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Improving our understanding of B cell transition to memory B cells (MBCs) and antibody-secreting cells (ASCs) is crucial for clinical monitoring and vaccine strategies. To explore these dynamics, we compared prepandemic antigen responses (influenza hemagglutinin, respiratory syncytial virus fusion glycoprotein, and tetanus toxoid) with recently encountered severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen responses in convalescent COVID-19 patients using spectral flow cytometry. Our analysis revealed the CD43+CD71+IgG+ activated B cell subset, highly enriched for SARS-CoV-2 specificities, as a juncture for ASC and MBC differentiation, with CD86+ phenotypically similar to ASCs and CD86- to IgG+ MBCs. Moreover, subpopulations within IgG+ MBCs were further identified based on CD73 and CD24 expression. Activated MBCs (CD73-/CD24lo) were predominantly SARS-CoV-2-specific, while resting MBCs (CD73+/CD24hi) recognized prepandemic antigens. A CD95- subcluster within resting MBCs accounted for over 40% of prepandemic-specific cells, indicating long-lasting memory. These findings advance our understanding of IgG+ MBC and ASC development stages, shedding light on the decision-making process guiding their differentiation.

Background: Severe fatigue and cognitive complaints are frequently reported after SARS-CoV-2 infection and may be accompanied by depressive symptoms and/or limitations in physical functioning. The long-term sequelae of COVID-19 may be influenced by biomedical, psychological, and social factors, the interplay of which is largely understudied over time. We aimed to investigate how the interplay of these factors contribute to the persistence of symptoms after COVID-19., Methods: RECoVERED, a prospective cohort study in Amsterdam, the Netherlands, enrolled participants aged⩾16 years after SARS-CoV-2 diagnosis. We used a structural network analysis to assess relationships between biomedical (initial COVID-19 severity, inflammation markers), psychological (illness perceptions, coping, resilience), and social factors (loneliness, negative life events) and persistent symptoms 24 months after initial disease (severe fatigue, difficulty concentrating, depressive symptoms and limitations in physical functioning). Causal discovery, an explorative data-driven approach testing all possible associations and retaining the most likely model, was performed., Results: Data from 235/303 participants (77.6%) who completed the month 24 study visit were analysed. The structural model revealed associations between the putative factors and outcomes. The outcomes clustered together with severe fatigue as its central point. Loneliness, fear avoidance in response to symptoms, and illness perceptions were directly linked to the outcomes. Biological (inflammatory markers) and clinical (severity of initial illness) variables were connected to the outcomes only via psychological or social variables., Conclusions: Our findings support a model where biomedical, psychological, and social factors contribute to the development of long-term sequelae of SARS-CoV-2 infection.

Background: After initial COVID-19, immune dysregulation may persist and drive post-acute sequelae of COVID-19 (PASC). We described longitudinal trajectories of cytokines in adults up to 6 months following SARS-CoV-2 infection and explored early predictors of PASC., Methods: RECoVERED is a prospective cohort of individuals with laboratory-confirmed SARS-CoV-2 infection between May 2020 and June 2021 in Amsterdam, the Netherlands. Serum was collected at weeks 4, 12 and 24 of follow-up. Monthly symptom questionnaires were completed from month 2 after COVID-19 onset onwards; lung diffusion capacity (DLCO) was tested at 6 months. Cytokine concentrations were analysed by human magnetic Luminex screening assay. We used a linear mixed-effects model to study log-concentrations of cytokines over time, assessing their association with socio-demographic and clinical characteristics that were included in the model as fixed effects., Results: 186/349 (53%) participants had ≥2 serum samples and were included in current analyses. Of these, 101/186 (54%: 45/101[45%] female, median age 55 years [IQR = 45-64]) reported PASC at 12 and 24 weeks after COVID-19 onset. We included 37 reference samples (17/37[46%] female, median age 49 years [IQR = 40-56]). In a multivariate model, PASC was associated with raised CRP and abnormal diffusion capacity with raised IL10, IL17, IL6, IP10 and TNFα at 24 weeks. Early (0-4 week) IL-1β and BMI at COVID-19 onset were predictive of PASC at 24 weeks., Conclusions: Our findings indicate that immune dysregulation plays an important role in PASC pathogenesis, especially among individuals with reduced pulmonary function. Early IL-1β shows promise as a predictor of PASC., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wynberg et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

