COVID-19 Outcomes and Vaccinations in Swedish Solid Organ Transplant Recipients 2020-2021: A Nationwide Multi-Register Comparative Cohort Study.

Increased COVID-19-related morbidity and mortality have been reported in solid organ transplant recipients (SOTRs). Most studies are underpowered for rigorous matching. We report infections, hospitalization, ICU care, mortality from COVID-19, and pertinent vaccination data in Swedish SOTRs 2020-2021. We conducted a nationwide cohort study, encompassing all Swedish residents. SOTRs were identified with ICD-10 codes and immunosuppressant prescriptions. Comparison cohorts were weighted based on a propensity score built from potential confounders (age, sex, comorbidities, socioeconomic factors, and geography), which achieved a good balance between SOTRs and non-SOTR groups. We included 10,372,033 individuals, including 9073 SOTRs. Of the SARS-CoV-2 infected, 47.3% of SOTRs and 19% of weighted comparator individuals were hospitalized. ICU care was given to 8% of infected SOTRs and 2% of weighted comparators. The case fatality rate was 7.7% in SOTRs, 6.2% in the weighted comparison cohort, and 1.3% in the unweighted comparison cohort. SOTRs had an increased risk of contracting COVID-19 (HR = 1.15 p < 0.001), being hospitalized (HR = 2.89 p < 0.001), receiving ICU care (HR = 4.59 p < 0.001), and dying (HR = 1.42 p < 0.001). SOTRs had much higher morbidity and mortality than the general population during 2020-2021. Also compared with weighted comparators, SOTRs had an increased risk of contracting COVID-19, being hospitalized, receiving ICU care, and dying. In Sweden, SOTRs were vaccinated earlier than weighted comparators. Lung transplant recipients had the worst outcomes. Excess mortality among SOTRs was concentrated in the second half of 2021.

Covid-19 vaccine effectiveness against post-covid-19 condition among 589 722 individuals in Sweden: population based cohort study.

OBJECTIVE: To investigate the effectiveness of primary covid-19 vaccination (first two doses and first booster dose within the recommended schedule) against post-covid-19 condition (PCC). DESIGN: Population based cohort study. SETTING: Swedish Covid-19 Investigation for Future Insights-a Population Epidemiology Approach using Register Linkage (SCIFI-PEARL) project, a register based cohort study in Sweden. PARTICIPANTS: All adults (≥18 years) with covid-19 first registered between 27 December 2020 and 9 February 2022 (n=589 722) in the two largest regions of Sweden. Individuals were followed from a first infection until death, emigration, vaccination, reinfection, a PCC diagnosis (ICD-10 diagnosis code U09.9), or end of follow-up (30 November 2022), whichever came first. Individuals who had received at least one dose of a covid-19 vaccine before infection were considered vaccinated. MAIN OUTCOME MEASURE: The primary outcome was a clinical diagnosis of PCC. Vaccine effectiveness against PCC was estimated using Cox regressions adjusted for age, sex, comorbidities (diabetes and cardiovascular, respiratory, and psychiatric disease), number of healthcare contacts during 2019, socioeconomic factors, and dominant virus variant at time of infection. RESULTS: Of 299 692 vaccinated individuals with covid-19, 1201 (0.4%) had a diagnosis of PCC during follow-up, compared with 4118 (1.4%) of 290 030 unvaccinated individuals. Covid-19 vaccination with any number of doses before infection was associated with a reduced risk of PCC (adjusted hazard ratio 0.42, 95% confidence interval 0.38 to 0.46), with a vaccine effectiveness of 58%. Of the vaccinated individuals, 21 111 received one dose only, 205 650 received two doses, and 72 931 received three or more doses. Vaccine effectiveness against PCC for one dose, two doses, and three or more doses was 21%, 59%, and 73%, respectively. CONCLUSIONS: The results of this study suggest a strong association between covid-19 vaccination before infection and reduced risk of receiving a diagnosis of PCC. The findings highlight the importance of primary vaccination against covid-19 to reduce the population burden of PCC.

Association between SARS-CoV-2 vaccination and healthcare contacts for menstrual disturbance and bleeding in women before and after menopause: nationwide, register based cohort study.

