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Rxivist combines biology preprints from bioRxiv and medRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 140,607 papers from 597,880 authors.

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1: Evidence for increased breakthrough rates of SARS-CoV-2 variants of concern in BNT162b2 mRNA vaccinated individuals
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Posted 09 Apr 2021

Evidence for increased breakthrough rates of SARS-CoV-2 variants of concern in BNT162b2 mRNA vaccinated individuals
46,537 downloads medRxiv epidemiology

Talia Kustin, Noam Harel, Uriah Finkel, Shay Perchik, Sheri Harari, Maayan Tahor, Itamar Caspi, Rachel Levy, Michael Leschinsky, Shifra Ken Dror, Galit Bergerzon, Hala Gadban, Faten Gadban, Eti Eliassian, Orit Shimron, Loulou Saleh, Haim Ben-Zvi, Doron Amichay, Anat Ben-Dor, Dana Sagas, Merav Strauss, Yonat Shemer Avni, Amit Huppert, Eldad Kepten, Ran D. Balicer, Doron Nezer, Shay Ben-Shachar, Adi Stern

The SARS-CoV-2 pandemic has been raging for over a year, creating global detrimental impact. The BNT162b2 mRNA vaccine has demonstrated high protection levels, yet apprehension exists that several variants of concerns (VOCs) can surmount the immune defenses generated by the vaccines. Neutralization assays have revealed some reduction in neutralization of VOCs B.1.1.7 and B.1.351, but the relevance of these assays in real life remains unclear. Here, we performed a case-control study that examined whether BNT162b2 vaccinees with documented SARS-CoV-2 infection were more likely to become infected with B.1.1.7 or B.1.351 compared with unvaccinated individuals. Vaccinees infected at least a week after the second dose were disproportionally infected with B.1.351 (odds ratio of 8:1). Those infected between two weeks after the first dose and one week after the second dose, were disproportionally infected by B.1.1.7 (odds ratio of 26:10), suggesting reduced vaccine effectiveness against both VOCs under different dosage/timing conditions. Nevertheless, the B.1.351 incidence in Israel to-date remains low and vaccine effectiveness remains high against B.1.1.7, among those fully vaccinated. These results overall suggest that vaccine breakthrough infection is more frequent with both VOCs, yet a combination of mass-vaccination with two doses coupled with non-pharmaceutical interventions control and contain their spread.

2: Dynamics of ORF1ab and N Gene among hospitalized COVID-19 positive cohorts: A hospital based retrospective study
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Posted 23 Nov 2020

Dynamics of ORF1ab and N Gene among hospitalized COVID-19 positive cohorts: A hospital based retrospective study
25,877 downloads medRxiv infectious diseases

Pojul Loying, Vaishali Sarma, Suranjana C. Hazarika, Monjuri Kataki, Dina Raja, Divyashree Medhi, Ridip Dutta, Achu Chena, Divya Daimary, Aakangkhita Choudhury, Lahari Saikia

1.ObjectiveThe present study hospital based retrospective study aimed at investigating the dynamics of ORF1ab and N gene from hospitalized COVID-19 positive cohorts considering the Ct values of both genes. Study design and MethodologyRetrospective analyses of Ct values were done from 115 hospitalized COVID-19 positive patients in different time interval. Patients were admitted to the hospital either by RAT or/and RT-PCR and first RT-PCR testing were made after 9 days of incubation followed by testing in every 3 days of interval till negative, subsequently release of the patients. ResultsWe have looked into the dynamics of ORF1ab and N gene and found that N gene require longer duration of days with 12.68 (S.D.{+/-}3.24) to become negative than ORF1ab with 12.09 (S.D.{+/-}2.88) days and it differs significantly (p=0.012; p<0.05). The persistent of N gene found in 46 patients out of 115 (39.65%) to the succeeding reading after 3 days. We have also looked into the mean differences in the between N and ORF1ab genes every readings separately and found that there were no significant differences between the mean Ct value of ORF1ab and N gene except in the day 3 (p=0.015; p<0.05). Further, we have looked into the relationship of age and gender of patients with the duration of positivity; however we did not find any significant role. ConclusionIn COVID-19 hospital positive cohorts, the persistent of positivity of N gene is significantly for more duration than ORF1ab. As the SARS-CoV-2 is a new virus and study on it is evolving, so, exhaustive study is required on the dynamic of N gene positivity persistent in relation to the other pathophysiological parameters for the management and control of COVID-19.

