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Background: Approximately two years ago, COVID-19 was declared a global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and through genomic surveillance, we have seen the emergence of variants of SARS-CoV-2. In the United States, over 78 million cases and >900,000 deaths attributable to COVID-19 have been reported. SCD was identified as a risk factor for severe COVID-19 disease in adults and pediatric patients. The emergence of novel SARs- CoV-2 variants has led to challenges in diagnosis, treatment, and prediction of long-term sequelae in individuals with SCD and COVID-19. Aim(s): We compare the overall seasonal variation of COVID-19 variants and patterns of healthcare utilization and clinical presentation over time in pediatric patients with SCD and COVID-19 at Children's National Hospital (CNH). Method(s): Our single-center, observational cohort study included 193 pediatric patients with SCD (0-21 years) with PCR-confirmed SARSCoV- 2 infection between March 31, 2020, and January 31, 2022. Per the SECURE SCD Registry definitions, clinical severity was classified as asymptomatic, mild, moderate, and severe. Result(s): A total of 193 unique patients with SCD and positive SARS-CoV-2 PCRs between March 2020-January 2022 were included in our registry. Most patients were female (51.8%), and the mean age was 11.2 years (SD 6.5 years). Most of the cohort resides in Maryland (N=135), and HbSS was the dominant genotype (69.4%). During the alpha dominant variant of the COVID-19 pandemic (March 2020- June 2021) there were 70 cases, followed by 40 cases during the Delta variant (July 2021- December 19, 2021), and 83 cases during the Omicron variant dominance (from December 20, 2021-January 31,2022). There were 149 patients (77%) that presented to the emergency department (ED) or were hospitalized. There were a total of 80 hospitalizations (41.5%), and a relative comparison showed that the percentage of hospitalizations was highest during the delta wave (47.5%) and lowest during the omicron wave (36.1%) (p= 0.407). ED-only utilization was highest in the era of omicron (43.4%, N=36), followed by delta (32.5%, N=13), and then alpha (30%, N=21)(p=0.197). The most common SCD-related complication was vaso-occlusive (VOC) pain (33%, N=64) which accounted for half of all hospital admissions (51%, N=41 of 80). Acute chest syndrome (ACS) was reported in 40% (N=32) of admitted patients and was highest in the alpha era (54.8%, N=17). The use of blood transfusion therapy was highest in the alpha (N=17) and delta (N=14) variants, while Remdesivir use was highest in omicron (N=15). A total of 6 patients received monoclonal antibodies (Delta, N=4;omicron, N=2). Throughout all the variants, there was a significant difference in COVID-19 clinical severity (p>0.005). Of the patients classified as asymptomatic (13%, N=25), seventy-two percent (n=18) were diagnosed during the alpha variant. Mild severity was the most prevalent (69%, N=134), with the omicron variant having the highest cases (51.5%, N=69). Severe cases were observed in all variants (6.7%, N=13) but were most prevalent during the alpha variant (46.2%, N=6). Summary - Conclusion(s): Interestingly, while the relative percentage of hospitalizations was lowest during the omicron wave, it saw the highest percentages of ER utilization. Overall, COVID-19 remains mild in pediatric patients with SCD, and notably, there was higher health care utilization in the omicron era.