OBJECTIVES: To evaluate the risks of any menstrual disturbance and bleeding following SARS-CoV-2 vaccination in women who are premenopausal or postmenopausal. DESIGN: A nationwide, register based cohort study. SETTING: All inpatient and specialised outpatient care in Sweden from 27 December 2020 to 28 February 2022. A subset covering primary care for 40% of the Swedish female population was also included. PARTICIPANTS: 2 946 448 Swedish women aged 12-74 years were included. Pregnant women, women living in nursing homes, and women with history of any menstruation or bleeding disorders, breast cancer, cancer of female genital organs, or who underwent a hysterectomy between 1 January 2015 and 26 December 2020 were excluded. INTERVENTIONS: SARS-CoV-2 vaccination, by vaccine product (BNT162b2, mRNA-1273, or ChAdOx1 nCoV-19 (AZD1222)) and dose (unvaccinated and first, second, and third dose) over two time windows (one to seven days, considered the control period, and 8-90 days). MAIN OUTCOME MEASURES: Healthcare contact (admission to hospital or visit) for menstrual disturbance or bleeding before or after menopause (diagnosed with the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes N91, N92, N93, N95). RESULTS: 2 580 007 (87.6%) of 2 946 448 women received at least one SARS-CoV-2 vaccination and 1 652 472 (64.0%) 2 580 007 of vaccinated women received three doses before the end of follow-up. The highest risks for bleeding in women who were postmenopausal were observed after the third dose, in the one to seven days risk window (hazard ratio 1.28 (95% confidence interval 1.01 to 1.62)) and in the 8-90 days risk window (1.25 (1.04 to 1.50)). The impact of adjustment for covariates was modest. Risk of postmenopausal bleeding suggested a 23-33% increased risk after 8-90 days with BNT162b2 and mRNA-1273 after the third dose, but the association with ChAdOx1 nCoV-19 was less clear. For menstrual disturbance or bleeding in women who were premenopausal, adjustment for covariates almost completely removed the weak associations noted in the crude analyses. CONCLUSIONS: Weak and inconsistent associations were observed between SARS-CoV-2 vaccination and healthcare contacts for bleeding in women who are postmenopausal, and even less evidence was recorded of an association for menstrual disturbance or bleeding in women who were premenopausal. These findings do not provide substantial support for a causal association between SARS-CoV-2 vaccination and healthcare contacts related to menstrual or bleeding disorders.

Plasmablasts in previously immunologically naïve COVID-19 patients express markers indicating mucosal homing and secrete antibodies cross-reacting with SARS-CoV-2 variants and other beta-coronaviruses.

Antigen-specific class-switched antibodies are detected at the same time or even before IgM in serum of non-vaccinated individuals infected with SARS-CoV-2. These derive from the first wave of plasmablasts formed. Hence, the phenotype and specificity of plasmablasts can reveal information about early B-cell activation. Here we have analyzed B cells and plasmablasts circulating in blood of COVID-19 patients not previously exposed to SARS-CoV-2 during and after disease. We find that during infection with the original Wuhan strain, plasmablasts in blood produce IgA1, IgG1, and IgM, and that most express CCR10 and integrin ß1, only some integrin ß7, while the majority lack CCR9. Plasmablast-secreted antibodies are reactive to the spike (S) and nucleocapsid (N) proteins of the Wuhan strain as well as later variants of concern, but also bind S proteins from endemic and non-circulating betacoronaviruses. In contrast, after recovery, antibodies produced from memory B cells target variants of SARS-CoV-2 and SARS-CoV-1 but compared to previously non-infected individuals do not show increased binding to endemic coronaviruses. This suggests that the early antibody response to a large extent stems from pre-existing cross-reactive class-switched memory B cells, and that although newly formed memory cells target the novel SARS-CoV-2 virus the numbers of broadly cross-reactive memory B cells do not increase extensively. The observations give insight into the role of pre-existing memory B cells in early antibody responses to novel pathogens and may explain why class-switched antibodies are detected early in the serum of COVID-19 patients.

