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The importance of salivary SARS-CoV-2 antibodies, following infection and vaccination, has not been fully established. 875 healthcare workers were sampled during the first wave in 2020 and 66 longitudinally in response to Pfizer BioNTech 162b2 vaccination. We measured SARS-CoV-2 total IgGAM and individual IgG, IgA and IgM antibodies. IgGAM seroprevalence was 39.9%; however, only 34.1% of seropositive individuals also had salivary antibodies. Infection generated serum IgG antibodies in 51.4% and IgA antibodies in 34.1% of individuals. In contrast, the salivary antibody responses were dominated by IgA (30.9% and 12% generating IgA and IgG antibodies, respectively). Post 2nd vaccination dose, in serum, 100% of infection naïve individuals had IgG and 82.8% had IgA responses; in saliva, 65.5% exhibited IgG and 55.2% IgA antibodies. Prior infection enhanced the vaccine antibody response in serum but no such difference was observed in saliva. Strong neutralisation responses were seen for serum 6 months post 2nd-vaccination dose (median 87.1%) compared to low neutralisation responses in saliva (median 1%). Intramuscular vaccination induces significant serum antibodies and to a lesser extent, salivary antibodies; however, salivary antibodies are typically non-neutralising. This study provides further evidence for the need of mucosal vaccines to elicit nasopharyngeal/oral protection. Although saliva is an attractive non-invasive sero-surveillance tool, due to distinct differences between systemic and oral antibody responses, it cannot be used as a proxy for serum antibody measurement. • Largest investigation of SARS-CoV-2 serum and salivary antibodies in 875 healthcare workers. • In-depth profiling of combined anti-Spike IgGAM and individual immunoglobulin classes. • Saliva is not equivalent to serum. [ABSTRACT FROM AUTHOR]

• IgG anti-SARS-CoV-2 Omicron spike glycoprotein antibodies were detected in 100% of health care workers, a real world population attending general practice for vaccination and haemodialysis patients 4 weeks after a third SARS-CoV-2 vaccine dose (Pfizer-BioNtech 162b2). • Against both Delta and Omicron variants, antibody levels were higher in the cohort who had previously received two doses of Astrazeneca ChAdOx1 nCoV-19 vaccine than two doses of Pfizer-Biontech 162b2. • Prior to this third vaccine dose and 6 months post second vaccine dose, there was evidence of significant waning of antibody reactivity against Delta and Omicron variants of concern, particularly in individuals initially receiving two doses of Astrazeneca ChAdOx1 nCoV-19. [ABSTRACT FROM AUTHOR]

• The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the rapid development of multiple vaccines which have been rolled out worldwide. • In the first phase of the UK vaccine programme, HCWs were amongst the first to be vaccinated. This offered an opportunity to observe the effect in one the largest groups of HCWs in the UK. • Our preliminary data suggests one dose of the vaccine is affording some protection and the probability of a member of staff testing positive for SARS CoV-2 given that they have been vaccinated with one dose is lower than for staff who have not been vaccinated. • However, a proportion of our vaccinated HCW are still acquiring SARS-CoV-2, an important message being that one dose of the vaccination will not prevent individuals from getting COVID-19 and potentially transmitting it. • We conclude that it is imperative staff remain vigilant once they are vaccinated, due to the ongoing potential for onwards transmission to patients and other HCWs. [ABSTRACT FROM AUTHOR]

• IgG anti-SARS-CoV-2 spike glycoprotein antibody levels were greatest after vaccination and lowest after natural non-hospitalised infection. • Using lateral flow tests incorporating wildtype (Wuhan) spike glycoprotein, 40 serum samples post second vaccine dose were positive. • Changing the spike glycoprotein in the lateral flow tests to that from Alpha or Beta or Gamma variants of concern resulted for all three variants, in 40/40 positive results albeit at lower levels. • Changing the spike glycoprotein in the lateral flow tests to that from the Delta variant of concern (VOC) resulted in 37/40 positive results. • The WHO standard NIBSC 20/136 had reactivity to Alpha, Beta and Gamma VOC down to 7 IU/ml and for the Delta VOC to 15 IU/ml. [ABSTRACT FROM AUTHOR]

Patients with some types of immunodeficiency can experience chronic or relapsing infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This leads to morbidity and mortality, infection control challenges, and the risk of evolution of novel viral variants. The optimal treatment for chronic coronavirus disease 2019 (COVID-19) is unknown. Our aim was to characterize a cohort of patients with chronic or relapsing COVID-19 disease and record treatment response. We conducted a UK physician survey to collect data on underlying diagnosis and demographics, clinical features, and treatment response of immunodeficient patients with chronic (lasting ≥21 days) or relapsing (≥2 episodes) of COVID-19. We identified 31 patients (median age 49 years). Their underlying immunodeficiency was most commonly characterized by antibody deficiency with absent or profoundly reduced peripheral B-cell levels; prior anti-CD20 therapy, and X-linked agammaglobulinemia. Their clinical features of COVID-19 were similar to those of the general population, but their median duration of symptomatic disease was 64 days (maximum 300 days) and individual patients experienced up to 5 episodes of illness. Remdesivir monotherapy (including when given for prolonged courses of ≤20 days) was associated with sustained viral clearance in 7 of 23 clinical episodes (30.4%), whereas the combination of remdesivir with convalescent plasma or anti-SARS-CoV-2 mAbs resulted in viral clearance in 13 of 14 episodes (92.8%). Patients receiving no therapy did not clear SARS-CoV-2. COVID-19 can present as a chronic or relapsing disease in patients with antibody deficiency. Remdesivir monotherapy is frequently associated with treatment failure, but the combination of remdesivir with antibody-based therapeutics holds promise. [ABSTRACT FROM AUTHOR]

As of November 2020, severe acute respiratory syndrome coronavirus 2 has resulted in 55 million infections worldwide and more than 1.3 million deaths from coronavirus disease 2019 (COVID-19). Outcomes following severe acute respiratory syndrome coronavirus 2 infection in individuals with primary immunodeficiency (PID) or symptomatic secondary immunodeficiency (SID) remain uncertain. We sought to document the outcomes of individuals with PID or symptomatic SID following COVID-19 in the United Kingdom. At the start of the COVID-19 pandemic, the United Kingdom Primary Immunodeficiency Network established a registry of cases to collate the nationwide outcomes of COVID-19 in individuals with PID or symptomatic SID and determine risk factors associated with morbidity and mortality from COVID-19 in these patient groups. A total of 100 patients had been enrolled by July 1, 2020, 60 with PID, 7 with other inborn errors of immunity including autoinflammatory diseases and C1 inhibitor deficiency, and 33 with symptomatic SID. In individuals with PID, 53.3% (32 of 60) were hospitalized, the infection-fatality ratio was 20.0% (12 of 60), the case-fatality ratio was 31.6% (12 of 38), and the inpatient mortality was 37.5% (12 of 32). Individuals with SID had worse outcomes than those with PID; 75.8% (25 of 33) were hospitalized, the infection-fatality ratio was 33.3% (11 of 33), the case-fatality ratio was 39.2% (11 of 28), and inpatient mortality was 44.0% (11 of 25). In comparison to the general population, adult patients with PID and symptomatic SID display greater morbidity and mortality from COVID-19. This increased risk must be reflected in public health guidelines to adequately protect vulnerable patients from exposure to the virus. [ABSTRACT FROM AUTHOR]