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Intro: With the first case of COVID-19 in Cuba on March 11, 2020, the Center for Genetic Engineering and Biotechnology in Havana began an extensive vaccine program. Two vaccines based on RBD recombinant protein were developed, one for systemic administration "Abdala" and one mucosal vaccine "Mambisa". Abdala received the EUA in July 2021 and "Mambisa" completed its clinical development as a booster dose for convalescent subjects. Method(s): Two doses (25 and 50 microg) and two schedules (0-14-28 and 1-28-56 days) were evaluated in phase I clinical trials with volunteers 19 to 54 years old. The phase II and III clinical trials were also double-blind, randomized, and placebo-controlled, and included respectively 660 and 48,000 volunteers from 19 to 80 years. The anti-RBD titers were evaluated using a quantitative ELISA system developed at the Center for Immunoassay, Havana Cuba, and ELECSYS system from Roche. The RBD to ACE2 plate-based binding competitive ELISA was performed to determine the inhibitory activity of the anti-RBD polyclonal sera on the binding of the hFc-ACE2 coated plates. The neutralization antibody titers were detected by a traditional virus microneutralization assay (MN50). Finding(s): The Abdala vaccine reached 92.28% efficacy. The epidemic was frankly under control in Cuba after the vaccine introduction having reached the highest levels of cases and mortality in July 2021 with the dominance of the Delta strain. The peak of the Omicron wave, unlike other countries, did not reach half of the cases of the Delta wave with a significant reduction in mortality. The mucosal vaccine candidate "Mambisa" completed its clinical development as a booster dose for convalescent subjects reaching the trial end-point. Conclusion(s): Vaccine composition based on RBD recombinant antigen alone is sufficient to achieve high vaccine efficacy comparable to mRNA and live vaccine platforms. The vaccine also protects against different viral variants including Delta and Omicron strains.Copyright © 2023
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Background: Delayed post-hypoxic leukoencephalopathy (DPHL) with associated microbleeds is a clinical entity presenting with cognitive impairment days or weeks after an episode of acute hypoxic brain injury. Case report: We describe a 68-year-old male with SARS-CoV2 infection who had cardiac arrest, required sedation and mechanical ventilation for 17 days, and after sedation was discontinued, he became unresponsive. Brain MRI showed diffuse confluent hyperintense signals in the subcortical white matter and multiple subcortical white matter microhemorrhages. EEG revealed diffuse attenuation of brain electrical activity with isolated polymorphic delta waves in the frontal region without epileptiform activity. Conclusion(s): Clinicians need to be aware that patients with Covid-19 can develop delayed post-hypoxic leukoencephalopathy.Copyright © 2022 The Authors
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Background & Purpose: In Ireland, general adult hospitals are often located independently of maternity units. The lack of onsite obstetric input can present a challenge to the general physician due to lack of exposure and training in the management of complex medical conditions in pregnancy. The global CoVid-19 pandemic saw a shift in admission rates across many demographics. Our audit sought to identify whether there was any change in medical admission rates, and subspecialty distributions in pregnant women during the CoVid-19 pandemic at our institution. Method(s): This was a retrospective audit of medical admissions 2016 - 2021. Data was collected from medical charts, and discharge summaries on hospital electronic system. Result(s): From 2019-2021, there were 55 pregnant patients admitted. 30.1% (n=17) were admitted under respiratory services. 64% (n=11) of these patients were admitted with a diagnosis of CoVid-19, with 7% (n=4) requiring ICU admission. Discussion(s): Overall, pregnancy related admissions account for a small percentage of general adult hospital admissions. There was evidence of an increased burden of respiratory admissions during the CoVid-19 pandemic, particularly in the third and fourth quarters of 2021, corresponding with the delta wave in Europe. There was a general shift in admissions during the CoVid era, with a reduction in admissions to non-respiratory services. This is likely secondary to an increased focus on outpatient management during this period. This audit highlights data in line with previous international studies, showing the disproportionate burden of severe CoVid-19 in pregnant patients. Pregnant patients are a vulnerable group when admitted to nonmaternity hospitals. Awareness of medical specialties encountering a higher proportion of patients during pregnancy allows targeting of training, including introduction of specialty-specific diagnostic/therapeutic algorithms, and co-ordination of simulated emergency training.
