• QAIS-DSNN: Tumor Area Segmentation of MRI Image with Optimized Quantum Matched-Filter Technique and Deep Spiking Neural Network

      Ahmadi, Mohsen; Sharifi, Abbas; Hassantabar, Shayan; Enayati, Saman (2021-01-21)
      Tumor segmentation in brain MRI images is a noted process that can make the tumor easier to diagnose and lead to effective radiotherapy planning. Providing and building intelligent medical systems can be considered as an aid for physicians. In many cases, the presented methods’ reliability is at a high level, and such systems are used directly. In recent decades, several methods of segmentation of various images, such as MRI, CT, and PET, have been proposed for brain tumors. Advanced brain tumor segmentation has been a challenging issue in the scientific community. The reason for this is the existence of various tumor dimensions with disproportionate boundaries in medical imaging. This research provides an optimized MRI segmentation method to diagnose tumors. It first offers a preprocessing approach to reduce noise with a new method called Quantum Matched-Filter Technique (QMFT). Then, the deep spiking neural network (DSNN) is implemented for segmentation using the conditional random field structure. However, a new algorithm called the Quantum Artificial Immune System (QAIS) is used in its SoftMax layer due to its slowness and nonsegmentation and the identification of suitable features for selection and extraction. The proposed approach, called QAIS-DSNN, has a high ability to segment and distinguish brain tumors from MRI images. The simulation results using the BraTS2018 dataset show that the accuracy of the proposed approach is 98.21%, average error-squared rate is 0.006, signal-to-noise ratio is 97.79 dB, and lesion structure criteria including the tumor nucleus are 80.15%. The improved tumor is 74.50%, and the entire tumor is 91.92%, which shows a functional advantage over similar previous methods. Also, the execution time of this method is 2.58 seconds.
    • Rapid Adoption of Telemedicine in Rheumatology Care During the COVID-19 Pandemic Highlights Training and Supervision Concerns Among Rheumatology Trainees

      The Global Rheumatology Alliance (2021-11-17)
      Objective: To evaluate the impact of telemedicine use during the coronavirus disease 2019 (COVID-19) pandemic on rheumatology trainees. Methods: A voluntary, anonymous, web-based survey was administered in English, Spanish, or French from August 19 to October 5, 2020. Adult and pediatric rheumatology trainees were invited to participate via social media and email. Using multiple-choice questions and Likert scales, the survey assessed prior and current telemedicine use, impact on training, and supervision after COVID-19 prompted rapid telemedicine implementation. Results: Surveys were received from 302 trainees from 33 countries, with 83% in adult rheumatology training programs. Reported telemedicine use increased from 13% before the pandemic to 82% during the pandemic. United States trainees predominantly used video visits, whereas outside the United States telemedicine was predominantly audio only. Most (65%) evaluated new patients using telemedicine. More respondents were comfortable using telemedicine for follow-up patients (69%) than for new patients (25%). Only 39% of respondents reported receiving telemedicine-focused training, including instruction on software, clinical skills, and billing, whereas more than half of United States trainees (59%) had training. Postconsultation verbal discussion was the most frequent form of supervision; 24% reported no supervision. Trainees found that telemedicine negatively impacted supervision (50%) and the quality of clinical teaching received (70%), with only 9% reporting a positive impact. Conclusions: Despite widespread uptake of telemedicine, a low proportion of trainees received telemedicine training, and many lacked comfort in evaluating patients, particularly new patients. Inadequate supervision and clinical teaching were areas of concern. If telemedicine remains in widespread use, ensuring appropriate trainee supervision and teaching should be prioritized.
    • Rapid epidemic expansion of the SARS-CoV-2 Omicron variant in southern Africa

      Institute for Genomics and Evolutionary Medicine (Temple University) (2021-12-21)
      The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic in southern Africa has been characterised by three distinct waves. The first was associated with a mix of SARS-CoV-2 lineages, whilst the second and third waves were driven by the Beta and Delta variants respectively1–3. In November 2021, genomic surveillance teams in South Africa and Botswana detected a new SARS-CoV-2 variant associated with a rapid resurgence of infections in Gauteng Province, South Africa. Within three days of the first genome being uploaded, it was designated a variant of concern (Omicron) by the World Health Organization and, within three weeks, had been identified in 87 countries. The Omicron variant is exceptional for carrying over 30 mutations in the spike glycoprotein, predicted to influence antibody neutralization and spike function4. Here, we describe the genomic profile and early transmission dynamics of Omicron, highlighting the rapid spread in regions with high levels of population immunity.
    • RASCL: Rapid Assessment Of SARS-CoV-2 Clades Through Molecular Sequence Analysis

