title: SARS-CoV-2 antibody magnitude and detectability are driven by disease severity, timing, and assay

abstract: Serosurveillance studies are critical for estimating SARS-CoV-2 transmission and immunity, but interpretation of results is currently limited by poorly defined variability in the performance of antibody assays to detect seroreactivity over time in individuals with different clinical presentations. We measured longitudinal antibody responses to SARS-CoV-2 in plasma samples from a diverse cohort of 128 individuals over 160 days using 14 binding and neutralization assays. For all assays, we found a consistent and strong effect of disease severity on antibody magnitude, with fever, cough, hospitalization, and oxygen requirement explaining much of this variation. We found that binding assays measuring responses to spike protein had consistently higher correlation with neutralization than those measuring responses to nucleocapsid, regardless of assay format and sample timing. However, assays varied substantially with respect to sensitivity during early convalescence and in time to seroreversion. Variations in sensitivity and durability were particularly dramatic for individuals with mild infection, who had consistently lower antibody titers and represent the majority of the infected population, with sensitivities often differing substantially from reported test characteristics (e.g., amongst commercial assays, sensitivity at 6 months ranged from 33% for ARCHITECT IgG to 98% for VITROS Total Ig). Thus, the ability to detect previous infection by SARS-CoV-2 is highly dependent on the severity of the initial infection, timing relative to infection, and the assay used. These findings have important implications for the design and interpretation of SARS-CoV-2 serosurveillance studies.


title: COVID Symptoms, Symptom Clusters, and Predictors for Becoming a Long-Hauler:Looking for Clarity in the Haze of the Pandemic

abstract: Emerging data suggest that the effects of infection with SARS-CoV-2 are far reaching extending beyond those with severe acute disease. Specifically, the presence of persistent symptoms after apparent resolution from COVID-19 have frequently been reported throughout the pandemic by individuals labeled as "long-haulers". The purpose of this study was to assess for symptoms at days 0-10 and 61+ among subjects with PCR-confirmed SARS-CoV-2 infection. The University of California COvid Research Data Set (UC CORDS) was used to identify 1407 records that met inclusion criteria. Symptoms attributable to COVID-19 were extracted from the electronic health record. Symptoms reported over the previous year prior to COVID-19 were excluded, using nonnegative matrix factorization (NMF) followed by graph lasso to assess relationships between symptoms. A model was developed predictive for becoming a long-hauler based on symptoms. 27% reported persistent symptoms after 60 days. Women were more likely to become long-haulers, and all age groups were represented with those aged 50 {+/-} 20 years comprising 72% of cases. Presenting symptoms included palpitations, chronic rhinitis, dysgeusia, chills, insomnia, hyperhidrosis, anxiety, sore throat, and headache among others. We identified 5 symptom clusters at day 61+: chest pain-cough, dyspnea-cough, anxiety-tachycardia, abdominal pain-nausea, and low back pain-joint pain. Long-haulers represent a very significant public health concern, and there are no guidelines to address their diagnosis and management. Additional studies are urgently needed that focus on the physical, mental, and emotional impact of long-term COVID-19 survivors who become long-haulers.

category: infectious diseases


title: SARS-CoV-2 Load does not Predict Transmissibility in College Students

abstract: SARS-CoV2 is highly contagious and the global spread has caused significant medical, social and economic impacts. Other than vaccination, effective public health measures, including contact tracing, isolation and quarantine, is critical for deterring viral transmission, preventing infection progression and resuming normal activities. Viral transmission is affected by many factors but the viral load and vitality could be among the most important ones. Although in vitro culture studies have indicated that the amount of virus isolated from infected people determines the successful rate of virus isolation, whether the viral load carried at the individual level would affect the transmissibility was not known. We aimed to determine whether the Ct value, a measurement of viral load by RT-PCR assay, could differentiate the spreader from the non-spreader in a population of college students. Our results indicate that while at the population level the Ct value is lower, suggesting a higher viral load, in the symptomatic spreaders than the asymptomatic non-spreaders, there is a significant overlap in the Ct values between the two groups. Thus Ct values, or the viral load, at the individual level could not predict the transmissibility. Our studies also suggest that a sensitive method to detect the presence of virus is needed to identify asymptomatic persons who may carry a low viral load but can still be infectious.


title: Age-dependent immune response to the Biontech/Pfizer BNT162b2 COVID-19 vaccination

abstract:
BackgroundThe SARS-CoV-2 pandemic has led to the development of various vaccines. Real-life data on immune responses elicited in the most vulnerable group of vaccinees over 80 years old is still underrepresented despite the prioritization of the elderly in vaccination campaigns.

MethodsWe conducted a cohort study with two age groups, young vaccinees below the age of 60 and elderly vaccinees over the age of 80, to compare their antibody responses to the first and second dose of the BNT162b2 COVID-19 vaccination.

ResultsWhile the majority of participants in both groups produced specific IgG antibody titers against SARS-CoV-2 spike protein, titers were significantly lower in elderly participants. Although the increment of antibody levels after the second immunization was higher in elderly participants, the absolute mean titer of this group remained lower than the <60 group. After the second vaccination, 31.3 % of the elderly had no detectable neutralizing antibodies in contrast to the younger group, in which only 2.2% had no detectable neutralizing antibodies.

ConclusionOur data suggests that lower frequencies of neutralizing antibodies after BNT162b2 vaccination in the elderly population may require earlier revaccination to ensure strong immunity and protection against infection.


title: Just 2% of SARS-CoV-2-positive individuals carry 90% of the virus circulating in communities

abstract: We analyze data from the Fall 2020 pandemic response efforts at the University of Colorado Boulder (USA), where more than 72,500 saliva samples were tested for SARS-CoV-2 using quantitative RT-PCR. All samples were collected from individuals who reported no symptoms associated with COVID-19 on the day of collection. From these, 1,405 positive cases were identified. The distribution of viral loads within these asymptomatic individuals was indistinguishable from what has been previously reported in symptomatic individuals. Regardless of symptomatic status, approximately 50% of individuals who test positive for SARS-CoV-2 seem to be in non-infectious phases of the disease, based on having low viral loads in a range from which live virus has rarely been isolated. We find that, at any given time, just 2% of individuals carry 90% of the virions circulating within communities, serving as viral "super-carriers" and possibly also super-spreaders.


title: Clinical course and risk factors for in-hospital mortality of 205 patients with SARS-CoV-2 pneumonia in Como, Lombardy Region, Italy

abstract:
ImportanceWith randomized clinical trials ongoing and vaccine still a long distance away, efforts to repurpose old medications used for other diseases provide hope for the treatment of COVID-19

ObjectivesTo examine the risk factors for in-hospital mortality and describe the effectiveness of different treatment strategies in a real-life setting of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia.

DesignReal-life single-center study during the Lombardy COVID-19 outbreak.

SettingValduce Hospital in Como, Lombardy Region, Italy.

Participants205 laboratory-confirmed patients presenting with SARS-Cov-2 pneumonia requiring hospitalization.

InterventionsAll patients received best supportive care and, based on their clinical needs and comorbidities, specific interventions that included the main drugs being tested for repurposing to treat COVID-19, such as hydroxychloroquine, anticoagulation, antiviral drugs, steroids or interleukin-6 pathway inhibitors.

Main outcomes and measuresClinical, laboratory and treatment characteristics were analyzed with univariate and multivariate logistic regression methods to explore their impact on in-hospital mortality and compared with current literature data.

ResultsUnivariate analyses for clinical variables showed prognostic significance for age equal or greater than 70 years (estimated 28-days survival: 21.4 vs 67.4%; p<0.0001), presence of 2 or more relevant comorbidities (35.3 vs 61.8%; p=0.0008), ratio of arterial oxygen partial pressure to fractional inspired oxygen (P/F) less than 200 at presentation (21-days survival: 14.7 vs 52.4%;p<0.0001), high levels of lactate dehydrogenase (LDH) (26.4 vs 65.3%; p=0.0001), and elevated C-reactive protein (CRP) values (25.4 vs 74.9%; p=0.0001), while no statistical significance was found for all the other clinical variables tested. At univariate analysis for the different treatment scheduled, prognostic significance for survival was showed for intermediate or therapeutic-dose anticoagulation (estimated 28-days survival: 37.1 vs 23.4%; p=0.0001), hydroxychloroquine (35.7 vs 27.3%; p=0.0029), early antiviral therapy with lopinavir/ritonavir (60.1 vs 22.4%; p<0.0001), late short-course of steroids (47.9 vs 18.2%; p<0.0001) or tocilizumab therapy (69.4 vs 29.4%; p=0.0059). Multivariable regression confirmed increasing odds of in-hospital death associated with age older than 70 years (odds ratio 3.26, 95% CI 1.81-5.86; p<0.0001) and showed a reduction in mortality for patients treated with anticoagulant (-0.37, 0.49-0.95; p=0.0273), antiviral (-1.22, 0.16-0.54; p<0.0001), or steroids (-0.59, 0.35-0.87; p=0.0117) therapy.

Conclusions and RelevanceResults from this real-life single-center experience are in agreement and confirm actual literature data on SARS-CoV-2 pneumonia, both in terms of clinical risk factors for in-hospital mortality and as regards the effectiveness of the different therapies proposed for the management of COVID-19 disease. Waiting the results from randomized clinical trials, these data could help clinicians to identify patients with poor prognosis at an early stage and guide the choice between the different treatments implied in COVID-19 disease.

KEY POINTSO_ST_ABSQuestionC_ST_ABSAmong the main drugs that have been tested for repurposing to treat COVID-19, what are the most effective medical treatments for SARS-CoV-2 pneumonia?

FindingsResults from these real-life cohort of 205 patients confirm at multivariate regression model an increasing odds of in-hospital death associated with age older than 70 years (OR 3.26) and a reduction in mortality for patients treated with anticoagulant (OR -0.37), antiviral lopinavir/ritonavir (OR -1.22), or steroids therapy (OR -0.59). In contrast, hydroxychloroquine and tocilizumab have not been confirmed to have a significant effect in the treatment of SARS-CoV-2 pneumonia, in accordance with the latest data from the international literature.

MeaningWaiting the results from randomized clinical trials, these data could help clinicians to identify patients with poor prognosis at an early stage and guide the choice between the different treatments implied in COVID-19 disease.


title: Dramatic Rise of Seroprevalence Rates of SARS-CoV-2 Antibodies among Healthy Blood Donors: The evolution of a Pandemic

abstract:
BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has resulted in more than 106 million cases of confirmed infection and more than 2.3 million deaths worldwide as of February 11th 2021. Seroprevalence studies are extremely useful in studying and assessing the epidemiological status in the community and the degree of spread. They help decision makers in implementing or relaxing mitigating measures to contain the disease in addition to other benefits.