3: SARS-CoV-2 RNA reverse-transcribed and integrated into the human genome
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Posted 13 Dec 2020

SARS-CoV-2 RNA reverse-transcribed and integrated into the human genome
23,966 downloads bioRxiv genomics

Liguo Zhang, Alexsia Richards, Andrew Khalil, Emile Wogram, Haiting Ma, Richard A. Young, Rudolf Jaenisch

Prolonged SARS-CoV-2 RNA shedding and recurrence of PCR-positive tests have been widely reported in patients after recovery, yet these patients most commonly are non-infectious. Here we investigated the possibility that SARS-CoV-2 RNAs can be reverse-transcribed and integrated into the human genome and that transcription of the integrated sequences might account for PCR-positive tests. In support of this hypothesis, we found chimeric transcripts consisting of viral fused to cellular sequences in published data sets of SARS-CoV-2 infected cultured cells and primary cells of patients, consistent with the transcription of viral sequences integrated into the genome. To experimentally corroborate the possibility of viral retro-integration, we describe evidence that SARS-CoV-2 RNAs can be reverse transcribed in human cells by reverse transcriptase (RT) from LINE-1 elements or by HIV-1 RT, and that these DNA sequences can be integrated into the cell genome and subsequently be transcribed. Human endogenous LINE-1 expression was induced upon SARS-CoV-2 infection or by cytokine exposure in cultured cells, suggesting a molecular mechanism for SARS-CoV-2 retro-integration in patients. This novel feature of SARS-CoV-2 infection may explain why patients can continue to produce viral RNA after recovery and suggests a new aspect of RNA virus replication.

4: Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees
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Posted 23 Apr 2021

Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees
23,476 downloads bioRxiv immunology

Pragya Yadav, Gajanan N Sapkal, Priya Abraham, Raches Ella, Gururaj Deshpande, Deepak Y Patil, Dimpal Nyayanit, Nivedita Gupta, Rima R Sahay, Anita M Shete, Samiran Panda, Balram Bhargava, V Krishna Mohan

The drastic rise in the number of cases in Maharashtra, India has created a matter of concern for public health experts. Twelve isolates of VUI lineage B.1.617 were propagated in VeroCCL81 cells and characterized. Convalescent sera of the COVID-19 cases and recipients of BBV152 (Covaxin) were able to neutralize VUI B.1.617.

5: Effectiveness of CoronaVac in the setting of high SARS-CoV-2 P.1 variant transmission in Brazil: A test-negative case-control study
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Posted 07 Apr 2021

Effectiveness of CoronaVac in the setting of high SARS-CoV-2 P.1 variant transmission in Brazil: A test-negative case-control study
22,013 downloads medRxiv infectious diseases

Matt Hitchings, Otavio T. Ranzani, Mario S.S. Torres, Silvano Barbosa de Oliveira, Maria Almiron, Rodrigo Said, Ryan Borg, Wade L Schulz, Roberto Dias de Oliveira, Patricia Vieira da Silva, Daniel Barros de Castro, Vanderson de Souza Sampaio, Bernardino Cláudio de Albuquerque, Tatyana Costa Amorim Ramos, Shadia Hussami Hauache Fraxe, Cristiano Fernandes da Costa, Felipe Gomes Naveca, André M. Siqueira, Wildo Navegantes de Araújo, Jason R. Andrews, Derek A.T. Cummings, Albert I. Ko, Julio Croda

Objectives To estimate the effectiveness of the CoronaVac COVID-19 vaccine in a setting of SARS-CoV-2 P.1 variant transmission. Design Matched test-negative case-control study to estimate the effectiveness of an inactivated vaccine, CoronaVac, with an early analysis of effectiveness following administration at least one vaccine dose and an analysis of effectiveness following administration of the complete two dose schedule. Setting Cohort of healthcare workers (HCWs) in Manaus, where P.1 accounted for 75% of genotyped SARS-CoV-2 samples at the peak of its epidemic. Participants For the early at-least-one-dose analysis, 53,176 HCWs residing in Manaus and aged 18 years or older, with complete information on age, residence, and vaccination status. For the two-dose analysis, 53,153 HCWs residing in Manaus and aged 18 years or older, with complete information on age, residence, and vaccination status. Main outcome measures The primary outcome was symptomatic SARS-CoV-2 infection. Results Among 53,153 HCWs eligible for the two-dose analysis, 47,170 (89%) received at least one dose of CoronaVac and 2,656 individuals (5%) underwent RT-PCR testing from 19 January, 2021 to 13 April, 2021. Of 3,195 RT-PCR tests, 885 (28%) were positive. 393 and 418 case-control pairs were selected for the early and two-dose analyses, respectively, matched on calendar time, age, and neighbourhood. In the early analysis, vaccination with at least one dose was associated with a 0.50-fold reduction (adjusted vaccine effectiveness, 49.6%, 95% CI 11.3 to 71.4) in the odds of symptomatic SARS-CoV-2 infection during the period 14 days or more after receiving the first dose. However, we estimated low effectiveness (adjusted VE 36.8%, 95% CI -54.9 to 74.2) of the two-dose schedule against symptomatic SARS-CoV-2 infection during the period 14 days or more after receiving the second dose. A finding that vaccinated individuals were much more likely to be infected than unvaccinated individuals in the period 0-13 days after first vaccination (aOR 2.11, 95% CI 1.36-3.27) suggests that among this population of healthcare workers, those at higher risk might take up vaccine earlier, leading to underestimation of its effectiveness. Conclusions Evidence from this test-negative study of the effectiveness of CoronaVac was mixed, and likely affected by bias in this setting. Administration of at least one vaccine dose showed effectiveness against symptomatic SARS-CoV-2 infection in the setting of epidemic P.1 transmission. However, the low estimated effectiveness of the two-dose schedule underscores the need to maintain non-pharmaceutical interventions while vaccination campaigns with CoronaVac are being implemented.