Longitudinal single-cell analysis of SARS-CoV-2-reactive B cells uncovers persistence of early-formed, antigen-specific clones.

Understanding persistence and evolution of B cell clones after COVID-19 infection and vaccination is crucial for predicting responses against emerging viral variants and optimizing vaccines. Here, we collected longitudinal samples from patients with severe COVID-19 every third to seventh day during hospitalization and every third month after recovery. We profiled their antigen-specific immune cell dynamics by combining single-cell RNA-Seq, Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-Seq), and B cell receptor-Seq (BCR-Seq) with oligo-tagged antigen baits. While the proportion of Spike receptor binding domain-specific memory B cells (MBC) increased from 3 months after infection, the other Spike- and Nucleocapsid-specific B cells remained constant. All patients showed ongoing class switching and sustained affinity maturation of antigen-specific cells, and affinity maturation was not significantly increased early after vaccine. B cell analysis revealed a polyclonal response with limited clonal expansion; nevertheless, some clones detected during hospitalization, as plasmablasts, persisted for up to 1 year, as MBC. Monoclonal antibodies derived from persistent B cell families increased their binding and neutralization breadth and started recognizing viral variants by 3 months after infection. Overall, our findings provide important insights into the clonal evolution and dynamics of antigen-specific B cell responses in longitudinally sampled patients infected with COVID-19.

A comprehensive characterization of patients diagnosed with post-COVID-19 condition in Sweden 16 months after the introduction of the International Classification of Diseases Tenth Revision diagnosis code (U09.9): a population-based cohort study.

OBJECTIVES: The objective of this study was to provide a comprehensive characterization of patients diagnosed with post-COVID-19 condition (PCC) during the first 16 months of use of the International Classification of Diseases revision 10 (ICD-10) diagnosis code U09.9 in Sweden. METHODS: We used data from national registers and primary health care databases for all adult inhabitants of the two largest regions in Sweden, comprising 4.1 million inhabitants (approximately 40% of the Swedish population). We present the cumulative incidence and incidence rate of PCC overall and among subgroups and describe patients with COVID-19 with or without PCC regarding sociodemographic characteristics, comorbidities, subsequent diseases, COVID-19 severity, and virus variants. RESULTS: Of all registered COVID-19 cases available for PCC diagnosis (n = 506,107), 2.0% (n = 10,196) had been diagnosed with PCC using ICD-10 code U09.9 as of February 15, 2022 in the two largest regions in Sweden. The cumulative incidence was higher among women than men (2.3% vs 1.6%, P <0.001). The majority of PCC cases (n = 7162, 70.2%) had not been hospitalized for COVID-19. This group was more commonly female (69.9% vs 52.9%, P <0.001), had a tertiary education (51.0% vs 44.1%, P <0.001), and was older (median age difference 5.7 years, P <0.001) than non-hospitalized patients with COVID-19 without PCC. CONCLUSION: This characterization furthers the understanding of patients diagnosed with PCC and could support policy makers with appropriate societal and health care resource allocation.

Effectiveness of COVID-19 Vaccines over 13 Months Covering the Period of the Emergence of the Omicron Variant in the Swedish Population.

BACKGROUND: We estimated real-world vaccine effectiveness (VE) against COVID-19 infection, hospitalization, ICU admission, and death up to 13 months after vaccination. VE before and after the emergence of Omicron was investigated. METHODS: We used registered data from the entire Swedish population above age 12 (n = 9,153,456). Cox regression with time-varying exposure was used to estimate weekly/monthly VE against COVID-19 outcomes from 27 December 2020 to 31 January 2022. The analyses were stratified by age, sex, and vaccine type (BNT162b2, mRNA-1273, and AZD1222). RESULTS: Two vaccine doses offered good long-lasting protection against infection before Omicron (VE were above 85% for all time intervals) but limited protection against Omicron infection (dropped to 43% by week four and no protection by week 14). For severe COVID-19 outcomes, higher VE was observed during the entire follow-up period. Among individuals above age 65, the mRNA vaccines showed better VE against infection than AZD1222 but similar high VE against hospitalization. CONCLUSIONS: Our findings provide strong evidence for long-term maintained protection against severe COVID-19 by the basic two-dose schedule, supporting more efforts to encourage unvaccinated persons to get the basic two doses, and encourage vaccinated persons to get a booster to ensure better population-level protection.