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Introduction: Post-COVID-19 autoimmune encephalitis is a rare manifestation following COVID-19. Most cases have not demonstrated solid evidence regarding their pathogenesis. Some believe it to be an immune process. Case presentation: In this case report, we present a case of a young female who presented to our emergency department with visual, auditory, and olfactory hallucinations after successfully treating COVID-19 two weeks prior to this visit. On examination, her vital signs were stable, but she was agitated, distressed, and hallucinating. Neurological examinations were normal. Laboratory investigations, including autoimmune profiles, were all negative. Magnetic resonance imaging of the brain showed non-specific changes in the bilateral frontal area. Electroencephalography (EEG) showed lateralized rhythmic delta activity (LRDA) arising more from the right occipital lobes. Autoimmune psychosis was suspected due to psychosis, abnormal imaging, and abnormal EEG findings. She was given corticosteroids and antipsychotic medication. Her symptoms improved within ten days. On follow-up, she remained well without any return of psychosis. Conclusion(s): Possible autoimmune pediatric encephalitis following COVID-19 is a rare entity that has scarcely been reported. The majority of the cases were reported to have been related to stress following the infection. To establish the correct diagnosis, an extensive workup, including an autoimmune profile, lumbar puncture, magnetic resonance imaging, and electroencephalography, is recommended.Copyright © 2022 The Author(s)
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Background. In-person learning is important for children with intellectual and developmental disabilities (IDD) because of the additional health, vocational, and functional services for students at these schools. It may be difficult to reduce SARS-CoV-2 transmission in IDD schools because students require assistance with activities of daily living such as eating, during which social distancing and masking cannot occur. Surveillance testing and cluster tracking in schools for children with IDD, which may be considered high-risk environments for transmissions, could have benefits for mitigating transmission and keeping students in schools. The objective of this study was to identify SARS-CoV-2 clusters in IDD specific schools to compare viral transmission in delta and BA.1 variant waves. Methods. A saliva-based PCR test was offered to students and staff for weekly SARS-CoV-2 screening at six Special School District (SSD) schools dedicated to children with IDD. Clusters, which are considered 2 or more positives cases in the same classroom having an epidemiological link, were then recorded. All weekly testing took place between November 23, 2020 and May 27, 2022. Clusters were recorded from November 15, 2021 to January 28, 2022. A Fisher's exact test was used to compare categorical variables. Results. 545 (90%) and 113 (16%) students participated in weekly testing. 160 participants tested positive throughout the study, 23 (14%) during the delta variant wave and 115 (72%) during the BA.1 variant wave. There was no significant variation in age, race, ethnicity, gender, or vaccination status between positive cases recorded from alpha, delta, and BA.1 variant waves (Table 1). Notably, the vaccination rate of positive participants was lower than the vaccination rate of participants who did not test positive. 42 clusters were recorded, 3 (7%) during the delta variant wave and 39 (93%) during the BA.1 variant wave (Fig. 1). Conclusion. The highly transmissible BA.1 variant resulted in an increase in clusters observed in IDD specific schools. Mitigation strategies for less transmissible alpha and delta waves were not as effective in reducing transmission during the BA.1 wave.
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Background. We characterize the evolution of symptoms in those with selfreported SARS-CoV-2 infections and the likelihood of seeking treatment or medical care during different waves of the pandemic. Methods. The NC-CCRP is a longitudinal observational study of 37,820 participants who completed a daily symptom log from April 2020 through February 2022, during which there were 5,167 self-reported COVID-19 infections. Three variant periods were defined as pre-delta, delta, and omicron, based on the predominant variant in North Carolina. Quasi-Poisson and logistic regression models adjusted for demographics and vaccination were used to assess COVID-19 symptoms and their duration and seeking treatment or hospitalization Results. Cough was the most reported symptom in all waves and increased from 77% pre-delta to 85% during omicron (p=0.001). Sore throat was more common during self-reported infections during omicron (71%), compared with 62% during delta and 54% pre-delta (p< 0.001). The largest change in proportion reporting a symptom was loss of taste or smell which decreased from 55% during pre-delta to 17% during omicron (p< 0.001). Compared with the pre-delta period, delta (incidence risk reduction, IRR 0.86;95% CI 0.79-0.93) and omicron (IRR 0.67;95% CI 0.61-0.73) were associated with lower symptom duration. Participants infected during the delta wave were more likely to seek treatment compared with either pre-delta (odds ratio, OR 1.32 95% CI 1.06-1.64) or omicron (OR 1.42;95% CI 1.21-1.67). Omicron period infections were associated with a lower likelihood of self-reported hospitalization compared with pre-delta (OR 0.26;95% CI 0.10-0.59) or delta (OR 0.26;95% CI 0.11-0.60). Vaccination was associated with a reduced likelihood of hospitalization (OR 0.35;95% CI 0.18-0.70). Proportion and Duration of Symptoms by Variant Wave;Unadjusted by Vaccination Status. Conclusion. Our study indicates evolution in symptom presentation and duration by variant period. The omicron wave was associated with shorter duration and lower severity of illness. Longitudinal tracking of symptomology and severity of a novel pathogen provide insights into the evolution of the pathogen in the community and is vital for public health and clinical response.
