SARS-CoV-2-specific memory B cells can persist in the elderly despite loss of neutralising antibodies

 Anna Jeffery-Smith, Alice R Burton, Sabela Lens, Chloe Rees-Spear, Monika Patel, Robin Gopal, Luke Muir, Felicity Aiano, Katie J Doores, J. Yimmy Chow, Shamez N Ladhani, Maria Zambon, Laura E McCoy, Mala K Maini

doi: https://doi.org/10.1101/2021.05.30.446322

This article is a preprint and has not been certified by peer review [what does this mean?].

PDF: https://www.biorxiv.org/content/10.1101/2021.05.30.446322v1.full.pdf

Abstract

Memory B cells (MBC) can provide a recall response able to supplement waning antibodies with an affinity-matured response better able to neutralise variant viruses. We studied a cohort of vulnerable elderly care home residents and younger staff, a high proportion of whom had lost neutralising antibodies (nAb), to investigate their reserve immunity from SARS-CoV-2-specific MBC. Class-switched spike and RBD-tetramer-binding MBC with a classical phenotype persisted five months post-mild/asymptomatic SARS-CoV-2 infection, irrespective of age. Spike/RBD-specific MBC remained detectable in the majority who had lost nAb, although at lower frequencies and with a reduced IgG/IgA isotype ratio. Functional spike/S1/RBD-specific recall was also detectable by ELISpot in some who had lost nAb, but was significantly impaired in the elderly, particularly to RBD. Our findings demonstrate persistence of SARS-CoV-2-specific MBC beyond loss of nAb, but highlight the need for careful monitoring of functional defects in RBD-specific B cell immunity in the elderly.

Competing Interest Statement

The authors have declared no competing interest.

https://www.biorxiv.org/content/10.1101/2021.05.30.446322v1

Small Airways Disease is a Post-Acute Sequelae of SARS-CoV-2 Infection

 Josalyn L. Cho,  

View ORCID ProfileRaul Villacreses, Prashant Nagpal, Junfeng Guo,  View ORCID ProfileAlejandro A. Pezzulo, Andrew L. Thurman,  View ORCID ProfileNabeel Y. Hamzeh, Robert J. Blount,  View ORCID ProfileSpyridon Fortis,  View ORCID ProfileEric A. Hoffman,  View ORCID ProfileJoseph Zabner,  View ORCID ProfileAlejandro P. Comellas

doi: https://doi.org/10.1101/2021.05.27.21257944

This article is a preprint and has not been certified by peer review [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

PDF: https://www.medrxiv.org/content/10.1101/2021.05.27.21257944v1.full.pdf

Abstract

Background The sequelae of SARS-CoV-2 infection on pulmonary structure and function remain incompletely characterized.

Methods Adults with confirmed COVID-19 who remained symptomatic more than thirty days following diagnosis were enrolled and classified as ambulatory, hospitalized or requiring the intensive care unit (ICU) based on the highest level of care received during acute infection. Symptoms, pulmonary function tests and chest computed tomography (CT) findings were compared across groups and to healthy controls. CT images were quantitatively analyzed using supervised machine-learning to measure regional ground glass opacities (GGO) and image-matching to measure regional air trapping. Comparisons were performed using univariate analyses and multivariate linear regression.

Results Of the 100 patients enrolled, 67 were in the ambulatory group. All groups commonly reported cough and dyspnea. Pulmonary function testing revealed restrictive physiology in the hospitalized and ICU groups but was normal in the ambulatory group. Among hospitalized and ICU patients, the mean percent of total lung classified as GGO was 13.2% and 28.7%, respectively, and was higher than in ambulatory patients (3.7%, P<0.001). The mean percentage of total lung affected by air trapping was 25.4%, 34.5% and 27.2% in the ambulatory, hospitalized and ICU groups and 7.3% in healthy controls (P<0.001). Air trapping measured by quantitative CT correlated with the residual volume to total lung capacity ratio (RV/TLC; ρ=0.6, P<0.001).

Conclusions Air trapping is present in patients with post-acute sequelae of COVID-19 and is independent of initial infection severity, suggesting obstruction at the level of the small airways. The long-term consequences are not known.