ObjectiveTo study the seroprevalence rates of SARS-CoV-2 antibodies among healthy blood donors in Jordan, at various points of time as the pandemic evolves in the community.

MethodsA total of 1374 blood donor were tested for the SARS-CoV-2 antibodies in 3 groups.

The first group of 746 and the second of 348 individuals were tested in June and September of 2020 respectively. The 3rd group of 292 were tested in early February of 2021. We utilized a qualitative assay that uses Electrochemiluminescence method (ECLIA) that has a specificity and sensitivity of 99.8% and 100% respectively.

ResultsThe first 2 groups representing the months of January to September of 2020, where the number of confirmed Covid-19 cases were several hundred to 3000 showed a seroprevalence rate of 0% (95% CI 0.00%, 0.51%). The 3rd group representing late January and early February 2021 when the number of reported confirmed case has reached 100 folds the numbers of September 2020, showed a seroprevalence of 27.4% (95% CI 22.5% and 32.9%).

Conclusionsa dramatic rise in seroprevalence of SARS-CoV-2 antibodies was seen among healthy blood donors in Jordan in parallel with wide-spread intracommunity transmission of the disease. This information is useful to assess the degree of herd immunity and provides for better understanding of the pandemic.


title: The impact of paternal alcohol, tobacco, caffeine use and physical activity on offspring mental health: A systematic review and meta-analysis

abstract:
BackgroundThere is some evidence that paternal health behaviours during and around pregnancy could be associated with offspring health outcomes. However, the impact that paternal health behaviours during pregnancy can have on offspring mental health is understudied and remains unclear.

MethodsWe conducted a systematic review and meta-analysis of articles in PubMed describing studies of potentially modifiable paternal health behaviours (tobacco smoking, alcohol consumption, caffeine consumption and physical activity) in the prenatal period in relation to offspring mental health.

ResultsTen studies were included and categorized by paternal health behaviour and offspring mental health outcome investigated. The narrative synthesis provided evidence of association between paternal health behaviours around pregnancy and offspring mental health problems, with the strongest evidence shown for tobacco use. Grouped by analysis type, two separate meta-analyses showed evidence of paternal smoking during pregnancy being associated with greater odds of ADHD in offspring (OR 1.42, 95% CI 1.02 to 1.99; HR 1.28, 95% CI 1.19 to 1.39).

ConclusionsOur review suggests that paternal tobacco smoking and alcohol consumption in the prenatal period are associated with poorer offspring mental health, particularly hyperactivity/ADHD. Future investigation using methods that allow stronger causal inference is needed to further investigate if these associations are causal.

category: epidemiology


title: Association between SARS-CoV-2 Transmission Risk, Viral Load, and Age: A Nationwide Study in Danish Households

abstract:
AimThe objective of this nationwide study was to investigate the association between SARS-CoV-2 transmissibility, viral load, and age of primary cases in Danish households.

BackgroundSpread in households represents a major mode of transmission of SARS-CoV-2. In order to take proper action against the spread of the disease, it is important to have a better understanding of transmission in the household domain--including the role of viral load of primary cases.

MethodsThe study was designed as an observational cohort study, using detailed administrative register data. We included the full population of Denmark and all SARS-CoV-2 tests (August 25, 2020 to February 10, 2021) to estimate transmissibility in house-holds comprising 2-6 people. RT-PCR Cycle threshold (Ct) values were used as a proxy for viral load.

ResultsWe identified 63,657 primary cases and 139,882 household members of which 21% tested positive by RT-PCR within a 1-14 day period after the primary case. There was an approximately linear association between Ct value of the sample and transmissibility, implying that cases with samples having a higher viral load were more transmissible than cases with samples having a lower viral load. However, even for primary cases with relatively high sample Ct values, the transmissibility was not negligible, e.g., for primary cases with a sample Ct value of 38, we found that 13% of the primary cases had at least one secondary household case. Moreover, 34% of all secondary cases were found in households with primary cases having sample Ct values >30. An increasing transmissibility with age of the primary cases for adults ([≥]20 years) and a decreasing transmissibility with age for children (<20 years) were found.

ConclusionsAlthough primary cases with sample high viral loads (low Ct values) were associated with higher SARS-CoV-2 transmissibility, we found no obvious cut-off for sample Ct values to eliminate transmissibility and a substantial amount of household transmission occurred in households where the primary cases had high sample Ct values (low viral load), The study further showed that transmissibility increases with age. These results have important public health implications, as they suggest that contact tracing should prioritize cases according to Ct values and age, and underline the importance of quick identification and isolation of cases. Furthermore, the study highlights that households can serve as a transmission bridge by creating connections between otherwise separate domains.


title: Association between SARS-CoV-2 Transmissibility, Viral Load, and Age in Households


title: COVID-19 test positivity: predictive value of various symptoms in a large community-based testing program in California

abstract:
BackgroundMuch of the early data on COVID-19 symptomatology was captured in the hospital setting. In a community setting the symptoms most predictive of SARS-CoV-2 positivity may be different. Data from the California sites of a COVID-19 community testing program are presented here.

MethodsPrior to being tested, participants in the Baseline COVID-19 Testing Program completed an online screener, in which they self-reported basic demographics and the presence or absence of 10 symptoms. Both positive and negative COVID-19 RT-PCR tests were linked back to the screener data. A multivariable model of positivity was fit using generalized estimating equations, adjusting for month of testing as a fixed effect and accounting for clustering of data within each test site.

ResultsAmong 547,018 first-time tests in California in 2020, positivity rates were 3.4%, 9.9%, and 19.8% for participants with no symptoms, 1 symptom, or 2 or more symptoms at the time of screening, respectively. All ten symptoms were individually associated with higher positivity rates, but only six of ten symptoms were associated with higher positivity when adjusting for other symptoms. Major symptoms with highest predictive value were recent loss of taste or smell, fever, and coughing with ORs of 3.27, 1.97, and 1.95, respectively. Shortness of breath and vomiting or diarrhea were negatively associated with positivity adjusting for other symptoms and, absent other symptoms, participants with these symptoms did not have significantly higher positivity rates than asymptomatic participants.

ConclusionsRecent loss of taste and smell should be elevated to a major symptom along with fever and coughing in public health messaging and in our community approach to testing and surveillance, while mild to moderate shortness of breath should be de-emphasized as a sensitive early predictor of COVID-19 positivity.

category: public and global health


title: COVID Seroprevalence, Symptoms and Mortality During the First Wave of SARS-CoV-2 in Canada

abstract:
BackgroundEfforts to stem Canadas SARS-CoV-2 pandemic can benefit from direct understanding of the prevalence, infection fatality rates (IFRs), and information on asymptomatic infection.

MethodsWe surveyed a representative sample of 19,994 adult Canadians about COVID symptoms and analyzed IgG antibodies against SARS-CoV-2 from self-collected dried blood spots (DBS) in 8,967 adults. A sensitive and specific chemiluminescence ELISA detected IgG to the spike trimer. We compared seroprevalence to deaths to establish IFRs and used mortality data to estimate infection levels in nursing home residents.

ResultsThe best estimate (high specificity) of adult seroprevalence nationally is 1.7%, but as high as 3.5% (high sensitivity) depending on assay cut-offs. The highest prevalence was in Ontario (2.4-3.9%) and in younger adults aged 18-39 years (2.5-4.4%). Based on mortality, we estimated 13-17% of nursing home residents became infected. The first viral wave infected 0.54-1.08 million adult Canadians, half of whom were <40 years old. The IFR outside nursing homes was 0.20-0.40%, but the COVID mortality rate in nursing home residents was >70 times higher than that in comparably-aged adults living in the community. Seropositivity correlated with COVID symptoms, particularly during March. Asymptomatic adults constituted about a quarter of definite seropositives, with a greater proportion in the elderly.

InterpretationCanada had relatively low infection prevalence and low IFRs in the community, but not in nursing homes, during the first viral wave. Self-collected DBS for antibody testing is a practicable strategy to monitor the ongoing second viral wave and, eventually, vaccine-induced immunity among Canadian adults.


title: Virological and serological characterization of critically ill patient with COVID-19 in the UK: a special focus on variant detection

abstract:
BackgroundTreatment of COVID-19 patients with convalescent plasma containing neutralising antibody to SARS-CoV-2 is under investigation as a means of reducing viral loads, ameliorating disease outcomes, and reducing mortality. However, its efficacy might be reduced in those infected with the emerging B.1.1.7 SARS-CoV-2 variant. Here, we report the diverse virological characteristics of UK patients enrolled in the Immunoglobulin Domain of the REMAP-CAP randomised controlled trial.

MethodsSARS-CoV-2 viral RNA was detected and quantified by real-time PCR in nasopharyngeal swabs obtained from study subjects within 48 hours of admission to intensive care unit. Antibody status was determined by spike-protein ELISA. B.1.1.7 strain was differentiated from other SARS-CoV-2 strains by two novel typing methods detecting the B.1.1.7-associated D1118H mutation with allele-specific probes and by restriction site polymorphism (SfcI).

FindingsOf 1260 subjects, 90% were PCR-positive with viral loads in nasopharyngeal swabs ranging from 72 international units [IUs]/ml to 1.7x1011 IU/ml. Median viral loads were 45-fold higher in those who were seronegative for IgG antibodies (n=314; 28%) compared to seropositives (n=804; 72%), reflecting in part the latter groups possible later disease stage on enrolment. Frequencies of B.1.1.7 infection increased from early November (<1%) to December 2020 (>60%). Anti-SARS-CoV-2 seronegative individuals infected with wild-type SARS-CoV-2 had significantly higher viral loads than seropositives (medians of 1.2x106 and 3.4 x104 IU/ml respectively; p=2x10-9). However, viral load distributions were elevated in both seropositive and seronegative subjects infected with B.1.1.7 (13.4x106 and 7.6x106 IU/ml; p=0.18).

InterpretationHigh viral loads in seropositive B.1.1.7-infected subjects are consistent with increased replication capacity and/or less effective clearance by innate or adaptive immune response of B.1.1.7 strain than wild-type. As viral genotype was associated with diverse virological and immunological phenotypes, metrics of viral load, antibody status and infecting strain should be used to define subgroups for analysis of treatment efficacy.


title: Early dynamics of circulating tumor DNA predict chemotherapy responses for patients with esophageal cancer

abstract:
PurposeWe investigated whether early circulating tumor DNA (ctDNA) changes, measured using digital PCR (dPCR), can predict later chemotherapy responses in esophageal squamous cell cancer (ESCC).