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Background. The COVID-19 pandemic has demonstrated the importance of pathogen genomic surveillance. At RKI, the German National Institute of Public Health, we established the Integrated Molecular Surveillance for SARS-CoV-2 (IMS-SC2) network to perform SARS-CoV-2 genomic surveillance. Methods. SARS-CoV-2 positive samples from laboratories distributed across Germany regularly undergo whole-genome sequencing at RKI. This surveillance instrument enables (i) almost-real-time monitoring of SARS-CoV-2 genomic diversity and evolution, (ii) in vitro assessment of vaccine coverage against emerging variants and (iii) genome-based estimates of SARS-CoV-2-incidences. Results. We report the results of our analyses of 3623 SARS-CoV-2 genomes collected between 12/1/2020 and 12/31/2021. All variants of concern were identified, at ratios equivalent to those in the 100-fold larger German GISAID sequence dataset from the same time period. Lineage distributions fluctuated over time, covering the rise of the Alpha and Delta, as well as the emergence of Omicron. Phylogenetic analysis confirmed variant assignments. Multiple mutations of concern emerged during the observation period. To model vaccine effectiveness in vitro, we employed authentic-virus neutralization assays, confirming that both the Beta and Zeta variants are capable of immune evasion. The IMS-SC2 sequence dataset facilitated an estimate of the SARS-CoV-2 incidence based on genetic evolution rates. Together with modelled vaccine efficacies, Delta-specific incidence estimation indicated that the German vaccination campaign contributed substantially to a deceleration of the nascent German Delta wave. Conclusion. This example illustrates that pathogen genomics enables a proactive approach to controlling a pandemic as the virus evolves. Molecular and genomic SARS-CoV-2 surveillance will be crucial during the post-pandemic future, informing public health policies including vaccination strategies. Of note, the IMS-SC2 infrastructure can be adapted to many other pathogens, serving as a blueprint for future efforts to increase genomic pathogen surveillance.
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Background. Pregnancy is one of the risk factor associated with the severity of Coronavirus Disease 2019 (COVID-19). The perinatal complications also known to be increased when pregnant women become infected with COVID-19. However, there were not enough studies involving pregnant women with severe COVID-19, especially in Korea. The purpose of this study was to analyze the cases of pregnant women with COVID-19 infection with various severities, and to compare and describe the clinical course and the effects on pregnancy and perinatal prognosis according to severity. Methods. We retrospectively analyzed the medical records of adults 18 years of age or older who were PCR-confirmed COVID-19 and proved pregnancy, from February 1, 2020 to January 31, 2022. Through the epidemiological investigation report, the patient's medical history, obstetric history, date of diagnosis and variants of COVID-19, and vaccination history were collected. Clinical symptoms, oxygen demand, chest imagings, treatment, perinatal complications, fetal conditions, delivery results, and complications were collected through medical records. Results. A total of 104 pregnant women with PCR-confirmed COVID-19 were hospitalized. The age at the time of diagnosis was 33 +/-4.24 (Mean +/- SD) years, and 4 patients (3.8%) were vaccinated with the COVID-19 vaccine. During hospital stay, the most common complaints were cough (99 patients, 95.2%) and fever (85 patients, 81.7%). Oxygen was applied in 40 patients (38.5%), and in 19 patients (18.3%) in severe cases. Thirty-seven patients (35.6%) delivered during isolation treatment. Critical COVID-19 patients group has statisticaly significant higher rate of preterm delivery compared with mild COVID-19 patient group (31.6 % versus 6.3 %, p=0.009). One patient died from septic shock caused by multidrug-resistant Acinetobacter baumannii during treatment. A total of 39 babies were born, of which 4 received postnatal oxygen therapy. Conclusion. Pregnant women with COVID-19 had higher mortality rates, aggravation rates, and premature birth rates compared to non-pregnant patients of the same age. In a situation where effective and safe COVID-19 treatments for pregnant women are limited, it is necessary to increase the vaccination rate to prevent undesired outcomes in both mother and child.