Competing Interest Statement

The authors have declared no competing interest.

Clinical Trial

This was not a clinical trial and just an observational cohort

Funding Statement

This work was supported by grants from the National Institutes of Health (R01HL112986 and S10OD018526 to EAH; R01HL136813, P01HL152960, P01HL091842, P30DK054759 and T32HL007638 to JZ).

https://www.medrxiv.org/content/10.1101/2021.05.27.21257944v1

In post-pandemic Europe, migrants will face digital fortress

 As the world begins to travel again, Europe is sending migrants a loud message: Stay away!

Greek border police are firing bursts of deafening noise from an armored truck over the frontier into Turkey. Mounted on the vehicle, the long-range acoustic device, or “sound cannon,” is the size of a small TV set but can match the volume of a jet engine.

It’s part of a vast array of physical and experimental new digital barriers being installed and tested during the quiet months of the coronavirus pandemic at the 200-kilometer (125-mile) Greek border with Turkey to stop people entering the European Union illegally.

A new steel wall, similar to recent construction on the U.S.-Mexico border, blocks commonly-used crossing points along the Evros River that separates the two countries.

Nearby observation towers are being fitted with long-range cameras, night vision, and multiple sensors. The data will be sent to control centers to flag suspicious movement using artificial intelligence analysis.

“We will have a clear ‘pre-border’ picture of what’s happening,” Police Maj. Dimonsthenis Kamargios, head of the region’s border guard authority, told the Associated Press.

The EU has poured 3 billion euros ($3.7 billion) into security tech research following the refugee crisis in 2015-16, when more than 1 million people — many escaping wars in Syria, Iraq and Afghanistan — fled to Greece and on to other EU countries.

The automated surveillance network being built on the Greek-Turkish border is aimed at detecting migrants early and deterring them from crossing, with river and land patrols using searchlights and long-range acoustic devices.

Key elements of the network will be launched by the end of the year, Kamargios said. “Our task is to prevent migrants from entering the country illegally. We need modern equipment and tools to do that.”

Researchers at universities around Europe, working with private firms, have developed futuristic surveillance and verification technology, and tested more than a dozen projects at Greek borders.

AI-powered lie detectors and virtual border-guard interview bots have been piloted, as well as efforts to integrate satellite data with footage from drones on land, air, sea and underwater. Palm scanners record the unique vein pattern in a person’s hand to use as a biometric identifier, and the makers of live camera reconstruction technology promise to erase foliage virtually, exposing people hiding near border areas.

Testing has also been conducted in Hungary, Latvia and elsewhere along the eastern EU perimeter.

The more aggressive migration strategy has been advanced by European policymakers over the past five years, funding deals with Mediterranean countries outside the bloc to hold migrants back and transforming the EU border protection agency, Frontex, from a coordination mechanism to a full-fledged multinational security force.

But regional migration deals have left the EU exposed to political pressure from neighbors.

Earlier this month, several thousand migrants crossed from Morocco into the Spanish enclave of Ceuta in a single day, prompting Spain to deploy the army. A similar crisis unfolded on the Greek-Turkish border and lasted three weeks last year.

Greece is pressing the EU to let Frontex patrol outside its territorial waters to stop migrants reaching Lesbos and other Greek islands, the most common route in Europe for illegal crossing in recent years.

Armed with new tech tools, European law enforcement authorities are leaning further outside borders.

Not all the surveillance programs being tested will be included in the new detection system, but human rights groups say the emerging technology will make it even harder for refugees fleeing wars and extreme hardship to find safety.

Patrick Breyer, a European lawmaker from Germany, has taken an EU research authority to court, demanding that details of the AI-powered lie detection program be made public.

“What we are seeing at the borders, and in treating foreign nationals generally, is that it’s often a testing field for technologies that are later used on Europeans as well. And that’s why everybody should care, in their own self-interest,” Breyer of the German Pirates Party told the AP.

He urged authorities to allow broad oversight of border surveillance methods to review ethical concerns and prevent the sale of the technology through private partners to authoritarian regimes outside the EU.

Ella Jakubowska, of the digital rights group EDRi, argued that EU officials were adopting “techno-solutionism” to sideline moral considerations in dealing with the complex issue of migration.

