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Science ; 2021 Apr 30.
Article in English | MEDLINE | ID: covidwho-1209815


SARS-CoV-2 vaccine rollout has coincided with the spread of variants of concern. We investigated if single dose vaccination, with or without prior infection, confers cross protective immunity to variants. We analyzed T and B cell responses after first dose vaccination with the Pfizer/BioNTech mRNA vaccine BNT162b2 in healthcare workers (HCW) followed longitudinally, with or without prior Wuhan-Hu-1 SARS-CoV-2 infection. After one dose, individuals with prior infection showed enhanced T cell immunity, antibody secreting memory B cell response to spike and neutralizing antibodies effective against B.1.1.7 and B.1.351. By comparison, HCW receiving one vaccine dose without prior infection showed reduced immunity against variants. B.1.1.7 and B.1.351 spike mutations resulted in increased, abrogated or unchanged T cell responses depending on human leukocyte antigen (HLA) polymorphisms. Single dose vaccination with BNT162b2 in the context of prior infection with a heterologous variant substantially enhances neutralizing antibody responses against variants.

Elife ; 92020 12 17.
Article in English | MEDLINE | ID: covidwho-1011747


Here, we describe the case of a COVID-19 patient who developed recurring ventilator-associated pneumonia caused by Pseudomonas aeruginosa that acquired increasing levels of antimicrobial resistance (AMR) in response to treatment. Metagenomic analysis revealed the AMR genotype, while immunological analysis revealed massive and escalating levels of T-cell activation. These were both SARS-CoV-2 and P. aeruginosa specific, and bystander activated, which may have contributed to this patient's persistent symptoms and radiological changes.

Anti-Bacterial Agents/therapeutic use , COVID-19/complications , Lymphocyte Activation , Pneumonia, Ventilator-Associated/drug therapy , Pseudomonas Infections/drug therapy , SARS-CoV-2 , T-Lymphocytes/immunology , Anti-Bacterial Agents/pharmacology , COVID-19/immunology , COVID-19/therapy , Drug Resistance, Multiple, Bacterial , Humans , Lung/microbiology , Male , Meropenem/pharmacology , Meropenem/therapeutic use , Metagenomics , Middle Aged , Piperacillin, Tazobactam Drug Combination/pharmacology , Piperacillin, Tazobactam Drug Combination/therapeutic use , Pneumonia, Ventilator-Associated/diagnostic imaging , Pneumonia, Ventilator-Associated/etiology , Pseudomonas Infections/diagnostic imaging , Pseudomonas Infections/etiology , Pseudomonas aeruginosa/isolation & purification , Recurrence , Respiration, Artificial
Sci Immunol ; 5(54)2020 12 23.
Article in English | MEDLINE | ID: covidwho-999191


Understanding the nature of immunity following mild/asymptomatic infection with SARS-CoV-2 is crucial to controlling the pandemic. We analyzed T cell and neutralizing antibody responses in 136 healthcare workers (HCW) 16-18 weeks after United Kingdom lockdown, 76 of whom had mild/asymptomatic SARS-CoV-2 infection captured by serial sampling. Neutralizing antibodies (nAb) were present in 89% of previously infected HCW. T cell responses tended to be lower following asymptomatic infection than in those reporting case-definition symptoms of COVID-19, while nAb titers were maintained irrespective of symptoms. T cell and antibody responses were sometimes discordant. Eleven percent lacked nAb and had undetectable T cell responses to spike protein but had T cells reactive with other SARS-CoV-2 antigens. Our findings suggest that the majority of individuals with mild or asymptomatic SARS-CoV-2 infection carry nAb complemented by multispecific T cell responses at 16-18 weeks after mild or asymptomatic SARS-CoV-2 infection.

Antibodies, Neutralizing/immunology , Asymptomatic Infections , COVID-19/immunology , T-Lymphocytes/immunology , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Antibodies, Viral/immunology , Case-Control Studies , Cross-Sectional Studies , Humans , SARS-CoV-2/immunology