Weeks Of Symptom Onset Research Articles

Accuracy of novel antigen rapid diagnostics for SARS-CoV-2: A living systematic review and meta-analysis.

SARS-CoV-2 antigen rapid diagnostic tests (Ag-RDTs) are increasingly being integrated in testing strategies around the world. Studies of the Ag-RDTs have shown variable performance. In this systematic review and meta-analysis, we assessed the clinical accuracy (sensitivity and specificity) of commercially available Ag-RDTs. We registered the review on PROSPERO (registration number: CRD42020225140). We systematically searched multiple databases (PubMed, Web of Science Core Collection, medRvix, bioRvix, and FIND) for publications evaluating the accuracy of Ag-RDTs for SARS-CoV-2 up until 30 April 2021. Descriptive analyses of all studies were performed, and when more than 4 studies were available, a random-effects meta-analysis was used to estimate pooled sensitivity and specificity in comparison to reverse transcription polymerase chain reaction (RT-PCR) testing. We assessed heterogeneity by subgroup analyses, and rated study quality and risk of bias using the QUADAS-2 assessment tool. From a total of 14,254 articles, we included 133 analytical and clinical studies resulting in 214 clinical accuracy datasets with 112,323 samples. Across all meta-analyzed samples, the pooled Ag-RDT sensitivity and specificity were 71.2% (95% CI 68.2% to 74.0%) and 98.9% (95% CI 98.6% to 99.1%), respectively. Sensitivity increased to 76.3% (95% CI 73.1% to 79.2%) if analysis was restricted to studies that followed the Ag-RDT manufacturers' instructions. LumiraDx showed the highest sensitivity, with 88.2% (95% CI 59.0% to 97.5%). Of instrument-free Ag-RDTs, Standard Q nasal performed best, with 80.2% sensitivity (95% CI 70.3% to 87.4%). Across all Ag-RDTs, sensitivity was markedly better on samples with lower RT-PCR cycle threshold (Ct) values, i.e., <20 (96.5%, 95% CI 92.6% to 98.4%) and <25 (95.8%, 95% CI 92.3% to 97.8%), in comparison to those with Ct ≥ 25 (50.7%, 95% CI 35.6% to 65.8%) and ≥30 (20.9%, 95% CI 12.5% to 32.8%). Testing in the first week from symptom onset resulted in substantially higher sensitivity (83.8%, 95% CI 76.3% to 89.2%) compared to testing after 1 week (61.5%, 95% CI 52.2% to 70.0%). The best Ag-RDT sensitivity was found with anterior nasal sampling (75.5%, 95% CI 70.4% to 79.9%), in comparison to other sample types (e.g., nasopharyngeal, 71.6%, 95% CI 68.1% to 74.9%), although CIs were overlapping. Concerns of bias were raised across all datasets, and financial support from the manufacturer was reported in 24.1% of datasets. Our analysis was limited by the included studies' heterogeneity in design and reporting. In this study we found that Ag-RDTs detect the vast majority of SARS-CoV-2-infected persons within the first week of symptom onset and those with high viral load. Thus, they can have high utility for diagnostic purposes in the early phase of disease, making them a valuable tool to fight the spread of SARS-CoV-2. Standardization in conduct and reporting of clinical accuracy studies would improve comparability and use of data.

Diagnostic Value of Nucleocapsid Protein in Blood for SARS-CoV-2 Infection.