The social patterning of Covid-19 vaccine uptake in older adults: A register-based cross-sectional study in Sweden.

BACKGROUND: A broad vaccination coverage is crucial for preventing the spread of Covid-19 and reduce serious illness or death. The aim of this study was to examine social inequalities in Covid-19 vaccination uptake as of 17th May 2021 among Swedish adults aged ≥ 60 years. METHODS: The study population comprised a general population cohort aged 60 years or older (n = 350,805), representative of the Swedish population. Data were collected through the nationwide linked multi-register observational study SCIFI-PEARL, and associations between sociodemographic determinants and Covid-19 vaccination uptake were analysed using logistic regression. Intersectional analyses of sociodemographic heterogeneity were performed by taking several overlapping social dimensions into account. Data availability extended to 17 May 2021. FINDINGS: The overall vaccination coverage was 87·2% by 17th May 2021. Younger age, male sex, lower income, living alone, and being born outside Sweden, were all associated with a lower uptake of vaccination. The lowest Covid-19 vaccination uptake was seen in individuals born in low-or middle-income countries, of which only 60% had received vaccination, with an odds ratio (OR) of not being vaccinated of 6·05 (95% CI: 5·85-6·26) compared to individuals born in Sweden. These associations persisted after adjustments for possible confounding factors. The intersectional analyses showed even larger variations in vaccination in cross-classified sociodemographic subgroups (ranging from 44% to 97%) with marked differences in uptake of vaccination within sociodemographic groups. INTERPRETATION: The uptake of Covid-19 vaccine during the spring of 2021 in Sweden varied substantially both between and within sociodemographic groups. The use of an intersectional approach, taking several overlapping social dimensions into account at the same time rather than only using one-dimensional measures, contributes to a better understanding of the complexity in the uptake of vaccination. FUNDING: SciLifeLab / Knut & Alice Wallenberg Foundation, Swedish Research Council, Swedish government ALF-agreement, FORMAS.

Longevity of anti-spike and anti-nucleocapsid antibodies after COVID-19 in solid organ transplant recipients compared to immunocompetent controls.

Solid organ transplant recipients (SOTRs) are on lifelong immunosuppression, which may interfere with adaptive immunity to COVID-19. The data on dynamics and duration of antibody response in SOTRs are limited. This longitudinal study examined the longevity of both anti-spike (S)- and anti-nucleocapsid (N)-specific IgG antibodies after COVID-19 in SOTRs compared to matched immunocompetent persons. SOTRs (n = 65) were matched with controls (n = 65) for COVID-19 disease severity, age, and sex in order of priority. Serum-IgG antibodies against N and S antigens of SARS-CoV-2 were analyzed. At 1 and 9 months after COVID-19, anti-S-IgG detectability decreased from 91% to 82% in SOTRs versus 100% to 95% in controls, whereas the anti-N-IgG decreased from 63% to 29% in SOTRs versus 89% to 46% in controls. A matched paired analysis showed SOTRs having significantly lower levels of anti-N-IgG at all time points (1 month p = .007, 3 months p < .001, 6 months p = .019, and 9 months p = .021) but not anti-S-IgG at any time points. A mixed-model analysis confirmed these findings except for anti-S-IgG at 1 month (p = .005) and identified severity score as the most important predictor of antibody response. SOTRs mount comparable S-specific, but not N-specific, antibody responses to SARS-CoV-2 infection compared to immunocompetent controls.

Longitudinal Follow Up of Immune Responses to SARS-CoV-2 in Health Care Workers in Sweden With Several Different Commercial IgG-Assays, Measurement of Neutralizing Antibodies and CD4+ T-Cell Responses.

