Immunogenicity and Safety of Beta Adjuvanted Recombinant Booster Vaccine (preprint)

Background. Variant-adaptated vaccines against coronavirus disease 2019 (COVID-19) as boosters are needed to increase a broader protection against SARS CoV-2 variants. New adjuvanted recombinant protein vaccines as heterologous boosters could maximize the response. Methods. In this randomized, single-blinded, multicenter trial, adults who had received two doses of Pfizer-BioNTech mRNA vaccine (BNT162b2) 3 to7 months before were randomly assigned to receive a boost of BNT162b2, Sanofi/GSK SARS-CoV-2 adjuvanted recombinant protein MV D614 (monovalent parental formulation) or SARS-CoV-2 adjuvanted recombinant protein MV B.1.351 vaccine (monovalent Beta formulation). The primary endpoint was the percentage of subjects with a [≥] 10-fold increase in neutralizing antibody titers for the Wuhan (D614) and B.1.351 (Beta) SARS-CoV-2 viral strains between day 0 and day 15. Findings. The percentages of participants whose neutralizing antibody titers against the Wuhan (D614) SARS-CoV-2 strain increased by a factor [≥]10 between day 0 and day 15 was 55.3% (95% CI 43.4-66.7) in MV D614 group (n=76), 76.1% (64.5-85.4) in MV B.1.351 (Beta) group (n=71) and 63.2% (51.3-73.9) in BNT162b2 group (n=76). These percentages were 44.7% (33.3-56.6), 84.5% (74.0-92.0) and 51.3% (39.6-63.0) for the B.1.351 (Beta) viral strain, respectively. Higher neutralizing antibodies rates against Delta and Omicron BA.1 variants were also elicited after Sanofi/GSK MV Beta vaccine compared to the other vaccines. Comparable reactogenicity profile was observed with the three vaccines. Interpretation. Heterologous boosting with the Sanofi/GSK Beta formulation vaccine resulted in a higher neutralizing antibody response against Beta variant but also the original strain and Delta and Omicron BA.1 variants, compared with mRNA BNT162b2 vaccine or the Sanofi/GSK MVD614 formulation. New vaccines containing Beta spike protein may represent an interesting strategy for broader protection against SARS CoV-2 variants.

Effect of SARS-CoV-2 vaccination on symptoms from post-acute COVID syndrome: results from the national VAXILONG survey (preprint)

Introduction: Few data are available concerning the effect of SARS-CoV-2 vaccination on the persistent symptoms associated with COVID-19, also called long-COVID or post-acute COVID-19 syndrome (PACS). Patients and methods: We conducted a nationwide online survey among adult patients with PACS as defined by symptoms persisting over 4 weeks following a confirmed or probable COVID-19, without any identified alternative diagnosis. Information concerning PACS symptoms, vaccine type and scheme and its effect on PACS symptoms were studied. Results: Six hundred and twenty surveys were completed and 567 satisfied the inclusion criteria and were analyzed. Respondents were 83.4% of women of median age 44 (IQR 25-75: 37-50). Initial infection was proven in 365 patients (64%) and 5.1% had been hospitalized to receive oxygen. 396 patients had received at least one injection of SARS-CoV-2 vaccine at the time of the survey, after a median of 357 [198-431] days following the initially-reported SARS-CoV-2 infection. Among the 380 patients who reported persistent symptoms at the time of SARS-CoV-2 vaccination, 201 (52.8%) reported variation of symptoms following the injection, without difference based on the type of vaccine used. After a complete vaccination scheme, 93.3% (28/30) of initially seronegative patients reported a positive anti-SARS-CoV-2 IgG. 170 PACS patients had not been vaccinated. The most common reasons for postponing SARS-CoV-2 vaccine were a fear of worsening PACS symptoms (55.9%) and the idea that vaccination was contraindicated because of PACS (15.6%). Conclusion: Our study suggests that SARS-CoV-2 vaccination is well tolerated in the majority of PACS patients and has good immunogenicity. Disseminating these reassuring data might prove crucial to increase vaccine coverage in patients with PACS.