BackgroundBiomarkers have been widely explored for coronavirus disease 2019 diagnosis. Both viral RNA or antigens (Ag) in the respiratory system and antibodies (Ab) in blood are used to identify active infection, transmission risk, and immune response but have limitations. This study investigated the diagnostic utility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid protein (N-Ag) in serum.MethodsWe retrospectively studied 208 randomly selected cases with SARS-CoV-2 infection confirmed by viral RNA test in swabs. N-Ag concentrations were measured in remnant serum samples, compared to viral RNA or Ab results, and correlated to electronic health records for clinical value evaluation.ResultsSerum N-Ag was detected during active infection as early as day 2 from symptom onset with a diagnostic sensitivity of 81.5%. Within 1 week of symptom onset, the diagnostic sensitivity and specificity reached 90.9% (95% CI, 85.1%–94.6%) and 98.3% (95% CI, 91.1%–99.9%), respectively. Moreover, serum N-Ag concentration closely correlated to disease severity, reflected by highest level of care, medical interventions, chest imaging, and the length of hospital stays. Longitudinal analysis revealed the simultaneous increase of Abs and decline of N-Ag.ConclusionsSerum N-Ag is a biomarker for SARS-CoV-2 acute infection with high diagnostic sensitivity and specificity compared to viral RNA in the respiratory system. There is a correlation between serum N-Ag concentrations and disease severity and an inverse relationship of N-Ag and Abs. The diagnostic value of serum N-Ag, as well as technical and practical advantages it could offer, may meet unsatisfied diagnostic and prognostic needs during the pandemic.

Unusual Presentation of Epstein-Barr Virus-Associated Cholestatic Hepatitis in an Infant

Epstein-Barr virus (EBV) infections are prevalent in the pediatric population but are subclinical in the majority of cases. Elevated transaminases in the acute setting rarely increase beyond 5 times the normal upper limit. We present a girl aged 1 y with fever, vomiting, and diarrhea. Although initial physical examination was unremarkable, she developed jaundice, hepatomegaly, abdominal distension, and a maculopapular rash during admission. Laboratory investigations revealed marked increase in transaminases (alanine aminotransferase 7,664.5 IU/L, aspartate aminotransferase 12,266 IU/L), elevated γ-glutamyl transferase (224 IU/L), and hyperbilirubinemia (total 130.7 µmol/L, direct 104.9 µmol/L). Abdominal ultrasound reported hepatomegaly with mild ascites. Serology revealed that both Monospot test and EBV immunoglobulin G were positive. With supportive therapy, improvement was noted within a week of symptom onset. We hereby elucidate the importance of considering EBV as a cause of acute cholestatic hepatitis in a very young pediatric patient who develops a rapid elevation of liver enzymes.

A retrospective analysis of emerging rabies: a neglected tropical disease in Sarawak, Malaysia.

Rabies, a neglected tropical disease (NTD), is a viral infection which is often fatal. Since 2017, a rabies epidemic has been declared in Sarawak, Malaysia. However, there is a lack of local epidemiological data and descriptions of local presentations of this disease. This was a retrospective analysis of a series of rabies cases encountered in Sibu Hospital, Sarawak from March 2020 to February 2021. Six cases of rabies were identified in this series, all with a mixture of upper motor neuron and lower motor neuron findings. Most cases did not seek medical attention upon dog bite and therefore effective post-exposure prophylaxis was not given. The incubation period varied from 17 days to 2 years. All cases died, with five cases succumbing to the illness within two weeks of symptom onset. The cumulative incidence for rabies in Sibu was estimated at 1.7 per 100,000 population. The lack of public awareness of the implication of animal bites and the immediate management in rabies-endemic regions are factors contributing to high rabies mortality.

Cancer as a prospective sequela of long COVID-19.

As the spread of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) continues to surge worldwide, our knowledge of coronavirus disease 2019 (COVID‐19) is rapidly expanding. Although most COVID‐19 patients recover within weeks of symptom onset, some experience lingering symptoms that last for months (“long COVID‐19”). Early reports of COVID‐19 sequelae, including cardiovascular, pulmonary, and neurological conditions, have raised concerns about the long‐term effects of COVID‐19, especially in hard‐hit communities. It is becoming increasingly evident that cancer patients are more susceptible to SARS‐CoV‐2 infection and are at a higher risk of severe COVID‐19 than the general population. Nevertheless, whether long COVID‐19 increases the risk of cancer in those with no prior malignancies, remains unclear. Given, the disproportionate impact of the disease on the African American community, yet another unanswered question is whether racial disparities are to be expected in COVID‐19 sequelae. Herein, we propose that long COVID‐19 may predispose recovered patients to cancer development and accelerate cancer progression. This hypothesis is based on growing evidence of the ability of SARS‐CoV‐2 to modulate oncogenic pathways, promote chronic low‐grade inflammation, and cause tissue damage. Comprehensive studies are urgently required to elucidate the effects of long COVID‐19 on cancer susceptibility.