DesignWe compared the dynamics of ctDNA and tumor volumes during chemotherapy in 42 ESCC. The accuracy of predictions of later chemotherapy responses were evaluated by the ratio of the variant allele frequency (VAF) of ctDNA (post-/pre-ctDNA) and the total tumor volume (post-/pre-volume) before and after an initial chemotherapy cycle using a receiver-operating characteristic curve analysis. Total positive and negative objective responses (ORs) were defined as either >50% or [≤]50% reductions, respectively, in the total tumor volume at the end of first-line chemotherapy.

ResultsMutation screening of 43 tumors from 42 patients revealed 96 mutations. The pretreatment dPCR-ctDNA data were informative in 38 patients, using 70 selected mutations (1-3 per patient). The areas under the curve (AUCs) for the post-/pre-volume and post-/pre-ctDNA levels used in predicting the total OR were 0.85 and 0.88, respectively. The optimal cutoff value of post-/pre-ctDNA was 0.13. In 90% (18/20) of patients with a post-/pre-volume [≥]50%, the total OR could be predicted by the post-/pre-ctDNA with high accuracy; the AUC by post-/pre-ctDNA was higher than that by post-/pre-volume (0.85 vs 0.76, respectively). Patients with low post-/pre-ctDNA (n = 18) had a significantly better overall survival rate than those with high post-/pre-ctDNA (n = 20; P = 0.03).

ConclusionsEarly ctDNA changes after an initial cycle of chemotherapy predict later responses to treatment with high accuracy in ESCC patients.

category: gastroenterology


title: ANTERIOR OR POSTERIOR ANKLE FOOT ORTHOSES FOR ANKLE SPASTICITY: WHICH ONE IS BETTER?

abstract:
BackgroudAnkle foot orthoses (AFOs) have been widely used in stroke patients to assist in safe, energy efficient walking. Since they provide mediolateral ankle stability during stance, adequate toes clearance during swing phase and also facilitation of heel strike.

ObjectiveTo compare the efficacy of anterior or posterior plastic ankle foot orthoses (AFOs) for ankle spasticity.

MethodsCrossover design with randomization for the interventions, blinded assessors was used. 20 patients with chronic stroke, Modified Ashworth scale (MAS) of ankle [≤] 2 and Tardieu angle [≥] 20 degrees. The participants were random to treat with anterior or posterior plastic AFOs and then were crossover to treat with the other one. Outcomes measurement was performed by using passive range of motion (PROM), MAS, walking velocity, stretch reflex surface EMG and walking surface EMG of medial gastrocnemius muscle. Patient satisfaction was evaluated at 1 month.

ResultsTwenty stroke patients with ankle spasticity were recruited. Mean age was 46.60(38-60) years old.Mean duration. of times since stroke was 9.35 (6-15) months. Comparison between two types of orthoses revealed statistically significant improvement of walking surface EMG of medial gastrocnemius muscles when using anterior plastic AFO more than posterior plastic AFO at p=0.015. Patients satisfaction were statistically significant higher when using anterior plastic AFO more than posterior plastic AFO at p<0.05.

ConclusionAnterior plastic AFO has more efficacy in reduced dynamic ankle spasticity during walking than posterior plastic AFO proven by comparison the dynamic electromyography changes in dynamic spasticity during walking.

category: rehabilitation medicine and physical therapy


title: Covid-19 impact on Parkinson's Disease patients treated by drugs or deep brain stimulation

abstract:
PurposeCovid-19 has affected all people, especially those with chronic diseases, including Parkinsons Disease (PD). Covid-19 may affect both motor and neuropsychiatric symptoms of PD patients. We intend to evaluate different aspects of Covid-19 impact on PD patients.

Methods647 PD patients were evaluated in terms of PD-related and Covid-19-related clinical presentations in addition to past medical history during the pandemic through an online questioner. They were compared with an age-matched control group consist of 673 individuals and a sample of the normal population consist of 1215 individuals.

ResultsThe prevalence of Covid-19 in PD patients was 11.28%. The mortality was 1.23% among PD patients. The prevalence of Covid-19 in PD patients who undergone DBS was 18.18%. No significant association was found between the duration of disease and the prevalence of Covid-19. A statistically significant higher prevalence of Covid-19 in PD patients who had direct contact with SARS-CoV-19 infected individuals was found. No statistically significant association has been found between the worsening of motor symptoms and Covid-19. PD patients and the normal population may differ in the prevalence of some psychological disorders, including anxiety and sleeping disorders, and Covid-19 may affect the psychological status.

ConclusionPD patients possibly follow tighter preventive protocols, which lead to lower prevalence and severity of Covid-19 and its consequences in these patients. Although it seems Covid-19 does not affect motor and psychological aspects of PD as much as it was expected, more accurate evaluations are suggested in order to clarify such effects.

category: neurology


title: Quantification of seizure termination patterns reveals limited pathways to seizure end

abstract:
Seizures result from a variety of pathologies and exhibit great diversity in their dynamics. Although many studies have examined the dynamics of seizure initiation, few have investigated the mechanisms leading to seizure termination. We examined intracranial recordings from patients with intractable focal epilepsy to differentiate seizure termination patterns and investigate whether these termination patterns are indicative of different underlying mechanisms.

Seizures (n=710) were recorded intracranially from 104 patients and visually classified as focal or secondarily generalized. Only two patterns emerged from this analysis: (a) those that end simultaneously across the brain (synchronous termination), and (b) those whose ictal activity terminates in some regions but continues in others (asynchronous termination). Finally, seizures ended with either an intermittent bursting pattern (burst suppression pattern), or continuous activity (continuous bursting). These findings allowed for a classification and quantification of the burst suppression ratio, absolute energy and network connectivity of all seizures and comparison across different seizure termination patterns.

We found that different termination patterns can manifest within a single patient, even in seizures originating from the same onset locations. Most seizures terminate with patterns of burst suppression regardless of generalization but that seizure that secondarily generalize show burst suppression patterns in 90% of cases, while only 60% of focal seizures exhibit burst suppression. Interestingly, we found similar absolute energy and burst suppression ratios in seizures with synchronous and asynchronous termination, while seizures with continuous bursting were found to be different from seizures with burst suppression, showing lower energy during seizure and lower burst suppression ratio at the start and end of seizure. Finally, network density was observed to increase with seizure progression, with significantly lower densities in seizures with continuous bursting compared to seizures with burst suppression.

Our study demonstrates that there are a limited number of seizure termination patterns, suggesting that, unlike seizure initiation, the number of mechanisms underlying seizure termination is constrained. The study of termination patterns may provide useful clues about how these seizures may be managed, which in turn may lead to more targeted modes of therapy for seizure control.


title: Molecular pathology and synaptic loss in primary tauopathies: UCB-J PET study

abstract:
The relationship between in vivo synaptic density and tau burden in primary tauopathies is key to understanding the impact of tauopathy on functional decline and in informing new early therapeutic strategies. In this cross-sectional observational study, we determine the in vivo relationship between synaptic density and molecular pathology, in the primary tauopathies of Progressive Supranuclear Palsy (PSP) and Corticobasal Degeneration (CBD), as a function of disease severity.

Twenty three patients with PSP, and twelve patients with Corticobasal Syndrome (CBS) were recruited from a tertiary referral centre. Nineteen education, sex and gender-matched control participants were recruited from the National Institute for Health Research  Join Dementia Research platform. Cerebral synaptic density and molecular pathology, in all participants, were estimated using PET imaging with the radioligands [11C]UCB-J and [18F]AV-1451, respectively. Patients with CBS also underwent amyloid PET imaging with [11C]PiB to exclude those with likely Alzheimers pathology - we refer to the amyloid negative cohort as having CBD although acknowledge other pathologies exist. Disease severity was assessed with the PSP rating scale; regional non-displaceable binding potentials (BPND) of [11C]UCB-J and [18F]AV-1451 were estimated in regions of interest from the Hammersmith Atlas, excluding those with known off-target binding for [18F]AV-1451. As an exploratory analysis, we also investigated the relationship between molecular pathology in cortical brain regions, and synaptic density in connected subcortical areas.

Across brain regions, there was a positive correlation between [11C]UCB-J and [18F]AV-1451 BPND ({beta}=0.4, t=4.7, p<0.0001). However, the direction of this correlation became less positive as a function of disease severity in patients ({beta} = -0.03, T = -4.0, p = 0.002). Between brain regions, cortical [18F]AV-1451 binding was negatively correlated with synaptic density in subcortical areas (caudate nucleus, putamen, and substantia nigra).

Brain regions with higher synaptic density are associated with a higher [18F]AV-1451 binding in PSP/CBD, but this association diminishes with disease severity. Moreover, higher cortical [18F]AV-1451 binding correlates with lower subcortical synaptic density. Longitudinal imaging is required to confirm the mediation of synaptic loss by molecular pathology. However, the effect of disease severity suggests a biphasic relationship between synaptic density and tauopathy, with synapse rich regions vulnerable to accrual of pathology, followed by a loss of synapses in response to pathology. Given the importance of synaptic function for cognition, our study elucidates the pathophysiology of primary tauopathies and may inform the design of future clinical trials.


title: Systematic review of the effects of pandemic confinements on body weight and their determinants

abstract: Pandemics and subsequent lifestyle restrictions such as  lockdowns may have unintended consequences, including alterations in body weight. Understanding the impact and the mechanisms affecting body weight is paramount for planning effective public health measures for both now and future "lockdown"-type situations. This systematic review assesses and the impact of pandemic confinement on body weight and to identifies contributory factors. A comprehensive literature search was performed in seven electronic databases and in gray sources from their inception until 1st July 2020 with an update in PubMed and Scopus on 1st February 2021. In total, 2,361 unique records were retrieved, of which 41 studies were identified eligible: 1 case control study, 14 cohort and 26 cross-sectional studies (469, 362 total participants). The participants ranged in age from 6-86 years. The proportion of female participants ranged from 37% to 100%. Pandemic confinements were associated with weight gain in 7.2%-72.4% of participants and weight loss in 11.1%-32.0% of participants. Weight gain ranged from 0.6 ({+/-}1.3) to 3.0 ({+/-}2.4) kg, and weight loss ranged from 2.0 ({+/-}1.4) to 2.9 ({+/-}1.5) kg. Weight gain occurred predominantly in participants who were already overweight or obese. Associated factors included increased consumption of unhealthy food with decreased intake of healthy fresh fruits and vegetables, changes in physical activity, and altered sleep patterns. Weight loss during the pandemic was observed in individuals with previous low weight, and those who ate less and were more physically active before lock down. Associated factors included increased intake of fruits and vegetables, drinking more water and consuming no alcohol. Maintaining a stable weight was more difficult in populations with reduced income, particularly in individuals with lower educational attainment. The findings of this systematic review highlight the short-term effects of pandemic confinements. Learning from the "lockdown" experience is fundamental if we are to prepare for the next wave; a holistic, reactive, tailored response is needed involving multiple providers.

category: nutrition


title: Seroprevalence and associated factors of maternal cytomegalovirus in Southern Ethiopia

abstract:
IntroductionCytomegalovirus (CMV) is the most common infection during pregnancy that poses the risk of congenital CMV infections (cCMV) worldwide. The aim of this study was to assess the seroprevalence and associated factors of CMV among pregnant women in Southern Ethiopia.

