Elevated SARS-CoV-2-Specific Antibody Levels in Patients with Post-COVID Syndrome

With the routine use of effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, the number of life-threatening coronavirus disease 2019 (COVID-19) courses have largely been reduced. However, multiple COVID-19 convalescents, even after asymptomatic to moderate disease, suffer from post-COVID syndrome, with relevant limitations in daily life. The pathophysiologic mechanisms of post-COVID syndrome are still elusive, with dysregulation of the immune system suggested as a central mechanism. Here, we assessed COVID-19 post-infectious symptoms (5–6 months after PCR-confirmed acute infection) together with the humoral immune response against SARS-CoV-2 in non-hospitalized COVID-19 convalescents, early (5–6 weeks) and late (5–6 months) after their first positive SARS-CoV-2 PCR result. Convalescents reporting several post-infectious symptoms (>3) showed higher anti-spike and anti-nucleocapsid antibody levels 5–6 weeks after PCR-confirmed infection with the latter remained increased 5–6 months after positive PCR. Likewise, a higher post-infectious symptom score was associated with increased antibody levels. Of note, convalescents displaying neuro-psychiatric symptoms such as restlessness, palpitations, irritability, and headache, as well as general symptoms such as fatigue/reduced power had higher SARS-CoV-2-specific antibody levels compared with asymptomatic cases. The increased humoral immune response in convalescents with post-COVID syndrome might be useful for the detection of individuals with an increased risk for post-COVID syndrome.

[1]  H. Volk,et al.  Author Correction: A prospective observational study of post-COVID-19 chronic fatigue syndrome following the first pandemic wave in Germany and biomarkers associated with symptom severity , 2022, Nature Communications.

[2]  T. Welte,et al.  [Frequency, spectrum and risk factors of long COVID]. , 2022, Innere Medizin.

[3]  H. Din,et al.  Anti-nucleocapsid antibody levels and pulmonary comorbid conditions are linked to post–COVID-19 syndrome , 2022, JCI insight.

[4]  Koichiro Yamamoto,et al.  Clinical Characteristics of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Diagnosed in Patients with Long COVID , 2022, Medicina.

[5]  J. Linseisen,et al.  Post-COVID-19 Fatigue and SARS-CoV-2 Specific Humoral and T-Cell Responses in Male and Female Outpatients , 2022, Frontiers in Immunology.

[6]  Thomas E. Nichols,et al.  SARS-CoV-2 is associated with changes in brain structure in UK Biobank , 2022, Nature.

[7]  M. Van Ranst,et al.  Lower persistence of anti-nucleocapsid compared to anti-spike antibodies up to one year after SARS-CoV-2 infection , 2022, Diagnostic Microbiology and Infectious Disease.

[8]  Inyoul Y. Lee,et al.  Multiple early factors anticipate post-acute COVID-19 sequelae , 2022, Cell.

[9]  E. Guedj,et al.  Visual interpretation of brain hypometabolism related to neurological long COVID: a French multicentric experience , 2021, European Journal of Nuclear Medicine and Molecular Imaging.

[10]  M. Peluso,et al.  Role of antibodies, inflammatory markers, and echocardiographic findings in postacute cardiopulmonary symptoms after SARS-CoV-2 infection , 2021, medRxiv.

[11]  K. Rabe,et al.  S1-Leitlinie Post-COVID/Long-COVID , 2021, Pneumologie.

[12]  M. Blaser,et al.  Determinants and Dynamics of SARS-CoV-2 Infection in a Diverse Population: 6-Month Evaluation of a Prospective Cohort Study , 2021, The Journal of infectious diseases.

[13]  R. Claus,et al.  One Year after Mild COVID-19: The Majority of Patients Maintain Specific Immunity, But One in Four Still Suffer from Long-Term Symptoms , 2021, Journal of clinical medicine.

[14]  A. Galiana,et al.  Antibody Response to SARS-CoV-2 is Associated with Long-term Clinical Outcome in Patients with COVID-19: a Longitudinal Study , 2021, Journal of Clinical Immunology.

[15]  Ryan J. Low,et al.  Characterizing long COVID in an international cohort: 7 months of symptoms and their impact , 2021, EClinicalMedicine.

[16]  U. Merle,et al.  Persistent Symptoms in Adult Patients 1 Year After Coronavirus Disease 2019 (COVID-19): A Prospective Cohort Study , 2021, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[17]  Marek Orzechowski,et al.  SARS‐CoV‐2 antibody persistence in COVID‐19 convalescent plasma donors: Dependency on assay format and applicability to serosurveillance , 2021, Transfusion.

[18]  P. Boscolo-Rizzo,et al.  Sequelae in adults at 12 months after mild‐to‐moderate coronavirus disease 2019 (COVID‐19) , 2021, International forum of allergy & rhinology.

[19]  M. Isola,et al.  Post-COVID-19 symptoms 6 months after acute infection among hospitalized and non-hospitalized patients , 2021, Clinical Microbiology and Infection.

[20]  S. Rosenkranz,et al.  Post-COVID syndrome in non-hospitalised patients with COVID-19: a longitudinal prospective cohort study , 2021, The Lancet Regional Health - Europe.