Vitreoretinal Findings in Nonarteritic Ischemic Optic Neuropathy.

Although nonarteritic anterior ischemic optic neuropathy (NAION) is considered a disorder that primarily affects the optic nerve head, optical coherence tomography (OCT) shows peripapillary and foveal subretinal fluid associated with optic disc swelling from NAION. We sought to further evaluate retinal and vitreous changes in patients with NAION. Patients diagnosed with NAION at the New England Eye Center between 2013 and 2017 were evaluated using OCT. The presence and distribution of subretinal fluid was analyzed. Evidence of other vitreoretinal changes, including vitreopapillary traction (VPT) and the presence of hyperreflective dots (HRD), were also determined. Twenty-five eyes from 20 patients who presented within 4 weeks of symptom onset were assessed. Peripapillary subretinal fluid was seen in 16 eyes (64%). Of those eyes, the subretinal fluid extended into the macula in 4 eyes (16%). Visual acuity improved in 2 of 4 eyes after subfoveal fluid resolution. Intraretinal cysts located in the peripapillary region were seen in 8 eyes (32%), HRD were noted in 11 (44.0%). There was no evidence of VPT. A substantial number of patients with NAION have subretinal fluid on OCT, consistent with prior reports. Resolution of subfoveal fluid may result in some recovery of visual acuity. Other retinal changes, such as intraretinal cysts and HRD, are present but have unclear implications. We did not find evidence of a primary role of VPT in the pathophysiology of NAION.

Viral Load Kinetics of Severe Acute Respiratory Syndrome Coronavirus 2 in Hospitalized Individuals With Coronavirus Disease 2019.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) kinetics remain understudied, including the impact of remdesivir. In hospitalized individuals, peak sputum viral load occurred in week 2 of symptoms, whereas viremia peaked within 1 week of symptom-onset, suggesting early systemic seeding of SARS-CoV-2. Remdesivir treatment was associated with faster viral decay.

A review on the diagnostic approaches of COVID-19 infection;features and limitations

Detection of coronavirus disease 2019 (COVID-19) in early stage is indispensible for outcome improvement and interruption of transmission chain. Clear understanding of the nature of the diagnostic tests for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and their challenges, collecting the most diagnostically valuable specimen at the right time from the right anatomic site, and interpretation of their findings is important. This review scrutinizes current challenges and interpretation of reverse transcriptase polymerase chain reaction (RT-PCR), as the reference method, loop-mediated isothermal amplification (LAMP), antibody and antigen detection, typical lung imaging characteristics and prominent abnormal changes in laboratory findings of patients with proven COVID-19, and describes how the results may vary over time. Bronchoalveolar lavage fluid and sputum specimens demonstrate the highest positive rates (93% and 72%, respectively) in molecular diagnosis of COVID-19. Alternatively, repeated RT-PCR assays can be performed;as over time, it is an increase in the likelihood of the SARS-CoV-2 being present in the nasopharynx. Combining clinical evidence with results of chest computed tomography (CT) and RT-PCR can minimize the risk of diagnostic errors. Elevated levels of interleukin 6 (IL-6) and D-dimer are thought to be closely associated with the occurrence of severe COVID-19 in adults, and their combined detection can serve as early factors predicting the severity of COVID-19. Moreover, elevated acute phase proteins are associated with a poor outcome in COVID-19. Serological diagnosis also is an important tool to understand the extent of COVID-19 in the community, and to identify individuals, who are immune. Antibodies begin to increase from the second week of symptom onset.

Clinical relevance of serum Krebs von den Lungen-6 levels in patients with coronavirus disease 2019.