“It is deeply troubling that, time and again, EU funds are poured into expensive technologies which are used in ways that criminalize, experiment with and dehumanize people on the move,” she said.

The London-based group Privacy International argued the tougher border policing would provide a political reward to European leaders who have adopted a hard line on migration.

“If people migrating are viewed only as a security problem to be deterred and challenged, the inevitable result is that governments will throw technology at controlling them,” said Edin Omanovic, an advocacy director at the group.

“It’s not hard to see why: across Europe we have autocrats looking for power by targeting foreigners, otherwise progressive leaders who have failed to come up with any alternatives to copying their agendas, and a rampant arms industry with vast access to decision-makers.”

Migration flows have slowed in many parts of Europe during the pandemic, interrupting an increase recorded over years. In Greece, for example, the number of arrivals dropped from nearly 75,000 in 2019 to 15,700 in 2020, a 78% decrease.

But the pressure is sure to return. Between 2000 and 2020, the world’s migrant population rose by more than 80% to reach 272 million, according to United Nations data, fast outpacing international population growth.

At the Greek border village of Poros, the breakfast discussion at a cafe was about the recent crisis on the Spanish-Moroccan border.

Many of the houses in the area are abandoned and in a gradual state of collapse, and life is adjusting to that reality.

Cows use the steel wall as a barrier for the wind and rest nearby.

Panagiotis Kyrgiannis, a Poros resident, says the wall and other preventive measures have brought migrant crossings to a dead stop.

“We are used to seeing them cross over and come through the village in groups of 80 or a 100,” he said. “We were not afraid. ... They don’t want to settle here. All of this that’s happening around us is not about us.”

https://apnews.com/article/middle-east-europe-migration-technology-health-c23251bec65ba45205a0851fab07e9b6

Vietnam's Pandemic Surge Trigger Supply Chain Concerns for Apple

 

• The pandemic resurgence has compromised Vietnam’s factory production locations that house Apple Inc AAPL 0.53% and Samsung Electronics Co Ltd OTCSSNLF suppliers, Reuters reports.
• Over 3,000 people have contracted the virus in 30 of its 63 cities and provinces since late April.
• Four business sources acknowledged operational hit following lockdown, which triggered supply chain disruption concerns.
• One Apple supplier had temporarily divided its workforce over two shifts.
• Vietnam had begun vaccinating workers in the two most affected provinces Bac Ninh and Bac Giang, based on the health ministry statement.
• Bac Ninh is responsible for significant Samsung operations and imposed a curfew and other travel restrictions. Vietnam accounts for 50% of Samsung’s global phone and tablet production.
• Last week, Vietnam’s government advised Bac Ninh and Bac Giang provinces to drive efforts to prevent an industrial production disruption. LG Electronics Inc OTCLGEIY, Foxconn Technology Co Ltd OTCFXCOF, and Luxshare have operations or supply chain companies in the area.
• A Xiaomi Corp XIACF 1.32%, Huawei Technologies Co., Ltd, Vivo Communication Technology Co. Ltd, and Guangdong Oppo Mobile Telecommunications Corp, Ltd supplier’s workers were living and working within the industrial zones in Bac Ninh.
• The government planned to gradually reopen four industrial parks closed a week earlier due to the pandemic.
• Some of the lower-tier South Korean suppliers were also struggling.

https://www.benzinga.com/news/21/05/21344353/vietnams-pandemic-surge-trigger-supply-chain-concerns-for-apple-samsung-reuters

Biotech week ahead, June 1

 After having declined through the first half of the week, biotech stocks staged a recovery to close higher in the trading week ended May 28. Broader market sentiment and company-specific news flow dictated stock moves during the week.

Ahead of Memorial Day, the Food and Drug Administration handed down several positive verdicts. Among the drugs approved were Bristol-Myers Squibb Company's BMY Zeposia for ulcerative colitis, Amgen, Inc.'s AMGN 1.12% KRAS G12C-inhibitor sotorasib for non-small cell lung cancer, and Biohaven Pharmaceutical Holding Company Ltd.'s BHVN 5.37% migraine treatment.