During the COVID-19 pandemic, levels of seasonal influenza virus circulation were unprecedentedly low, leading to concerns that a lack of exposure to influenza viruses, combined with waning antibody titres, could result in larger and/or more severe post-pandemic seasonal influenza epidemics. However, in most countries the first post-pandemic influenza season was not unusually large and/or severe. Here, based on an analysis of historical influenza virus epidemic patterns from 2002 to 2019, we show that historic lulls in influenza virus circulation had relatively minor impacts on subsequent epidemic size and that epidemic size was more substantially impacted by season-specific effects unrelated to the magnitude of circulation in prior seasons. From measurements of antibody levels from serum samples collected each year from 2017 to 2021, we show that the rate of waning of antibody titres against influenza virus during the pandemic was smaller than assumed in predictive models. Taken together, these results partially explain why the re-emergence of seasonal influenza virus epidemics was less dramatic than anticipated and suggest that influenza virus epidemic dynamics are not currently amenable to multi-season prediction., (© 2024. The Author(s).)

Neutrophils are important players in COVID-19, contributing to tissue damage by release of inflammatory mediators, including ROS and neutrophil elastase. Longitudinal studies on the effects of COVID-19 on neutrophil phenotype and function are scarce. Here, we longitudinally investigated the phenotype and degranulation of neutrophils in COVID-19 patients (28 nonhospitalized and 35 hospitalized patients) compared with 17 healthy donors (HDs). We assessed phenotype, degranulation, CXCL8 (IL-8) release, and ROS generation within 8 days, at one or 6 month(s) after COVID-19 diagnosis. For degranulation and ROS production, we stimulated neutrophils, either with ssRNA and TNF or granulocyte-macrophage colony-stimulating factor and N-Formylmethionyl-leucyl-phenylalanine. During active COVID-19, neutrophils from hospitalized patients were more immature than from HDs and were impaired in degranulation and ROS generation, while neutrophils from nonhospitalized patients only demonstrated reduced CD66b + granule release and ROS production. Baseline CD63 expression, indicative of primary granule release, and CXCL8 production by neutrophils from hospitalized patients were elevated for up to 6 months. These findings show that patients hospitalized due to COVID-19, but not nonhospitalized patients, demonstrated an aberrant neutrophil phenotype, degranulation, CXCL8 release, and ROS generation that partially persists up to 6 months after infection., (© 2023 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.)

Objective: To investigate to what extent individuals report clinically relevant levels of depression, anxiety, post-traumatic stress disorder (PTSD) symptoms and concentration problems up to 12 months following COVID-19 symptom onset, using validated questionnaires., Methods: RECoVERED, a prospective cohort study in Amsterdam, the Netherlands, enrolled both hospitalized and community-dwelling adult participants diagnosed with SARS-CoV-2. Symptoms of depression and anxiety were assessed with the Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7 1, 3, 6 and 12 months following illness onset. The DSM-V PTSD checklist was administered at month 3 and 9. Concentration problems were assessed using the Checklist Individual Strength concentration subscale at month 1 and 12. Generalized Estimating Equations were used to determine factors related with clinically relevant levels of depression-, anxiety- and PTSD-symptoms and concentration problems over time., Results: In 303 individuals, the prevalence of clinically relevant symptoms of depression, anxiety and concentration problems was 10.6% (95%CI = 7.2-15.4), 7.0% (95%CI = 4.4-11.2) and 33.6% (95%CI = 27.7-40.1), respectively, twelve months after infection. Nine months after illness onset, 4.2% (95%CI = 2.3-7.7) scored within the clinical range of PTSD. Risk factors for an increased likelihood of reporting mental health problems during follow up included initial severe/critical COVID-19, non-Dutch origin, psychological problems prior to COVID-19 and being infected during the first COVID-19 wave., Conclusion: Our findings highlight that a minority of patients with COVID-19 face clinically relevant symptoms of depression, anxiety or PTSD up to 12 months after infection. The prevalence of concentration problems was high. This study contributes to the identification of specific groups for which support after initial illness is indicated., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interests., (Copyright © 2023. Published by Elsevier Inc.)