6: Epidemiological description and analysis of RdRp, E and N genes dynamic by RT-PCR of SARS-CoV-2 in Moroccan population: Experience of the National Reference Laboratory (LNR)-UM6SS
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Posted 20 Jun 2020

Epidemiological description and analysis of RdRp, E and N genes dynamic by RT-PCR of SARS-CoV-2 in Moroccan population: Experience of the National Reference Laboratory (LNR)-UM6SS
21,946 downloads medRxiv infectious diseases

Houda Benrahma, Idrissa Diawara, Imane Smyej, Jalila Rahoui, Nida Meskaouni, Rachid Benmessaoud, Khadija Arouro, Khadija Jaras, Zahra Adam, Salma Nahir, Zineb Aouzal, Hajar Elguazzar, Leila Jeddane, Fadwa Ousti, Jalila Elbakkouri, Chakib Nejjari

The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a new infectious disease that first emerged in Hubei province, China, in December 2019. On 2 March 2020, the Moroccan Ministry of Health confirmed the first COVID-19 case in Morocco. The new virus SARS-CoV-2 was identified in the sample of a Moroccan expatriate residing in Italy. Without a therapeutic vaccine or specific antiviral drugs, early detection and isolation become essential against novel Coronavirus. This study aims to analyze the epidemiological profile of the SARS-CoV-2 in Moroccan cases and to investigate the dynamic of RdRp gene, N gene, and E gene in patients from diagnosis until the recovery. Among 859 Covid-19 RT-PCR tests realized for 285 patients, 133 cases had positive results Covid-19. 9 % of these cases present the 3 genes RdRp, N, and E, 47% only the RdRp gene, 2% with RdRp and N gene, 26% cases are positives with N gene, and 16 % with N and E gene. The analysis of the Covid-19 genes (RdRp, N, and E) dynamic reveal that more than 6% stay positive with detection of the N and E gene, and 14% with the N gene after 12 days of treatment. The median period from positive to the first negative Covid-19 RT-PCR tests was 6.8{+/-}2.24 days for 44% cases, 14.31 {+/-} 2.4 days for 30%, and 22.67 {+/-} 1.21 days for 4%. This a first description of the Moroccan COVID-19 cases and the analysis of the dynamic of the 3 genes RdRp, N, and E. The analysis of our population can help to involved in the care of patients.

7: Understanding the effectiveness of government interventions in Europe's second wave of COVID-19
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Posted 26 Mar 2021

Understanding the effectiveness of government interventions in Europe's second wave of COVID-19
21,562 downloads medRxiv epidemiology

Mrinank Sharma, Sören Mindermann, Charlie Rogers-Smith, Gavin Leech, Benedict Snodin, Janvi Ahuja, Jonas B. Sandbrink, Joshua Teperowski Monrad, George Altman, Gurpreet Dhaliwal, Lukas Finnveden, Alexander John Norman, Sebastian B. Oehm, Julia Fabienne Sandkühler, Thomas Mellan, Jan Kulveit, Leonid Chindelevitch, Seth Flaxman, Yarin Gal, Swapnil Mishra, Jan Markus Brauner, Samir Bhatt

As European governments face resurging waves of COVID-19, non-pharmaceutical interventions (NPIs) continue to be the primary tool for infection control. However, updated estimates of their relative effectiveness have been absent for Europe's second wave, largely due to a lack of collated data that considers the increased subnational variation and diversity of NPIs. We collect the largest dataset of NPI implementation dates in Europe, spanning 114 subnational areas in 7 countries, with a systematic categorisation of interventions tailored to the second wave. Using a hierarchical Bayesian transmission model, we estimate the effectiveness of 17 NPIs from local case and death data. We manually validate the data, address limitations in modelling from previous studies, and extensively test the robustness of our estimates. The combined effect of all NPIs was smaller relative to estimates from the first half of 2020, indicating the strong influence of safety measures and individual protective behaviours--such as distancing--that persisted after the first wave. Closing specific businesses was highly effective. Gathering restrictions were highly effective but only for the strictest limits. We find smaller effects for closing educational institutions compared to the first wave, suggesting that safer operation of schools was possible with a set of stringent safety measures including testing and tracing, preventing mixing, and smaller classes. These results underscore that effectiveness estimates from the early stage of an epidemic are measured relative to pre-pandemic behaviour. Updated estimates are required to inform policy in an ongoing pandemic.