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Background. Droplet digital PCR (ddPCR) has been shown to be more sensitive and precise in the quantification of SARS-CoV-2 when compared to traditional quantitative RT-PCR. Multiple studies have explored associations between SARS-CoV-2 viral load and patient outcomes;however, few have used ddPCR technology. Here we investigated the associations between viral load measured using ddPCR and clinical presentation and outcomes. Methods. We performed a retrospective observational study of individuals who tested positive for COVID-19 at the VA San Diego between August 2020 and December 2021. SARS-CoV-2 viral load from nasopharyngeal swabs was determined using ddPCR. Baseline demographics, past medical history, clinical course, and laboratory data were ed from the chart. Results. A total of 696 individuals were included, 86% (n=603) of whom were male. The average age was 50-years-old [range: 19-98]. Three-quarters of individuals (76%, n=528) were unvaccinated at diagnosis. Frequency of comorbidities are shown in Table 1. The majority of individuals developed symptoms with 75% (n=516) reporting respiratory symptoms, 47% (n=317) fever, 34% (n=230) GI symptoms, and 23% (n=161) loss of taste and/or smell. A total of 24% of veterans were evaluated only in the emergency department, 21% (n=149) were admitted to the hospital;9% (n=60) required ICU level of care, 33% of these (n=20) required intubation, and 16 individuals died during hospitalization. SARS-CoV-2 log10 viral load was not associated with age, and only a weak correlation was seen with time from onset of symptoms (r2=-0.1, p=0.04). No association was observed between viral load and peak CRP, ferritin, d-dimer, or nadir absolute lymphocyte count. Mean viral load was significantly higher in veterans reporting fever (5.0 vs 5.4, p=0.02) and respiratory symptoms (4.7 vs 5.3, p=0.01). Interestingly, vaccinated veterans also had higher viral loads(5.8 vs 5.0, p< 0.0001). Conclusion. Fever and respiratory symptoms were associated with higher viral loads as expected. The association of vaccination with higher viral load may reflect selection bias for infections in the delta wave. Future work will include multivariate analyses to adjust for medical history and timing of sampling.
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Background. The COVID-19 Community Research Partnership (CCRP) is a large multicenter healthcare system-based study of the COVID-19 pandemic, including factors impacting risk of infection and hospitalization. The CCRP includes a subset of immunocompromised (IC) participants with varying vaccination status over time. Methods. We conducted an observational cohort study of 2,515 IC and 41,941 non-IC CCRP participants who contributed electronic health record data and daily electronic surveys to self-report COVID-19 symptoms, test results, and vaccinations from April 2020 to March 2022. The IC population included those with stem cell transplant, HIV, cancer, autoimmune disease, or solid organ transplant. The latter 3 must have also had an active systemic therapy to meet the IC condition (e.g. chemotherapy, immune modulator, steroid). Logistic regression was used to investigate risk of COVID-19 and hospitalization among IC participants and according to vaccine status within viral variant time periods (pre-delta, delta, omicron). Results. IC conditions included cancer (51%), autoimmune (41%), solid organ/ stem cell transplant (9%), and HIV (7%). The IC group was older and had more comorbidities. 95% of vaccine recipients received an mRNA vaccine. More vaccine breakthrough infections occurred in the IC group than non-IC group (36.1% vs 29.5%, p< 0.001). IC participants were less likely to remain COVID-19 free over time if vaccinated but not boosted (Fig 1A). However, after receiving a booster there was no difference in COVID-19 cases between the groups (Fig 1B). IC participants were more likely to be hospitalized with COVID-19 (OR 2.85;95% CI 1.69-4.76), but vaccination reduced risk for hospitalization (OR 0.26;95% CI 0.08-0.8). Receipt of a booster dose reduced risk of COVID-19 among IC participants during the delta wave (IRR 0.52;95% CI 0.28-0.94) but not during omicron. However, during omicron risk of hospitalization in the IC group was reduced by a booster dose (OR 0.13;95% CI 0.02-0.72). Conclusion. IC individuals were at increased risk for COVID-19 hospitalizations and breakthrough infections. After receiving a booster, IC participants were conferred the same level of protection from infection as their non-IC counterparts, highlighting the importance of boosters for these individuals. (Figure Presented).
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Introduction: The SARS-CoV-2 pandemic has disproportionately affected obstetric patients, with outcomes differing between viral variants. The Delta variant was associated with more severe disease than previous variants [1]. The Omicron variant exhibits increased transmissibility and became predominant by mid-December 2021 [2]. We aimed to compare outcomes between women presenting in Delta and Omicron waves at our tertiary obstetric centre. Methods: Caldicott Guardian approval was obtained and ethical approval waived. All women admitted to Princess Royal Maternity, Glasgow, between 01/05/2021–30/11/2021 (Delta) and 01/12/2021– 27/01/2022 (Omicron) with a positive SARS-CoV-2 test were included. Womenwere assigned a primary diagnosis of COVID-19 if admitted for >24 h due to symptoms of SARS-CoV-2 infection. Advanced respiratory support was defined as continuous positive airway pressure, high flow nasal oxygen or ventilation. Results: Forty-eight women had confirmed SARS-CoV-2 infection during the 7-month Delta wave, compared with 29 in the 2-month Omicron wave. Women were more likely have COVID-19 as a primary diagnosis in the Delta compared with Omicron wave (Table). Patients admitted during the Omicron compared with Delta wave were less likely to require advanced respiratory support or be admitted to critical care. There were two emergent deliveries performed in critical care during the Delta wave, and none in the Omicron wave. (Table Presented) Discussion:We observed reduced disease severity during the Omicron wave: women admitted during this time were more likely to have SARS-CoV-2 as an incidental diagnosis, with reduced requirements for advanced respiratory support and critical care. The increased number of cases likely reflects the high transmissibility of this variant, having implications for resource management and service provision. Our data are from a single centre, and we await further data on the effect of the Omicron variant in obstetric patients.