Background: We used data from a prospective cohort to explore 2-year trajectories of 'long COVID' (persistent symptoms after SARS-CoV-2 infection) and their association with illness perception., Methods: RECoVERED participants (adults; prospectively enrolled following laboratory-confirmed SARS-CoV-2 infection, May 2020-June 2021) completed symptom questionnaires at months 2-12, 18 and 24, and the Brief Illness Perception Questionnaire (B-IPQ) at months 1, 6 and 12. Using group-based trajectory models (GBTM), we modelled symptoms (mean total numbers and proportion with four specific complaints), including age, sex, BMI and timing of infection as covariates. In a multivariable linear mixed-effects model, we assessed the association between symptom trajectories and repeated B-IPQ scores., Results: Among 292 participants (42% female; median age 51 [IQR = 36-62]), four trajectories were identified, ranging from Trajectory 4 (8.9%; 6 + symptoms) to Trajectory 1 (24.8%; no symptoms). The occurrence of fatigue and myalgia increased among 23% and 12% of participants, respectively. Individuals in Trajectory 4 experienced more negative adjusted B-IPQ scores over time than those in Trajectories 1-3., Conclusions: We observed little fluctuation in the total number of symptoms, but individual symptoms may develop as others resolve. Reporting a greater number of symptoms was congruent with more negative illness perception over time., Competing Interests: The authors have no relevant conflicts of interests to declare., (© 2023 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Background: There is increasing data that show a persistently impaired pulmonary function upon recovery after severe infection. Little is known however about the extent, recovery and determinants of pulmonary impairment across the full spectrum of COVID-19 severity over time., Methods: In a well characterized, prospective cohort of both hospitalised and non-hospitalised individuals with SARS-CoV-2 infection, the RECoVERED study, pulmonary function (diffusing capacity for carbon monoxide (DLCO)) and spirometry) was measured until one year after disease onset. Additionally, data on sociodemographics, clinical characteristics, symptoms, and health-related quality of life (HRQL) were collected. Pulmonary function and these determinants were modelled over time using mixed-effect linear regression. Determinants of pulmonary function impairment at 12 months after disease onset were identified using logistic regression., Findings: Between May 2020 and December 2021, 301 of 349 participants underwent at least one pulmonary function test. After one year of follow-up, 25% of the participants had an impaired pulmonary function which translates in 11%, 22%, and 48% of the participants with mild, moderate and severe/critical COVID-19. Improvement in DLCO among the participants continued over the period across one, six and twelve months. Being older, having more than three comorbidities (p<0·001) and initial severe/critical disease (p<0·001) were associated with slower improvement of pulmonary function over time, adjusted for age and sex. HRQL improved over time and at 12 months was comparable to individuals without impaired pulmonary function., Interpretation: The prevalence of impaired pulmonary function after twelve months of follow-up, was still significant among those with initially moderate or severe/critical COVID-19. Pulmonary function increased over time in most of the severity groups. These data imply that guidelines regarding revalidation after COVID-19 should target individuals with moderate and severe/critical disease severities., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 van Willigen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: During the first two years of the COVID-19 pandemic, the circulation of seasonal influenza viruses was unprecedentedly low. This led to concerns that the lack of immune stimulation to influenza viruses combined with waning antibody titres could lead to increased susceptibility to influenza in subsequent seasons, resulting in larger and more severe epidemics., Methods: We analyzed historical influenza virus epidemiological data from 2003-2019 to assess the historical frequency of near-absence of seasonal influenza virus circulation and its impact on the size and severity of subsequent epidemics. Additionally, we measured haemagglutination inhibition-based antibody titres against seasonal influenza viruses using longitudinal serum samples from 165 healthy adults, collected before and during the COVID-19 pandemic, and estimated how antibody titres against seasonal influenza waned during the first two years of the pandemic., Findings: Low country-level prevalence of influenza virus (sub)types over one or more years occurred frequently before the COVID-19 pandemic and had relatively small impacts on subsequent epidemic size and severity. Additionally, antibody titres against seasonal influenza viruses waned negligibly during the first two years of the pandemic., Interpretation: The commonly held notion that lulls in influenza virus circulation, as observed during the COVID-19 pandemic, will lead to larger and/or more severe