Background: The risk of SARS-CoV-2 infection among health care workers (HCWs) is a concern, but studies that conclusively determine whether HCWs are over-represented remain limited. Furthermore, methods used to confirm past infection vary and the immunological response after mild COVID-19 is still not well defined. Method: 314 HCWs were recruited from a Swedish Infectious Diseases clinic caring for COVID-19 patients. IgG antibodies were measured using two commercial assays (Abbot Architect nucleocapsid (N)-assay and YHLO iFlash-1800 N and spike (S)-assays) at five time-points, from March 2020 to January 2021, covering two pandemic waves. Seroprevalence was assessed in matched blood donors at three time-points. More extensive analyses were performed in 190 HCWs in September/October 2020, including two additional IgG-assays (DiaSorin LiaisonXL S1/S2 and Abbot Architect receptor-binding domain (RBD)-assays), neutralizing antibodies (NAbs), and CD4+ T-cell reactivity using an in-house developed in vitro whole-blood assay based on flow cytometric detection of activated cells after stimulation with Spike S1-subunit or Spike, Membrane and Nucleocapsid (SMN) overlapping peptide pools. Findings: Seroprevalence was higher among HCWs compared to sex and age-matched blood donors at all time-points. Seropositivity increased from 6.4% to 16.3% among HCWs between May 2020 and January 2021, compared to 3.6% to 11.9% among blood donors. We found significant correlations and high levels of agreement between NAbs and all four commercial IgG-assays. At 200-300 days post PCR-verified infection, there was a wide variation in sensitivity between the commercial IgG-assays, ranging from <30% in the N-assay to >90% in the RBD-assay. There was only moderate agreement between NAbs and CD4+ T-cell reactivity to S1 or SMN. Pre-existing CD4+ T-cell reactivity was present in similar proportions among HCW who subsequently became infected and those that did not. Conclusions: HCWs in COVID-19 patient care in Sweden have been infected with SARS-CoV-2 at a higher rate compared to blood donors. We demonstrate substantial variation between different IgG-assays and propose that multiple serological targets should be used to verify past infection. Our data suggest that CD4+ T-cell reactivity is not a suitable measure of past infection and does not reliably indicate protection from infection in naive individuals.

Correction: Serum-IgG responses to SARS-CoV-2 after mild and severe COVID-19 infection and analysis of IgG non-responders.

[This corrects the article DOI: 10.1371/journal.pone.0241104.].

Mucosal Immune Responses Against an Oral Enterotoxigenic Escherichia coli Vaccine Evaluated in Clinical Trials.

Enterotoxigenic Escherichia coli (ETEC) is a leading cause of mortality and morbidity in children in low-income countries. We have tested an oral ETEC vaccine, ETVAX, consisting of inactivated E coli overexpressing the most prevalent colonization factors and a toxoid, LCTBA, administered together with a mucosal adjuvant, double-mutant heat-labile toxin (dmLT), for capacity to induce mucosal immune responses and immunological memory against the primary vaccine antigens, ie, colonization factors, heat-labile toxin B-subunit and O antigen. The studies show that ETVAX could induce strong intestine-derived and/or fecal immune responses in a majority of vaccinated Swedish adults and in different age groups, including infants, in Bangladesh.

No difference in biomarkers of ischemic heart injury and heart failure in patients with COVID-19 who received treatment with chloroquine phosphate and those who did not.

BACKGROUND: Chloroquine was promoted as a COVID-19 therapeutic early in the pandemic. Most countries have since discontinued the use of chloroquine due to lack of evidence of any benefit and the risk of severe adverse events. The primary aim of this study was to examine if administering chloroquine during COVID-19 imposed an increased risk of ischemic heart injury or heart failure. METHODS: Medical records, laboratory findings, and electrocardiograms of patients with COVID-19 who were treated with 500 mg chloroquine phosphate daily and controls not treated with chloroquine were reviewed retrospectively. Controls were matched in age and severity of disease. RESULTS: We included 20 patients receiving chloroquine (500 mg twice daily) for an average of five days, and 40 controls. The groups were comparable regarding demographics and biochemical analyses including C-reactive protein, thrombocytes, and creatinine. There were no statistically significant differences in cardiac biomarkers or in electrocardiograms. Median troponin T was 10,8 ng/L in the study group and 17.9 ng/L in the control group, whereas median NT-proBNP was 399 ng/L in patients receiving chloroquine and 349 ng/L in the controls. CONCLUSIONS: We found no increased risk of ischemic heart injury or heart failure as a result of administering chloroquine. However, the use of chloroquine to treat COVID-19 outside of clinical trials is not recommended, considering the lack of evidence of its effectiveness, as well as the elevated risk of fatal arrythmias.