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Objective: NA Background: Creutzfeldt-Jakob disease (CJD) is an extremely rare but fatal neurodegenerative disease with incidence of one in a million worldwide, and few than 1000 cases per year in the United States per year. Design/Methods: NA Case Summary: We present two probable CJD cases seen in the same hospital within one month. Case one was a 67-year-old white female, former psychology practice manager, presenting with worsening cognition, vertigo, behavioral changes and 15 lb weight loss over 6 months. Exam findings significant for MoCA of 17/30 (decreased to 15/30 after one week), constant right eye shut, mild dysmetria in both lower extremities, a wide based gait with small strides. Blood work and initial Spinal fluid studies were negative. Continuous EEG showing occasional right temporal slow, frequent generalized rhythmic theta and delta slowing. MRI brain findings were suggestive of CJD with hyperintensities in bilateral caudate nucleus and putamen. Patient did not respond to high dose steroid. Case two was a 78-year-old white male, admitted for deterioration in cognition, gait, speech, fatigue and intermittent body jerking. Progression of his symptoms was so rapid, from a highly functional retired funeral director, he became minimal speech, loss of ADL within 3 months. Exam was significant for orientation to self only, global aphasia, muscle weakness and startle myoclonus. Blood work and initial spinal fluid studies were negative. MRI brain showed asymmetric cortically based diffuse restriction within cingulate, caudate nucleus also left temporoparietal. EEG showed generalized rhythmic delta activity. CSF from both cases eventually showed positive RT-QuIC, 14-3-3 protein and highly elevated T-Tau protein. Conclusions: CJD is a transmittable, reportable disease. Two cases seen in the same hospital within one month skews from the previously known CJD prevalence. Surveillance and investigation on the reason of regional CJD arise during COVID-19 pandemic may prove to be important and urgent.
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Background: COVID-19 can cause placental histopathological changes through associated inflammatory responses, maternal hypoxia and hypoperfusion, with subsequent placental microvasculopathy and fetal hypoxia. We hypothesise that these placental changes will cause placental insufficiency, as reflected by histopathological abnormalities and fetal distress on a cardiotocography (CTG), that correlates with disease severity. Methods: During the Delta wave, Monash Medical Centre was the only referral centre for pregnant women with COVID-19 in Victoria, Australia. Three groups undergoing caesarean section prior to the onset of labour were identified: 13 women with severe COVID-19 requiring hospitalisation, 53 with asymptomatic/ mild illness and 10 with placental insufficiency without COVID-19. CTGs and placental histology were analysed for evidence of maternal and fetal hypoxia. Results: Placental histology was obtained in 12/13 of severe, 40/53 asymptomatic/mild and 8/8 cases of placental insufficiency without COVID-19. Histopathological abnormalities were associated with COVID-19 disease severity;severe (8/12, 67%) and asymptomatic/mild (24/40, 60%) compared with 100% (8/8) in the placental insufficiency group. Maternal vascular malperfusion was seen in 58%, 15% and 75% and inflammatory changes in 17%, 30% and 0%, respectively (Table 1). Abnormal CTGs reflecting fetal hypoxia were seen in 77% of severe COVID-19 cases and in 49% with asymptomatic/mild illness (Table 2). Conclusions: Both mild/asymptomatic and severe COVID-19 illness are associated with high rates of CTG and placental abnormalities. These changes are similar to those seen with other causes of placental insufficiency. Therefore, increased surveillance and delivery from >37 weeks should be considered in women with COVID-19 in pregnancy, regardless of disease severity. (Table Presented).
