Medicine, Research & Experimental

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Article Biochemistry & Molecular Biology

Long-term cardiovascular outcomes of COVID-19

Yan Xie, Evan Xu, Benjamin Bowe, Ziyad Al-Aly

Summary: Individuals with COVID-19, even those who were not hospitalized during the acute phase of the infection, are at an increased long-term risk of various cardiovascular disorders. A study using national healthcare databases found that beyond the first 30 days after infection, individuals with COVID-19 have an elevated risk of developing cerebrovascular disorders, heart diseases, and other cardiovascular complications. The risk increases depending on the care setting during the acute phase.

NATURE MEDICINE (2022)

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Article Biochemistry & Molecular Biology

An infectious SARS-CoV-2 B.1.1.529 Omicron virus escapes neutralization by therapeutic monoclonal antibodies

Laura A. VanBlargan, John M. Errico, Peter J. Halfmann, Seth J. Zost, James E. Crowe, Lisa A. Purcell, Yoshihiro Kawaoka, Davide Corti, Daved H. Fremont, Michael S. Diamond

Summary: The emergence of the B.1.1.529 Omicron variant raises concerns about the efficacy of antibody countermeasures. This study shows that some of the antibodies currently in clinical use may lose their ability to neutralize the Omicron variant.

NATURE MEDICINE (2022)

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Article Biochemistry & Molecular Biology

Emergence of SARS-CoV-2 Omicron lineages BA.4 and BA.5 in South Africa

Houriiyah Tegally, Monika Moir, Josie Everatt, Marta Giovanetti, Cathrine Scheepers, Eduan Wilkinson, Kathleen Subramoney, Zinhle Makatini, Sikhulile Moyo, Daniel G. Amoako, Cheryl Baxter, Christian L. Althaus, Ugochukwu J. Anyaneji, Dikeledi Kekana, Raquel Viana, Jennifer Giandhari, Richard J. Lessells, Tongai Maponga, Dorcas Maruapula, Wonderful Choga, Mogomotsi Matshaba, Mpaphi B. Mbulawa, Nokukhanya Msomi, Yeshnee Naidoo, Sureshnee Pillay, Tomasz Janusz Sanko, James E. San, Lesley Scott, Lavanya Singh, Nonkululeko A. Magini, Pamela Smith-Lawrence, Wendy Stevens, Graeme Dor, Derek Tshiabuila, Nicole Wolter, Wolfgang Preiser, Florette K. Treurnicht, Marietjie Venter, Georginah Chiloane, Caitlyn McIntyre, Aine O'Toole, Christopher Ruis, Thomas P. Peacock, Cornelius Roemer, Sergei L. Kosakovsky Pond, Carolyn Williamson, Oliver G. Pybus, Jinal N. Bhiman, Allison Glass, Darren P. Martin, Ben Jackson, Andrew Rambaut, Oluwakemi Laguda-Akingba, Simani Gaseitsiwe, Anne von Gottberg, Tulio de Oliveira, Armand Phillip Bester, Mathilda Claassen, Deelan Doolabh, Innocent Mudau, Nokuzola Mbhele, Susan Engelbrecht, Dominique Goedhals, Diana Hardie, Nei-Yuan Hsiao, Arash Iranzadeh, Arshad Ismail, Rageema Joseph, Arisha Maharaj, Boitshoko Mahlangu, Kamela Mahlakwane, Ashlyn Davis, Gert Marais, Koleka Mlisana, Anele Mnguni, Thabo Mohale, Gerald Motsatsi, Peter Mwangi, Noxolo Ntuli, Martin Nyaga, Luicer Olubayo, Botshelo Radibe, Yajna Ramphal, Upasana Ramphal, Wilhelmina Strasheim, Naume Tebeila, Stephanie van Wyk, Shannon Wilson, Alexander G. Lucaci, Steven Weaver, Akhil Maharaj, Yusasha Pillay, Michaela Davids, Adriano Mendes, Simnikiwe Mayaphi