MethodA cross-sectional study was conducted on consecutive women attending the delivery ward at Hawassa comprehensive and specialized hospital. Blood samples collected at the time of delivery were tested for CMV IgG and IgM using ELISA. Study participants responded to a questionnaire about obstetric history and socio-demographic characteristics. Data analysis was performed using SPSS version 20.0 software. Chi-square, bivariable and multivariable logistic regression were used to identify characteristics independently associated with the sero-status of CMV.

ResultsSeropositivity for CMV IgM antibodies was 8.2% (49/600) (95% CI: 6 -10.5%), whereas the CMV IgG was 88.6% (532/600), (95% CI: 89.5 - 94.0%). Seroprevalence was higher in women of older age, currently unmarried and having nursery schooled children. Moreover CMV seropositivity was significantly associated with any of detected curable STIs. Seroprevalence was not significantly related to previous adverse pregnancy outcome, gravidity, being a child day care occupant mother, and birth weight of the newborn.

ConclusionIn the present study, we identified a high rate of CMV IgM seropositivity among pregnant women in southern Ethiopia. Given that there is no existing CMV diagnosis, special attention should be designed for pregnant women in parallel to the existing antenatal care facility. Besides, training health care professionals will support awareness conception among pregnant women concerning the sequels of CMV infection during pregnancy.

Key questionsO_ST_ABSWhat is already known?C_ST_ABSO_LICytomegalovirus is the most common infection during pregnancy that can cause congenital CMV infections and known to cause long-term sequelae including sensorineural hearing loss of the developing fetus.
C_LIO_LIHowever, data on maternal CMV infection lacking in Ethiopia besides there is no maternal CMV diagnostics and screening service for pregnant women.
C_LI

What are the new findings?O_LIA high prevalence 8.3% of CMV IgM and 88.6% of CMV IgG documented.
C_LIO_LISeroprevalence associated with older age women, currently unmarried and having nursery schooled children in the household. Also CMV seropositivity was significantly associated with any of detected curable STIs.
C_LI

What do the new findings imply?O_LIKnown that there is no existing maternal CMV screening in Ethiopia, understanding the burden and the effect of maternal CMV infection will offer important information to the health care providers to prevent a sequel to the developing fetus.
C_LIO_LIThe current study provides valuable information on the associated factors with maternal CMV infection hence, training health care professionals will support awareness conception among pregnant women concerning the sequels for CMV infection during pregnancy.
C_LI

category: obstetrics and gynecology


title: The optics of the human eye at 8.6 μm lateral resolution

abstract: Ocular optics is normally estimated based on 2,600 measurement points within the pupil of the eye, which implies a lateral resolution of approximately 175 microns for a 9 mm pupil diameter. This is because information below this resolution is not thought to be relevant or even possible to obtain with current measurement systems. In this work, we characterize the in vivo ocular optics of the human eye with a lateral resolution of 8.6 microns, which implies roughly 1 million measurement points for a pupil diameter of 9 mm. The results suggest that the normal human eye presents a series of hitherto unknown optical patterns with amplitudes between 200 and 300 nm and is made up of a series of in-phase peaks and valleys. If the results are analysed at only high lateral frequencies, the human eye is also found to contain a whole range of new information. This discovery could have a great impact on the way we understand some fundamental mechanisms of human vision and could be of outstanding utility in certain fields of ophthalmology.

category: ophthalmology


title: Meta-analytic findings on lower reading skills in children with cochlear implants

abstract: This meta-analysis study aims to quantify the group differences in reading skills between children with cochlear implants and their hearing peers and between children with cochlear implants and children with hearing aids (aged between 3 to 18 years old). Of the 5,642 articles screened, 47 articles met predetermined inclusion criteria (published between 2002 and 2019). The robust variance estimation based meta-analysis models were used to synthesize all the effect sizes. Children with cochlear implants scored significantly lower than their hearing peers in phonological awareness (g = - 1.62, p < .001), vocabulary (g = -1.50, p < .001), decoding (g = -1.24, p < .001), and reading comprehension (g = -1.39, p < .001), but not for fluency (g = -.67, p = .054). Compared to children with hearing aids, children with cochlear implants scored significantly lower in phonological awareness (g = -.30, p = .028). The percentage of unilateral cochlear implant negatively impacts the group difference between children with cochlear implants and their hearing peers. Findings from this study confirm a positive shift in reading outcomes for profoundly deaf children due to cochlear implantation. Some children with cochlear implants may need additional supports in educational settings.

category: otolaryngology


title: Meta-analytic findings on reading in children with cochlear implants


title: The effect of stimulus duration on preferences for gain adjustments in speech

abstract:
ObjectivesIn the personalisation of hearing aid fittings, gain is often adjusted to suit patient preferences using live speech. When using brief sentences as stimuli, the minimum gain adjustments necessary to elicit consistent preferences ( preference thresholds) were previously found to be much greater than typical adjustments in current practice. The current study examined the role of duration on preference thresholds.

DesignParticipants heard 2, 4 and 6-s segments of a continuous monologue presented successively in pairs. The first segment of each pair was presented at each individuals real-ear or prescribed gain. The second segment was presented with a {+/-}0-12 dB gain adjustment in one of three frequency bands. Participants judged whether the second was "better", "worse" or "no different" from the first.

Study SampleTwenty-nine adults, all with hearing-aid experience.

ResultsThe minimum gain adjustments needed to elicit "better" or "worse" judgments decreased with increasing duration for most adjustments. Inter-participant agreement and intra-participant reliability increased with increasing duration up to 4 s, then remained stable.

ConclusionsProviding longer stimuli improves the likelihood of patients providing reliable judgments of hearing-aid gain adjustments, but the effect is limited, and alternative fitting methods may be more viable for effective hearing-aid personalisation.


title: The effect of stimulus duration on preferences for gain adjustments when listening to speech


title: Soluble angiotensin-converting enzyme 2 is transiently elevated in COVID-19 and correlates with specific inflammatory and endothelial markers

abstract:
RationaleAngiotensin-converting enzyme 2 (ACE2) is the main entry receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but how SARS-CoV-2 interactions with ACE2 influences the renin-angiotensin system (RAS) in Coronavirus disease 2019 (COVID-19) is unknown.

ObjectiveTo measure circulating ACE2 and ACE levels in COVID-19 patients and investigate association with risk factors, outcome and inflammatory markers.

Methods and resultsSoluble ACE2 (sACE2) and sACE concentrations were measured by ELISA in plasma samples from 114 hospital-treated COVID-19 patients and 10 healthy controls. Follow-up samples after four months were available for 58/114 patients. Von Willebrand factor (VWF), factor VIII (fVIII), D-dimer, interleukin 6 (IL-6), tumor necrosis factor  and plasminogen activator inhibitor 1 (PAI-1) had previously been determined. Levels of sACE2 were higher in COVID-19 patients than in healthy controls, median 5.0 (interquartile range 2.8-11.8) ng/ml versus 1.4 (1.1-1.6) ng/ml, p < 0.0001. sACE2 was higher in men than women, but were not affected by other risk factors for severe COVID-19. sACE 2 decreased to 2.3 (1.6-3.9) ng/ml at follow-up, p < 0.0001, but remained higher than in healthy controls, p=0.012. Follow-up sACE2 levels were higher with increasing age, BMI, total number of comorbidities, for patients with diabetes and patients on RAS-inhibition. sACE was marginally lower during COVID-19 compared with at follow-up, 57 (45-70) ng/ml versus 72 (52-87) ng/ml, p=0.008. Levels of sACE2 and sACE did not differ depending on survival or disease severity (care level, respiratory support). sACE2 during COVID-19 correlated with VWF, fVIII and D-dimer, while sACE correlated with IL-6, TNF and PAI-1.

ConclusionssACE2 was transiently elevated in COVID-19, likely due to increased shedding from infected cells. sACE2 and sACE during COVID-19 differed distinctly in their correlations with markers of inflammation and endothelial dysfunction, suggesting release from different cell types and/or vascular beds.

category: cardiovascular medicine


title: Redesigning SARS-CoV-2 clinical RT-qPCR assays for wastewater RT-ddPCR

abstract: COVID-19 wastewater surveillance has gained widespread acceptance to monitor community infection trends. Wastewater samples primarily differ from clinical samples by having low viral concentrations due to dilution, and high levels of PCR inhibitors. Therefore, wastewater samples should be processed by appropriately designed and optimized molecular workflows to accurately quantify targets. Digital PCR has shown to be more sensitive and resilient to environmental matrix inhibition. However, most SARS-CoV-2 assays have been designed for clinical use on RT-qPCR instruments, then adopted to digital PCR platforms. But it is unknown whether clinical RT-qPCR assays are adequate to use on digital PCR platforms. Here we designed an N and E gene multiplex (ddCoV_N and ddCoV_E) specifically for RT-ddPCR and benchmarked them against the nCoV_N2 and E_Sarbeco assays. ddCoV_N and ddCoV_E have equivalent limits of detections and wastewater sample concentrations to NCoV_N2 and E_Sarbeco but showed improved signal-to-noise ratios that eased interpretation and ability to multiplex. From GISAID downloaded unique sequences analyzed, 2.12% and 0.83% present a mismatch or would not be detected by the used primer/probe combination for the ddCoV_N and ddCoV_E, respectively.


title: Short-stay admissions and lower staffing associated with larger COVID-19 outbreaks in Maryland nursing homes

abstract:
ObjectivesIdentify facility factors associated with a larger COVID-19 outbreak among residents in Maryland nursing homes (NHs).