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Background: SARS-CoV2 antibody testing is an important auxillary test especially for retrospective diagnosis or in patients with long COVID-19 or multisystem inflammatory syndrome of childhood. Epidemiological serology studies may also assist public health planning. Access to formal laboratory testing is not universal in many low-and middle-income (LMIC) countries and rapid lateral flow antibody tests are an attractive alternative. Performance of these tests has been inconsistent. A large-scale study was undertaken in South Africa, during the beta and delta waves, to assess the field-based performance of rapid point of care (POC) COVID-19 antibody tests. Methods: Symptomatic, ambulatory persons under investigation (PUIs) aged 18 years and older, presenting for SARS-CoV-2 diagnosis at public health facilities in three provinces, South Africa were enrolled at baseline. All patients completed a questionnaire regarding symptoms. Nasopharyngeal swabs were taken and processed for SARS-CoV-2 PCR testing using a GeneXpert (Cepheid, USA), or manual assay (ThermoFisher TaqPath assay or Seegene Allplex assay) on a real-time platform at routine accredited National Health Laboratory Service laboratories as per routine national protocols. Concomitantly, trained study staff performed three facility-based POC lateral flow antibody tests on a on a fingerstick sample and blood was collected for formal serology. POC tests were selected following a rapid in-laboratory evaluation. Asymptomatic contacts of people with confirmed COVID-19 were recruited into the asymptomatic study arm and rapid tests and PCR were performed. PCR and rapid positive patients and 500 negative controls were followed up at 5-14 days. Antibody tests were compared with formal serology performed on 2 platforms-Euroimmun (Euroimmun, Lubeck) IgA and IgG anti-S antibodies and Abbott Architect IgG test. Results: The sensitivity (S), specificity (Sp), positive (PPV) and negative predictive (NPV) values of tests for PUIs and contacts were calculated (Table 1)∗. Analyses using serology as a reference are forthcoming. Conclusion: Compared with PCR, performance of rapid POC COVID-19 antibody tests was poor with low sensitivity. This may reflect the patient cohort tested as humoral responses typically develop from day 7-14. The tests are unlikely to be useful for acute diagnosis but sensitivity may improve at later timepoints and further follow up data will be analysed by duration of symptom onset, severity of symptoms and wave (beta versus delta).
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Background: Access to SARS-CoV-2 polymerase chain reaction (PCR) testing is a bottleneck globally, especially in low-and middle-income countries (LMICs). Reliable point-of-care (POC) diagnostics for coronavirus disease 2019 (COVID-19) are cheaper and easier to scale-up than PCR especially in LMICs, and will facilitate interruption of transmission. We report the field-based effectiveness of rapid point-of-care (POC) antigen COVID-19 tests during the beta and delta waves, in South Africa. Methods: We enrolled symptomatic, ambulatory persons under investigation (PUIs) aged 18 years and older, presenting for SARS-CoV-2 diagnosis at public health facilities in three provinces, South Africa. All patients completed a questionnaire regarding symptoms. Nasopharyngeal swabs were taken and processed for SARS-CoV-2 PCR testing using either GeneXpert (Cepheid, USA), or with a manual assay (ThermoFisher TaqPath assay or Seegene Allplex assay) on a real-time PCR platform at routine, accredited National Health Laboratory Service laboratories, as per routine national protocols. Concomitantly, trained study staff performed three facility-based POC antigen tests on a nasal/nasopharyngeal swab, as recommended by the manufacturer. Asymptomatic contacts of people with confirmed COVID-19 were recruited into the asymptomatic study arm and rapid tests and PCR were performed. The sensitivity (S), specificity (Sp), positive (PPV) and negative predictive (NPV) values of tests for PUIs and contacts were calculated using PCR as the reference standard. Results: Between Oct 2020-2021 1816 participants were enrolled;472 (26%) tested PCR or rapid test positive;235 positives (49.8%) and 532 negatives were followed up at 5-14 days;574 asymptomatic contacts were enrolled, of which 21 (3.7%) were PCR positive. Performance of the three antigen tests are shown in Table 1∗. Conclusion: In a real world setting, during the beta and delta waves, compared with PCR the sensitivity of rapid antigen tests ranged from 35-68%. This may reflect low viral loads at diagnosis. Further work will compare antigen test performance in patients with high versus lower cycle threshold (Ct) values. Meanwhile, PCR testing capacity needs urgent scale-up in LMICs and improved POC diagnostics are needed to facilitate COVID-19 diagnosis in LMICs.