Recent MMR vaccination in health care workers and Covid-19: A test negative case-control study.

BACKGROUND: It has been hypothesised that the measles-mumps-rubella (MMR) vaccine may afford cross-protection against SARS-CoV-2 which may contribute to the wide variability in disease severity of Covid-19. METHODS: We employed a test negative case-control study, utilising a recent measles outbreak during which many healthcare workers received the MMR vaccine, to investigate the potential protective effect of MMR against SARS-CoV-2 in 5905 subjects (n = 805 males, n = 5100 females). RESULTS: The odds ratio for testing positive for SARS-CoV-2, in recently MMR-vaccinated compared to not recently MMR-vaccinated individuals was 0.91 (95% CI 0.76, 1.09). An interaction analysis showed a significant interaction for sex. After sex-stratification, the odds ratio for testing positive for males was 0.43 (95% CI 0.24, 0.79, P = 0.006), and 1.01 (95% CI 0.83, 1.22, P = 0.92) for females. CONCLUSION: Our results indicate that there may be a protective effect of the MMR vaccine against SARS-CoV-2 in males but not females.

A Systems Biology Approach Identifies B Cell Maturation Antigen (BCMA) as a Biomarker Reflecting Oral Vaccine Induced IgA Antibody Responses in Humans.

Vaccines against enteric diseases could improve global health. Despite this, only a few oral vaccines are currently available for human use. One way to facilitate such vaccine development could be to identify a practical and relatively low cost biomarker assay to assess oral vaccine induced primary and memory IgA immune responses in humans. Such an IgA biomarker assay could complement antigen-specific immune response measurements, enabling more oral vaccine candidates to be tested, whilst also reducing the work and costs associated with early oral vaccine development. With this in mind, we take a holistic systems biology approach to compare the transcriptional signatures of peripheral blood mononuclear cells isolated from volunteers, who following two oral priming doses with the oral cholera vaccine Dukoral®, had either strong or no vaccine specific IgA responses. Using this bioinformatical method, we identify TNFRSF17, a gene encoding the B cell maturation antigen (BCMA), as a candidate biomarker of oral vaccine induced IgA immune responses. We then assess the ability of BCMA to reflect oral vaccine induced primary and memory IgA responses using an ELISA BCMA assay on a larger number of samples collected in clinical trials with Dukoral® and the oral enterotoxigenic Escherichia coli vaccine candidate ETVAX. We find significant correlations between levels of BCMA and vaccine antigen-specific IgA in antibodies in lymphocyte secretion (ALS) specimens, as well as with proportions of circulating plasmablasts detected by flow cytometry. Importantly, our results suggest that levels of BCMA detected early after primary mucosal vaccination may be a biomarker for induction of long-lived vaccine specific memory B cell responses, which are otherwise difficult to measure in clinical vaccine trials. In addition, we find that ALS-BCMA responses in individuals vaccinated with ETVAX plus the adjuvant double mutant heat-labile toxin (dmLT) are significantly higher than in subjects given ETVAX only. We therefore propose that as ALS-BCMA responses may reflect the total vaccine induced IgA responses to oral vaccination, this BCMA ELISA assay could also be used to estimate the total adjuvant effect on vaccine induced-antibody responses, independently of antigen specificity, further supporting the usefulness of the assay.

COVID-19 in solid organ transplant recipients: A national cohort study from Sweden.