The clinical relevance of Krebs von den Lungen-6 (KL-6) levels in patients with coronavirus disease 2019 (COVID-19) is unclear. This study aimed to evaluate the correlation between KL-6 levels, laboratory parameters, and clinical outcomes. We enrolled 364 patients with confirmed COVID-19 who were hospitalized within 1 week of symptom onset. Their serum KL-6 level was measured on admission. Demographic data, symptoms, comorbidities, and laboratory parameters were recorded at the time of admission. Days to nucleic acid conversion and days of hospitalization were defined as clinical outcomes for evaluating the clinical relevance of serum KL-6 levels in COVID-19. Patients with elevated KL-6 levels were significantly older; had more reported instances of fever, cough, fatigue, and wheezing; and a longer hospital stays than those with normal KL-6 levels; the difference was statistically significant (p < 0.001). Furthermore, KL-6 levels was associated with the days of hospitalization and various laboratory parameters that influence the severity and prognosis of COVID-19. Elevated KL-6 levels have also been shown to be an independent risk factor for prolonged hospitalization. Our data suggest that serum KL-6 levels on admission can serve as an indicator for assessing the clinical outcomes of COVID-19.

Autoimmune encephalitis after Japanese encephalitis in children: A prospective study

ObjectiveTo explore anti-neuronal surface antibodies and identify associated serum predictors of autoimmune encephalitis after Japanese encephalitis (JE). MethodsThis prospective study first detected anti-neuronal surface antibodies and cytokines in the serum and cerebrospinal fluid (CSF) of JE patients within one week of symptom onset. Anti-neuronal surface antibodies and cytokines in the serum were detected on day 21 post-JE. If the patients relapsed during the convalescent phase, we simultaneously detected JE virus RNA and cytokines in the CSF, as well as anti-neuronal surface antibodies in the serum and CSF. ResultsAll 31 patients were negative for anti-neuronal surface antibodies at the onset of JE in the serum and CSF. During the convalescent phase, five patients developed autoimmune encephalitis (two had anti-N-methyl-d-aspartate receptor [NMDAR] antibodies, one had γ-aminobutyric acid-B receptor [GABABR] antibodies, and two had other antibodies against unknown neuronal surface antigens). Patients who developed autoimmune encephalitis experienced more severe outcomes than those who did not at the one-year follow-up (p = 0.044). The levels of serum CXCL13 and IL-6, as well as CXCL13, BAFF, CXCL10, and MMP-9 in the CSF were increased in the convalescent phase compared to the acute phase in patients who developed autoimmune encephalitis (p < 0.05). ConclusionIn addition to anti-NMDAR antibodies, anti-GABABR antibodies and antibodies against unknown neuronal surface antigens can trigger autoimmune encephalitis following JE. Patients who developed autoimmune encephalitis had a poorer prognosis at the one-year follow-up. Serum CXCL13 may represent a predictor of autoimmune encephalitis after JE.

Comparative Study of Chemosensory Dysfunction in COVID-19 in 2 Geographically Distinct Regions.

To directly compare the prevalence of chemosensory dysfunction (smell and taste) in geographically distinct regions with the same questionnaires. A cross-sectional study was performed to evaluate the self-reported symptoms among adults (older than 18 years) who underwent COVID-19 testing at an ambulatory assessment center in Canada and at a hospital in Israel between March 16, 2020, and August 19, 2020. The primary outcome was the prevalence of self-reported chemosensory dysfunction (anosmia/hypomsia and dysgeusia/ageusia). Subgroup analysis was performed to evaluate the prevalence of chemosensory deficits among the outpatients. We identified a total of 350 COVID-19-positive patients (138 Canadians and 212 Israelis). The overall prevalence of chemosensory dysfunction was 47.1%. There was a higher proportion of chemosensory deficits among Canadians compared to Israelis (66.7% vs 34.4%, P < .01). A subgroup analysis for outpatients (never hospitalized) still identified a higher prevalence of chemosensory dysfunction among Canadians compared to Israelis (68.2% vs 36.1%, P < 0.01). A majority of patients recovered their sense of smell after 4 weeks of symptom onset. Although the prevalence of chemosensory deficit in COVID-19 was found to be similar to previously published reports, the prevalence can vary significantly across different geographical regions. Therefore, it is important to obtain regionally specific data so that the symptom of anosmia/dysgeusia can be used as a guide for screening for the clinical diagnosis of COVID-19.