      Institute for Genomics and Evolutionary Medicine (2022-01-18)
      An important component of efforts to manage the ongoing COVID19 pandemic is the Rapid Assessment of how natural selection contributes to the emergence and proliferation of potentially dangerous SARS-CoV-2 lineages and CLades (RASCL). The RASCL pipeline enables continuous comparative phylogenetics-based selection analyses of rapidly growing clade-focused genome surveillance datasets, such as those produced following the initial detection of potentially dangerous variants. From such datasets RASCL automatically generates down-sampled codon alignments of individual genes/ORFs containing contextualizing background reference sequences, analyzes these with a battery of selection tests, and outputs results as both machine readable JSON files, and interactive notebook-based visualizations.
    • Rate of Decompensation of Normoxic Emergency Department Patients with SARS-CoV-2

      Schreyer, Kraftin; Isenberg, Derek; Satz, Wayne A.; Lucas, Nicole; Rosenbaum, Jennifer; Zandrow, Gregory; Gentle, Nina T.; Schreyer|0000-0001-8955-2060; Isenberg|0000-0001-5814-1023; Lucas|0000-0002-5251-2230 (2021-04-02)
      Introduction: As of October 30, 2020, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over 44 million people worldwide and killed over 1.1 million people. In the emergency department (ED), patients who need supplemental oxygen or respiratory support are admitted to the hospital, but the course of normoxic patients with SARS-CoV-2 infection is unknown. In our health system, the policy during the coronavirus 2019 (COVID-19) pandemic was to admit all patients with abnormal chest imaging (CXR) regardless of their oxygen level. We also admitted febrile patients with respiratory complaints who resided in congregate living. We describe the rate of decompensation among patients admitted with suspected SARS-CoV-2 infection but who were not hypoxemic in the ED. Methods: This is a retrospective observational study of patients admitted to our health system between March 1–May 5, 2020 with suspected SARS-CoV-2 infection. We queried our registry to find patients who were admitted to the hospital but had no recorded oxygen saturation of <92% in the ED and received no supplemental oxygen prior to admission. Our primary outcome was decompensation at 72 hours, defined by the need for respiratory support (oxygen, high-flow nasal cannula, non-invasive ventilation, or intubation). Results: A total of 840 patients met our inclusion criteria. Of those patients, 376 (45%) tested positive for SARS-CoV-2. Sixty patients (7.1%) with suspected COVID-19 required respiratory support at 72 hours including 27 (3%) of confirmed SARS-CoV-2 positive patients. Among the 376 patients who tested positive for SARS-CoV-2, 54 patients (14%) had normal CXR in the ED. One-third of patients with normal CXRs decompensated at 72 hours. Seven SARS-CoV-2 positive patients in our cohort died during their hospitalization, of whom five had normal CXRs on admission. Conclusion: Sixty (7.1%) of suspected COVID-19 patients hospitalized at 72 hours required respiratory support despite being normoxic in the ED. Further research should look to identify the normoxic SARS-CoV-2 patients at risk for decompensation.
    • #RealCollege 2021: Basic Needs Insecurity During the Ongoing Pandemic

      The Hope Center for College, Community, and Justice (Temple University) (Temple University. The Hope Center for College, Community, and Justice, 2021-03-31)
      Entering the fall 2020 term, higher education was reeling from the coronavirus pandemic. Enrollment was down—particularly among students most at risk of basic needs insecurity; fewer students had completed the Free Application for Federal Student Aid (FAFSA); and college retention rates had dropped. Students and faculty were stressed and anxious. By the end of the term, more than 267,000 Americans died. At the same time, the federal government pumped an unprecedented $6 billion into student emergency aid via the Coronavirus Aid, Relief, and Economic Security (CARES) Act. This report examines the pandemic’s impact on #RealCollege students who were able to continue their education in this challenging environment. Using our sixth annual #RealCollege Survey, fielded in fall 2020, we assessed students’ basic needs security and their well-being, as indicated by employment status, academic engagement, and mental health. In total, over 195,000 students from 130 two-year colleges and 72 four-year colleges and universities responded to the 2020 #RealCollege Survey.
    • Recent Smell Loss Is the Best Predictor of COVID-19 Among Individuals With Recent Respiratory Symptoms