Eton Pharmaceuticals, Inc. ETON 16.84%, meanwhile, faced a rejection, as the regulator turned down its new drug application for dehydrated alcohol injection as a treatment option for methanol poisoning.

Provention Bio, Inc. 

PRVB 28.75% had a mixed week, as it rallied strongly Tuesday in reaction to the briefing document released ahead of the Adcom meeting. The stock retreated by as much following the Adcom verdict. Investors did not quite relish the company's statement that, despite the positive FDA panel vote, approval for its type 1 diabetes treatment could still be delayed due to issues raised by the regulator regarding the comparability of the pharmacokinetic profile.

Pieris Pharmaceuticals, Inc. PIRS 9.71% was among the biggest gainers of the week following its pact with Roche Holding AG's RHHBY 0.62% Genentech unit. Meanwhile, Larimar Therapeutics, Inc. LRMR 3.37% shares suffered a massive sell-off after an early-stage study of Friedreich ataxia treatment was put on hold.

Here are the key catalysts for the unfolding week.

Conferences

The Jefferies Virtual Healthcare Conference: June 1-4
European League Against Rheumatism, or EULAR, 2021 Virtual Conference: June 2-5
12th C1-Inhibitor Deficiency and Angioedema Workshop: June 3-6
American Society of Clinical Oncology, or ASCO, Annual Meeting: June 4-8

PDUFA Dates

The FDA is scheduled to rule on Alkermes plc's ALKS 0.49% resubmitted new drug application for ALKS 3831, a combo drug comprising olanzapine and samidorphan, as a treatment option adults with schizophrenia and bipolar I disorder. The prescription drug user fee act, or PDUFA, date – the date by which the FDA is required to announce its decision – has been fixed for Tuesday, June 1.

SCYNEXIS, Inc. SCYX 2.46% awaits FDA verdict on its NDA for ibrexafungerp by the PDUFA goal date of Tuesday, June 1. Ibrexafungerp is being evaluated for the treatment of vulvovaginal candidiasis, also known as vaginal yeast infections. The therapeutic candidate is to get Brexafemme as its trade name.

The FDA has fixed a PDUFA goal date of Saturday, June 5, for deciding on Liminal BioSciences Inc.'s LMNL 4.49% biologic license application for Ryplazim or plasminogen. The investigational asset is being evaluated for treating patients with clinical signs and symptoms associated with congenital plasminogen deficiency.

Clinical Readouts/Data Presentations

EULAR Meeting Presentations

Kezar Life Sciences, Inc. KZR 2.39%: Final data from MISSION Phase 1b trial, the 25-week safety and tolerability study investigating up to 75-mg weekly dosing of KZR-616 in 47 patients with systemic lupus erythematous (Wednesday, June 2, 4:30 p.m.)

Aurinia Pharmaceuticals Inc. AUPH 1.97%: Supportive interim analysis of its AURORA 2 Phase 3 continuation study that is evaluating Lupkynis for the treatment of lupus nephritis

ASCO Presentations

Here's a list of companies presenting at the conference, and the list is not comprehensive.

Seagen Inc. SGEN 2.81%: updated results of the EV-103 and EV-201 clinical trials for Padcev (enfortumab vedotin-ejfv) in locally advanced or metastatic urothelial cancer and additional data from the HER2CLIMB trial of Tukysa (tucatinib) in previously treated HER2+ metastatic breast cancer patients.

Magenta Therapeutics, Inc. MGTA 2.49%: Initial mobilization, collection, engraftment and disease outcome data from Phase 2 study of MGTA-145 plus plerixafor in multiple myeloma

Immunocore Holdings plc IMCR 3.64%: Data from Phase 3 study comparing tebentafusp vs. investigator's choice in first line metastatic uveal melanoma

Jounce Therapeutics, Inc. JNCE 0.63%: Data from Phase 1 study of JTX-8064 as monotherapy and in combination with anti-PD-1 in adult patients with advanced solid tumors

BeyondSpring Inc. BYSI 2.17%: Data from Phase 1 study of Plinabulin, in combination with Bristol-Myers Squibb's Opdivo and Yervoy in the treatment of 2nd and 3rd line small cell lung cancer