A67 DELAYED PRESENTATION AND SURGICAL MANAGEMENT OF PRIMARY PNEUMOCOCCAL PERITONITIS

Abstract Background S. pneumoniae intraabdominal infections are rare in healthy individuals, but the literature reveals a female dominance for primary peritonitis in the early post-partum period. Limited studies exist evaluating the timing of surgical management. Aims We present a case of primary pneumococcal peritonitis in which the presentation and surgical intervention was delayed. Methods A case chart review and literature review was conducted. Results A 41-year-old female with a spontaneous vaginal delivery 4 months prior presented with progressive abdominal pain, distention, and emesis over 10 days. She was septic with a firm, distended abdomen and rebound tenderness. A CT revealed significant panenteritis and ascites. She received intravenous fluids and was empirically started on ceftriaxone, vancomycin and metronidazole. The gastrointestinal virus panel, stool cultures and C. difficile toxin were negative. However, her blood cultures revealed Strep. pneumoniae and the purulent peritoneal fluid contained gram-positive cocci. Despite sensitivity to ceftriaxone, and several paracenteses, her ascites, pain and new fever continued. Twenty-eight days after admission, she underwent a laparoscopic abdominal lysis of adhesions and drainage of three intraabdominal abscess collections. Cultures of the purulent peritoneal fluid were negative. She was stepped down to amoxicillin-clavulanate and discharged six weeks after symptom onset. Despite the development of pneumococcal vaccines, worldwide S. pneumoniae is a common pathogen with high morbidity and mortality. It is a rare cause of intraabdominal infections; however, primary peritonitis has been widely recognized in children. Prior to antibiotics, the mortality of pneumococcal peritonitis was 31.5–100%. Secondary pneumococcal peritonitis is established in adult patients with cirrhosis, nephrotic syndrome and immunocompromised conditions. In healthy individuals, pneumococcal peritonitis often mimics appendicitis and is diagnosed with positive blood cultures. The majority of primary pneumococcal peritonitis cases occur in females, are associated with the early post-partum period (less than two months), IUD placement, and pelvic inflammatory disease. Theories of pathogenesis include direct hematogenous spread or translocation. Transient colonization of the genital tract after IUD placement or during the post-partum period may allow for ascension from the fallopian tubes into the peritoneum. The majority of cases undergo surgery within one week of symptom onset. While it has not been studied in randomized trials, early surgical intervention for source control may decrease morbidity and hospital stay. Conclusions Primary pneumococcal peritonitis has a female predominance and can occur later in the post-partum period than previously reported. Surgery should be considered early to achieve source control and improve patient outcomes. Funding Agencies None

Correlation of RT-PCR Cycle Threshold Value and Chest Computed Tomography Scan Severity Score in Patients with COVID-19: A Cross-sectional Study

Introduction: Chest Computed Tomography (CT) scan for Coronavirus Disease-2019 pneumonia is used widely and viral load is predicted by the Cycle threshold (Ct) values of Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR). Studies correlating viral load in Severe Acute Respiratory Syndrome- Coronavirus-2 (SARS-CoV-2) RT-PCR positive patients and severity of chest CT scan are limited. Aim: To find an association between viral load and chest CT findings. Materials and Methods: This was a cross-sectional study conducted on patients admitted to Believers Church Medical College Hospital, Thiruvalla, Kerala between September 2020 to March 2021. TrueNat RT-PCR test was performed on nasopharyngeal swabs, targeting the Orf1 gene of SARS-CoV-2 and results were quantified as Cycle threshold (Ct) values. Chest CT-Total Severity Score (TSS) ranged from 0-40 and was calculated by summing up the acute inflammatory lesions in each of the five lobes of both the lungs. Correlation was assessed using Spearman’s Correlation Coefficient. Independent sample t-test and one-way Analysis of Variance (ANOVA) were used for comparison of means. Results: Of the 102 patients in the study [mean age of the patients 64.13±13.17 years and majority were males (70.6%)], 11 had lung changes unrelated to COVID-19. There was an inverse relationship between viral load Ct value of SARS-CoV-2 in nasopharyngeal specimens and TSS of chest CT scan. The mean viral load was highest in patients with mild (21.48±8.31), moderate (21.22±6.30) and severe (24.19±4.67) CT involvement. There was a significant difference between mean duration to symptom onset and chest CT scan among those with a high viral load (4.97±2.65) compared to those with a low viral load (6.81±4.5), (p-value=0.01). Among those who died due to COVID- 19, (12/13) 92.3% were above 60 years of age. Presence of co- morbidities/dyspnoea/fever at presentation did not have any significant association with TSS severity. Conclusion: Viral load is not a critical factor that influences pulmonary manifestations in COVID-19, nor in-hospital mortality. CT scan may be more useful to detect lung involvement when done nearing or after the first week of symptom onset, irrespective of the viral load. Viral load can be important in predicting transmissibility and to minimise potential spread, whereas chest CT can help identify cases requiring extensive medical care.