      Gerkin, Richard C.; Ohla, Kathrin; Veldhuizen, Maria G.; Joseph, Paule V.; Kelly, Christine E.; Bakke, Alyssa J.; Steele, Kimberley E.; Farruggia, Michael C.; Pellegrino, Robert; Pepino, Marta Y.; Bouysset, Cédric; Soler, Graciela M.; Pereda-Loth, Veronica; Dibattista, Michele; Cooper, Keiland W.; Croijmans, Ilja; Di Pizio, Antonella; Ozdener, Mehmet Hakan; Fjaeldstad, Alexander W.; Lin, Cailu; Sandell, Mari A.; Singh, Preet B.; Brindha, V. Evelyn; Olsson, Shannon B.; Saraiva, Luis R.; Ahuja, Gaurav; Alwashahi, Mohammed K.; Bhutani, Surabhi; D'Errico, Anna; Fornazieri, Marco A.; Golebiowski, Jérôme; Hwang, Liang Dar; Öztürk, Lina; Roura, Eugeni; Spinelli, Sara; Whitcroft, Katherine L.; Faraji, Farhoud; Fischmeister, Florian Ph S.; Heinbockel, Thomas; Hsieh, Julien W.; Huart, Caroline; Konstantinidis, Iordanis; Menini, Anna; Morini, Gabriella; Olofsson, Jonas K.; Philpott, Carl M.; Pierron, Denis; Shields, Vonnie D.C.; Voznessenskaya, Vera V.; Albayay, Javier; Altundag, Aytug; Bensafi, Moustafa; Bock, María Adelaida; Calcinoni, Orietta; Fredborg, William; Laudamiel, Christophe; Lim, Juyun; Lundström, Johan N.; Macchi, Alberto; Meyer, Pablo; Moein, Shima T.; Santamaría, Enrique; Sengupta, Debarka; Dominguez, Paloma Rohlfs; Yanik, Hüseyin; Hummel, Thomas; Hayes, John E.; Reed, Danielle R.; Niv, Masha Y.; Munger, Steven D.; Parma, Valentina (2020-12-25)
      In a preregistered, cross-sectional study, we investigated whether olfactory loss is a reliable predictor of COVID-19 using a crowdsourced questionnaire in 23 languages to assess symptoms in individuals self-reporting recent respiratory illness. We quantified changes in chemosensory abilities during the course of the respiratory illness using 0–100 visual analog scales (VAS) for participants reporting a positive (C19+; n = 4148) or negative (C19−; n = 546) COVID-19 laboratory test outcome. Logistic regression models identified univariate and multivariate predictors of COVID-19 status and post-COVID-19 olfactory recovery. Both C19+ and C19− groups exhibited smell loss, but it was significantly larger in C19+ participants (mean ± SD, C19+: −82.5 ± 27.2 points; C19−: −59.8 ± 37.7). Smell loss during illness was the best predictor of COVID-19 in both univariate and multivariate models (ROC AUC = 0.72). Additional variables provide negligible model improvement. VAS ratings of smell loss were more predictive than binary chemosensory yes/no-questions or other cardinal symptoms (e.g., fever). Olfactory recovery within 40 days of respiratory symptom onset was reported for ~50% of participants and was best predicted by time since respiratory symptom onset. We find that quantified smell loss is the best predictor of COVID-19 amongst those with symptoms of respiratory illness. To aid clinicians and contact tracers in identifying individuals with a high likelihood of having COVID-19, we propose a novel 0–10 scale to screen for recent olfactory loss, the ODoR-19. We find that numeric ratings ≤2 indicate high odds of symptomatic COVID-19 (4 < OR < 10). Once independently validated, this tool could be deployed when viral lab tests are impractical or unavailable.
    • Recent zoonotic spillover and tropism shift of a Canine Coronavirus is associated with relaxed selection and putative loss of function in NTD subdomain of spike protein