8: Robust spike antibody responses and increased reactogenicity in seropositive individuals after a single dose of SARS-CoV-2 mRNA vaccine
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Posted 01 Feb 2021

Robust spike antibody responses and increased reactogenicity in seropositive individuals after a single dose of SARS-CoV-2 mRNA vaccine
19,150 downloads medRxiv allergy and immunology

Florian Krammer, Komal Srivastava, PARIS team, Viviana Simon

As COVID-19 vaccines are getting rolled out, an important question is arising: Should individuals who already had a SARS-CoV-2 infection receive one or two shots of the currently authorized mRNA vaccines. In this short report, we are providing evidence that the antibody response to the first vaccine dose in individuals with pre-existing immunity is equal to or even exceeds the titers found in naive individuals after the second dose. We also show that the reactogenicity is significantly higher in individuals who already have been infected with SARS-CoV-2 in the past. Changing the policy to give these individuals only one dose of vaccine would not negatively impact on their antibody titers, spare them from unnecessary pain and free up many urgently needed vaccine doses.

9: SARS-CoV-2 Spike Protein Impairs Endothelial Function via Downregulation of ACE2
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Posted 04 Dec 2020

SARS-CoV-2 Spike Protein Impairs Endothelial Function via Downregulation of ACE2
18,194 downloads bioRxiv pathology

Yuyang Lei, Jiao Zhang, Cara R. Schiavon, Ming He, Lili Chen, Hui Shen, Yichi Zhang, Qian Yin, Yoshitake Cho, Leonardo Andrade, Gerry S. Shadel, Mark Hepokoski, Ting Lei, Hongliang Wang, Jin Zhang, Jason X.-J. Yuan, Atul Malhotra, Uri Manor, Shengpeng Wang, Zu-Yi Yuan, John Y-J. Shyy

Coronavirus disease 2019 (COVID-19) includes the cardiovascular complications in addition to respiratory disease. SARS-CoV-2 infection impairs endothelial function and induces vascular inflammation, leading to endotheliitis. SARS-CoV-2 infection relies on the binding of Spike glycoprotein (S protein) to angiotensin converting enzyme 2 (ACE2) in the host cells. We show here that S protein alone can damage vascular endothelial cells (ECs) in vitro and in vivo, manifested by impaired mitochondrial function, decreased ACE2 expression and eNOS activity, and increased glycolysis. The underlying mechanism involves S protein downregulation of AMPK and upregulation of MDM2, causing ACE2 destabilization. Thus, the S protein-exerted vascular endothelial damage via ACE2 downregulation overrides the decreased virus infectivity.

10: #AstraZeneca vaccine disinformation on Twitter
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Posted 16 Apr 2021

#AstraZeneca vaccine disinformation on Twitter
18,014 downloads medRxiv health informatics

Dariusz Jemielniak, Yaroslav Krempovych

We analyzed 50,080 tweets about #AstraZeneca in English from 2021. We found that the news most common in the frequently retweeted tweets abound in negative information, and in many cases come from media sources well-known for disinformation. Also, we found that RT, a Russian state-sponsored news website, as well as Al Arabiya, a Saudi-owned news website, are frequently retweeted with information about the vaccine. Our analysis identified large coordination networks involved in political astroturfing and vaccine diplomacy in South Asia but also vaccine advocacy networks associated with European Commission employees. Our results show that Twitter discourse about #AstraZeneca is filled with disinformation and bad press, and may be distributed not only organically by anti-vaxxer activists, but also systematically by professional sources.

11: Decreased SARS-CoV-2 viral load following vaccination
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Posted 08 Feb 2021

Decreased SARS-CoV-2 viral load following vaccination
15,728 downloads medRxiv infectious diseases

Matan Levine-Tiefenbrun, Idan Yelin, Rachel Katz, Esma Herzel, Ziv Golan, Licita Schreiber, Tamar Wolf, Varda Nadler, Amir Ben-Tov, Jacob Kuint, Sivan Gazit, Tal Patalon, Gabriel Chodick, Roy Kishony

Beyond their substantial protection of individual vaccinees, it is hoped that the COVID-19 vaccines would reduce viral load in breakthrough infections thereby further suppress onward transmission. Here, analyzing positive SARS-CoV-2 test results following inoculation with the BNT162b2 mRNA vaccine, we find that the viral load is reduced 4-fold for infections occurring 12-28 days after the first dose of vaccine. These reduced viral loads hint to lower infectiousness, further contributing to vaccine impact on virus spread.

