019.

Chronic nausea and vomiting syndrome (CNVS), one of a functional gastroduodenal disorder, was identified in an 8-year-old girl and a 13-year-old boy who had complained of nausea for more than 4 months following coronavirus disease 2019 (COVID-19) due to normality of their head computed tomography and upper gastrointestinal tract images. The patients' symptoms responded quickly to acotiamide, a medication that is effective for treating functional dyspepsia (FD). Despite being a distinct illness from FD, CNVS is also a functional gastrointestinal disorder, and acotiamide may be just as effective for CNVS following COVID-19 as for FD.

Prevalence and risk factors of adverse effects after the first COVID-19 booster dose: evidence from Greece (preprint)

Background: In general, COVID-19 vaccines are safe and effective, but minor adverse effects are common. Objective: To estimate the prevalence of adverse effects after the first COVID-19 booster dose, and to identify possible risk factors. Material and methods: We conducted a cross-sectional study with a convenience sample in Greece during November 2022. We measured several adverse effects after the booster dose, such as pain at the injection site, swelling at the injection site, fatigue, muscle pain, headaches, fever, chills, nausea, etc. We considered gender, age, chronic disease, self-assessment of health status, COVID-19 diagnosis, and self-assessment of COVID-19 course as possible predictors of adverse effects. Results: In our sample, 96% developed at least one adverse effect. Half of the participants (50.2%) developed one to five adverse effects, 35.9% developed six to ten adverse effects, and 9.5% developed 11 to 16 adverse effects. Mean number of adverse effects was 5.5. The most frequent adverse effects were pain at the injection site (84.3%), fatigue (70.8%), muscle pain (61%), swelling at the injection site (55.2%), headache (49.8%), fever (42.9%), and chills (41%). Females developed more adverse effects than males (p<0.001). Also, we found a positive relationship between severity of COVID-19 symptoms and adverse effects of COVID-19 vaccines (p=0.005). Moreover, younger age was associated with increased adverse effects (p<0.001). Conclusions: Almost all participants in our study developed minor adverse effects after the booster dose. Female gender, worse clinical course of COVID-19, and decreased age were associated with increased adverse effects.

Oral SARS-CoV-2 host responses predict the early COVID-19 disease course (preprint)

Objectives: Oral fluids provide ready detection of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and host responses. This study sought to determine relationships between oral virus, oral anti-SARS-CoV-2-specific antibodies, and symptoms. Methods: Saliva/throat wash (saliva/TW) were collected from asymptomatic and symptomatic, nasopharyngeal (NP) SARS-CoV-2 RT-qPCR+, subjects (n=47). SARS-CoV-2 RT-qPCR, N-antigen detection by immunoblot and lateral flow assay (LFA) were performed. RT-qPCR targeting viral subgenomic RNA (sgRNA) was sequence confirmed. SARS-CoV-2-anti-S protein RBD LFA assessed IgM and IgG responses. Structural analysis identified host salivary molecules analogous to SARS-CoV-2-N-antigen. Statistical analyses were performed. Results: At baseline, LFA-detected N-antigen was immunoblot-confirmed in 82% of TW. However, only 3/17 were saliva/TW qPCR+. Sixty percent of saliva and 83% of TW demonstrated persistent N-antigen at 4 weeks. N-antigen LFA signal in three negative subjects suggested potential cross-detection of 4 structurally analogous salivary RNA binding proteins (alignment 19-29aa, RMSD 1-1.5 Angstroms). At entry, symptomatic subjects demonstrated replication-associated sgRNA junctions, were IgG+ (94%/100% in saliva/TW), and IgM+ (75%/63%). At 4 weeks, SARS-CoV-2 IgG (100%/83%) and IgM (80%/67%) persisted. Oral IgG correlated 100% with NP+PCR status. Cough and fatigue severity (p=0.0008 and 0.016), and presence of nausea, weakness, and composite upper respiratory symptoms (p=0.005, 0.037 and 0.017) were negatively associated with oral IgM. Female oral IgM levels were higher than male (p=0.056). Conclusion: Important to transmission and disease course, oral viral replication and persistence showed clear relationships with select symptoms, early Ig responses, and gender during early infection. N-antigen cross-reactivity may reflect mimicry of structurally analogous host proteins.

The challenges in diagnosis of multisystem inflammatory syndrome in children (MISC), comparison of MISC and drug eruption: A case report (preprint)

Unusual manifestations are possible for multi-system inflammatory syndrome brought on by SARS-Cov2 infection. Early diagnosis and effective treatment have a direct impact on the outcome. Every young patient who presents to the clinic with a fever, skin rash, stomach discomfort, or cardiovascular complications has to be evaluated for this potentially fatal disease. It is also of utmost importance to differentiate MIS-C from drug hypersensitivity (DHS). MIS-c highly resembles DHS but leads to more complications and a higher mortality rate. We report a 9-year-old female who initially presented with generalized abdominal pain, nausea, vomiting, and cough. She gradually developed an acute abdomen and was admitted for surgical management of a suspected perforated appendix. Her condition deteriorated despite surgery and medical treatment. Differentiating drug allergy from this new emerging syndrome can be difficult. Herein we discuss about it.