      Institute for Genomics and Evolutionary Medicine (Temple University) (2021-11-17)
      A recent study reported the occurrence of Canine Coronavirus (CCoV) in nasopharyngeal swabs from a small number of patients hospitalized with pneumonia during a 2017-18 period in Sarawak, Malaysia. Because the genome sequence for one of these isolates is available, we conducted comparative evolutionary analyses of the spike gene of this strain (CCoV-HuPn-2018), with other available Alphacoronavirus 1 spike sequences. The most N-terminus subdomain (0-domain) of the CCoV-HuPn-2018 spike protein has sequence similarity to Transmissible Gastroenteritis Virus (TGEV) and CCoV2b strains, but not to other members of the type II Alphacoronaviruses (i.e., CCoV2a and Feline CoV2-FCoV2). This 0-domain in CCoV-HuPn-2018 has evidence for relaxed selection pressure, an increased rate of molecular evolution, and a number of unique amino acid substitutions relative to CCoV2b and TGEV sequences. A region of the 0-domain determined to be key to sialic acid binding and pathogenesis in TGEV had clear differences in amino acid sequences in CCoV-HuPn-2018 relative to both CCoV2b (enteric) and TGEV (enteric and respiratory). The 0-domain of CCoV-HuPn-2018 also had several sites inferred to be under positive diversifying selection, including sites within the signal peptide. Downstream of the 0-domain, FCoV2 shared sequence similarity to the CCoV2b and TGEV sequences, with analyses of this larger alignment identifying positively selected sites in the putative Receptor Binding Domain (RBD) and Connector Domain (CD). Recombination analyses strongly implicated a particular FCoV2 strain in the recombinant history of CCoV-HuPn-2018 with molecular divergence times estimated at around 60 years ago. We hypothesize that CCoV-HuPn-2018 had an enteric origin, but that it has lost that particular tropism, because of mutations in the sialic acid binding region of the spike 0-domain. As selection pressure on this region was reduced, the virus evolved a respiratory tropism, analogous to other Alphacoronavirus 1, such as Porcine Respiratory Coronavirus (PRCV), that have lost this region entirely. We also suggest that signals of positive selection in the signal peptide as well as other changes in the 0-domain of CCoV-HuPn-2018 could represent an adaptive role in this new host and that this could be in part due to the different spatial distribution of the N-linked glycan repertoire for this strain.
    • Recombination and purifying selection preserves covariant movements of mosaic SARS-CoV-2 protein S

      Tagliamonte, Massimiliano S.; Abid, Nabil; Ostrov, David A.; Chillemi, Giovanni; Pond, Sergei; Salemi, Marco; Mavian, Carla; 0000-0003-4817-4029 (2020-06-10)
      In depth evolutionary and structural analyses of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) isolated from bats, pangolins, and humans are necessary to assess the role of natural selection and recombination in the emergence of the current pandemic strain. The SARS-CoV-2 S glycoprotein unique features have been associated with efficient viral spread in the human population. Phylogeny-based and genetic algorithm methods clearly show that recombination events between viral progenitors infecting animal hosts led to a mosaic structure in the S gene. We identified recombination coldspots in the S glycoprotein and strong purifying selection. Moreover, although there is little evidence of diversifying positive selection during host-switching, structural analysis suggests that some of the residues emerged along the ancestral lineage of current pandemic strains may contribute to enhanced ability to infect human cells. Interestingly, recombination did not affect the long-range covariant movements of SARS-CoV-2 S glycoprotein monomer in pre-fusion conformation but, on the contrary, could contribute to the observed overall viral efficiency. Our dynamic simulations revealed that the movements between the host cell receptor binding domain (RBD) and the novel furin-like cleavage site are correlated. We identified threonine 333 (under purifying selection), at the beginning of the RBD, as the hinge of the opening/closing mechanism of the SARS-CoV-2 S glycoprotein monomer functional to hACE2 binding. Our findings support a scenario where ancestral recombination and fixation of amino acid residues in the RBD of the S glycoprotein generated a virus with unique features, capable of extremely efficient infection of the human host.
    • Repeated COVID-19 relapse during post-discharge surveillance with viral shedding lasting for 67 days in a recovered patient infected with SARS-CoV-2

      Liu, Fang; Cai, Zhao-bin; Huang, Jin-song; Niu, Hai-ying; Yu, Wen-yan; Zhang, Yan; Yan, Ting-bo; Chen, Chen; Liu, Yuan; Xu, Ai-fang (2020-08-06)
      A case who revealed the longest duration of viral shedding (67 days) in current reports, presented complicated characteristic on the relapse of COVID-19 due to the inconsistent performance of chest radiography and SARS-CoV-2-RNA detection after discharge. Lopinavir-interferon α2b boosted ribavirin following with lopinavir boosted budesonide might be a potent treatment for viral clearance.
    • Response to: ‘Correspondence on ‘Preliminary predictive criteria for COVID-19 cytokine storm’’ by Tampe et al