DesignObservational

Setting and ParticipantsAll Maryland NHs.

MethodsResident COVID-19 cases were collected for each Maryland NH from January 1, 2020 through July 1, 2020. Cumulative COVID-19 incidence through July 1, 2020 was collected for each county and Baltimore City. Facility characteristics for each Maryland NH were collected from time periods prior to January 1, 2020. NH outbreaks were defined as larger when total resident COVID-19 cases exceeded 10% of licensed beds. Descriptive and multivariable analyses were conducted to assess the strongest predictors for the primary outcome of larger COVID-19 outbreak.

ResultsNHs located in counties with high cumulative incidence of COVID-19 were more likely to have larger outbreaks (OR 4.5, 95% CI 2.3-8.7, p<0.01). NHs with at least 100 beds were more likely to have larger outbreaks, especially among facilities with >140 licensed beds (100-140 beds vs <100 beds: OR 1.9, 95% CI 0.9-4.1, p=0.09; >140 beds vs <100 beds: OR 2.9, 95% CI 1.3-6.1, p<0.01). NHs with more short-stay residents (OR 2.2, 95% CI 1.1-4.8, p=0.04) or fewer Certified Nursing Assistant hours daily (OR 2.6, 95% CI 1.3-5.3, p<0.01) also were more likely to have larger outbreaks. Resident race and gender were not significant predictors of larger outbreaks after adjustment for other factors.

ConclusionsLarge NHs with lower staffing levels and many short-stay residents in counties with high COVID-19 incidence were at increased risk for COVID-19 outbreaks. Understanding the characteristics of nursing homes associated with larger outbreaks can help us prepare for the next pandemic.

Brief summaryMaryland nursing homes in counties with a high COVID-19 incidence, more licensed beds, a higher proportion of short-stay residents, or lower CNA staffing hours were more likely to have a larger outbreak early in the pandemic.


title: Maternal Levels of Acute Phase Proteins in Early Pregnancy and Risk of Autism Spectrum Disorders in Offspring

abstract: Previous research supports a contribution of early-life immune disturbances in the etiology of autism spectrum disorders (ASD). Biomarker studies of the maternal innate (non-adaptive) immune status related to ASD risk have focused on one of the acute phase proteins (APP), C-reactive protein (CRP), with conflicting results. We evaluated levels of eight different APP in maternal serum samples drawn in first trimester, from 318 mothers to ASD-cases and 429 mothers to ASD-unaffected controls, nested within the register-based Stockholm Youth Cohort. Overall, we found no general trend of high levels of maternal APP being associated with increased risk of ASD. In contrast, maternal levels of CRP in the lowest compared to the middle tertile were associated with increased risk of ASD without ID or ADHD in offspring (OR = 2.15, 95 % CI 1.17-3.93). Further, levels of maternal ferritin in the lowest (OR = 1.82, 95 % CI 1.19-2.78) and highest (OR = 1.74, 95 % CI 1.16-2.60) tertiles were associated with increased risk of any ASD diagnosis in offspring, with stronger associations still between the lowest (OR = 3.58, 95 % CI 1.79-7.17) and highest (OR = 3.20, 95 % CI 1.62-6.29) tertiles of ferritin and risk of ASD with ID. The biological interpretation of lower CRP-levels among mothers to ASD-cases is not clear but might be related to the function of the maternal innate immune system. The finding of aberrant levels of ferritin conferring risk of ASD-phenotypes indicates a plausibly important role of iron during neurodevelopment.


title: Testing DNA-methylation and blood-chemistry measures of biological aging in models of Black-White disparities in healthspan characteristics

abstract: Biological aging is a proposed mechanism through which social determinants drive health disparities. We conducted proof-of-concept testing of eight DNA-methylation and blood-chemistry quantifications of biological aging as mediators of disparities in healthspan between Black and White participants in the United States Health and Retirement Study (HRS; n=9005). We quantified biological aging from four DNA-methylation "clocks" (Horvath, Hannum, PhenoAge, and GrimAge), a DNA-methylation Pace of Aging (DunedinPoAm), and three blood-chemistry measures (PhenoAge, Klemera-Doubal method Biological Age, and homeostatic dysregulation). We quantified Black-White disparities in healthspan from cross-sectional and longitudinal data on physical-performance tests, self-reported activities of daily living (ADL) limitations and physician-diagnosed chronic diseases, self-rated health, and survival. DNA-methylation and blood-chemistry quantifications of biological aging were moderately correlated (Pearson-r range 0.1-0.4). GrimAge, DunedinPoAm and all three blood-chemistry measures were associated with healthspan characteristics (e.g. mortality effect-size range 1.71-2.32) and showed evidence of more advanced/faster biological aging in Black compared with White participants (Cohens d=.4-.5). These measures accounted for 13-95% of Black-White differences in healthspan-related characteristics. Findings that Black Americans are biologically older and aging more rapidly than White Americans of the same chronological age suggest that eliminating disparities in the pace of aging can contribute building to aging health equity.


title: Testing Black-White disparities in biological aging in older adults in the United States: analysis of DNA-methylation and blood-chemistry methods


title: Geographic disparities in COVID-19 case rates are not reflected in seropositivity rates using a neighborhood survey in Chicago

abstract: To date, COVID-19 case rates are disproportionately higher in Black and Latinx communities across the U.S., leading to more hospitalizations and deaths in those communities. These differences in case rates are evident in comparisons of Chicago neighborhoods with differing race/ethnicities of their residents. Disparities could be due to neighborhoods with more adverse health outcomes associated with poverty and other social determinants of health experiencing higher prevalence of SARS-CoV-2 infection or due to greater morbidity and mortality resulting from equivalent SARS-CoV-2 infection prevalence. We surveyed five pairs of adjacent ZIP codes in Chicago with disparate COVID-19 case rates for highly specific and quantitative serological evidence of any prior infection by SARS-CoV-2 to compare with their disparate COVID-19 case rates. Dried blood spot samples were self-collected at home by internet-recruited participants in summer 2020, shortly after Chicagos first wave of the COVID-19 pandemic. Pairs of neighboring ZIP codes with very different COVID-19 case rates had similar seropositivity rates for anti-SARS-CoV-2 receptor binding domain IgG antibodies. Overall, these findings of comparable exposure to SARS-CoV-2 across neighborhoods with very disparate COVID-19 case rates are consistent with social determinants of health, and the comorbidities related to them, driving differences in COVID-19 rates across neighborhoods.


title: Self-reported symptoms, self-reported viral testing result and seroprevalence of SARS CoV-2 among a community sample in Essex County New Jersey: A brief report.

abstract:
BackgroundSARS-CoV-2, the virus that causes COVID-19, has rapidly spread globally beginning in late 2019. Early areas impacted by this pandemic in the US include Essex County, New Jersey. Beyond understanding the prevalence of active infections and deaths, it is important to understand the true burden of infection in the community, as indicated by seroprevalence of antibodies directed to the virus. Understanding the spectrum of disease is key to the effectiveness of primary prevention and control measures and the design of interventions against transmission of infection.

MethodsWe utilized venue-based-sampling (VBS), implemented by a community partner, to sample members of the community in Essex County. In VBS the venues are randomized as a proxy for randomizing the attendees of the venues. We asked standard demographic questions, questions about symptoms and PCR testing and previous antibody testing. Participants provide a blood sample collected by finger stick with the Neoteryx Mitra Collection device. Samples were tested using a novel ELISA based approached developed by our team.

ResultsFrom September 15, 2020 to December 22, 2020, we conducted 92 randomly selected sampling events where we approached 1349 individuals for screening. Of these, 924 consented and had complete data for analysis. Only 6.5% of the sample reported any COVID-19 like symptoms while 45.9% had sought out a COVID-19 test. In total 13 (1.4%) participants received a positive SARS-CoV-2 PCR test result. While 33 participants (2.6%) sought a SARS-CoV-2 antibody test, only 0.5% of the sample reported a positive antibody result. Testing in this study identified 83 (9.0%) participants positive for SARS-CoV-2 antibodies.

ConclusionWe recruited a large sample of the population of Essex County, New Jersey using VBS, electronic surveys, novel sample collection and lab methods. Our findings suggest that the burden of SARS-Cov-2 is slightly more than six times than that suggested by PCR testing. This burden is higher than most estimates obtained through studies of remnant blood samples from hospitals (4.2%), samples from staff at a public-school system (2.9%), and residents of a California county recruited with targeted Facebook ads (1.5%). (9-11) Moreover, with only 6.5% of the sample reporting any COVID-19-like symptoms, our finding suggests that the number of asymptomatic persons may be close to 1.5 times greater than anyone reporting symptoms.


title: The Missing Link: A Closed Form Solution to the Kermack and McKendrick Model Equations

abstract: Susceptible-infectious-recovered (SIR) models are widely used for estimating the dynamics of epidemics. Such models project that containment measures "flatten the curve", i.e., reduce but delay the peak in daily infections, cause a longer epidemic, and increase the death toll. These projections have entered common understanding; individuals and governments often advocate lifting containment measures such as social distancing to shift the peak forward, limit societal and economic disruption, and reduce mortality. It was, then, an extraordinary surprise to discover that COVID-19 pandemic data exhibit phenomenology opposite to the projections of SIR models. With the knowledge that the commonly used SIR equations only approximate the original equations developed to describe epidemics, we identified a closed form solution to the original epidemic equations. Unlike the commonly used approximations, the closed form solution replicates the observed phenomenology and quantitates pandemic dynamics with simple analytical tools for policy makers. The complete solution is validated using independently measured mobility data and accurately predicts COVID-19 case numbers in multiple countries.


title: Combining explainable machine learning, demographic and multi-omic data to identify precision medicine strategies for inflammatory bowel disease

abstract:
Inflammatory bowel diseases (IBDs), including ulcerative colitis and Crohns disease, affect several million individuals worldwide. These diseases are heterogeneous at the clinical, immunological and genetic levels and result from a complex interaction between the host and environmental factors. Investigating drug efficacy in cultured human fresh IBD tissues can improve our understanding of the reasons why certain medications are more or less effective for different patients.

We propose an explainable machine learning (ML) approach that combines bioinformatics and domain insight, to informatively integrate multi-modal data to predict inter-patient specific variation in drug response. Using explanation of our models, we interpret the models predictions inferring unique combinations of important features associated with human tissue pharmacological responses. The inferred multi-modal features originate from multi-omic data (genomic and transcriptomic), demographic, medicinal and pharmacological data and all are associated with drug efficacy generated by a preclinical human fresh IBD tissue assay.