subsequent epidemics might not be fully warranted, and it is likely that post-lull seasons will be similar in size and severity to pre-lull seasons., Funding: European Research Council, Netherlands Organization for Scientific Research, Royal Dutch Academy of Sciences, Public Health Service of Amsterdam., Research in Context: Evidence before this study: During the first years of the COVID-19 pandemic, the incidence of seasonal influenza was unusually low, leading to widespread concerns of exceptionally large and/or severe influenza epidemics in the coming years. We searched PubMed and Google Scholar using a combination of search terms (i.e., "seasonal influenza", "SARS-CoV-2", "COVID-19", "low incidence", "waning rates", "immune protection") and critically considered published articles and preprints that studied or reviewed the low incidence of seasonal influenza viruses since the start of the COVID-19 pandemic and its potential impact on future seasonal influenza epidemics. We found a substantial body of work describing how influenza virus circulation was reduced during the COVID-19 pandemic, and a number of studies projecting the size of future epidemics, each positing that post-pandemic epidemics are likely to be larger than those observed pre-pandemic. However, it remains unclear to what extent the assumed relationship between accumulated susceptibility and subsequent epidemic size holds, and it remains unknown to what extent antibody levels have waned during the COVID-19 pandemic. Both are potentially crucial for accurate prediction of post-pandemic epidemic sizes. Added value of this study: We find that the relationship between epidemic size and severity and the magnitude of circulation in the preceding season(s) is decidedly more complex than assumed, with the magnitude of influenza circulation in preceding seasons having only limited effects on subsequent epidemic size and severity. Rather, epidemic size and severity are dominated by season-specific effects unrelated to the magnitude of circulation in the preceding season(s). Similarly, we find that antibody levels waned only modestly during the COVID-19 pandemic. Implications of all the available evidence: The lack of changes observed in the patterns of measured antibody titres against seasonal influenza viruses in adults and nearly two decades of epidemiological data suggest that post-pandemic epidemic sizes will likely be similar to those observed pre-pandemic, and challenge the commonly held notion that the widespread concern that the near-absence of seasonal influenza virus circulation during the COVID-19 pandemic, or potential future lulls, are likely to result in larger influenza epidemics in subsequent years.

Background: Currently, there is limited evidence about the long-term impact on physical, social and emotional functioning, i.e. health-related quality of life (HRQL) after mild or moderate COVID-19 not requiring hospitalization. We compared HRQL among persons with initial mild, moderate or severe/critical COVID-19 at 1 and 12 months following illness onset with Dutch population norms and investigated the impact of restrictive public health control measures on HRQL., Methods: RECoVERED, a prospective cohort study in Amsterdam, the Netherlands, enrolled adult participants after confirmed SARS-CoV-2 diagnosis. HRQL was assessed with the Medical Outcomes Study Short Form 36-item health survey (SF-36). SF-36 scores were converted to standard scores based on an age- and sex-matched representative reference sample of the Dutch population. Differences in HRQL over time were compared among persons with initial mild, moderate or severe/critical COVID-19 using mixed linear models adjusted for potential confounders., Results: By December 2021, 349 persons were enrolled of whom 269 completed at least one SF-36 form (77%). One month after illness onset, HRQL was significantly below population norms on all SF-36 domains except general health and bodily pain among persons with mild COVID-19. After 12 months, persons with mild COVID-19 had HRQL within population norms, whereas persons with moderate or severe/critical COVID-19 had HRQL below population norms on more than half of the SF-36 domains. Dutch-origin participants had significantly better HRQL than participants with a migration background. Participants with three or more COVID-19 high-risk comorbidities had worse HRQL than part participants with fewer comorbidities. Participants who completed the SF-36 when restrictive public health control measures applied reported less limitations in social and physical functioning and less impaired mental health than participants who completed the SF-36 when no restrictive measures applied., Conclusions: Twelve months after illness onset, persons with initial mild COVID-19 had HRQL within population norms, whereas persons with initial moderate or severe/critical COVID-19 still had impaired HRQL. Having a migration background and a higher number of COVID-19 high-risk comorbidities were associated with worse HRQL. Interestingly, HRQL was less impaired during periods when restrictive public health control measures were in place compared to periods without., (© 2022. The Author(s).)

