Factors influencing the immune response over 15 months after SARS-CoV-2 infection: A longitudinal population-wide study in the Faroe Islands.

BACKGROUND: The durability of SARS-CoV-2 antibody response and the resulting immunity to COVID-19 is unclear. OBJECTIVES: To investigate long-term humoral immunity to SARS-CoV-2. METHODS: In this nationwide, longitudinal study, we determined antibody response in 411 patients aged 0-93 years from two waves of infections (March to December 2020) contributing 1063 blood samples. Each individual had blood drawn on 4-5 occasions 1-15 months after disease onset. We measured total anti-SARS-CoV-2 receptor-binding domain (RBD) antibody using a qualitative RBD sandwich ELISA, IgM, IgG and IgA levels using an quantitative in-house ELISA-based assay  and neutralizing antibodies (NAbs) using an in-house ELISA-based pseudoneutralizing assay. IgG subclasses were analyzed in a subset of samples by ELISA-based assay. We used nonlinear models to study the durability of SARS-CoV-2 antibody responses and its influence over time. RESULTS: After 15 months, 94% still had detectable circulating antibodies, mainly the IgG isotype, and 92% had detectable NAbs. The distribution of IgG antibodies varied significantly over time, characterized by a biphasic pattern with an initial decline followed by a plateau after approximately 7 months. However, the NAbs remained relatively stable throughout the period. The strength of the antibody response was influenced by smoking and hospitalization, with lower IgG levels in smokers and higher levels in hospitalized individuals. Antibody stability over time was mainly associated with male sex and older age with higher initial levels but more marked decrease. CONCLUSIONS: The humoral immune response to SARS-CoV-2 infection varies depending on behavioral factors and disease severity, and antibody stability over 15 months was associated with sex and age.

Comparison of 16 Serological SARS-CoV-2 Immunoassays in 16 Clinical Laboratories.

Serological assays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are needed to support clinical diagnosis and epidemiological investigations. Recently, assays for large-scale detection of total antibodies (Ab), immunoglobulin G (IgG), and IgM against SARS-CoV-2 antigens have been developed, but there are limited data on the diagnostic accuracy of these assays. This study was a Danish national collaboration and evaluated 15 commercial and one in-house anti-SARS-CoV-2 assays in 16 laboratories. Sensitivity was evaluated using 150 samples from individuals with asymptomatic, mild, or moderate COVID-19, nonhospitalized or hospitalized, confirmed by nucleic acid amplification tests (NAAT); samples were collected 13 to 73 days either from symptom onset or from positive NAAT (patients without symptoms). Specificity and cross-reactivity were evaluated in samples collected prior to the SARS-CoV-2 epidemic from >586 blood donors and patients with autoimmune diseases, cytomegalovirus or Epstein-Barr virus infections, and acute viral infections. A specificity of ≥99% was achieved by all total-Ab and IgG assays except one, DiaSorin Liaison XL IgG (97.2%). Sensitivities in descending order were Wantai ELISA total Ab (96.7%), CUH-NOVO in-house ELISA total Ab (96.0%), Ortho Vitros total Ab (95.3%), YHLO iFlash IgG (94.0%), Ortho Vitros IgG (93.3%), Siemens Atellica total Ab (93.2%), Roche Elecsys total Ab (92.7%), Abbott Architect IgG (90.0%), Abbott Alinity IgG (median 88.0%), DiaSorin Liaison XL IgG (median 84.6%), Siemens Vista total Ab (81.0%), Euroimmun/ELISA IgG (78.0%), and Snibe Maglumi IgG (median 78.0%). However, confidence intervals overlapped for several assays. The IgM results were variable, with the Wantai IgM ELISA showing the highest sensitivity (82.7%) and specificity (99%). The rate of seropositivity increased with time from symptom onset and symptom severity.

Self-Reported Long COVID and Its Association with the Presence of SARS-CoV-2 Antibodies in a Danish Cohort up to 12 Months after Infection.