Summary: The genomic characterization of the SARS-CoV-2 Omicron lineages BA.4 and BA.5, responsible for the fifth wave of the COVID-19 pandemic in South Africa, reveals their continued viral diversification and sheds light on the potential mechanisms that allow these new lineages to outcompete their predecessors. These new lineages, BA.4 and BA.5, share identical spike proteins with BA.2 but have certain differences such as the presence of the 69-70 deletion, L452R, F486V, and the wild-type amino acid at Q493. They can be identified by the S-gene target failure, a proxy marker associated with the 69-70 deletion. BA.4 and BA.5 have rapidly replaced BA.2 and have become the dominant lineages in South Africa.

NATURE MEDICINE (2022)

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Article Biochemistry & Molecular Biology

Phylogenomic characterization and signs of microevolution in the 2022 multi-country outbreak of monkeypox virus

Joana Isidro, Vitor Borges, Miguel Pinto, Daniel Sobral, Joao Dourado Santos, Alexandra Nunes, Veronica Mixao, Rita Ferreira, Daniela Santos, Silvia Duarte, Luis Vieira, Maria Jose Borrego, Sofia Nuncio, Isabel Lopes de Carvalho, Ana Pelerito, Rita Cordeiro, Joao Paulo Gomes

Summary: In this study, shotgun metagenomics were used to rapidly reconstruct and characterize the genome sequences of the largest monkeypox virus outbreak in non-endemic countries so far. The findings indicate that the outbreak most likely has a single origin and that the virus belongs to clade 3. Furthermore, the study suggests the involvement of host APOBEC3 in viral evolution and reveals signs of ongoing microevolution in the virus.

NATURE MEDICINE (2022)

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Article Biochemistry & Molecular Biology

Effectiveness of mRNA-1273 against SARS-CoV-2 Omicron and Delta variants

Hung Fu Tseng, Bradley K. Ackerson, Yi Luo, Lina S. Sy, Carla A. Talarico, Yun Tian, Katia J. Bruxvoort, Julia E. Tubert, Ana Florea, Jennifer H. Ku, Gina S. Lee, Soon Kyu Choi, Harpreet S. Takhar, Michael Aragones, Lei Qian

Summary: A test-negative case-control analysis using data from a diverse population in California, USA, demonstrates that vaccine efficacy of a three-dose regimen of the mRNA-1273 COVID-19 vaccine is reduced against infection with the Omicron SARS-CoV-2 variant in comparison to Delta, but that efficacy against hospitalization remained high for both variants.

NATURE MEDICINE (2022)

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Article Biochemistry & Molecular Biology

Long COVID after breakthrough SARS-CoV-2 infection

Ziyad Al-Aly, Benjamin Bowe, Yan Xie

Summary: This study analyzed the US Department of Veterans Affairs national healthcare databases to investigate the occurrence of Long COVID and death risk after breakthrough SARS-CoV-2 infection. The findings showed that vaccination significantly reduced the risk of death and post-acute sequelae but did not eliminate them completely. These results underscore the importance of further research on prevention and post-acute care for breakthrough infections.

NATURE MEDICINE (2022)

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Article Biochemistry & Molecular Biology

Risks of myocarditis, pericarditis, and cardiac arrhythmias associated with COVID-19 vaccination or SARS-CoV-2 infection

Martina Patone, Xue W. Mei, Lahiru Handunnetthi, Sharon Dixon, Francesco Zaccardi, Manu Shankar-Hari, Peter Watkinson, Kamlesh Khunti, Anthony Harnden, Carol A. C. Coupland, Keith M. Channon, Nicholas L. Mills, Aziz Sheikh, Julia Hippisley-Cox

Summary: The study found that there is an increased risk of myocarditis associated with the first dose of ChAdOx1 and BNT162b2 vaccines, as well as the first and second doses of the mRNA-1273 vaccine in the 1-28 days post-vaccination period. Additionally, individuals with SARS-CoV-2 infection also face a greater risk of myocarditis, pericarditis, and cardiac arrhythmia.