Large-scale vaccination campaigns have prevented countless hospitalizations and deaths due to COVID-19. However, the emergence of SARS-CoV-2 variants that escape from immunity challenges the effectiveness of current vaccines. Given this continuing evolution, an important question is when and how to update SARS-CoV-2 vaccines to antigenically match circulating variants, similarly to seasonal influenza viruses where antigenic drift necessitates periodic vaccine updates. Here, we studied SARS-CoV-2 antigenic drift by assessing neutralizing activity against variants of concern (VOCs) in a set of sera from patients infected with viral sequence-confirmed VOCs. Infections with D614G or Alpha strains induced the broadest immunity, whereas individuals infected with other VOCs had more strain-specific responses. Omicron BA.1 and BA.2 were substantially resistant to neutralization by sera elicited by all other variants. Antigenic cartography revealed that Omicron BA.1 and BA.2 were antigenically most distinct from D614G, associated with immune escape, and possibly will require vaccine updates to ensure vaccine effectiveness., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Few robust longitudinal data on long-term coronavirus disease 2019 (COVID-19) symptoms are available. We evaluated symptom onset, severity and recovery across the full spectrum of disease severity, up to one year after illness onset., Methods: The RECoVERED Study is a prospective cohort study based in Amsterdam, the Netherlands. Participants aged ≥18 years were enrolled following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnosis via the local public health service and from hospitals. Standardized symptom questionnaires were completed at enrollment, 1 week and month later, and monthly thereafter. Clinical severity was defined according to World Health Organization (WHO) criteria. Kaplan-Meier methods were used to compare time from illness onset to symptom recovery, by clinical severity. We examined determinants of time to recovery using multivariable Cox proportional hazards models., Results: Between 11 May 2020 and 1 May 2021, 342 COVID-19 patients (192 [56%] male) were enrolled, of whom 99/342 (29%) had mild, 145/342 (42%) moderate, 56/342 (16%) severe, and 42/342 (12%) critical disease. The proportion of participants who reported at least 1 persistent symptom at 12 weeks after illness onset was greater in those with severe/critical disease (86.7% [95% confidence interval {CI} = 76.5-92.7%]) compared to those with mild or moderate disease (30.7% [95% CI = 21.1-40.9%] and 63.8% [95% CI = 54.8-71.5%], respectively). At 12 months after illness onset, two-fifths of participants (40.7% [95% CI = 34.2-7.1]) continued to report ≥1 symptom. Recovery was slower in female compared to male participants (adjusted hazard ratio [aHR] 0.65 [95% CI = .47-.92]) and those with a body mass index [BMI]  ≥30kg/m2 compared to BMI <25kg/m2 (hazard ratio [HR] 0.62 [95% CI = .39-.97])., Conclusions: COVID-19 symptoms persisted for one year after illness onset, even in some individuals with mild disease. Female sex and obesity were the most important determinants of speed of recovery from symptoms., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Symptoms of post-acute sequelae of COVID-19 (PASC) may improve following SARS-CoV-2 vaccination. However few prospective data that also explore the underlying biological mechanism are available. We assessed the effect of vaccination on symptomatology of participants with PASC, and compared antibody dynamics between those with and without PASC., Methods: RECoVERED is a prospective cohort study of adult patients with mild to critical COVID-19, enrolled from illness onset. Among participants with PASC, vaccinated participants were exact-matched 1:1 on age, sex, obesity status and time since illness onset to unvaccinated participants. Between matched pairs, we compared the monthly mean numbers of symptoms over a 3-month follow-up period, and, using exact logistic