      Caricchio, Roberto; Gallucci, Marcello; Dass, Chandra; Zhang, Xinyan; Gallucci, Stefania; Fleece, David; Bromberg, Michael; Criner, Gerard J.; Caricchio|0000-0002-1379-1118 (2021-01-07)
    • Retrospective analysis of high flow nasal therapy in COVID-19-related moderate-to-severe hypoxaemic respiratory failure

      Patel, Maulin; Gangemi, Andrew; Marron, Robert; Chowdhury, Junad; Yousef, Ibraheem; Zheng, Matthew; Mills, Nicole; Tragesser, Lauren; Giurintano, Julie; Gupta, Rohit; Gordon, Matthew; Rali, Parth; D'Alonso, Gilbert; Fleece, David; Zhao, Huaqing; Patlakh, Nicole; Criner, Gerard; 0000-0001-6558-1924; 0000-0002-8764-6538; 0000-0003-2775-2918; 0000-0002-0953-4768| (2020-08-26)
      Invasive mechanical has been associated with high mortality in COVID-19. Alternative therapy of high flow nasal therapy (HFNT) has been greatly debated around the world for use in COVID-19 pandemic due to concern for increased healthcare worker transmission.This was a retrospective analysis of consecutive patients admitted to Temple University Hospital in Philadelphia, Pennsylvania, from 10 March 2020 to 24 April 2020 with moderate-to-severe respiratory failure treated with HFNT. Primary outcome was prevention of intubation. Of the 445 patients with COVID-19, 104 met our inclusion criteria. The average age was 60.66 (+13.50) years, 49 (47.12 %) were female, 53 (50.96%) were African-American, 23 (22.12%) Hispanic. Forty-three patients (43.43%) were smokers. Saturation to fraction ratio and chest X-ray scores had a statistically significant improvement from day 1 to day 7. 67 of 104 (64.42%) were able to avoid invasive mechanical ventilation in our cohort. Incidence of hospital-associated/ventilator-associated pneumonia was 2.9%. Overall, mortality was 14.44% (n=15) in our cohort with 13 (34.4%) in the progressed to intubation group and 2 (2.9%) in the non-intubation group. Mortality and incidence of pneumonia was statistically higher in the progressed to intubation group.
    • Reviewing COVID-19 Modelling amidst Recent United States Protests

      Fasehun, Luther-King; 0000-0002-8798-5433 (2020-07-06)
    • Rhinovirus and Innate Immune Function of Airway Epithelium

      Ganjian, Haleh; Rajput, Charu; Elzoheiry, Manal; Sajjan, Umadevi; 0000-0001-7420-9307; 0000-0002-5756-3651 (2020-06-19)
      Airway epithelial cells, which lines the respiratory mucosa is in direct contact with the environment. Airway epithelial cells are the primary target for rhinovirus and other inhaled pathogens. In response to rhinovirus infection, airway epithelial cells mount both pro-inflammatory responses and antiviral innate immune responses to clear the virus efficiently. Some of the antiviral responses include the expression of IFNs, endoplasmic reticulum stress induced unfolded protein response and autophagy. Airway epithelial cells also recruits other innate immune cells to establish antiviral state and resolve the inflammation in the lungs. In patients with chronic lung disease, these responses may be either defective or induced in excess leading to deficient clearing of virus and sustained inflammation. In this review, we will discuss the mechanisms underlying antiviral innate immunity and the dysregulation of some of these mechanisms in patients with chronic lung diseases.
    • Safety and immunogenicity of a Recombinant Stabilized Prefusion SARS-CoV-2 Spike Protein Vaccine (MVCCOV1901) Adjuvanted with CpG 1018 and Aluminum Hydroxide in healthy adults: A Phase 1, dose-escalation study