12: Correlation between Chest CT Severity Scores and the Clinical Parameters of Adult Patients with COVID-19 pneumonia
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Posted 20 Oct 2020

Correlation between Chest CT Severity Scores and the Clinical Parameters of Adult Patients with COVID-19 pneumonia
13,280 downloads medRxiv radiology and imaging

Ghufran Aref Saeed, Waqar Gaba, Asad Shah, Abeer Ahmed Al Helali, Emadullah Raidullah, Ameirah Bader Al Ali, Mohammed Elghazali, Deena Yousef Ahmed, Shaikha Ghanam Al Kaabi, Safaa Almazrouei

PurposeOur aim is to correlate the clinical condition of patients with COVID-19 infection with the 25 Point CT severity score by Chang et al (devised for assessment of ARDS in patients with SARS in 2005). Material and MethodsData of consecutive symptomatic patients who were suspected to have COVID-19 infection and presented to our hospital, was collected from March to April 2020. All patients underwent two consecutive RT-PCR tests and had a non-contrast HRCT scan done at presentation. From the original cohort of 1062 patients, 160 patients were excluded leaving a total number of 902 patients. ResultsThe mean age was 44.2 {+/-}11.9 years [85.3%males, 14.7%females]. CT severity score found to be positively correlated with lymphopenia, increased serum CRP, d-dimer and ferritin levels (p < 0.0001). The oxygen requirements as well as length of hospital stay were increasing with the increase of scan severity. ConclusionThe 25-point CT severity score correlates well with the COVID-19 clinical severity. Our data suggest that chest CT scoring system can aid in predicting COVID-19 disease outcome and significantly correlates with lab tests and oxygen requirements.

13: Features of C-reactive protein in COVID-19 patients with different ages, clinical types and outcomes: a cohort study
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Posted 31 Oct 2020

Features of C-reactive protein in COVID-19 patients with different ages, clinical types and outcomes: a cohort study
13,107 downloads medRxiv infectious diseases

Gaojing Qu, Guoxin Huang, Meiling Zhang, Hui Yu, Xiaoming Song, Haoming Zhu, Lei Chen, Yunfu Wang, Bin Pei

BackgroundTo characterize C-reactive protein (CRP) changes features from patients with coronavirus disease 2019 (COVID-19) and to quantify the correlation between CRP value and clinical classification. MethodsThis was a bidirectional observational cohort study. All laboratory confirmed COVID-19 patients hospitalized in Xiangyang No.1 Peoples Hospital were included. Patients general information, clinical type, CRP value and outcome were collected. Patients were grouped according to the age, clinical type and outcome, and their CRP were compared. The CRP value, age gender, and clinical type were used to build a categorical regression model to investigate the association between CRP and clinical type. ResultsThe 131 patients aged 50.13{+/-}17.13 years old. There were 4 mild, 88 moderate, 21 severe and 18 critical cases. Statistical significance of CRP median exists between different clinical types and ages. There were 10 deaths and 121 cases have been discharged. The CRP in death group dramatically increased continuously until died, while increased firstly and decreased later in the survivor and survivor in critical type. The categorical regression model also showed that CRP and age had significant coefficient. During the first 15 days from symptom onset, the maximum of CRP ranged between 0.47-53.37 mg/L were related to mild combined with moderate type, ranged 53.84-107.08 mg/L were related to severe type, and 107.42-150.00 mg/L were related to the critical type. ConclusionsCRP showed different distribution feature and existed differences in various ages, clinical types and outcomes of COVID-19 patients. The features corresponded with disease progression.

14: More than 50 Long-term effects of COVID-19: a systematic review and meta-analysis
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Posted 29 Jan 2021

More than 50 Long-term effects of COVID-19: a systematic review and meta-analysis
12,535 downloads medRxiv infectious diseases

Sandra Lopez-Leon, Talia Wegman-Ostrosky, Carol Perelman, Rosalinda Sepulveda, Paulina A Rebolledo, Angelica Cuapio, Sonia Villapol

COVID-19, caused by SARS-CoV-2, can involve sequelae and other medical complications that last weeks to months after initial recovery, which has come to be called Long-COVID or COVID long-haulers. This systematic review and meta-analysis aims to identify studies assessing long-term effects of COVID-19 and estimates the prevalence of each symptom, sign, or laboratory parameter of patients at a post-COVID-19 stage. LitCOVID (PubMed and Medline) and Embase were searched by two independent researchers. All articles with original data for detecting long-term COVID-19 published before 1st of January 2021 and with a minimum of 100 patients were included. For effects reported in two or more studies, meta-analyses using a random-effects model were performed using the MetaXL software to estimate the pooled prevalence with 95% CI. Heterogeneity was assessed using I2 statistics. The Preferred Reporting Items for Systematic Reviewers and Meta-analysis (PRISMA) reporting guideline was followed. A total of 18,251 publications were identified, of which 15 met the inclusion criteria. The prevalence of 55 long-term effects was estimated, 21 meta-analyses were performed, and 47,910 patients were included. The follow-up time ranged from 15 to 110 days post-viral infection. The age of the study participants ranged between 17 and 87 years. It was estimated that 80% (95% CI 65-92) of the patients that were infected with SARS-CoV-2 developed one or more long-term symptoms. The five most common symptoms were fatigue (58%), headache (44%), attention disorder (27%), hair loss (25%), and dyspnea (24%). All meta-analyses showed medium (n=2) to high heterogeneity (n=13). In order to have a better understanding, future studies need to stratify by sex, age, previous comorbidities, severity of COVID-19 (ranging from asymptomatic to severe), and duration of each symptom. From the clinical perspective, multi-disciplinary teams are crucial to developing preventive measures, rehabilitation techniques, and clinical management strategies with whole-patient perspectives designed to address long COVID-19 care.