Sensei Biotherapeutics, Inc. SNSE 0.4%: Data from combination study of SNS-301 with Merck & Co., Inc.'s MRK 0.09% Keytruda in patients with advanced squamous cell carcinoma of the head and neck

Vincerx Pharma, Inc. VINC 2.46%: Phase 1 dose-escalation safety and efficacy data for VIP152 in relapsed/refractory chronic lymphocytic leukemia and Richter syndrome

Alkermes: Data from ARTISTRY-1 and ARTISTRY-2 clinical trials evaluating nemvaleukin alfa (nemvaleukin) in solid tumors

Allogene Therapeutics, Inc. ALLO 3.84%: first presentation of data from the dose escalation Phase 1 ALPHA study of ALLO-501 in relapsed/refractory non-Hodgkin lymphoma

Bolt Biotherapeutics, Inc. BOLT 4.84%: Preliminary results from a Phase 1/2 study of BDC-1001 in patients with advanced HER2-expressing solid tumors.

Deciphera Pharmaceuticals, Inc. DCPH 0.74%: Updated data from the Phase 1b/2 study of rebastinib in combination with paclitaxel in the endometrial cancer cohort

Delcath Systems, Inc. DCTH 3.58%: : Preliminary results of FOCUS phase 3 trial of percutaneous hepatic perfusion with melphalan for patients with ocular melanoma liver metastases

Allogene & Cellectis S.A. CLLS 1.69%: Initial results from patients treated with consolidation dosing of ALLO-501A

Immutep Limited IMMP 4.56%: Results from a phase 2 study of eftilagimod alpha and Keytruda in patients with PD-L1 unselected metastatic non-small cell lung carcinoma as well as phase 2 study of eftilagimod alpha and Keytruda in patients with PD-L1 unselected metastatic second-line squamous head and neck carcinoma.

Agenus Inc. AGEN 1.19%: New Phase 1 clinical data for AGEN2373 in in patients with advanced solid tumors

Merus N.V. MRUS 0.48%: Interim analysis of data from the phase 1/2 eNRGY trial of Zenocutuzumab in patients with NRG1+ cancers

Surface Oncology, Inc. SURF 4.99%: Data from the Phase 1 study of SRF388 in advanced solid tumors

NexImmune, Inc. NEXI 3.23%: Data from preliminary analysis of a Phase 1/2 study of NEXI-001 for the treatment of relapsed acute myeloid leukemia after allogeneic hematopoietic cell transplantation

TRACON Pharmaceuticals, Inc. TCON 1.17%: Preliminary data for Uliledlimab in combination with Roche Holding AG's RHHBY 0.62% Tecentriq in patients with advanced cancer

Clovis Oncology, Inc. CLVS 1.72%: Updated Phase 1b results from Lucitanib and Opdivo in patients with advanced solid tumors

Heat Biologics, Inc. HTBX 2.64%: Interim results of viagenpumatucel-L plus Opdivo in previously treated patients with advanced non-small cell lung cancer

Cellectar Biosciences, Inc. CLRB 3.14%: Data from Phase 2a study of CLR 131 in Waldenstrom's macroglobulinemia

Forma Therapeutics Holdings, Inc. FMTX 4.46%: Results from a planned interim analysis of a phase 2 study of olutasidenib in relapsed/refractory mIDH1 acute myeloid leukemia

ADC Therapeutics SA ADCT 2.43%: data from Phase 1b study to evaluate camidanlumab tesirine as monotherapy in patients with advanced solid tumor

Tyme Technologies, Inc. TYME 4.05%: Data from Phase 2 Study of SM-88 in Ewing's and Other Sarcomas
Epizyme, Inc. EPZM 1.56%: Results of the phase 1b soft-tissue sarcoma portion of the study of tazemetostat plus doxorubicin as frontline therapy for advanced epithelioid sarcoma

Veru Inc. VERU 0.11%: Data from Phase 2 study of enobosarm in advanced AR+/estrogen receptor+ breast cancer

