The eCRF contained information on gender, age, symptoms of COVID-19, rt-PCR test result, comorbidities and medication, treatment, and outcome. Table 1 Patient demographics. thead th align=”left” rowspan=”1″ colspan=”1″ /th th align=”center” rowspan=”1″ colspan=”1″ Community patients /th th align=”center” rowspan=”1″ colspan=”1″ Hospitalized patients /th th align=”left” rowspan=”1″ colspan=”1″ /th /thead Total:n = 38n = 14Age (mean, range)49 (19C80)60 (45C75)nsDays since diagnose median (range)188 (171C245)182 (154C204)nsFemale17 (45%)6 (43%)nsMale21 (55%)8 (57%)nsWith any comorbidity (incl BMI 30 obesity grade 1)14 (37%)11(79%)P 0.008Known comorbidity (CBMI)14 (37%)9 (64%)P = 0.077Diabetes2 (5%)2 (14%)nsHypertension6 (16%)6 (43%)p = Dapson 0.04Asthma4 (11%)1 (7%)nsChronic lung disease (excluding asthma)0 (0%)2 BTLA (14%)nsChronic heart disease4 (11%)5 (36%)P = 0.05Chronic renal disease0 (0%)1 (7%)naChronic hepatic disease0 (0%)1 (7%)naChronic neurological disease0 (0%)1(7%)naCancer1 (3%)1 (7%)naBMI m2/kg (median)24.627.1p = 0.05 Open in a separate window The demographics of the SARS-Cov-2 infected patients recruited during the first pandemic wave in March/April in Bergen, Norway. Supporting information files. Abstract Background Neutralizing antibodies are important for protection against the pandemic SARS-CoV-2 virus, and long-term memory responses determine the risk of re-infection or boosting Dapson after vaccination. T-cellular responses are considered important for partial protection against novel variants of concern. Methods A prospective cohort of hospitalized (n = 14) and community (n = 38) patients with rt-PCR confirmed SARS-CoV-2 infection were recruited. Blood samples and clinical data were collected when diagnosed and at 6 months. Serum samples were analyzed for SARS-CoV-2-spike specific antibodies using ELISA (IgG, IgA, IgM), pseudotype neutralization and microneutralization assays. Peripheral blood mononuclear cells were investigated for virus-specific T-cell responses in the interferon- and interleukin-2 fluorescent-linked immunosorbent spot (FluroSpot) assay. Results We found durable SARS-CoV-2 spike- and internal protein specific T-cellular responses in patients with persistent antibodies at 6 months. Significantly higher IL-2 and IFN- secreting T-cell responses as well as SARS-CoV-2 specific IgG and neutralizing antibodies were detected in hospitalized compared to community patients. The immune response was impacted by age, gender, comorbidity and severity of illness, reflecting clinical observations. Conclusions SARS-CoV-2 specific T-cellular and antibody responses persisted for 6 months post confirmed infection. In previously infected patients, re-exposure or vaccination will boost long-term immunity, possibly providing protection against re-infection with variant viruses. Introduction The novel severe acute respiratory coronavirus 2 (SARS-CoV-2) was first reported in humans in Wuhan, China, causing severe viral pneumonia and death. The virus has subsequentially spread globally, causing the most devastating pandemic since the Spanish influenza A/H1N1 in 1918. The clinical characteristics of SARS-CoV-2 disease have been well described [1, 2]. SARS-CoV-2 virus is primarily a trigger for an immunological illness, which affects several organ systems. The severity of illness is dependent on age and comorbidity and related to the individuals primary immunological response. The quality of the long-term immune response determines the risk of re-infection. Detailed immunological knowledge, however, is limited and primarily focused on antibody responses. Early clinical observations of gender differences during acute infection found that males had a higher risk of severe disease and mortality [3, 4]. Dapson These findings have been supported by reports of immunological differences related to gender, such as less robust T-cell responses in males  and findings of sex differences in immune responses to vaccines and infection . Most infected people seroconvert but reports of antibody waning and heterogeneity in antibody responses among infected people, have caused concern for the long-term protection after infection and particularly with the ongoing vaccination campaign [7, 8] The protective antibody level is unknown, and there is no agreed correlate of protection to date . Community protection is the goal of SARS-CoV-2 mass vaccination. Similarly, protection from re-infection is dependent upon long-term memory elicited after primary infection. The immune response is essential and correlates with the severity of SARS-CoV-2 infection [10, 11]. Eighteen months has passed since the start of the pandemic and the global research conducted is unprecedented in speed and magnitude. Naturally, there is substantially less knowledge of durable immune responses after SARS-CoV-2 compared to acute immune responses. T cells support antibody production by providing a Dapson prolonged B-cell response. However, the evidence of re-infection and short-lived immunity against the human coronaviruses (HCoV) has raised concern that immunity could be short lived . With antibody titers waning over time, cellular immune responses, both B and T cells will be vital in limiting disease severity [13, 14]. Indeed, cellular protection has been confirmed in an animal challenge model . Although recent studies find robust cellular immune responses post-infection, their longevity is unknown, however reports of more than six months and reports of persistent MBCs in the elderly despite reduction in neutralizing antibodies have been made . Encouragingly, cellular responses after SARS in 2003 were found up to 6 years post-infection and are thought to last longer compared to antibody responses . Here we report on durable SARS-CoV-2 specific antibody and T-cellular immune responses 6 months post-infection in rt-PCR (reverse transcription polymerase chain reaction) confirmed cases of varying disease severity (community and hospitalized patients) in a prospective cohort study. Methods Patients and study design Patients were prospectively recruited during the first pandemic wave in Bergen, Norway (March- June 2020) from patients diagnosed at a centralized out-patient clinic (n = 86, mildly to moderately ill), and from hospitalized patients (n = 14 with moderate to severe disease needing oxygen or ICU treatment). Informed consent was obtained prior to recruitment (from the next of kin.
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