To pharmacologically assess patient variation in response to IBD treatment, we used the reduction in the release of the inflammatory cytokine TNF from the fresh IBD tissues in the presence or absence of test drugs, as a measure of drug efficacy. The TNF pathway is a common target in current therapies for IBD; we initially explored the effects of a mitogen-activated protein kinase (MAPK) inhibitor on the production of TNF; however, we later show the approach can be applied to other targets, test drugs or mechanisms of interest. Our best model was able to predict TNF levels from a combination of integrated demographic, medicinal and genomic features with an error as low as 4.98% on unseen patients. We incorporated transcriptomic data to validate and expand insights from genomic features. Our results showed variations in drug effectiveness between patients that differed in gender, age or condition and linked new genetic polymorphisms in our cohort of IBD patients to variation in response to the anti-inflammatory treatment BIRB796 (Doramapimod).

Our approach models drug response in a relevant human tissue model of IBD while also identifying its most predictive features as part of a transparent ML-based precision medicine strategy.

category: pharmacology and therapeutics


title: Estimating the levels and trends of family planning indicators in 436 sub-national areas across 26 countries in sub-Saharan Africa

abstract:
BackgroundScaling up access to safe, effective, and voluntary family planning (FP) services to achieve universal access for women and families will require increased commitment by countries and international organizations. On the way toward universal access, quantitative family planning goals have also been established by the United Nations through the sustainable development goals (SDGs). Here, we present a model-based framework that can help monitor progress toward these goals at the sub-national and demographic subgroup scale.

MethodsWe utilize 90 demographic health surveys for 26 countries that contain associated geographic position system data. We extract survey cluster level data to fit multiple small area estimation models that estimate FP indicators by administrative unit one and two regions as well as different demographic subgroups.

FindingsWe find significant variation of modern contraceptive prevalence rates (mCPR), unmet need, and demand satisfied by country, sub-national region, and demographic subgroup. Our model-based estimates show that on average for 436 administrative unit one regions, mCPR has increased at a rate of 0.75% per year and unmet need has decreased by 0.26% per year. There are also striking differences of FP indicators by demographic subgroup; for example, unmet need can be up to 40% different based on age and parity.

InterpretationWe have developed a framework to help monitor progress, provide insights about the inequitable progress by region and demographic groups, and account for the sparsity of available data. These results and framework can help policy-makers better allocate and target interventions to help achieve family planning goals.

FundingThis publication is based on models and data analysis performed by the Institute for Disease Modeling at the Bill & Melinda Gates Foundation.


title: Sharing positive changes made during COVID-19 national lockdown: a multi-method co-production study

abstract:
ObjectiveA multi-method co-production study was designed to share psychosocial insights into the adoption of positive changes made during COVID-19 national lockdown in Scotland. We examined: i) the psychosocial patterning of positive changes, ii) the psychosocial processes by which positive change was realised, and worked with partner organizations to share our insights.

MethodsA sequential multi-method design included an online survey (n=2445) assessing positive changes in sleep and physical activity patterns, socio-demographics, mood, social support, coping, and resilience, with multivariate logistic regression analysis. We also employed interviews with a purposive diverse sub-sample of people self-reporting high levels of positive change (n=48) and used thematic analysis. Finally, partnership work translated insights into positive change-sharing targeted resources.

ResultsThe survey identified positive change was significantly patterned by age, gender and vulnerability to COVID-19. Higher positive reframing and higher active coping were associated with higher levels of cross-domain positive change. Higher symptoms of depression, planning, and self-distraction were associated with less cross-domain positive change. Thematic analysis showed the centrality of perceptions of time, opportunities to self-reflect and engage with the natural world, access support in diverse ways, actively build routine and purposefully build self-efficacy and a sense of control were key to initiating positive change. Our partner organizations focused on the rapid co-production of a series of online resources that shared study insights.

ConclusionsOur study, based around a salutogenic ethos and the constraints of COVID-19, sought to identify and share insights into achieving positive changes at a time of international crisis.


title: Schooling amidst a pandemic: parents' perceptions about reopening schools and anticipated challenges during COVID-19

abstract:
IntroductionDuring the COVID-19 pandemic, numerous states in the United States instituted measures to close schools or shift them to virtual platforms. Understanding parents preferences for sending their children back to school, and their experiences with distance learning is critical for informing school reopening guidelines. This study characterizes parents plans to send their children to school, and examines the challenges associated with school closures during the 2020-2021 academic year.

MethodsA national-level cross-sectional online survey was conducted in September 2020. Focusing on a subset of 510 respondents, who were parents of school-aged children, we examined variations in parents plans for their children to return to school by their demographic and family characteristics, and challenges they anticipated during the school-year using multivariable logistic regressions.

ResultsFifty percent of respondents (n=249) said that they would send their children back to school, 18% (n=92) stated it would depend on what the district plans for school reopening, and 32% (n=160) would not send their children back to school. No demographic characteristics were significantly associated with parents plans to not return their children to school. Overall, parents reported high-level of access to digital technology to support their childs learning needs (84%). However, those who reported challenges with distance learning due to a lack of childcare were less likely not to return their children to school (aOR=0.33, 95% CI: 0.17, 0.64). Parents who reported requiring supervision after school had higher odds of having plans to not return their children to school (aOR=1.97, 95% CI: 1.03, 3.79). Parents viewed COVID-19 vaccines and face masks important for resuming in-person classes.

DiscussionAbout one-third of parents surveyed objected to their children returning to school despite facing challenges with distance learning. Besides access to vaccines and face masks, our findings highlight the need to better equip parents to support remote learning, and childcare.


title: Efficacy of a Spatial Repellent for Control of Aedes-Borne Virus Transmission: A Cluster Randomized Trial in Iquitos, Peru

abstract:
Over half the worlds population is at risk for viruses transmitted by Aedes mosquitoes, such as, dengue and Zika. The primary vector, Aedes aegypti, thrives in urban environments. Despite decades of effort, cases and geographic range of Aedes-borne viruses (ABV) continue to expand. Rigorously proven vector control interventions that measure protective efficacy against ABV diseases is limited to Wolbachia in a single trial in Indonesia, and do not include any chemical intervention. Spatial repellents, a new option for efficient deployment, are designed to decrease human exposure to ABV by releasing active ingredients into the air that disrupt mosquito-human contact. A parallel, cluster-randomized controlled trial was conducted in Iquitos, Peru to quantify the impact of a transfluthrin-based spatial repellent on human ABV infection. From 2,907 households across 26 clusters (13 per arm), 1,578 participants were assessed for seroconversion (primary endpoint) by survival analysis. Incidence of acute disease was calculated among 16,683 participants (secondary endpoint). Adult mosquito collections were conducted to compare Ae. aegypti abundance, blood-fed rate and parity status through mixed effect difference-in-difference analyses. The spatial repellent significantly reduced ABV infection by 34{middle dot}1% (1-sided 95% CI lower limit, 6{middle dot}9%; 1-sided p-value=0{middle dot}0236, z=1{middle dot}98). Aedes aegypti abundance and blood-fed rates were significantly reduced by 28{middle dot}6% (95% CI 24{middle dot}1%, {infty}); z=-9{middle dot}11) and 12{middle dot}4% (95% CI 4{middle dot}2%, {infty}); z=-2{middle dot}43), respectively. Our trial provides the first conclusive statistical evidence from a pre-planned cluster randomized controlled clinical trial with a pre-defined effect size on the primary endpoint that was appropriate powered to prospectively quantify and statistically test for a difference in the impact of a chemical intervention, in this case a spatial repellent, to reduce the risk of ABV transmission compared to a placebo.

Significance StatementVector interventions are needed for Aedes-borne viral diseases (dengue, Zika, chikungunya, and yellow fever) prevention, but their application is hindered by the lack of evidence proving they prevent infection or disease. Our research reports the first conclusive statistical evidence from a pre-planned, prospective cluster-randomized, controlled clinical trial (cRCT) of significant protective efficacy (34.1% hazard estimate) against human Aedes-borne virus (ABV) infection by a chemical-based vector control intervention, the most commonly used intervention category among all ABV World Health Organization recommendations. A previous trial against malaria in Indonesia indicated a positive trend but did not detect a significant effect. Results from our ABV study will help guide public health authorities responsible for operational management and world-wide prevention of ABV, and incentivize new strategies for disease prevention.


title: Comparing Vaccination Strategies in Canada Under Different Assumptions

abstract:
This paper estimates the outcomes of two different COVID-19 vaccination strategies in Canada for the mRNA vaccines currently approved for Emergency Use Authorization (EUA), modelled on the vaccination and effectiveness of the Pfizer vaccine which is likely to be more widely administered in Canada. The first strategy is the manufacturer recommended standard of two doses (two-dose strategy) given within 21 days apart versus a strategy of giving a larger group a single dose of vaccine (first-dose-for-most strategy) by delaying the second injection.

Three parameters are varied in the course of 36 estimation scenarios of the population-level effects of the two vaccination strategies. The first is the effectiveness of a single dose of vaccine at preventing disease, the second is the effectiveness of the vaccine at preventing transmission of the virus, and the third is the rate of transmission of the virus during the course of the simulations.

Over the course of the different scenarios, the first-dose-for-most strategy was superior in reducing disease transmission in all scenarios where vaccination is assumed to have an effect on viral transmission. The results for fatalities was mixed, with the first-dose-for-most strategy being superior in cases where a higher first-dose effectiveness at preventing disease was assumed.

Finally, in the best-guess scenarios where a 75% reduction in disease transmission and a 92.6% effectiveness at preventing disease from a single dose were used, the first-dose-for-most strategy was superior in a situation with reduced vaccine doses available, and switching to the first-dose-for-most strategy earlier helped to prevent a higher proportion of cases and deaths.


title: Automated analysis of PSMA-PET/CT studies using convolutional neural networks

abstract:
PurposeProstate-specific membrane antigen (PSMA) PET/CT has shown to be more sensitive and accurate than conventional imaging. Visual interpretation of the images causes both intra- and inter-reader disagreement and there is therefore a need for objective methods to analyze the images. The aim of this study was to develop an artificial intelligence (AI) tool for PSMA PET/CT and to evaluate the influence of the tool on inter-reader variability.