15: Viral cultures for COVID-19 infectivity assessment. Systematic review
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Posted 04 Aug 2020

Viral cultures for COVID-19 infectivity assessment. Systematic review
11,213 downloads medRxiv epidemiology

Tom Jefferson, Elizabeth Spencer, Jon Brassey, Carl Heneghan

Objective To review the evidence from studies comparing SARS-CoV-2 culture, with the results of reverse transcriptase polymerase chain reaction (RT-PCR). Methods We searched LitCovid, medRxiv, Google Scholar and the WHO Covid-19 database for Covid-19 using the terms viral culture or viral replication and associated synonyms up to 10 September 2020. We carried out citation matching and included studies reporting attempts to culture or observe SARS-CoV-2 matching with cutoffs for RT-PCR positivity. One reviewer extracted data for each study and a second reviewer checked end edited the extraction and summarised the narratively by sample: fecal, respiratory, environment, blood or mixed. Where necessary we wrote to corresponding authors of the included or background papers for additional information. We assessed quality using a modified QUADAS 2 risk of bias tool. This is the fourth version of this review that was first published on the 4th of August and updated on the 21t of August, on the 3rd and 10th of September. Results We included 29 studies reporting culturing or observing tissue invasion by SARS-CoV in sputum, naso or oropharyngeal, urine, stool, blood and environmental samples from patients diagnosed with Covid-19. The data are suggestive of a relation between the time from collection of a specimen to test, cycle threshold and symptom severity. The quality of the studies was moderate with lack of standardised reporting. Twelve studies reported that Ct values were significantly lower and log copies higher in samples producing live virus culture. Five studies reported no growth in samples based on a Ct cut-off value. These values ranged from CT > 24 for no growth to Ct > 34 or more. Two studies report a strong relationship between Ct value and ability to recover infectious virus and that the odds of live virus culture reduced by 33% for every one unit increase in Ct. A cut-off RT-PCR Ct > 30 was associated with non-infectious samples. One study that analysed the NSP, N and E gene fragments of the PCR result reported different cut-off thresholds depending on the gene fragment analysed. The duration of RNA shedding detected by PCR was far longer compared to detection of live culture. Six out of eight studies reported RNA shedding for longer than 14 days. Yet, infectivity declines after day 8 even among cases with ongoing high viral loads. A very small proportion of people re-testing positive after hospital discharge or with high Ct are likely to be infectious. Conclusion Prospective routine testing of reference and culture specimens are necessary for each country involved in the pandemic to establish the usefulness and reliability of PCR for Covid-19 and its relation to patient factors. Infectivity is related to the date of onset of symptoms and cycle threshold level. A binary Yes / No approach to the interpretation RT-PCR unvalidated against viral culture will result in false positives with possible segregation of large numbers of people who are no longer infectious and hence not a threat to public health.

16: Barriers to online learning in the time of COVID-19: A national survey of medical students in the Philippines
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Posted 18 Jul 2020

Barriers to online learning in the time of COVID-19: A national survey of medical students in the Philippines
11,167 downloads medRxiv medical education

Ronnie E Baticulon, Nicole Rose I Alberto, Maria Beatriz C Baron, Robert Earl C Mabulay, Lloyd Gabriel T Rizada, Jinno Jenkin Sy, Christl Jan S Tiu, Charlie A Clarion, John Carlo B Reyes

INTRODUCTION: In March 2020, the coronavirus disease 2019 (COVID-19) pandemic forced medical schools in the Philippines to stop face-to-face learning activities and abruptly shift to an online curriculum. This study aimed to identify barriers to online learning from the perspective of medical students in a developing country. METHOD: The authors sent out an electronic survey to medical students in the Philippines from 11 to 24 May 2020. Using a combination of multiple choice, Likert scale, and open-ended questions, the following data were obtained: demographics, medical school information, access to technological resources, study habits, living conditions, self-assessment of capacity for and perceived barriers to online learning, and proposed interventions. Descriptive statistics were calculated. Responses were compared between student subgroups using nonparametric tests. RESULTS: Among 3,670 medical students, 3,421 (93%) owned a smartphone and 3,043 (83%) had a laptop or desktop computer. To access online resources, 2,916 (79%) had a postpaid internet subscription while 696 (19%) used prepaid mobile data. Under prevailing conditions, only 1,505 students (41%) considered themselves physically and mentally capable of engaging in online learning. Barriers were classified under five categories: technological, individual, domestic, institutional, and community barriers. Most frequently encountered were difficulty adjusting learning styles, having to perform responsibilities at home, and poor communication between educators and learners. CONCLUSION: Medical students in the Philippines confronted several interrelated barriers as they tried to adapt to online learning. By implementing student-centered interventions, medical schools and educators play a significant role in addressing these challenges during the COVID-19 pandemic and beyond.