Purple Biotech Ltd. PPBT 8.76%: Initial data from Phase 1/2 study of NT219 in adults with advanced solid tumors and head and neck cancer
Panbela Therapeutics, Inc. PBLA 0.7%: Additional data from phase 1 trial of SBP101 in pancreatic cancer

Harpoon Therapeutics, Inc. HARP 1.68%: updated interim Phase 1 data for HPN424 for prostate cancer

Kadmon Holdings, Inc. KDMN 1.79%: Initial safety data from the Phase 1 clinical trial of KD033 in patients with metastatic or locally advanced solid tumors

G1 Therapeutics, Inc. GTHX 2.29%: Phase 1 data for Rintodestrant, in combination with palbociclib for ER+/HER2- advanced breast cancer

Adaptimmune Therapeutics plc ADAP 0.4%: Initial data from its Phase 2 SPEARHEAD-1 trial, with afamitresgene autoleucel in synovial sarcoma and myxoid/ round cell liposarcoma

MacroGenics, Inc. MGNX 2%: Data from Phase 1 dose-escalation study of MGC018 in patients with advanced solid tumors

Fate Therapeutics, Inc. FATE 0.46%: New FT516 Phase 1 data for B-cell lymphoma

VBI Vaccines Inc. VBIV 1.82%: Updated Phase 2a portion of the Phase 1/2a study of VBI-1901, its cancer vaccine immunotherapeutic candidate, in recurrent glioblastoma patients,

Aprea Therapeutics, Inc. APRE 1.69%: Phase 1/2 clinical trial of Eprenetapop in relapsed/refractory gastric, bladder and non-small cell lung cancers

ImmunoGen, Inc. IMGN 0.49%: Data from the FORWARD II study evaluating mirvetuximab soravtansine in combination with Avastin in patients with medium and high folate receptor alpha (FRα)-expressing recurrent ovarian cancer for whom a non-platinum based combination regimen is appropriate

BeiGene, Ltd. BGNE 2.14%: Initial data from the Phase 3 study of tislelizumab in second-line advanced unresectable or metastatic esophageal squamous cell carcinoma and initial data from the Phase 2 trial of tislelizumab in patients with previously treated, locally advanced unresectable or metastatic microsatellite instability-high or mismatch repair deficient solid tumors

Advaxis, Inc. ADXS 2.75%: Updated data from the Phase 1/2 study evaluating ADXS-503 in combination with Keytruda in patients with metastatic non-small-cell lung cancer

Alpine Immune Sciences, Inc. ALPN 4.41%: Data from the Phase 1 dose escalation clinical trial of ALPN-202 monotherapy in advanced malignancies

I-Mab IMAB 7.83%: Data from the Phase 1 study of uliledlimab in combination with Tecentriq in patients with advanced cancer

TG Therapeutics, Inc. TGTX 3.81%: Data from the study of TG-1701 in chronic lymphocytic leukemia and lymphoma

Oncolytics Biotech Inc. ONCY 0.66%: Clinical and biomarker data demonstrating clinical proof-of-concept for pelareorep-checkpoint inhibitor combination therapy in pancreatic cancer.

Salarius Pharmaceuticals, Inc. SLRX 1.54%: Phase 1 trial of seclidemstat in patients with relapsed/refractory Ewing sarcoma and Phase 1 expansion trial of seclidemstat with and without topotecan and cyclophosphamide in patients with relapsed or refractory Ewing sarcoma and select sarcomas

C1-Inhibitor Deficiency & Angioedema Workshop Presentations

KalVista Pharmaceuticals, Inc. KALV 0.6%: Analysis of pharmacokinetic and pharmacodynamic profile of KVD900 and attack symptom severity from a phase 2 cross-over trial in patients with hereditary angioedema type I and II (Saturday, June 5)

Earnings

CTI BioPharma Corp. CTIC 0.42% (Tuesday, after the close)

IPO Quiet Period Expiry

Valneva SE VALN 4.55%
Anebulo Pharmaceuticals, Inc. ANEB 2.5%
Talaris Therapeutics, Inc.

  TALS 6.28%     
https://www.benzinga.com/general/biotech/21/05/21351378/the-week-ahead-in-biotech-asco-presentations-front-and-center-fda-decisions-due-for-scynexis-limi