      Hsieh, Szu-Min; Liu, Wang-Da; Huang, Yu-Shan; Lin, Yi-Jiun; Hsieh, Erh-Fang; Lian, Wei-Cheng; Chen, Charles; Janssen, Robert; Shih, Shin-Ru; Huang, Chung-Guei; Tai, I-Chen; Chang, Shan-Chwen (2021-06-26)
      Background: This was a phase 1, dose-escalation open-label trial to evaluate the safety and immunogenicity of MVCsingle bondCOV1901, a SARS-CoV-2 S-2P protein vaccine adjuvanted with aluminum hydroxide and CpG 1018. Methods: Between September 28 and November 13 2020, 77 participants were screened. Of these, 45 healthy adults from 20 to 49 years of age were to be administered two doses of MVCsingle bondCOV1901 in doses of 5 μg, 15 μg, or 25 μg of spike protein at 28 days apart. There were 15 participants in each dose group; all were followed for 28 days after the second dose at the time of the interim analysis. Adverse events and laboratory data were recorded for the safety evaluation. Blood samples were collected for humoral, and cellular immune response at various time points. Trial Registration: ClinicalTrials.gov NCT 04487210. Findings: Solicited adverse events were mostly mild and similar. No subject experienced fever. After the second dose, the geometric mean titers (GMTs) for SARS-CoV-2 spike-specific immunoglobulin G were 7178.2, 7746.1, 11,220.6 in the 5 μg, 15 μg, and 25 μg dose groups, respectively. The neutralizing activity were detected in both methods. (Day 43 GMTs, 538.5, 993.1, and 1905.8 for pseudovirus; and 33.3, 76.3, and 167.4 for wild-type virus). The cellular immune response induced by MVCsingle bondCOV1901 demonstrated substantially higher numbers of IFN-γ- producing cells, suggesting a Th1-skewed immune response. Interpretation: The MVCsingle bondCOV1901 vaccine was well tolerated and elicited robust immune responses and is suitable for further development. Funding: Medigen Vaccine Biologics Corporation.
    • Safety and Immunogenicity of CpG 1018 and Aluminium Hydroxide-Adjuvanted SARS-CoV-2 S-2P Protein Vaccine MVC-COV1901: A Large-Scale Double-Blind, Randomised, Placebo-Controlled Phase 2 Trial

      Szu-Min, Hsieh; Liu, Ming-Che; Chen, Yen-Hsu; Lee, Wen-Sen; Hwang, Shinn-Jang; Cheng, Shu-Hsing; Ko, Wen-Chien; Hwang, Kao-Pin; Wang, Ning-Chi; Lee, Yu-Lin; Lin, Yi-Ling; Shih, Shin-Ru; Huang, Chung-Guei; Liao, Chun-Che; Liang, Jian-Jong; Chang, Chih-Shin; Chen, Charles; Lien, Chia En; Tai, I-Chen; Lin, Tzou-Yien (2021-08-08)
      Background: We have assessed the safety and immunogenicity of the COVID-19 vaccine MVC-COV1901, a recombinant protein vaccine containing prefusion-stabilized spike protein S-2P adjuvanted with CpG 1018 and aluminium hydroxide. Methods: This is a phase 2, prospective, randomised, double-blind, placebo-controlled, and multi-centre study to evaluate the safety, tolerability, and immunogenicity of the SARS-CoV-2 vaccine candidate MVC-COV1901. The study comprised 3,844 participants of ≥ 20 years who were generally healthy or with stable pre-existing medical conditions. The study participants were randomly assigned in a 6:1 ratio to receive either MVC-COV1901 containing 15 μg of S-2P protein or placebo containing saline. Participants received two doses of MVC-COV1901 or placebo, administered 28 days apart via intramuscular injection. The primary outcomes were to evaluate the safety, tolerability, and immunogenicity of MVC-COV1901 from Day 1 (the day of first vaccination) to Day 57 (28 days after the second dose). Immunogenicity of MVC-COV1901 was assessed through geometric mean titres (GMT) and seroconversion rates (SCR) of neutralising antibody and antigen-specific immunoglobulin. This clinical trial is registered at ClinicalTrials.gov: NCT04695652. Findings: From the start of this phase 2 trial to the time of interim analysis, no vaccine-related Serious Adverse Events (SAEs) were recorded. The most common solicited adverse events across all study participants were pain at the injection site (64%), and malaise/fatigue (35%). Fever was rarely reported (<1%). For all participants in the MVC-COV1901 group, at 28 days after the second dose against wild type SARS-CoV-2 virus, the GMT was 662·3 (408 IU/mL), the GMT ratio was 163·2, and the seroconversion rate was 99·8%. Interpretation: MVC-COV1901 shows good safety profiles and promising immunogenicity responses. The current data supports MVC-COV1901 to enter phase 3 efficacy trials and could enable regulatory considerations for Emergency Use Authorisation (EUA). Funding: Medigen Vaccine Biologics Corporation and Taiwan Centres for Disease Control.
    • Sampling bias and incorrect rooting make phylogenetic network tracing of SARS-COV-2 infections unreliable