Saliva and COVID 19: Current dental perspective.

Oral health care providers are at a higher risk of being infected by novel coronavirus due to close proximity to patient's face and exposure to saliva while working on the patient. Thus, there is an urgent need to interpret the available literature in order to establish safe practices for dental professionals as well as limit the spread of infection through saliva. The study intends to provide up-to-date, compiled evidence-based information related to saliva and its association with COVID-19. It further provides suggestions for safe practices in dentistry in current pandemic times. Oral symptoms may be strongly suggestive of early diagnosis and disease progression in COVID-19 patients. Viral loads in saliva are reported higher than standard nasopharyngeal swabs in few studies, majorly in the 1st week of symptom onset. Besides, salivary diagnostics has many additional advantages of being noninvasive, comfortable to the patients with the possibility of point-of-care testing for diagnosing COVID-19. High-efficiency particulate arrestor filter, rubber dam application and high-volume evacuator can reduce spatter and droplets/aerosol production. Povidone-iodine-based mouthwash maybe mouthwash of choice before any dental examination or procedures due to its ability to decrease severe acute respiratory syndrome- coronavirus 2 viral loads in the mouth. Salivary diagnostics related to COVID-19 should be integral part of dental teaching programs. There is a tremendous scope to study saliva in health and diseases.

Case Study Using Nebulized Isomerized Linoleic Acid (LA) for Outpatient Treatment of Symptomatic COVID-19.

We report the resolution of COVID-19 related symptoms in 6 days in two moderate to high risk COVID-19 patients (CDC, 2020) treated with nebulized 0.5 ml 11 mM LA every 4 hours around the clock for 7 days in an outpatient setting. The lipid potassium salt LA is Generally Recognized As Safe (GRAS) by the FDA (Food Additive). We report that in vitro testing of LA 4.4-50.2 mM showed 99% kill-rate of COVID-19 in 2 minutes. Pulmonary symptoms resolved and pulse oximetry levels normalized within the same week of symptom onset, returning to their normal marital relations on day 6. This compares to the median recovery time of two weeks from onset of symptoms for mild, and three to six weeks for severe COVID-19 cases (WHO, 2020). LA with its capacity to provide an affordable intervention within a home environment deserves further study to determine if it reduces severity, length of symptoms, and complications of COVID-19.