17: The impact of SARS-CoV-2 vaccines on antibody responses in the general population in the United Kingdom
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Posted 23 Apr 2021

The impact of SARS-CoV-2 vaccines on antibody responses in the general population in the United Kingdom
11,148 downloads medRxiv infectious diseases

Jia Wei, Nicole Stoesser, Philippa C Matthews, Ruth Studley, Iain Bell, John I Bell, John N Newton, Jeremy Farrar, Ian Diamond, Emma Rourke, Alison Howarth, Brian D Marsden, Sarah Hoosdally, E. Yvonne Jones, David I. Stuart, Derrick W Crook, Tim EA Peto, Koen B Pouwels, David W Eyre, A Sarah Walker, COVID-19 Infection Survey team

Real-world data on antibody response post-vaccination in the general population are limited. 45,965 adults in the UK's national COVID-19 Infection Survey receiving Pfizer-BioNTech or Oxford-AstraZeneca vaccines had 111,360 anti-spike IgG measurements. Without prior infection, seroconversion rates and quantitative antibody levels post single dose were lower in older individuals, especially >60y. Two doses achieved high responses across all ages, particularly increasing seroconversion in older people, to similar levels to those achieved after prior infection followed by a single dose. Antibody levels rose more slowly and to lower levels with Oxford-AstraZeneca vs Pfizer-BioNTech, but waned following a single Pfizer-BioNTech dose. Latent class models identified four responder phenotypes: older people, males, and those having long-term health conditions were more commonly 'low responders'. Where supplies are limited, vaccines should be prioritised for those not previously infected, and second doses to individuals >60y. Further data on the relationship between vaccine-mediated protection and antibody responses are needed.

18: Who funded the research behind the Oxford-AstraZeneca COVID-19 vaccine? - Approximating the funding to the University of Oxford for the research and development of the ChAdOx vaccine technology
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Posted 10 Apr 2021

Who funded the research behind the Oxford-AstraZeneca COVID-19 vaccine? - Approximating the funding to the University of Oxford for the research and development of the ChAdOx vaccine technology
10,261 downloads medRxiv health policy

Samuel Cross, Yeanuk Rho, Henna Reddy, Toby Pepperrell, Florence Rodgers, Rhiannon Osborne, Ayolola Eni-Olotu, Rishi Banerjee, Sabrina Wimmer, Sarai Mirjam Keestra

Objectives: The Oxford-AstraZeneca COVID-19 vaccine (ChAdOx1 nCoV-19 or Vaxzevira) builds on nearly two decades of research and development (R&D) into Chimpanzee adenovirus-vectored vaccine (ChAdOx) technology at the University of Oxford. This study aims to approximate the funding for the R&D of the ChAdOx technology and the Oxford-AstraZeneca vaccine, and assess the transparency of funding reporting mechanisms. Design: We conducted a scoping review and publication history analysis of the principal investigators to reconstruct the funding for the R&D of the ChAdOx technology. We matched award numbers with publicly-accessible grant databases. We filed Freedom Of Information (FOI) requests to the University of Oxford for the disclosure of all grants for ChAdOx R&D. Results: We identified 100 peer-reviewed articles relevant to ChAdOx technology published between 01/2002 and 10/2020, extracting 577 mentions of funding bodies from funding acknowledgement statements. Government funders from overseas were mentioned 158 (27.4%), the U.K. government 147 (25.5%) and charitable funders 138 (23.9%) times. Grant award numbers were identified for 215 (37.3%) mentions, amounts were available in the public realm for 121 (21.0%) mentions. Based on the FOIs, until 01/2020, the European Commision (34.0%), Wellcome Trust (20.4%) and CEPI (17.5%) were the biggest funders of ChAdOx R&D. From 01/2020, the U.K. Department of Health and Social Care was the single largest funder (89.3%). The identified R&D funding was GBP104,226,076 reported in the FOIs, and GBP228,466,771 reconstructed from the literature search. Conclusions: Our study identified that public funding accounted for 97.1-99.0% of the funding towards the R&D of ChAdOx and the Oxford-AstraZeneca vaccine. We furthermore encountered a severe lack of transparency in research funding reporting mechanisms.

