ABSTRACT
We studied the clinical and immunological outcomes of covid-19 infection in strictly consecutive patients with CLL from a well-defined area during the first 13 months of the pandemic. Sixty patients with a median age of 71 years (range 43-97) were identified. Median CIRS was 8 (4-20), median BMI 25 (19-42) and 65% were men. Patients had indolent CLL (n=38), were previously treated (n=12) or had ongoing therapy (n=10, among which seven received BTKi). Forty-six patients (77%) were hospitalized due to severe covid-19 and among them, 11 (24%) were admitted to the intensive care unit (ICU). Severe covid-19 was equally distributed across subgroups irrespective of age, gender, BMI, CLL status except for comorbidities (CIRS >6, p<0.05). Fourteen patients (23%) died;age ≥75 years was the only significant risk factor (p<0.05, uni- and multivariate analyses). Comparing months 1-6 vs. 7-13 of the pandemic, death rates were reduced from 32 to 18%, ICU admission from 37 to 15% and hospitalizations remained frequent (86 vs. 71%). Seroconversion occurred in 34/41 tested patients (83%) and anti-SARS-CoV-2 antibodies remained detectable at 6 and 12 months of follow-up in 17/22 and 8/11 patients, respectively. In-depth immunological analysis revealed that 13/17 tested patients had neutralizing antibodies (including all 12 patients that were also seropositive in conventional serology in this cohort), and 19/28 (68%) had antibodies in saliva. SARS-CoV- 2-specific T-cells (IFN-gamma ELISpot) were detected in 14/17 patients (82%). We conclude that covid-19 in non-selected CLL patients continued to result in a high admission rate even among young early-stage patients. A robust and durable B and/or T cell immunity was observed in most convalescents.
ABSTRACT
BACKGROUND: In Sweden, social restrictions to contain SARS-CoV-2 have primarily relied upon voluntary adherence to a set of recommendations. Strict lockdowns have not been enforced, potentially affecting viral dissemination. To understand the levels of past SARS-CoV-2 infection in the Stockholm population before the start of mass vaccinations, healthy blood donors and pregnant women (n = 5,100) were sampled at random between 14 March 2020 and 28 February 2021. METHODS: In this cross-sectional prospective study, otherwise-healthy blood donors (n = 2,600) and pregnant women (n = 2,500) were sampled for consecutive weeks (at four intervals) throughout the study period. Sera from all participants and a cohort of historical (negative) controls (n = 595) were screened for IgG responses against stabilized trimers of the SARS-CoV-2 spike (S) glycoprotein and the smaller receptor-binding domain (RBD). As a complement to standard analytical approaches, a probabilistic (cut-off independent) Bayesian framework that assigns likelihood of past infection was used to analyse data over time. SETTING: Healthy participant samples were randomly selected from their respective pools through Karolinska University Hospital. The study was carried out in accordance with Swedish Ethical Review Authority: registration number 2020-01807. PARTICIPANTS: No participants were symptomatic at sampling, and blood donors were all over the age of 18. No additional metadata were available from the participants. RESULTS: Blood donors and pregnant women showed a similar seroprevalence. After a steep rise at the start of the pandemic, the seroprevalence trajectory increased steadily in approach to the winter second wave of infections, approaching 15% of all individuals surveyed by 13 December 2020. By the end of February 2021, 19% of the population tested seropositive. Notably, 96% of seropositive healthy donors screened (n = 56) developed neutralizing antibody responses at titres comparable to or higher than those observed in clinical trials of SARS-CoV-2 spike mRNA vaccination, supporting that mild infection engenders a competent B-cell response. CONCLUSIONS: These data indicate that in the first year since the start of community transmission, seropositivity levels in metropolitan in Stockholm had reached approximately one in five persons, providing important baseline seroprevalence information prior to the start of vaccination.