      Mavian, Carla; Pond, Sergei; Marini, Simone; Magalis, Brittany Rife; Vandamme, Anne-Mieke; Dellicour, Simon; Scarpino, Samuel V.; Houldcroft, Charlotte; Villabona-Arenas, Julian; Paisie, Taylor K.; Trovão, Nídia S.; Boucher, Christina; Zhang, Yun; Scheuermann, Richard H.; Gascuel, Olivier; Lam, Tommy Tsan-Yuk; Suchard, Marc A.; Abecasis, Ana; Wilkinson, Eduan; de Oliveira, Tulio; Bento, Ana I.; Schmidt, Heiko A.; Martin, Darren; Hadfield, James; Faria, Nuno; Grubaugh, Nathan D.; Neher, Richard A.; Baele, Guy; Lemey, Philippe; Stadler, Tanja; Albert, Jan; Crandall, Keith A.; Leitner, Thomas; Stamatakis, Alexandros; Prosperi, Mattia; Salemi, Marco; 0000-0003-4817-4029 (2020-05-07)
    • SARS-CoV-2 antibody prevalence in Sierra Leone, March 2021: a cross-sectional, nationally representative, age-stratified serosurvey

      Barrie, Mohamed Bailor; Lakoh, Sulaiman; Kelly, J. Daniel; Kanu, Joseph Sam; Squire, James; Koroma, Zikan; Bah, Silleh; Sankoh, Osman; Brima, Abdulai; Ansumana, Rashid; Goldberg, Sarah A.; Chitre, Smit; Osuagwu, Chidinma; Maeda, Justin; Barekye, Bernard; Numbere, Tamuno-Wari; Abdulaziz, Mohammed; Mounts, Anthony; Blanton, Curtis; Singh, Tushar; Samai, Mohamed; Vandi, Mohamed A.; Richardson, Eugene T. (2021-07-05)
      Background: As of 26 March 2021, the Africa CDC had reported 4,159,055 cases of COVID-19 and 111,357 deaths among the 55 African Union Member States; however, no country has published a nationally representative serosurvey as of May 2021. Such data are vital for understanding the pandemic’s progression on the continent, evaluating containment measures, and policy planning. Methods: We conducted a cross-sectional, nationally representative, age-stratified serosurvey in Sierra Leone in March 2021 by randomly selecting 120 Enumeration Areas throughout the country and 10 randomly selected households in each of these. One to two persons per selected household were interviewed to collect information on socio-demographics, symptoms suggestive of COVID-19, exposure history to laboratory-confirmed COVID-19 cases, and history of COVID-19 illness. Capillary blood was collected by fingerstick, and blood samples were tested using the Hangzhou Biotest Biotech RightSign COVID-19 IgG/IgM Rapid Test Cassette. Total seroprevalence was was estimated after applying sampling weights. Findings: The overall weighted seroprevalence was 2.6% (95% CI 1.9-3.4). This is 43 times higher than the reported number of cases. Rural seropositivity was 1.8% (95% CI 1.0-2.5), and urban seropositivity was 4.2% (95% CI 2.6-5.7). Interpretation: Although overall seroprevalence was low compared to countries in Europe and the Americas (suggesting relatively successful containment in Sierra Leone), our findings indicate enormous underreporting of active cases. This has ramifications for the country’s third wave (which started in June 2021), where the average number of daily reported cases was 87 by the end of the month—this could potentially be on the order of 3,700 actual infections, calling for stronger containment measures in a country with only 0.2% of people fully vaccinated. It may also reflect significant underreporting of incidence and mortality across the continent. Funding: This study was supported by NIAID K08 AI139361, the Sierra Leone Ministry of Health and Sanitation, and the Africa CDC.
    • SARS-CoV-2 antibody prevalence in Sierra Leone, March 2021: a cross-sectional, nationally representative, age-stratified serosurvey