regression, the proportion of participants who fully recovered from PASC. Finally, we assessed the association between PACS status and rate of decay of spike- and RBD-binding IgG titers up to 9 months after illness onset using Bayesian hierarchical linear regression., Findings: Of 349 enrolled participants, 316 (90.5%) had ≥3 months of follow-up, of whom 186 (58.9%) developed PASC. Among 36 matched pairs with PASC, the mean number of symptoms reported each month during 3 months of follow-up were comparable between vaccinated and unvaccinated groups. Odds of full recovery from PASC also did not differ between matched pairs (OR 1.57 [95%CI 0.46-5.84]) within 3 months after the matched time-point. The median half-life of spike- and RBD-binding IgG levels were, in days (95%CrI), 233 (183-324) and 181 (147-230) among participants with PASC, and 170 (125-252) and 144 (113-196) among those without PASC, respectively., Interpretation: Our study found no strong evidence to suggest that vaccination improves symptoms of PASC. This was corroborated by comparable spike- and RBD-binding IgG waning trajectories between those with and without PASC, refuting any immunological basis for a therapeutic effect of vaccination on PASC., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: A.B. received a grant from ANRS in the past 36 months and participated on the Data Safety Monitoring Board or Advisory Board for ZonMw for a study conducted by the Amsterdam University Medical Centers, location Amsterdam Medical Center. G.d.B. served as a paid member of the scientific advisory board of ExeVir in the past 36 months, and is a patent holder of INV 2020-039 both through their institution. All other authors report no potential conflicts., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Emerging and future SARS-CoV-2 variants may jeopardize the effectiveness of vaccination campaigns. Therefore, it is important to know how the different vaccines perform against diverse SARS-CoV-2 variants., Methods and Findings: In a prospective cohort of 165 SARS-CoV-2 naive health care workers in the Netherlands, vaccinated with either one of four vaccines (BNT162b2, mRNA-1273, AZD1222 or Ad26.COV2.S), we performed a head-to-head comparison of the ability of sera to recognize and neutralize SARS-CoV-2 variants of concern (VOCs; Alpha, Beta, Gamma, Delta and Omicron). Repeated serum sampling was performed 5 times during a year (from January 2021 till January 2022), including before and after booster vaccination with BNT162b2. Four weeks after completing the initial vaccination series, SARS-CoV-2 wild-type neutralizing antibody titers were highest in recipients of mRNA-1273, followed by recipients of BNT162b2 (geometric mean titers (GMT) of 358 [95% CI 231-556] and 214 [95% CI 153-299], respectively; p<0.05), and substantially lower in those vaccinated with the adenovirus vector-based vaccines AZD1222 and Ad26.COV2.S (GMT of 18 [95% CI 11-30] and 14 [95% CI 8-25] IU/ml, respectively; p<0.001). VOCs neutralization was reduced in all vaccine groups, with the greatest reduction in neutralization GMT observed against the Omicron variant (fold change 0.03 [95% CI 0.02-0.04], p<0.001). The booster BNT162b2 vaccination increased neutralizing antibody titers for all groups with substantial improvement against the VOCs including the Omicron variant. We used linear regression and linear mixed model analysis. All results were adjusted for possible confounding of age and sex. Study limitations include the lack of cellular immunity data., Conclusions: Overall, this study shows that the mRNA vaccines appear superior to adenovirus vector-based vaccines in inducing neutralizing antibodies against VOCs four weeks after initial vaccination and after booster vaccination, which implies the use of mRNA vaccines for both initial and booster vaccination., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Amsterdam UMC filed a patent application on SARS-CoV-2 monoclonal antibodies including the ones used in this manuscript.