[21]  Henrik Nielsen,et al.  Post-acute effects of SARS-CoV-2 infection in individuals not requiring hospital admission: a Danish population-based cohort study , 2021, The Lancet Infectious Diseases.

[22]  A. Vassall,et al.  Count the cost of disability caused by COVID-19 , 2021, Nature.

[23]  Paul J. Harrison,et al.  6-month neurological and psychiatric outcomes in 236 379 survivors of COVID-19: a retrospective cohort study using electronic health records , 2021, The Lancet Psychiatry.

[24]  W. Lim,et al.  Long Covid in adults discharged from UK hospitals after Covid-19: A prospective, multicentre cohort study using the ISARIC WHO Clinical Characterisation Protocol , 2021, The Lancet Regional Health - Europe.

[25]  D. Brodie,et al.  Post-acute COVID-19 syndrome , 2021, Nature Medicine.

[26]  H. Rammensee,et al.  T cell and antibody kinetics delineate SARS-CoV-2 peptides mediating long-term immune responses in COVID-19 convalescent individuals , 2021, Science Translational Medicine.

[27]  David A. Drew,et al.  Attributes and predictors of long COVID , 2021, Nature Medicine.

[28]  R. Tedder,et al.  The Association Between Antibody Response to Severe Acute Respiratory Syndrome Coronavirus 2 Infection and Post–COVID-19 Syndrome in Healthcare Workers , 2021, The Journal of infectious diseases.

[29]  M. Brady,et al.  Multiorgan impairment in low-risk individuals with post-COVID-19 syndrome: a prospective, community-based study , 2021, BMJ Open.

[30]  J. Dogné,et al.  Persistence of Anti-SARS-CoV-2 Antibodies Depends on the Analytical Kit: A Report for Up to 10 Months after Infection , 2021, Microorganisms.

[31]  Cecilia S Lee,et al.  Hospitalization and mortality associated with SARS-CoV-2 viral clades in COVID-19 , 2021, Scientific Reports.

[32]  M. Van Ranst,et al.  Longitudinal follow-up of IgG anti-nucleocapsid antibodies in SARS-CoV-2 infected patients up to eight months after infection , 2021, Journal of Clinical Virology.

[33]  N. Hopkinson,et al.  COVID-19 and what comes after? , 2021, Thorax.

[34]  H. Ullum,et al.  Acute and persistent symptoms in non-hospitalized PCR-confirmed COVID-19 patients , 2021, Scientific Reports.

[35]  M. Nussenzweig,et al.  Evolution of antibody immunity to SARS-CoV-2 , 2021, Nature.

[36]  Guohui Fan,et al.  RETRACTED: 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study , 2021, The Lancet.

[37]  Seung-sik Hwang,et al.  Disease severity classification and COVID-19 outcomes, Republic of Korea. , 2020, Bulletin of the World Health Organization.

[38]  K. Stavem,et al.  Persistent symptoms 1.5–6 months after COVID-19 in non-hospitalised subjects: a population-based cohort study , 2020, Thorax.

[39]  J. Knight,et al.  Prothrombotic autoantibodies in serum from patients hospitalized with COVID-19 , 2020, Science Translational Medicine.

[40]  A. Baig Chronic COVID syndrome: Need for an appropriate medical terminology for long‐COVID and COVID long‐haulers , 2020, Journal of medical virology.

[41]  Zhenshun Cheng,et al.  Reduced numbers of T cells and B cells correlates with persistent SARS-CoV-2 presence in non-severe COVID-19 patients , 2020, Scientific Reports.

[42]  Junhua Li,et al.  A compromised specific humoral immune response against the SARS-CoV-2 receptor-binding domain is related to viral persistence and periodic shedding in the gastrointestinal tract , 2020, Cellular & Molecular Immunology.

[43]  William T. Hu,et al.  Extrafollicular B cell responses correlate with neutralizing antibodies and morbidity in COVID-19 , 2020, Nature Immunology.

[44]  H. Rammensee,et al.  SARS-CoV-2-derived peptides define heterologous and COVID-19-induced T cell recognition , 2020, Nature immunology.

[45]  R. Kaiser,et al.  RNAemia Corresponds to Disease Severity and Antibody Response in Hospitalized COVID-19 Patients , 2020, Viruses.

[46]  N. Maskell,et al.  Patient outcomes after hospitalisation with COVID-19 and implications for follow-up; results from a prospective UK cohort. , 2020, medRxiv.

[47]  M. Gisslén,et al.  Serum-IgG responses to SARS-CoV-2 after mild and severe COVID-19 infection and analysis of IgG non-responders , 2020, medRxiv.

[48]  H. Krumholz,et al.  Extrapulmonary manifestations of COVID-19 , 2020, Nature Medicine.

[49]  Zunyou Wu,et al.  Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. , 2020, JAMA.

[50]  C. Scheibenbogen,et al.  Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Evidence for an autoimmune disease. , 2018, Autoimmunity reviews.

[51]  L. Jason,et al.  Predictors of post-infectious chronic fatigue syndrome in adolescents , 2014, Health psychology and behavioral medicine.

[52]  Glenn Regehr,et al.  Measuring Self-assessment: Current State of the Art , 2002, Advances in health sciences education : theory and practice.

[53]  G. Maddox,et al.  Self-assessment of health: a longitudinal study of elderly subjects. , 1973, Journal of health and social behavior.