NATURE MEDICINE (2022)

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Article Biochemistry & Molecular Biology

The SGLT2 inhibitor empagliflozin in patients hospitalized for acute heart failure: a multinational randomized trial

Adriaan A. Voors, Christiane E. Angermann, John R. Teerlink, Sean P. Collins, Mikhail Kosiborod, Jan Biegus, Joao Pedro Ferreira, Michael E. Nassif, Mitchell A. Psotka, Jasper Tromp, C. Jan Willem Borleffs, Changsheng Ma, Joseph Comin-Colet, Michael Fu, Stefan P. Janssens, Robert G. Kiss, Robert J. Mentz, Yasushi Sakata, Henrik Schirmer, Morten Schou, P. Christian Schulze, Lenka Spinarova, Maurizio Volterrani, Jerzy K. Wranicz, Uwe Zeymer, Shelley Zieroth, Martina Brueckmann, Jonathan P. Blatchford, Afshin Salsali, Piotr Ponikowski

Summary: The sodium-glucose cotransporter 2 inhibitor empagliflozin improves clinical outcomes in patients hospitalized for acute heart failure, regardless of ejection fraction or the presence of diabetes.

NATURE MEDICINE (2022)

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Review Biochemistry & Molecular Biology

AI in health and medicine

Pranav Rajpurkar, Emma Chen, Oishi Banerjee, Eric J. Topol

Summary: This Review discusses the potential of AI to reshape medicine and make healthcare more accurate, efficient, and accessible. It covers recent progress in medical AI, including advances in medical image analysis, non-image data sources, and human-AI collaboration. The article also addresses technical and ethical challenges, such as data scarcity and racial bias.

NATURE MEDICINE (2022)

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Article Biochemistry & Molecular Biology

Neutralizing antibodies against the SARS-CoV-2 Omicron variant BA.1 following homologous and heterologous CoronaVac or BNT162b2 vaccination

Samuel M. S. Cheng, Chris Ka Pun Mok, Yonna W. Y. Leung, Susanna S. Ng, Karl C. K. Chan, Fanny W. Ko, Chunke Chen, Karen Yiu, Bosco H. S. Lam, Eric H. Y. Lau, Ken K. P. Chan, Leo L. H. Luk, John K. C. Li, Leo C. H. Tsang, Leo L. M. Poon, David S. C. Hui, Malik Peiris

Summary: Specific antibody levels against the SARS-CoV-2 Omicron variant decrease significantly after two doses of BNT162b2 or CoronaVac vaccines, but can be markedly increased with a booster dose of BNT162b2. Individuals who previously received two doses of BNT162b2 or CoronaVac showed reduced serum antibody titers against Omicron, while a BNT162b2 booster dose increased the antibody levels in the majority of individuals. This suggests mRNA vaccine boosters may be necessary in countries primarily using CoronaVac vaccines to combat the spread of Omicron.

NATURE MEDICINE (2022)

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Article Biochemistry & Molecular Biology

mRNA booster immunization elicits potent neutralizing serum activity against the SARS-CoV-2 Omicron variant

Henning Gruell, Kanika Vanshylla, Pinkus Tober-Lau, David Hillus, Philipp Schommers, Clara Lehmann, Florian Kurth, Leif E. Sander, Florian Klein

Summary: This study demonstrates that neutralization of the SARS-CoV-2 Omicron variant is greatly reduced in individuals who received two doses of the COVID-19 vaccine or have recovered from the disease, but is significantly increased after a booster vaccine dose.