ApproachWe have recently trained AI tools to automatically segment organs, detect tumors, and quantify volume and tracer uptake of tumors in PET/CT. The primary prostate gland tumor, bone metastases, and lymph nodes were analyzed in patients with prostate cancer. These studies were based on non-PSMA targeting PET tracers. In this study an AI tool for PSMA PET/CT was developed based on our previous AI tools. Letting three physicians analyze ten PSMA PET/CT studies first without support from the AI tool and at a second occasion with the support of the AI tool assessed the influence of the tool. A two-sided sign test was used to analyze the number of cases with increased and decreased variability with support of the AI tool.

ResultsThe range between the physicians in prostate tumor total lesion uptake (TLU) decreased for all ten patients with AI support (p=0.002) and decreased in bone metastases TLU for nine patients and increased in one patient (p=0.01). Regarding the number of detected lymph nodes the physicians agreed in on average 72% of the lesions without AI support and this number decreased to 65% with AI support.

ConclusionsPhysicians supported by an AI tool for automated analysis of PSMA-PET/CT studies showed significantly less inter-reader variability in the quantification of primary prostate tumors and bone metastases than when performing a completely manual analysis. A similar effect was not found for lymph node lesions. The tool may facilitate comparisons of studies from different centers, pooling data within multicenter trials and performing meta-analysis. We invite researchers to apply and evaluate our AI tool for their PSMA PET/CT studies. The AI tool is therefore available upon reasonable request for research purposes at www.recomia.org.

category: radiology and imaging


title: Total nodule number is an independent prognostic factor in resected stage III non-small cell lung cancer: a deep learning powered study

abstract: Almost every lung cancer patient has multiple pulmonary nodules while the significance of nodule multiplicity in locally advanced non-small cell lung cancer (NSCLC) remained unclear. This study explores the relationship between deep learning detected total nodule number (TNN) and survival outcomes in patients with surgical resected stage I-III NSCLC. Patients who underwent surgical resection for stage I-III NSCLC with accessible preoperative chest CT scan from 2005 to 2018 were identified from our database. Deep learning-based AI algorithms using convolutional neural networks (CNN) was applied for pulmonary nodule (PN) detection and classification. Of the 2126 patients, a total number of 33410 PNs were detected by AI. Median TNN detected per person was 12 (IQR 7-20). AI-detected TNN (analyzed as continuous variable) was independent prognostic factor for both RFS (HR 1.012, 95% CI 1.002-1.022, p = 0.021) and OS (HR 1.013, 95% CI 1.002-1.025, p = 0.021) in multivariate analyses of stage III cohort; while it was not significantly associated with survival in stage I and II cohorts. In terms of nodule categories, the numbers of upper-lobe nodule, same-side nodule, other-side nodule, solid nodule, and even solid nodule at small size ([≤] 6mm) were independent prognostic factors; while the numbers of middle/lower-lobe nodule, same-lobe nodule, subsolid nodule, calcific nodule and perifissural nodule were not associated with survival. In survival tree analysis, rather than using traditional IIIA and IIIB classification, the model grouped cases by AI-detected TNN (lower vs. higher: log-rank p < 0.001), which showed superior discrimination of survival in stage III cohort. In conclusion, AI-detected TNN was significantly associated with survival in patients with surgical resected stage III NSCLC. Lower TNN detected on preoperative CT scan indicated better prognosis in patients who underwent complete surgical resection.


title: Automatic detection of pituitary microadenoma from magnetic resonance imaging using deep learning algorithms

abstract: Pituitary microadenoma (PM) is often difficult to detect by MR imaging alone. We employed a computer-aided PM diagnosis (PM-CAD) system based on deep learning to assist radiologists in clinical workflow. We enrolled 1,228 participants and stratified into 3 non-overlapping cohorts for training, validation and testing purposes. Our PM-CAD system outperformed 6 existing established convolutional neural network models for detection of PM. In test dataset, diagnostic accuracy of PM-CAD system was comparable to radiologists with > 10 years of professional expertise (94% versus 95%). The diagnostic accuracy in internal and external dataset was 94% and 90%, respectively. Importantly, PM-CAD system detected the presence of PM that had been previously misdiagnosed by radiologists. This is the first report showing that PM-CAD system is a viable tool for detecting PM. Our results suggest that PM-CAD system is applicable to radiology departments, especially in primary health care institutions.


title: Economic Benefits of COVID-19 Screening Tests with a Vaccine Rollout

abstract: This note estimates the costs and benefits of a nationwide COVID-19 screening testing program in the presence of vaccine distribution. Even for an optimistic vaccine rollout scenario, a well-designed federally-funded screening testing program, coupled with self-isolation of those who test positive, pays for itself in terms of increased GDP and is projected to save 20,000 or more lives. The sooner the testing program is put in place, the greater are its net economic benefits. This note updates the December 9, 2020 version to include updated deaths data, later dates for rolling out the screening testing program, and the spread of more contagious variants such as the B.1.1. 7 variant.

category: health economics


title: An Explainable Artificial Intelligence based Prospective Framework for COVID-19 Risk Prediction

abstract: Given the spread of COVID-19 to vast geographical regions and populations, it is not feasible to undergo or recommend the RT-PCR based tests to all individuals with flu-like symptoms. The reach of RT-PCR based testing is still limited due to the high cost of the test and huge population in few countries. Thus, alternative methods for COVID-19 infection risk prediction can be useful. We built an explainable artificial intelligence (AI) based integrated web-based prospective framework for COVID-19 risk prediction. We employed a two-step procedure for the non-clinical prediction of COVID19 infection risk. In the first step we assess the initial risk of COVID19 infection based on carefully selected parameters associated with COVID-19 positive symptoms from recent research. Generally, X-ray scans are cheaper and easily available in most government and private health centres. Therefore, based on the outcome of the computed initial risk in first step, we further provide an optional prediction using the chest X-ray scans in the second step of our proposed AI based prospective framework. Since there is a bottleneck to undergo an expensive RT-PCR based confirmatory test in economically backward nations, this is a crucial part of our explainable AI based prospective framework. The initial risk assessment outcome is analysed in combination with the advanced deep learning-based analysis of chest X-ray scans to provide an accurate prediction of COVID-19 infection risk. This prospective web-based AI framework can be employed in limited resource settings after clinical validation in future. The cost and time associated with the adoption of this prospective AI based prospective framework will be minimal and hence it will be beneficial to majority of the population living in low-income settings such as small towns and rural areas that have limited access to advanced healthcare facilities.

category: health informatics


title: Association Between HIV PrEP Indications and Use in a National Sexual Network Study of Men Who Have Sex with Men

abstract:
BackgroundHIV preexposure prophylaxis (PrEP) is effective in preventing HIV transmission. US Public Health Service (USPHS) clinical practice guidelines define biobehavioral indications for initiation. To assess guideline implementation, it is critical to quantify PrEP non-users who are indicated and PrEP users who are not indicated.

MethodsUsing data from a national web-based study of men who have sex with men (MSM) between 2017 and 2019, we estimated the association between PrEP use and PrEP indications. Log-binomial regression was used to estimate the relationship between PrEP indications and PrEP use, adjusted for geography and demographics.

ResultsOf 3508 sexually active, HIV-negative MSM, 34% met indications for PrEP. The proportion with current PrEP use was 32% among those meeting indications and 11% among those without indications. Nearly 40% of those currently using PrEP did not meet indications for PrEP, and 68% of MSM with indications for PrEP were not currently using PrEP. After adjusting for geography and demographics, MSM with PrEP indications were about 3 times as likely to be currently using PrEP. This association varied slightly by geography and demography.

ConclusionsIndications for PrEP strongly predicted current PrEP use among MSM. However, we identified substantial misalignment between indications and use in both directions (indicated MSM who were not benefitting from PrEP, and MSM taking PrEP while not presently being indicated). This calls for further implementation efforts to improve PrEP delivery to those most in need during periods of elevated sexual risk.

category: hiv aids


title: Evaluation of accuracy, exclusivity, limit-of-detection and ease-of-use of LumiraDx™ - Antigen-detecting point-of-care device for SARS-CoV-2

abstract:
BackgroundRapid antigen-detecting tests (Ag-RDTs) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can transform pandemic control. Thus far, sensitivity ([≤]85%) of lateral-flow assays has limited scale-up. Conceivably, microfluidic immunofluorescence Ag-RDTs could increase sensitivity for SARS-CoV-2 detection.

Materials and MethodsThis multi-centre diagnostic accuracy study investigated performance of the microfluidic immunofluorescence LumiraDx assay, enrolling symptomatic and asymptomatic participants with suspected SARS-CoV-2 infection. Participants collected a supervised nasal mid-turbinate (NMT) self-swab for Ag-RDT testing, in addition to a professionally-collected nasopharyngeal (NP) swab for routine testing with reverse transcriptase polymerase chain reaction (RT-PCR). Results were compared to calculate sensitivity and specificity. Sub-analyses investigated the results by viral load, symptom presence and duration. An analytical study assessed exclusivity and limit-of-detection (LOD). In addition, we evaluated ease-of-use.

ResultsStudy conduct was between November 2nd 2020 and January 21st 2021. 761 participants were enrolled, with 486 participants reporting symptoms on testing day. 120 out of 146 RT-PCR positive cases were detected positive by LumiraDx, resulting in a sensitivity of 82.2% (95% CI: 75.2%-87.5%). Specificity was 99.3% (CI: 98.3-99.7%). Sensitivity was increased in individuals with viral load [≥] 7 log10 SARS-CoV2 RNA copies/ml (93.8%; CI: 86.2%-97.3%). Testing against common respiratory commensals and pathogens showed no cross-reactivity and LOD was estimated to be 2-56 PFU/mL. The ease-of-use-assessment was favourable for lower throughput settings.

ConclusionThe LumiraDx assay showed excellent analytical sensitivity, exclusivity and clinical specificity with good clinical sensitivity using supervised NMT self-sampling.


title: Kinetics of SARS-CoV-2 anti-s IgG after BNT162b2 vaccination

abstract:
Deployment of the BNT162b2 mRNA Covid-19 Vaccine in Israel began in December 2020.

This is a retrospective analysis of serological data, describing SARS-CoV-2 anti-S IgG kinetics in 116 Israeli healthcare workers administrated the BNT162b2 vaccine.

Seroconversion occurred by day 14 in all individuals, with IgG levels peaking approximately 30 days post inoculation.