      Barrie, Mohamed Bailor; Lakoh, Sulaiman; Kelly, J. Daniel; Sam Kanu, Joseph; Squire, James Sylvester; Koroma, Zikan; Bah, Silleh; Sankoh, Osman; Brima, Abdulai; Ansumana, Rashid; Goldberg, Sarah A.; Chitre, Smit; Osuagwu, Chidinma; Frankfurter, Raphael; Maeda, Justin; Barekye, Bernard; Numbere, Tamuno-Wari; Abdulaziz, Mohammed; Mounts, Anthony; Blanton, Curtis; Singh, Tushar; Samai, Mohamed; Vandi, Mohamed; Richardson, Eugene T. (2021-11-11)
      Introduction: As of 26 March 2021, the Africa Centres for Disease Control and Prevention had reported 4 159 055 cases of COVID-19 and 111 357 deaths among the 55 African Union member states; however, no country has published a nationally representative serosurvey as of October 2021. Such data are vital for understanding the pandemic’s progression on the continent, evaluating containment measures, and policy planning. Methods: We conducted a cross-sectional, nationally representative, age-stratified serosurvey in Sierra Leone in March 2021 by randomly selecting 120 Enumeration Areas throughout the country and 10 randomly selected households in each of these. One to two persons per selected household were interviewed to collect information on sociodemographics, symptoms suggestive of COVID-19, exposure history to laboratory-confirmed COVID-19 cases, and history of COVID-19 illness. Capillary blood was collected by fingerstick, and blood samples were tested using the Hangzhou Biotest Biotech RightSign COVID-19 IgG/IgM Rapid Test Cassette. Total seroprevalence was estimated after applying sampling weights. Results: The overall weighted seroprevalence was 2.6% (95% CI 1.9% to 3.4%). This was 43 times higher than the reported number of cases. Rural seropositivity was 1.8% (95% CI 1.0% to 2.5%), and urban seropositivity was 4.2% (95% CI 2.6% to 5.7%). Discussion: Overall seroprevalence was low compared with countries in Europe and the Americas (suggesting relatively successful containment in Sierra Leone). This has ramifications for the country’s third wave (which started in June 2021), during which the average number of daily reported cases was 87 by the end of the month:this could potentially be on the order of 3700 actual infections per day, calling for stronger containment measures in a country with only 0.2% of people fully vaccinated. It may also reflect significant under-reporting of incidence and mortality across the continent.
    • SARS-CoV-2 BNT162b2 vaccine–induced humoral response and reactogenicity in individuals with prior COVID-19 disease

      Kelsen, Steven G.; Braverman, Alan S.; Aksoy, Mark O.; Hayman, Jacob A.; Patel, Puja S.; Rajput, Charu; Zhao, Huaqing; Fisher, Susan G.; Ruggieri, Michael; GENTILE, NINA; Zhao|0000-0002-0953-4768; Ruggieri Sr.|0000-0003-3052-3630; Gentile|0000-0002-1222-5966 (2022-01-12)
      BACKGROUND. Most individuals with prior COVID-19 disease manifest long-term protective immune responses against reinfection. Accordingly, we tested the hypothesis that humoral immune and reactogenicity responses to a SARS-CoV-2 mRNA vaccine differ in individuals with and without prior COVID-19 disease. METHODS. Health care workers (n = 61) with (n = 30) and without (n = 31) prior COVID-19 disease received two 30 μg doses of Pfizer BNT162b2 vaccine 3 weeks apart. Serum IgG antibody against the spike receptor-binding domain; serum neutralizing activity; and vaccine reactogenicity were assessed longitudinally every 2 weeks for 56 days after the first injection. RESULTS. The COVID-19 group manifested more rapid increases in spike IgG antibody and serum neutralizing activity after the first vaccine dose but showed little or no increase after the second dose compared with the infection-naive group. In fact, spike IgG was at its maximum level after the first dose in 36% of the COVID-19 group versus 0% of the infection-naive group. Peak IgG antibody levels were lower but appeared to fall more slowly in the COVID-19 group versus the infection-naive group. Finally, adverse systemic reactions, e.g., fever, headache, and malaise, were more frequent and lasted longer after both the first and second injection in the COVID-19 group than in the infection-naive group. CONCLUSION. Individuals with prior COVID-19 disease demonstrate a robust, accelerated humoral immune response to the first dose but an attenuated response to the second dose of BNT162b2 vaccine compared with controls. The COVID-19 group also experienced greater reactogenicity. Humoral responses and reactogenicity to BNT162b2 differ qualitatively and quantitatively in individuals with prior COVID-19 disease compared with infection-naive individuals. FUNDING. This work was supported by Temple University institutional funds.