Neuromyelitis Optica Spectrum Disorder After BIBP COVID-19 Vaccine: A Case Report (preprint)

Background: With the availability of the COVID-19 vaccine, post-vaccination neurological complications have occasionally been reported. Case presentation: We present a case of neuromyelitis optica spectrum disorder (NMOSD) that developed 1 month after the second dose of BIBP COVID-19 vaccine (SARS-CoV-2-Vaccine [Vero Cell] Inactived). The patient presented itching, numbness of the hand and right side of the face, associated with nausea, vomiting and hiccups. Brain MRI showed lesions in the area postrema, medulla, and bilateral hypothalamus, typical of NMOSD. Serum antibodies to anti-AQP4 and anti-MOG were negative. Conclusions: The pathogenesis of NMOSD development and the vaccine is still unknown. The presentation of NMOSD is generally aggressive and disabling, it is important for the neurologist to be attentive to the highly variable clinical presentation after vaccination against COVID-9 for early diagnosis and effective treatment.

Effect of gastrointestinal symptoms and skipping breakfast on anxiety and depression in quarantined Chinese college students during the COVID-19 pandemic: A cross sectional survey (preprint)

Background: Strict quarantine is an effective measure to prevent the spread of the Coronavirus disease (COVID-19) pandemic, but it probably increases the risk of anxiety and depression. We aimed to evaluate the anxiety and depression among quarantined college students at school during the COVID-19 pandemic and investigate whether gastrointestinal discomfort related-factors and skipping breakfast lead to increased risk of anxiety and depression. Methods: 384 quarantined college students in Shanghai China were recruited in this cross-sectional study from April 5th to May 29th, 2022. Generalized Anxiety Disorder (GAD-7) and Patient Health Questionnaire (PHQ-9) were used to assess anxiety and depression, respectively.Results: The prevalence of anxiety and depression were 56.8% and 62.8%, respectively. Longer quarantine duration, higher education level, skipping breakfast, stomachache or abdominal pain, and nausea or dyspepsia were the risk factors for anxiety. Moreover, longer quarantine duration, being woman, skipping breakfast, stomachache or abdominal pain, and nausea or dyspepsia increased the risk of depression. Notably, regularly physical exercising and taking positive attitude towards COVID-19 can reduce the risk of anxiety and depression. Conclusions: More attention should be paid to anxiety and depression of quarantined college students and universities should provide timely psychological monitoring and intervention services to mitigate the impact of negative emotions on students. And effectively relieving gastrointestinal symptoms, insisting on eat breakfast, regularly exercising, and taking a positive attitude towards to COVID-19 might contribute to preventing the anxiety and depression for those college students experiencing a long-term quarantine.

A Phase 2/3 observer-blind, randomized, controlled study to determine the safety and immunogenicity of SARS-CoV-2 recombinant spike protein vaccine in Indian children and adolescents aged 2 to 17 years (preprint)

Background: A recombinant, adjuvanted COVID-19 vaccine, SII-NVX-CoV2373 was manufactured in India and evaluated in Indian children and adolescents to assess safety and immunogenicity. Methods: This was a Phase 2/3 observer-blind, randomized, controlled study in children and adolescents aged 2 to 17 years. Participants were randomly assigned in 3:1 ratio to receive two doses of SII-NVX-CoV2373 or placebo on day 1 and day 22. Solicited adverse events (AEs) were collected for 7 days after each vaccination. Unsolicited AEs were collected for 35 days following first dose and serious AEs (SAEs) and adverse events of special interest (AESI) were collected throughout the study. Anti S IgG and neutralizing antibodies against the SARS-CoV-2 were measured at baseline, day 22, day 36 and day 180. Variant immune responses were assessed in a subset of participants at baseline, day 36 and day 180. Primary objectives were to demonstrate non-inferiority of SII-NVX-CoV2373 in each pediatric age group (12 to 17 years and 2 to 11 years, separately) to that in adults in terms of ratio of titers of both anti-S IgG and neutralizing antibodies 14 days after the second dose (day 36). Non-inferiority was to be concluded if the lower bound of 95% CI of the ratio was >0.67. Results: A total of 920 children and adolescents (460 in each age cohort; 12 to 17 years and 2 to 11 years) were randomized and vaccinated. The demographic and baseline characteristics between the two groups were comparable in both age groups. After the second dose, there were more than 100-fold rise in anti-S IgG GMEUs and more than 84-fold rise in neutralizing antibodies GMTs from baseline in the participants who received SII-NVX-CoV2373. The GMTs in both age groups were non-inferior to those observed in Indian adults. The seroconversion rate was [≥] 98% (anti-S IgG) and [≥] 97.9% (neutralizing antibodies) in both age groups, respectively. Similar findings were seen in the baseline seronegative participants. SII-NVX-CoV2373 also showed robust responses against various variants of concern. Injection site pain, tenderness, swelling, erythema and fever, headache, malaise, fatigue, myalgia, arthralgia, nausea and vomiting were the common solicited adverse events which were transient and resolved without any sequelae. Throughout the study, only two causally unrelated SAEs and no AESI were reported. Conclusion: SII-NVX-CoV2373 has been found safe and well tolerated in children and adolescents of 2 to 17 years. The vaccine was highly immunogenic and the immune response was non-inferior to that in adults.