Assessment of Pediatric Optic Neuritis Visual Acuity Outcomes at 6 Months

Optic neuritis (ON) in children is uncommon. There are limited prospective data for visual acuity (VA) outcomes, associated diseases, and neuroimaging findings. Prospective data from a large sample would be useful for counseling families on treatment decisions and prognosis. To prospectively study children with a first episode of ON, describe VA after 6 months, and ascertain the network's (Pediatric Eye Disease Investigator Group and Neuro-Ophthalmology Research Disease Investigator Consortium) ability to enroll pediatric patients with ON prospectively. This nonrandomized cohort study was conducted from September 20, 2016, to July 20, 2018, at 23 sites in the United States and Canada in pediatric ophthalmology or neuro-ophthalmology clinics. A total of 44 children (aged 3-15 years) presented with a first episode of ON (visual loss, pain on eye movements, or both) within 2 weeks of symptom onset and at least 1 of the following in the affected eye: a distance high-contrast VA (HCVA) deficit of at least 0.2 logMAR below age-based norms, diminished color vision, abnormal visual field, or optic disc swelling. Exclusion criteria included preexisting ocular abnormalities or a previous episode of ON. Primary outcomes were monocular HCVA and low-contrast VA at 6 months. Secondary outcomes were neuroimaging, associated diagnoses, and antibodies for neuromyelitis optica and myelin oligodendrocyte glycoprotein. A total of 44 children (mean age [SD], 10.2 [3.5] years; 26 boys [59%]; 23 White individuals [52%]; 54 eyes) were enrolled in the study. Sixteen patients (36%) had bilateral ON. Magnetic resonance imaging revealed white matter lesions in 23 children (52%). Of these children, 8 had myelin oligodendrocyte glycoprotein-associated demyelination (18%), 7 had acute disseminated encephalomyelitis (16%), 5 had multiple sclerosis (11%), and 3 had neuromyelitis optica (7%). The baseline mean HCVA was 0.95 logMAR (20/200), which improved by a mean 0.76 logMAR (95% CI, 0.54-0.99; range, -0.70 to 1.80) to 0.12 logMAR (20/25) at 6 months. The baseline mean distance low-contrast VA was 1.49 logMAR (20/640) and improved by a mean 0.72 logMAR (95% CI, 0.54-0.89; range, -0.20 to 1.50) to 0.73 logMAR (20/100) at 6 months. Baseline HCVA was worse in younger participants (aged <10 years) with associated neurologic autoimmune diagnoses, white matter lesions, and in those of non-White race and non-Hispanic ethnicity. The data did not suggest a statistically significant association between baseline factors and improvement in HCVA. The study network did not reach its targeted enrollment of 100 pediatric patients with ON over 2 years. This indicates that future treatment trials may need to use different inclusion criteria or plan a longer enrollment period to account for the rarity of the disease. Despite poor VA at presentation, most children had marked improvement by 6 months. Associated neurologic autoimmune diagnoses were common. These findings can be used to counsel families about the disease.

SARS-CoV-2 RT-PCR profile in 298 Indian COVID-19 patients: a retrospective observational study.

BackgroundDespite being in the 5th month of pandemic, knowledge with respect to viral dynamics, infectivity and RT-PCR positivity continues to evolve.AimTo analyse the SARS CoV-2 nucleic acid RT-PCR profiles in COVID-19 patients.DesignIt was a retrospective, observational study conducted at COVID facilities under AIIMS, New Delhi.MethodsPatients admitted with laboratory confirmed COVID-19 were eligible for enrolment. Patients with incomplete details, or only single PCR tests were excluded. Data regarding demographic details, comorbidities, treatment received and results of SARS-CoV-2 RT-PCR performed on nasopharyngeal and oropharyngeal swabs, collected at different time points, was retrieved from the hospital records.Results298 patients were included, majority were males (75·8%) with mean age of 39·07 years (0·6–88 years). The mean duration from symptom onset to first positive RT-PCR was 4·7 days (SD 3·67), while that of symptom onset to last positive test was 17·83 days (SD 6·22). Proportions of positive RT-PCR tests were 100%, 49%, 24%, 8·7% and 20·6% in the 1st, 2nd, 3rd, 4th & >4 weeks of illness. 12 symptomatic patients had prolonged positive test results even after 3 weeks of symptom onset. Age > = 60 years was associated with prolonged RT-PCR positivity (statistically significant).ConclusionThis study showed that the average period of PCR positivity is more than 2 weeks in COVID-19 patients; elderly patients have prolonged duration of RT-PCR positivity and requires further follow up.