Background: Severe fatigue can persist for months after coronavirus disease 2019 (COVID-19) onset. This longitudinal study describes fatigue severity and its determinants up to 12 months after illness onset across the full spectrum of COVID-19 severity., Methods: RECoVERED, a prospective cohort study in Amsterdam, the Netherlands, enrolled participants aged ≥16 years after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnosis. Fatigue was measured using the validated Short Fatigue Questionnaire (SFQ; range 4-28) at months 1, 3, 6, 9, and 12 of follow-up. Fatigue severity was modeled over time using mixed-effects linear regression. Determinants of severe fatigue (SFQ ≥18) at 6 months since illness onset (ie, persistent fatigue) were identified using logistic regression., Results: Between May 2020 and July 2021, 303 participants completed at least 1 fatigue questionnaire. Twelve months after illness onset, 17.4% (95% CI, 6.7% to 38.3%), 21.6% (95% CI, 11.2% to 37.7%), and 44.8% (95% CI, 28.0% to 62.9%) of participants with mild, moderate, and severe/critical COVID-19 (World Health Organization definition), respectively, experienced severe fatigue. When adjusting for age and sex, having ≥3 comorbidities ( P  = .007), severe/critical COVID-19 ( P  = .002), low mood ( P  < .001), and dyspnea in the first 2 weeks of illness ( P  = .001) were associated with more severe fatigue over time. Severe/critical COVID-19 (adjusted odds ratio [aOR], 3.37; 95% CI, 1.28 to 8.93) and low mood at enrollment (aOR, 2.43; 95% CI, 1.11 to 5.29) were associated with persistent fatigue. Recovery rarely occurred beyond 6 months after illness onset, regardless of COVID-19 severity., Conclusions: The occurrence of severe fatigue in our cohort was high, especially among those with initially severe/critical COVID-19, with little recovery beyond 6 months after illness onset. Our findings highlight an urgent need for improved understanding of persistent severe fatigue following COVID-19 to help inform prevention and intervention., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

The urgent need for, but limited availability of, SARS-CoV-2 vaccines worldwide has led to widespread consideration of dose-sparing strategies. Here, we evaluate the SARS-CoV-2-specific antibody responses following BNT162b2 vaccination in 150 previously SARS-CoV-2-infected individuals from a population-based cohort. One week after first vaccine dose, spike protein antibody levels are 27-fold higher and neutralizing antibody titers 12-fold higher, exceeding titers of fully vaccinated SARS-CoV-2-naive controls, with minimal additional boosting after the second dose. Neutralizing antibody titers against four variants of concern increase after vaccination; however, overall neutralization breadth does not improve. Pre-vaccination neutralizing antibody titers and time since infection have the largest positive effect on titers following vaccination. COVID-19 severity and the presence of comorbidities have no discernible impact on vaccine response. In conclusion, a single dose of BNT162b2 vaccine up to 15 months after SARS-CoV-2 infection offers higher neutralizing antibody titers than 2 vaccine doses in SARS-CoV-2-naive individuals., Competing Interests: The authors declare no competing interests., (© 2021.)

Emerging SARS-CoV-2 variants of concern (VOCs) pose a threat to human immunity induced by natural infection and vaccination. We assessed the recognition of three VOCs (B.1.1.7, B.1.351, and P.1) in cohorts of COVID-19 convalescent patients ( n = 69) and Pfizer-BioNTech vaccine recipients ( n = 50). Spike binding and neutralization against all three VOCs were substantially reduced in most individuals, with the largest four- to sevenfold reduction in neutralization being observed against B.1.351. While hospitalized patients with COVID-19 and vaccinees maintained sufficient neutralizing titers against all three VOCs, 39% of nonhospitalized patients exhibited no detectable neutralization against B.1.351. Moreover, monoclonal neutralizing antibodies show sharp reductions in their binding kinetics and neutralizing potential to B.1.351 and P.1 but not to B.1.1.7. These data have implications for the degree to which pre-existing immunity can protect against subsequent infection with VOCs and informs policy makers of susceptibility to globally circulating SARS-CoV-2 VOCs.