Solid organ transplant (SOT) recipients run a high risk for adverse outcomes from COVID-19, with reported mortality around 19%. We retrospectively reviewed all known Swedish SOT recipients with RT-PCR confirmed COVID-19 between March 1 and November 20, 2020 and analyzed patient characteristics, management, and outcome. We identified 230 patients with a median age of 54.0 years (13.2), who were predominantly male (64%). Most patients were hospitalized (64%), but 36% remained outpatients. Age >50 and male sex were among predictors of transition from outpatient to inpatient status. National early warning Score 2 (NEWS2) at presentation was higher in non-survivors. Thirty-day all-cause mortality was 9.6% (15.0% for inpatients), increased with age and BMI, and was higher in men. Renal function decreased during COVID-19 but recovered in most patients. SARS-CoV-2 antibodies were identified in 78% of patients at 1-2 months post-infection. Nucleocapsid-specific antibodies decreased to 38% after 6-7 months, while spike-specific antibody responses were more durable. Seroprevalence in 559 asymptomatic patients was 1.4%. Many patients can be managed on an outpatient basis aided by risk stratification with age, sex, and NEWS2 score. Factors associated with adverse outcomes include older age, male sex, greater BMI, and a higher NEWS2 score.

Comparable endemic coronavirus nucleoprotein-specific antibodies in mild and severe Covid-19 patients.

The severity of disease of Covid-19 is highly variable, ranging from asymptomatic to critical respiratory disease and death. Potential cross-reactive immune responses between SARS-CoV-2 and endemic coronavirus (eCoV) may hypothetically contribute to this variability. We herein studied if eCoV nucleoprotein (N)-specific antibodies in the sera of patients with mild or severe Covid-19 are associated with Covid-19 severity. There were comparable levels of eCoV N-specific antibodies early and during the first month of infection in Covid-19 patients with mild and severe symptoms, and healthy SARS-CoV-2-negative subjects. These results warrant further studies to investigate the potential role of eCoV-specific antibodies in immunity to SARS-CoV-2 infection.

Serum-IgG responses to SARS-CoV-2 after mild and severe COVID-19 infection and analysis of IgG non-responders.

BACKGROUND: To accurately interpret COVID-19 seroprevalence surveys, knowledge of serum-IgG responses to SARS-CoV-2 with a better understanding of patients who do not seroconvert, is imperative. This study aimed to describe serum-IgG responses to SARS-CoV-2 in a cohort of patients with both severe and mild COVID-19, including extended studies of patients who remained seronegative more than 90 days post symptom onset. METHODS: SARS-CoV-2-specific IgG antibody levels were quantified using two clinically validated and widely used commercial serological assays (Architect, Abbott Laboratories and iFlash 1800, YHLO), detecting antibodies against the spike and nucleocapsid proteins. RESULTS: Forty-seven patients (mean age 49 years, 38% female) were included. All (15/15) patients with severe symptoms and 29/32 (90.6%) patients with mild symptoms of COVID-19 developed SARS-CoV-2-specific IgG antibodies in serum. Time to seroconversion was significantly shorter (median 11 vs. 22 days, P = 0.04) in patients with severe compared to mild symptoms. Of the three patients without detectable IgG-responses after >90 days, all had detectable virus-neutralizing antibodies and in two, spike-protein receptor binding domain-specific IgG was detected with an in-house assay. Antibody titers were preserved during follow-up and all patients who seroconverted, irrespective of the severity of symptoms, still had detectable IgG levels >75 days post symptom onset. CONCLUSIONS: Patients with severe COVID-19 both seroconvert earlier and develop higher concentrations of SARS-CoV-2-specific IgG than patients with mild symptoms. Of those patients who not develop detectable IgG antibodies, all have detectable virus-neutralizing antibodies, suggesting immunity. Our results showing that not all COVID-19 patients develop detectable IgG using two validated commercial clinical methods, even over time, are vital for the interpretation of COVID-19 seroprevalence surveys.

[At least 68 vaccine candidates under development]. / Minst ett 70-tal möjliga vacciner mot sars-cov-2 är nu på gång.

The development of vaccines against SARS-CoV-2 is progressing at an unparalleled speed. As of the 29th of March, there were at least 68 vaccine candidates comprising several different vaccine designs, including whole killed virus, subunit, attenuated, viral vector, DNA and mRNA vaccines. Whilst it usually takes 10-15 years to develop a vaccine, it has only taken just over 9 weeks from the publication of the viral genetic sequence for the first vaccine candidate to reach clinical testing. Development has been expediated by using existing technological platforms and by performing preclinical and clinical testing simultaneously.