NATURE MEDICINE (2022)

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Article Biochemistry & Molecular Biology

Ancestral SARS-CoV-2-specific T cells cross-recognize the Omicron variant

Yu Gao, Curtis Cai, Alba Grifoni, Thomas R. Muller, Julia Niessl, Anna Olofsson, Marion Humbert, Lotta Hansson, Anders Osterborg, Peter Bergman, Puran Chen, Annika Olsson, Johan K. Sandberg, Daniela Weiskopf, David A. Price, Hans-Gustaf Ljunggren, Annika C. Karlsson, Alessandro Sette, Soo Aleman, Marcus Buggert

Summary: This study found that SARS-CoV-2 spike-specific CD4(+) and CD8(+) T cells induced by prior infection or BNT162b2 vaccination provide extensive immune coverage against the Omicron variant. Additionally, T cells induced by BNT162b2 vaccination exhibit higher cross-reactivity to the Omicron variant compared to T cells induced by prior SARS-CoV-2 infection.

NATURE MEDICINE (2022)

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Article Biochemistry & Molecular Biology

Neutralizing antibodies against the SARS-CoV-2 Delta and Omicron variants following heterologous CoronaVac plus BNT162b2 booster vaccination

Eddy Perez-Then, Carolina Lucas, Valter Silva Monteiro, Marija Miric, Vivian Brache, Leila Cochon, Chantal B. F. Vogels, Amyn A. Malik, Elena De la Cruz, Aidelis Jorge, Margarita De los Santos, Patricia Leon, Mallery Breban, Kendall Billig, Inci Yildirim, Claire Pearson, Randy Downing, Emily Gagnon, Anthony Muyombwe, Jafar Razeq, Melissa Campbell, Albert Ko, Saad B. Omer, Nathan D. Grubaugh, Sten H. Vermund, Akiko Iwasaki

Summary: The study found that a BNT162b2 mRNA vaccine booster can enhance neutralizing antibodies against the Omicron variant in individuals who received two doses of the CoronaVac vaccine, but antibody titers remain lower compared to the ancestral virus and the Delta variant.

NATURE MEDICINE (2022)

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Article Biochemistry & Molecular Biology

Effectiveness of COVID-19 booster vaccines against COVID-19-related symptoms, hospitalization and death in England

Nick Andrews, Julia Stowe, Freja Kirsebom, Samuel Toffa, Ruchira Sachdeva, Charlotte Gower, Mary Ramsay, Jamie Lopez Bernal

Summary: This study examined the relative and absolute effectiveness of mRNA booster vaccination against COVID-19. The results showed that the booster dose of BNT162b2 or mRNA-1273 had a relative effectiveness ranging from 85% to 95% against symptomatic disease, and an absolute effectiveness ranging from 94% to 97%. For hospitalization or death, the absolute effectiveness of the BNT162b2 booster ranged from 97% to 99% in all age groups. The study provides real-world evidence of significantly increased protection from the booster vaccine dose against mild and severe disease.

NATURE MEDICINE (2022)

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Article Biochemistry & Molecular Biology

Serum neutralization of SARS-CoV-2 Omicron sublineages BA.1 and BA.2 in patients receiving monoclonal antibodies

Timothee Bruel, Jerome Hadjadj, Piet Maes, Delphine Planas, Aymeric Seve, Isabelle Staropoli, Florence Guivel-Benhassine, Francoise Porrot, William-Henry Bolland, Yann Nguyen, Marion Casadevall, Caroline Charre, Helene Pere, David Veyer, Matthieu Prot, Artem Baidaliuk, Lize Cuypers, Cyril Planchais, Hugo Mouquet, Guy Baele, Luc Mouthon, Laurent Hocqueloux, Etienne Simon-Loriere, Emmanuel Andre, Benjamin Terrier, Thierry Prazuck, Olivier Schwartz

Summary: There are differences in neutralizing activity of therapeutic antibodies against the SARS-CoV-2 Omicron BA.1 and BA.2 sublineages, and immunocompromised individuals treated with antibodies show elevated antibody levels but reduced neutralization against Omicron. Breakthrough infections with the Omicron variant are observed in some immunocompromised individuals despite antibody treatment.