Acceptability of the COVID-19 Vaccine Among Patients with Rheumatic Diseases and Healthcare Professionals: A Cross-Sectional Study in 19 Arab Countries (preprint)

Background: The COVID-19 vaccines raised hopes of returning to normalcy; however, their acceptability remains contested and has never been evaluated in an international study from the Arab countries. The objectives of this study were to assess the acceptability of the COVID-19 vaccine in patients with chronic rheumatic diseases and healthcare professionals (HCPs) in the Arab countries and to identify the factors associated with this acceptability.Methods: The ARCOVAX (Arab League of Associations for Rheumatology (ArLAR) COVID Vaccination) study utilized a web-based survey disseminated in Arabic, English, and French through multiple social media platforms, mass emails, and WhatsApp messages. Acceptability was defined as: participants already vaccinated or willing to take the vaccine. Demographic data and perceptions and concerns about vaccination were presented descriptively; factors associated with acceptability were identified using logistic regression models.Findings: A total of 3,176 participants from 19 Arab countries completed the survey in April/ May 2021 (1,595 patients and 1,517 HCPs); 59% of HCPs and 29% of patients were vaccinated. Vaccine acceptability was significantly lower in patients (63%) compared to HCPs (81%) (p<0.001). Among the non-vaccinated patients, 57% of the undecided and 40% of those who refused vaccination were willing to take the vaccine if their physician recommended it. Vaccine acceptability was associated with a higher country gross domestic product, a higher perceived importance of self-vaccination, previous influenza vaccination, fear of COVID-19, and fewer concerns about vaccine side effects.Interpretation: Acceptability of the COVID-19 vaccine was lower in patients compared to HCPs but may be substantially improved if the physician recommended the vaccine. Addressing the main determinants of acceptability may facilitate vaccine uptake in the Arab countries.Funding: None to declare. Declaration of Interest: None to declare. Ethical Approval: The study was approved by the scientific committee of the ArLAR and by the Institutional Review Boards of the Saint-Joseph University, Beirut (Tfem-2021), and Specialized Medical Center, Riyadh (H-01-R-056).

Refining “long-COVID” by a prospective multimodal evaluation of patients with long-term symptoms related to SARS-CoV-2 infection (preprint)

Background COVID-19 long-haulers or “long-COVID” represent 10% of COVID-19 patients and remain understudied. Methods In this prospective study, we recruited 30 consecutive patients seeking medical help for persistent symptoms (> 30 days) attributed to COVID-19. All reported a viral illness compatible with COVID-19. The patients underwent a multi-modal evaluation including clinical, psychological, virological, specific immunological assays and were followed longitudinally. Results The median age was 40 [interquartile range: 35-54] and 18 (60%) were female. After a median time of 152 [102-164] days after symptom onset, fever, cough and dyspnea were less frequently reported as compared with the initial presentation, but paresthesia and burning pain emerged in 18 (60%) and 13 (43%) patients, respectively. The clinical examination was unremarkable in all patients although the median fatigue and pain visual analogic scales were 7 [5-8] and 5 [2-6], respectively. Extensive biological studies were unremarkable, as were multiplex cytokine and ultra-sensitive interferon-a2 measurements. At this time, nasopharyngeal swab and stool RT-PCR were negative for all tested patients. Using SARS-CoV-2 serology and IFN-γ ELISPOT, we found evidence of a previous SARS-CoV-2 infection in 50% (15/30) of patients, with objective evidence of lack or waning of immune response in two. Finally, psychiatric evaluation showed that 11 (36.7%), 13 (43.3%) and 9 (30%) patients had a positive screening for anxiety, depression and post-traumatic stress disorder, respectively. Conclusions Half of patients seeking medical help for long-COVID lack SARS-CoV-2 immunity. The presence of SARS-CoV-2 immunity did not cluster clinically or biologically long haulers, who reported severe fatigue, altered quality of life, and exhibited psychological distress. Key points Among 30 consecutive patients reporting persistent symptoms (median 6 months) self-attributed to COVID-19, pain, fatigue and disability were reported in virtually all patients. More than one third of patients suffer from psychological disorders such as anxiety, depression and/or post-traumatic stress disorder, regardless of SARS-CoV-2 immunity. At the time of evaluation, only 50% of patients had cellular and/or humoral sign of a past SARS-CoV-2, and serology positivity varied depending of the kit used. Exhaustive clinical, biological and immunological evaluations failed to find an alternative diagnosis, or to identify specific cytokine signature including type I interferon.