The majority of long coronavirus disease (COVID) symptoms are not specific to COVID-19 and could be explained by other conditions. The present study aimed to explore whether Danish individuals with a perception that they suffer from long COVID have antibodies against the nucleocapsid antigen, as a proxy for detecting previous infection. The study was conducted in February and March 2021, right after the second surge of the COVID-19 pandemic in Denmark. All members of the social media group on Facebook "Covidramte med senfølger" ("long COVID sufferers'') above the age of 17 years and living in Denmark were invited to participate in a short electronic questionnaire about long COVID risk factors and symptoms. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid (N) protein was detected in blood samples as a proxy for natural SARS-CoV-2 infection. The final study population comprised 341 participants (90.6% females) who completed blood sampling and answered the questionnaire. A total of 232 (68%) were seropositive (median age, 49.5 years; interquartile range [IQR], 41 to 55 years; 90.1% females). There was no significant difference between sexes and serostatus. Seronegative and seropositive individuals had a similar burden of symptoms that could be attributed to long COVID. Time since perceived COVID-19 was significantly longer in the group of seronegative individuals than the seropositive ones (P < 0.001). This study suggests that long-COVID sufferers are mostly women and showed that a third of the participants did not have detectable anti-N-protein antibodies. It emphasizes the importance of early confirmation of COVID-19, as this study indicates an overlap between long-COVID symptoms and symptoms that are possibly of another origin. IMPORTANCE This cohort study included questionnaire data as well as anti-nucleocapsid antibody analysis, allowing us to determine whether participants were seropositive due to vaccination or natural infection. The study emphasizes the importance of early confirmation of COVID-19, as antibodies recede with time, and it indicates an overlap between long COVID symptoms and symptoms possibly of another origin.

Anti-SARS-CoV-2 Seropositivity Among Medical Students in Copenhagen.

BACKGROUND: Health care workers are at a higher risk of getting infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) than the general population. Knowledge about medical students' exposure to SARS-CoV-2 is lacking. Thus, we measured the prevalence of SARS-CoV-2 antibodies in a cohort of Danish medical students. METHODS: We invited all medical students at the University of Copenhagen (UCPH) to participate. Students underwent venous blood sampling and a questionnaire about work-life behaviors possibly associated with SARS-CoV-2 exposure and coronavirus disease 2019 (COVID-19) symptoms. Samples were analyzed for total immunoglobulin G (IgG) antibodies against SARS-CoV-2, and seropositive samples were screened for IgG, immunoglobulin M, and immunoglobulin A antibodies. We determined associations between seropositivity and clinical and social activities and self-reported symptoms. RESULTS: Between October 19 and 26, 1120 students participated in the questionnaire and 1096 were included. Of all included, 379 (34.58%) were seropositive. Seropositivity was associated with attendance at 2 parties at UCPH, on February 29 and March 6, 2020 (odds ratio [OR], 5.96; 95% CI, 4.34-8.24; P < .001). Four hundred sixty-one students (42.06%) worked with COVID-19 patients, which was significantly associated with seropositivity (OR, 1.38; 95% CI, 1.03-1.85; P = .033). The symptom most associated with seropositivity was loss of smell and/or taste (n = 183 of all, 31.35%; OR, 24.48; 95% CI, 15.49-40.60; P < .001). Bachelor's students were significantly more likely to be seropositive than Master's students (42.28% vs 16.87%; P < .001). CONCLUSIONS: Medical students have the highest reported seropositivity in the Danish health care system. In this cohort of students at UCPH, seropositivity was associated with social behavior markers and, to a lesser extent, with self-reported contact with SARS-CoV-2-infected patients.

Complement related pattern recognition molecules as markers of short-term mortality in intensive care patients.

OBJECTIVES: To evaluate the complement related pattern recognition molecules (PRMs) PTX3, MBL, CL-11, ficolin-2 and -3, along with the established marker CRP, to predict 28-day mortality and disease severity of sepsis in patients admitted to the intensive care unit (ICU). METHODS: In a single-center, prospective, observational study 547 patients were included over a period of 18 months. Blood samples were obtained at admission to the ICU and the following 4 days. RESULTS: PTX3 baseline levels were significantly higher in non-survivors compared to survivors, whereas MBL and ficolin-2 levels were significantly lower in non-survivors compared to survivors. A PTX3 level above the median was independently associated with 28-day mortality in the adjusted analysis including age, sex, chronic disease and immunosuppression (HR 1.87, 95% CI [1.41-2.48], p < 0.0001), while a MBL level above the median was associated with increased chance of survival (HR 0.75, 95% CI [0.57-0.98], p = 0.034). Ficolin-2 was only borderline significant (HR 0.79, 95% CI [0.60-1.03], p = 0.084). In a ROC analysis PTX3 was superior to CRP in predicting septic shock. CONCLUSIONS: PTX3, MBL and CRP levels were independently associated with 28-day mortality in ICU patients. PTX3 was a better marker of septic shock compared to CRP.