NATURE MEDICINE (2022)

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Article Medicine, Research & Experimental

Antibodies to watch in 2022

Helene Kaplon, Alicia Chenoweth, Silvia Crescioli, Janice M. Reichert

Summary: This article provides a summary of key events in the development of commercial antibody therapeutics in 2021 and a glimpse into potential events in 2022. The regulatory review process for antibody therapeutics targeting the SARS-CoV-2 coronavirus has been expedited, leading to emergency use authorizations and full approvals in multiple countries. Additionally, the late-stage commercial clinical pipeline for antibody therapeutics, excluding those for COVID-19, has seen significant growth over the past year.

MABS (2022)

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Article Biochemistry & Molecular Biology

Symptoms and risk factors for long COVID in non-hospitalized adults

Anuradhaa Subramanian, Krishnarajah Nirantharakumar, Sarah Hughes, Puja Myles, Tim Williams, Krishna M. Gokhale, Tom Taverner, Joht Singh Chandan, Kirsty Brown, Nikita Simms-Williams, Anoop D. Shah, Megha Singh, Farah Kidy, Kelvin Okoth, Richard Hotham, Nasir Bashir, Neil Cockburn, Siang Ing Lee, Grace M. Turner, Georgios V. Gkoutos, Olalekan Lee Aiyegbusi, Christel McMullan, Alastair K. Denniston, Elizabeth Sapey, Janet M. Lord, David C. Wraith, Edward Leggett, Clare Iles, Tom Marshall, Malcolm J. Price, Steven Marwaha, Elin Haf Davies, Louise J. Jackson, Karen L. Matthews, Jenny Camaradou, Melanie Calvert, Shamil Haroon

Summary: A retrospective analysis of primary care records in the United Kingdom reveals individual symptoms associated with SARS-CoV-2 infections, which persisted for 12 weeks or more after infection, as well as risk factors associated with developing long COVID.

NATURE MEDICINE (2022)

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Article Instruments & Instrumentation

Intranasal drug delivery: opportunities and toxicologic challenges during drug development

Lea-Adriana Keller, Olivia Merkel, Andreas Popp

Summary: In the last decade, there has been a growing interest in intranasal drug delivery in pharmaceutical R&D. This review article highlights the advantages of nasal delivery for local and systemic drug delivery, as well as for CNS indications, compared to conventional systemic approaches. However, formulation limitations and toxicological considerations remain areas that need further optimization in this field.

DRUG DELIVERY AND TRANSLATIONAL RESEARCH (2022)

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Article Biochemistry & Molecular Biology

Safety, tolerability and viral kinetics during SARS-CoV-2 human challenge in young adults

Ben Killingley, Alex J. Mann, Mariya Kalinova, Alison Boyers, Niluka Goonawardane, Jie Zhou, Kate Lindsell, Samanjit S. Hare, Jonathan Brown, Rebecca Frise, Emma Smith, Claire Hopkins, Nicolas Noulin, Brandon Londt, Tom Wilkinson, Stephen Harden, Helen McShane, Mark Baillet, Anthony Gilbert, Michael Jacobs, Christine Charman, Priya Mande, Jonathan S. Nguyen-Van-Tam, Malcolm G. Semple, Robert C. Read, Neil M. Ferguson, Peter J. Openshaw, Garth Rapeport, Wendy S. Barclay, Andrew P. Catchpole, Christopher Chiu

Summary: This study establishes a new SARS-CoV-2 human challenge model and investigates the viral kinetics during primary infection. The findings have implications for public health recommendations and strategies to control the transmission of SARS-CoV-2.

NATURE MEDICINE (2022)

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Review Biotechnology & Applied Microbiology

Key chemokines direct migration of immune cells in solid tumors

Karan Kohli, Venu G. Pillarisetty, Teresa S. Kim

Summary: Immune cell infiltration into solid tumors and their interactions with chemokine receptors play a crucial role in tumor growth and the balance between effector and immunosuppressive cells. This review discusses the implications of dysregulated chemokine signaling in the tumor microenvironment and the potential for targeting chemokine signaling in cancer immunotherapy.

CANCER GENE THERAPY (2022)

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