Transmission of SARS-CoV-2: A Review of Viral, Host, and Environmental Factors.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of coronavirus disease 2019 (COVID-19), has spread globally in a few short months. Substantial evidence now supports preliminary conclusions about transmission that can inform rational, evidence-based policies and reduce misinformation on this critical topic. This article presents a comprehensive review of the evidence on transmission of this virus. Although several experimental studies have cultured live virus from aerosols and surfaces hours after inoculation, the real-world studies that detect viral RNA in the environment report very low levels, and few have isolated viable virus. Strong evidence from case and cluster reports indicates that respiratory transmission is dominant, with proximity and ventilation being key determinants of transmission risk. In the few cases where direct contact or fomite transmission is presumed, respiratory transmission has not been completely excluded. Infectiousness peaks around a day before symptom onset and declines within a week of symptom onset, and no late linked transmissions (after a patient has had symptoms for about a week) have been documented. The virus has heterogeneous transmission dynamics: Most persons do not transmit virus, whereas some cause many secondary cases in transmission clusters called "superspreading events." Evidence-based policies and practices should incorporate the accumulating knowledge about transmission of SARS-CoV-2 to help educate the public and slow the spread of this virus.

Features of intracranial hemorrhage in cerebral venous thrombosis.

Cerebral venous thrombosis (CVT) is associated with intracranial hemorrhage. To identify clinical and imaging features of CVT-associated intracranial hemorrhage. We hypothesized that higher clot burden would be associated with a higher risk of intracranial hemorrhage. We performed a retrospective analysis of an international, multicenter cohort of patients with confirmed cerebral venous thrombosis who underwent computed tomography within 2weeks of symptom onset. Clinical and imaging features were compared between patients with and without intracranial hemorrhage. Clot burden was assessed by counting the number of thrombosed venous sinuses and veins on confirmatory imaging. We enrolled 260 patients from 10 institutions in Europe and Mexico. The mean age was 42years and 74% were female. Intracranial hemorrhage was found in 102 (39%). Among them parenchymal hemorrhage occurred in 64 (63%), in addition, small juxta-cortical hemorrhage was found in 30 (29%), subarachnoid hemorrhage in 24 (24%) and subdural hemorrhage in 11 (11%). Multiple concomitant types of hemorrhage occurred in 23 (23%). Older age and superior sagittal thrombosis involvement were associated with presence of hemorrhage. The number of thrombosed venous sinuses was not associated with intracranial hemorrhage (median number IQRInterquartile ratio] of sinuses/veins involved with hemorrhage 2 (1-3) vs. 2 (1-3) without hemorrhage, p = 0.4). The high rate of intracranial hemorrhage in cerebral venous thrombosis is not explained by widespread involvement of the venous sinuses. Superior sagittal sinus involvement is associated with higher bleeding risk.

Four point-of-care lateral flow immunoassays for diagnosis of COVID-19 and for assessing dynamics of antibody responses to SARS-CoV-2

We aimed to evaluate the role of rapid serological tests in the management of coronavirus disease 2019 (COVID-19) patients. This retrospective study enrolled 16 real-time reverse transcription polymerase chain reaction-confirmed symptomatic patients with COVID-19 and 58 COVID-19 negative patients at a medical center in Taiwan over a 3-month period. Serial serum samples were collected and tested for antibody response using four point-of-care (POC) lateral flow immunoassays (LFIA) (ALLTEST 2019-nCoV IgG/IgM Rapid Test, Dynamiker 2019-nCoV IgG/IgM Rapid Test, ASK COVID-19 IgG/IgM Rapid Test, and Wondfo SARS-CoV-2 Antibody Test). Time-dependent detection sensitivity and timeliness of seroconversion were determined and compared between the four POC rapid tests. The overall sensitivity and specificity of the four tests for detecting anti-SARS-CoV-2 antibodies after 3 weeks of symptom onset were 100% and 100%, respectively. There was no significant difference between the rapid tests used for detection of IgM and IgG separately and those used for detection of combined total antibody (mainly IgM/IgG). There was no significant difference between the four POC rapid tests in terms of time required for determining seroconversion of COVID-19. Patients with COVID-19 with pneumonia demonstrated shorter seroconversion time than those without pneumonia. Though the POC antibody rapid tests based on LFIA showed reliable performance in the detection of SARS-CoV-2-specific antibodies, the results of these tests should be interpreted and applied appropriately in the context of antibody dynamic of COVID-19 infection. COVID-19 patients complicated with pneumonia exhibited earlier anti-SARS-CoV-2 antibody response than COVID-19 patients without pneumonia.