19: COVID-19 in India: State-wise Analysis and Prediction
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Posted 29 Apr 2020

COVID-19 in India: State-wise Analysis and Prediction
9,904 downloads medRxiv public and global health

Palash Ghosh, Rik Ghosh, Bibhas Chakraborty

Coronavirus disease 2019 (COVID-19), a highly infectious disease, was first detected in Wuhan, China, in December 2019. The disease has spread to 212 countries and territories around the world and infected (confirmed) more than three million people. In India, the disease was first detected on 30 January 2020 in Kerala in a student who returned from Wuhan. The total (cumulative) number of confirmed infected people is more than 37000 till now across India (3 May 2020). Most of the research and newspaper articles focus on the number of infected people in the entire country. However, given the size and diversity of India, it may be a good idea to look at the spread of the disease in each state separately, along with the entire country. For example, currently, Maharashtra has more than 10000 confirmed cumulative infected cases, whereas West Bengal has less than 800 confirmed infected cases (1 May 2020). The approaches to address the pandemic in the two states must be different due to limited resources. In this article, we will focus the infected people in each state (restricting to only those states with enough data for prediction) and build three growth models to predict infected people for that state in the next 30 days. The impact of preventive measures on daily infected-rate is discussed for each state.

20: Evaluation of antibody testing for SARS-Cov-2 using ELISA and lateral flow immunoassays
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Posted 20 Apr 2020

Evaluation of antibody testing for SARS-Cov-2 using ELISA and lateral flow immunoassays
9,838 downloads medRxiv infectious diseases

Emily R Adams, Mark Ainsworth, Rekha Anand, Monique I Andersson, Kathryn Auckland, J Kenneth Baillie, Eleanor Barnes, Sally Beer, John Bell, Tamsin Berry, Sagida Bibi, Miles Carroll, Senthil Chinnakannan, Elizabeth Clutterbuck, Richard J Cornall, Derrick Crook, Thushan De Silva, Wanwisa Dejnirattisai, Kate E. Dingle, Christina Dold, Alexis Espinosa, David W Eyre, Helen Farmer, Maria Fernandez Mendoza, Dominique Georgiou, Sarah J Hoosdally, Alistair Hunter, Katie Jeffrey, Paul Klenerman, Julian C Knight, Clarice Knowles, Andrew J Kwok, Ullrich Leuschner, Robert Levin, Chang Liu, Cesar Lopez-Camacho, Jose Carlos Martinez Garrido, Philippa C Matthews, Hannah McGivern, Alexander J Mentzer, Jonathan Milton, Juthathip Mongkolsapaya, Shona C. Moore, Marta S Oliveira, Fiona Pereira, Elena Perez Lopez, Timothy Peto, Rutger J Ploeg, Andrew Pollard, Tessa Prince, David J. Roberts, Justine K Rudkin, Veronica Sanchez, Gavin R Screaton, Malcolm G Semple, Donal Skelly, Jose Slon-Campos, Elliot Nathan Smith, Alberto Jose Sobrino Diaz, Julie Staves, David Stuart, Piyada Supasa, Tomas Surik, Hannah Thraves, Pat Tsang, Lance Turtle, Ann Sarah Walker, Beibei Wang, Charlotte Washington, Nicholas Watkins, James Whitehouse

ABSTRACT Objectives: The COVID-19 pandemic caused >1 million infections during January-March 2020. There is an urgent need for reliable antibody detection approaches to support diagnosis, vaccine development, safe release of individuals from quarantine, and population lock-down exit strategies. We set out to evaluate the performance of ELISA and lateral flow immunoassay (LFIA) devices. Design: We tested plasma for COVID (SARS-CoV-2) IgM and IgG antibodies by ELISA and using nine different LFIA devices. Setting: We performed laboratory work at the University of Oxford. Participants: We used a panel of plasma samples from individuals who have had confirmed COVID infection based on a PCR result (n=40), and pre-pandemic negative control samples banked in the UK prior to December-2019 (n=142). Main outcome measures: We recorded optical density results from ELISA experiments and positive/negative/invalid results from LFIA devices. Results: ELISA detected IgM or IgG in 34/40 individuals with a confirmed history of COVID infection (sensitivity 85%, 95%CI 70-94%), vs. 0/50 pre-pandemic controls (specificity 100% [95%CI 93-100%]). IgG levels were detected in 31/31 COVID-positive individuals tested [&ge;]10 days after symptom onset (sensitivity 100%, 95%CI 89-100%). IgG titres rose during the 3 weeks post symptom onset and began to fall by 8 weeks, but remained above the detection threshold. Point estimates for the sensitivity of LFIA devices ranged from 55-70% versus RT-PCR and 65-85% versus ELISA, with specificity 95-100% and 93-100% respectively. Within the limits of the study size, the performance of most LFIA devices was similar. Conclusions: Currently available commercial LFIA devices do not perform sufficiently well for individual patient applications. ELISA can be calibrated to be specific for detecting and quantifying SARS-CoV-2 IgM and IgG and is highly sensitive for IgG from 10 days following first symptoms.

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