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Background: The highly contagious Delta variant of COVID-19 accounts for more than 80% of SARS-CoV-2 cases in the fall of 2021. Our aim was to determine whether molecular methods for variant and lineage detection could be utilized at autopsy to examine pathologic findings of Delta variant as compared to non-Delta variant cases. Design: We evaluated the lungs from 20 decedents with death due to SARS-CoV-2 confirmed by antemortem nasopharyngeal RTPCR in July and August 2021 (Delta wave), as well as from 40 autopsy cases prior to February 2021 with death due to SARS-CoV- 2. The patient population included males and females, with an age range of 37-67 years in the Delta group, and 44-79 In the non- Delta group. The population demographic was considered at risk for death due to COVID-19, and only one decedent, with immunosuppression, was known to be vaccinated. Lung specimens were examined on H&E and with SARS-CoV-2 nucleocapsid immunostain (IHC). Results: The time from initial symptoms to death averaged 9 days within the Delta wave and 16 days in non-Delta cases. Steroids, anticoagulation, antibiotics, and monoclonal antibody infusion were frequently part of the clinical treatment of Delta wave cases. Notably, SARS-CoV-2 PCR of lung swabs at autopsy were positive in all but one case examined in the Delta variant group, and viral genome RNA sequencing from lung at autopsy confirmed Delta variant lineage. In both groups, gross features of the lungs included edema, while grossly identifiable thrombi were more commonly seen in non-Delta variant cases. Histologic examination revealed diffuse alveolar damage (DAD) in all cases, most commonly early stage DAD in Delta variant cases. SARS-CoV-2 IHC demonstrated patchy to strong positivity in the alveoli of the majority of Delta variant cases - a finding not frequently seen in non-Delta cases. Figure 1 - 15 Conclusions: Our study is the first to incorporate PCR and viral genome sequencing from the lung at autopsy to correlate the Delta variant wave with histopathologic findings - a technique that may be useful in identifying important pathologic features of future variants. While the finding of DAD remains the same across viral variants, the majority of Delta cases showed a significant presence of SARS-CoV-2 in the lung by IHC, with minimal inflammatory infiltrate and reduced thrombotic complication. Whether these findings are the result of a shorter time interval between disease onset and death, therapeutic intervention, or increased viral load remains to be determined.
ABSTRACT
INTRODUCTION: There are increasing reports of a pediatric multisystem inflammatory syndrome associated with coronavirus disease 2019 (COVID-19) that presents with varying clinical features, but includes features of Kawasaki disease or toxic shock syndrome. Symptoms include fever, rash, abdominal pain, vomiting, and diarrhea. Many patients present without any respiratory symptoms and testing for SARS-CoV-2 is often negative. METHODS: A retrospective chart review was performed. RESULTS: A 7-year-old previously healthy male presented with 3 days of fevers up to 102.4F, headaches, abdominal pain, and intractable vomiting. Both parents had tested positive for SARS-CoV-2 four weeks prior. Nasopharyngeal swab tested positive for SARS-CoV-2 RNA. Echocardiogram was normal. CT venogram of his head was negative for any pathology. He developed severe neck pain and persistent headache during his hospitalization. Soon after receiving hydroxychloroquine, he developed a facial rash and altered mental status with episodes of aphasia, agitation, and pinpoint pupils. He then became unresponsive with left gaze deviation. A non-contrast head CT and CT angiography were negative. He was given levetiracetam and cefazolin and transferred to the pediatric intensive care unit. An electroencephalogram (EEG) showed no epileptiform activity. Over the following 7 hours, the EEG demonstrated left frontotemporal slowing, which progressed into a loss of fast activity over the right hemisphere with increased delta activity in the left hemisphere, then abruptly changed to generalized voltage attenuation.He rapidly lost brainstem reflexes, developing fixed and dilated pupils. Repeat CT scan revealed diffuse cerebral edema with loss of gray-white differentiation. Lab results then were consistent with severe inflammation. An intracranial pressure monitor revealed pressures greater than 76 mmHg. His exam soon became consistent with brain death. Pathologic evaluation showed diffuse cerebral edema with perivascular mononuclear infiltrates. CONCLUSION: The cause of this pediatric multi-system inflammatory syndrome is unclear and the mechanism by which SARS-CoV-2 affects the nervous system is unknown. Pediatric patients with COVID-19 and neurologic symptoms should be closely monitored as they can rapidly decline due to fulminant cerebral edema.