This study demonstrated the kinetics of the antibody response post vaccination with BNT162b2. The robustness of seroconversion was observed, alongside a statistically significant difference in IgG levels between employees over and younger 50 years of afge. Further research is required in order to examine the antibody kinetics overtime, as well as whether the age-dependent difference persists.


title: Efficacy of Nitazoxanide in reducing the viral load in COVID-19 patients. Randomized, placebo-controlled, single-blinded, parallel group, pilot study.

abstract:
The fast spread of COVID-19 has overcrowded Public Health Systems facilities in major countries due to the large number of seriously ill patients, particularly those requiring admission to intensive care units. Reducing viral load, along with other recommended epidemiological measures, such as social distancing and home confinement, can in time significantly help to reduce the infection R0 (Basic Reproductive Rate) and then mitigate disease burden. Early negativization or otherwise reduction of the viral load can potentially diminish disease severity, resulting in a better-controlled public health response, avoiding collapse of healthcare systems. Nitazoxanide, a widely used thiazolide approved by the FDA as an antiparasitic drug, also approved in Brazil for Norovirus and Rotavirus treatments, has an excellent safety record for a variety of indications. Nitazoxanide exhibits activity in vitro against MERS-CoV and other coronaviruses; and a specific antiviral effect (in micro molar doses) against SARS-CoV-2. The objective of this study was to evaluate the efficacy and safety of Nitazoxanide in reducing the SARS-COV 2 viral load within 7 days of treatment in respiratory samples from COVID-19-infected patients with mild to moderate disease, compared to placebo. An interim analysis showed that the ratio of patients with a viral load reduction [≥] 35% from baseline up to day 7 of treatment was significantly greater for Nitazoxanide compared to placebo (47.8% vs. 15.4%; {Delta} 34.6%; 95% CI: 64.7; 4.6: p = 0.037).

KEY POINTSO_ST_ABSState of the ArtC_ST_ABSO_LIDifferent studies conclude that viral load (VL) would correlate with morbidity, mortality and contagiousness of COVID-19.
C_LIO_LIEarly negativization or reduction of the viral load can potentially reduce the severity of this disease.
C_LIO_LIIn vitro data demonstrated a specific antiviral effect of Nitazoxanide for SARS-CoV-2.
C_LI

Article contributionO_LINitazoxanide showed a statistically significant difference versus placebo in the number of patients who had their viral load reduced by at least 35% in mild to moderate COVID-19 disease.
C_LIO_LIThe observed antiviral effect in vitro would seems to be verified in patients with mild to moderate COVID-19 infection, which should be confirmed by studies with a larger cohort of patients.
C_LI


title: Providing a safe, in-person, residential college experience during the COVID-19 pandemic

abstract: Due to the COVID-19 pandemic, higher education institutions were forced to make difficult decisions regarding the 2020-2021 academic year. Many institutions decided to have courses in an online remote format, others decided to attempt an in-person experience, while still others took a hybrid approach. Hope College (Holland, MI) decided that an in-person semester would be safer and more equitable for students. To achieve this at a residential college required broad collaboration across multiple stakeholders. Here, we share lessons learned and detail Hope Colleges model, including wastewater surveillance, comprehensive testing, contact tracing and isolation procedures, that allowed us to deliver on our commitment of an in-person, residential college experience.


title: HiSpike: A high-throughput cost effective sequencing method for the SARS-CoV-2 spike gene

abstract: The changing nature of the corona virus of the SARS-CoV-2 pandemic poses unprecedented challenges to the worlds health systems. New and virulent emerging spike gene variants, such as the UK 20I/501Y.V1 and South African 20H/501Y.V2, could jeopardize global efforts to produce immunity and reduce mortality. These challenges require effective real-time genomic surveillance solutions that the medical community can quickly adopt. The SARS-CoV-2 spike protein mediates host receptor recognition and entry into the cell and therefore, it is most susceptible to generation of variants with increased transmissibility and pathogenicity. The spike protein is also the primary target of neutralizing antibodies in COVID-19 patients and the most common antigen for induction of effective vaccine immunity. Therefore, tight monitoring of the spike protein gene variants is key to mitigating COVID-19 spread and vaccine escape mutants. Currently, the ARTIC method for SARS-CoV-2 whole genome sequencing is applied worldwide. However, this method commonly requires more than 96 hours (4-5 days) from start to finish and at present high sample sequence demands, sequencing resources are quickly exhausted. In this work, we present HiSpike, a method for high-throughput targeted next generation sequencing (NGS) of the spike gene. This simple three-step method can be completed in less than 30 hours and can sequence 10-fold more samples compared to the conventional ARTIC method and at a fraction of the cost. HiSpike was proven valid, and has identified, at high quality, multiple spike variants from real-time field samples, such as the UK and the South African variants. This method will certainly be effective in discovering future spike mutations. Therefore, running HiSpike for full sequencing of the spike gene of all positive SARS-CoV-2 samples could be considered for near real-time detection of known and emerging spike mutations as they evolve. HiSpike provides affordable sequencing options to help laboratories conserve resources, hence it provides a tool for widespread monitoring, that can support critical knowledge-based decisions.


title: Evaluation of sample collection and transport strategies to enhance yield, accessibility, and biosafety of COVID-19 RT-PCR testing

abstract: Sensitive, accessible, and biosafe sampling methods for COVID-19 reverse-transcriptase polymerase chain reaction (RT-PCR) assays are needed for frequent and widespread testing. We systematically evaluated diagnostic yield across different sample collection and transport workflows, including the incorporation of a viral inactivation buffer. We prospectively collected nasal swabs, oral swabs, and saliva, from 52 COVID-19 RT-PCR-confirmed patients, and nasopharyngeal (NP) swabs from 37 patients. Nasal and oral swabs were placed in both viral transport media (VTM) and eNAT, a sterilizing transport buffer, prior to testing with the Xpert Xpress SARS-CoV-2 (Xpert) test. The sensitivity of each sampling strategy was compared using a composite positive standard. Overall, swab specimens collected in eNAT showed superior sensitivity compared to swabs in VTM (70% vs 57%, P=0.0022). Direct saliva 90.5%, (95% CI: 82%, 95%), followed by NP swabs in VTM and saliva in eNAT, was significantly more sensitive than nasal swabs in VTM (50%, P<0.001) or eNAT (67.8%, P=0.0012) and oral swabs in VTM (50%, P<0.0001) or eNAT (56%, P<0.0001). Saliva and use of eNAT buffer each increased detection of SARS-CoV-2 with the Xpert test; however, no single sample matrix identified all positive cases.


title: Model-based evaluation of transmissibility and reinfection for the P.1 variant of the SARS-CoV-2

abstract:
O_TEXTBOXSummary boxO_ST_ABSWhat is already known about this topic?C_ST_ABSA new variant of concern of SARS-CoV-2 (P.1). emerged in the city of Manaus in November 2020. Since then, a sharp increase in COVID-19 cases in Manaus led to the collapse of the health system in early 2021.

What is added by this report?Transmissibility and reinfection of P.1 were estimated using an epidemiological model-based fitting and public health data. The transmissibility is 2.5 times greater than the wild variant and reinfection probability is 6.4% on average.

What are the implications for public health practice?This new variant poses a global threat due to its very high transmissibility. The results highlight the need to urgently monitor and contain its spread.

C_TEXTBOX


title: Model-based estimation of transmissibility and reinfection of SARS-CoV-2 P.1 variant


title: Genome sequencing and analysis of an emergent SARS-CoV-2 variant characterized by multiple spike protein mutations detected from the Central Visayas Region of the Philippines

abstract: The emergence of SARS-CoV-2 variants of concern such as the B.1.1.7, B.1.35 and the P.1 have prompted calls for governments worldwide to increase their genomic biosurveillance efforts. Globally, quarantine and outbreak management measures have been implemented to stem the introduction of these variants and to monitor any emerging variants of potential clinical significance domestically. Here, we describe the emergence of a new SARS-CoV-2 lineage, mainly from the Central Visayas region of the Philippines. This emergent variant is characterized by 13 lineage-defining mutations, including the co-occurrence of the E484K, N501Y, and P681H mutations at the spike protein region, as well as three additional radical amino acid replacements towards the C-terminal end of the said protein. A three-amino acid deletion at positions 141 to 143 (LGV141_143del) in the spike protein was likewise seen in a region preceding the 144Y deletion found in the B.1.1.7 variant. A single amino acid replacement, K2Q, at the N-terminus of ORF8 was also shared by all 33 samples sequenced. The mutation profile of this new virus variant warrants closer investigation due to its potential public health implications. The current distribution of this emergent variant in the Philippines and its transmission are being monitored and addressed by relevant public health agencies to stem its spread in nearby islands and regions in the country.


title: Obesity is associated with an altered baseline and post-vaccination influenza antibody repertoire

abstract:
As highlighted by the ongoing COVID-19 pandemic, vaccination is critical for infectious disease prevention and control. Obesity is associated with increased morbidity and mortality from respiratory virus infections. While obese individuals respond to influenza vaccination, what is considered a seroprotective response may not fully protect the global obese population. In a cohort vaccinated with the 2010-2011 trivalent inactivated influenza vaccine, baseline immune history and vaccination responses were found to significantly differ in obese individuals compared to healthy controls, especially towards the 2009 pandemic strain of A/H1N1 influenza virus. Young, obese individuals displayed responses skewed towards linear peptides versus conformational antigens, suggesting aberrant obese immune response. Overall, these data have vital implications for the next generation of influenza vaccines, and towards the current SARS-CoV-2 vaccination campaign.

One Sentence SummaryObese individuals have altered baseline and post-vaccination influenza antibody repertoires.


title: Diagnostic Performance and Characteristics of Anterior Nasal Collection for the SARS-CoV-2 Antigen Test: A Prospective Study in Japan

abstract: We conducted a prospective study in Japan to evaluate the diagnostic performance of the antigen test QuickNavi-COVID19 Ag using anterior nasal samples and to compare the degrees of coughs or sneezes induction and the severity of pain between anterior nasal collection and nasopharyngeal collection. A total of 862 participants were included in the analysis. In comparison to the findings of reverse transcription PCR using nasopharyngeal samples, the antigen test using anterior nasal samples showed 72.5% sensitivity (95% confidence interval [CI]: 58.3%-84.1%) and 100% specificity (95% CI: 99.3%-100%). Anterior nasal collection was associated with a significantly lower degree of coughs or sneezes induction and the severity of pain in comparison to nasopharyngeal collection (p < 0.001). The antigen test using anterior nasal samples showed moderate sensitivity but was less painful and induced fewer coughs or sneezes.