ANTI-TNF THERAPY for IMMUNE MEDIATED INFLAMMATORY DISEASES MAY BE ASSOCIATED with LOWER ANTIBODY LEVELS and VIRUS NEUTRALIZATION EFFICACY FOLLOWING SARS-COV-2 MRNA VACCINATION

Background: The impact of immunosuppressants on COVID-19 vaccination response and durability in patients with immune-mediated infammatory diseases (IMID) is yet to be fully characterized. Humoral response may be attenuated in these patients especially those on B cell depleting therapy and higher doses of corticosteroids, but data regarding other immunosuppressants are scarce. Objectives: We aimed to investigate antibody and T cell responses and durability to SARS-CoV-2 mRNA vaccines (BNT162b and/or mRNA 1273) in IMID patients on immunomodulatory maintenance therapy other than B-cell depleting therapy and corticosteroids. Methods: This prospective observational cohort study examined the immuno-genicity of SARS-CoV-2 mRNA vaccines in adult patients with IMIDs (psoriatic arthritis, psoriasis, infammatory bowel disease and rheumatoid arthritis) with or without maintenance immunosuppressive therapies (anti-TNF, methotrexate/azathioprine [MTX/AZA], anti-TNF + MTX/AZA, anti IL12/23, anti-IL-17, anti-IL23) compared to healthy controls. Automated ELISA for IgGs to spike trimer, spike receptor binding domain (RBD) and the nucleocapsid (NP) and T-cell release of 9 cytokines (IFNg, IL2, IL4, IL17A, TNF) and cytotoxic molecules (sFasL, GzmA, GzmB, Perforinin) in cell culture supernatants following stimulation with spike or NP peptide arrays were conducted at 4 time points: T1=pre vaccination, T2=me-dian 26 days after dose 1, T3=median 16 days after dose 2 and T4=median 106 days after dose 2. Neutralization assays against four SARS-CoV-2 variants (wild type, delta, beta and gamma) were conducted at T3. Results: We followed 150 subjects: 26 healthy controls and 124 IMID patients: 9 untreated, 44 on anti-TNF, 16 on anti-TNF with MTX/AZA, 10 on anti-IL23, 28 on anti-IL12/23, 9 on anti-IL17, 8 on MTX/AZA (Table 1). Most patients mounted antibody and T cell responses with increases from dose 1 to dose 2 (100% sero-conversion at T3) and some decline by T4, with variability within groups. Antibody levels and neutralization efficacy was lower in anti-TNFgroups (anti-TNF, anti-TNF + MTX/AZA) compared to controls and waned by T4 (Figure 1). T cell responses were not consistently different between groups. Pooled data showed a higher antibody response to mRNA-1273 compared to BNT162b. Conclusion: Following 2 doses of mRNA vaccination there is 100% seroconver-sion in IMID patients on maintenance therapy. Antibody levels and neutralization efficacy in anti-TNF group are lower than controls, and wane substantially by 3 months after dose 2. These fndings highlight the need for third dose in patients undergoing treatment with anti-TNF therapy and continued monitoring of immunity in these patient groups, taking into consideration newer variants and additional vaccine doses.

IMMUNE RESPONSE AFTER COVID-19 VACCINATION DURING MAINTANACE THERAPY IN IMMUNE-MEDIATED INFLAMMATORY DISEASES: AN OBSERVATIONAL COHORT STUDY

BACKGROUND Little is known about the impact of immunosuppressants on COVID-19 vaccination in patients with immune-mediated inflammatory diseases (IMID). Although humoral response may be attenuated in patients using immunomodulators (IMM) and TNFinhibitors (anti-TNF), data regarding cellular response are scarce and conflicting. This study was aimed to identify immune response to COVID-19 vaccination in IMID patients. METHODS A prospective observational multicentre cohort study was conducted to examine the immunogenicity of mRNA vaccines to SARS-CoV-2 in adult IMID patients using immunosuppressive therapy (anti-TNF, IMM, anti-TNF+IMM, anti-IL12/23, anti-IL-17, anti-IL-23) or no therapy as compared to healthy controls (HC). Patient details and vaccination history were recorded. Blood samples were drawn at 3 time points: before, 3-4 weeks after first and 2 weeks after second vaccination. Humoral immune response to S and RBD proteins were assessed by ELISA. Neutralization was tested against 4 variants of SARS-CoV-2 by surrogate neutralization ELISA. Cellular immune responses were determined based on analysis of 9 secreted cytokines and cytotoxic molecules after stimulation of PBMC with S peptide pools. Response to N protein was used to assess SARS-CoV-2 exposure. RESULTS A total of 159 subjects (133 IMID patients and 26 HC) were included in this study (median age 42 years [IQR 30-53], 52% male). Of 133 IMID patients, 87 had inflammatory bowel disease, 23 psoriatic arthritis, 18 psoriasis, 11 ankylosing spondylarthritis and 4 rheumatoid arthritis. Of these, 44 used anti-TNF, 9 IMM, 18 anti-TNF+IMM, 33 anti-IL-12/23, 9 anti-IL-17, 10 anti-IL-23 therapy and 10 no therapy. All subjects received 2 doses of mRNA vaccines (2x Pfizer, 2x Moderna or mixed) between December 2020 and September 2021. The vast majority of subjects had minimal binding antibody and T cell responses to N, indicating they were COVID-19 naïve. After dose 1, anti-TNF group had lower IL-2 vs untreated IMID (p<0.01), and the anti-IL-23 group had lower IFN-g vs HC (p<0.01), though there was wide variation in responses within groups. Following dose 2, median responses between groups were mostly similar, but antibody responses were significantly lower in patients on anti-TNF as compared to HC in subjects that received two doses of Pfizer (p=0.01). Pooled data for all subjects combined show a higher response to Moderna over Pfizer in ELISA, neutralization and T cell readouts, and a lower response for those over 60 years of age after dose 2. Longer follow-up is in process to monitor the durability of these responses over time and after third dose. CONCLUSION Immune responses after 2 doses of mRNA vaccines in immunocompromised IMID patients largely reach the level of that of HC albeit antibody responses in the anti-TNF group are weaker and with wide variability between subjects within some groups

Impact of lockdown period on chronic diseases

Objectives: In the wake of COVID-19 pandemic, strict lockdown measures posed many challenges in managing chronic diseases such as hypertension and diabetes. The impact of lockdown on physical and biochemical parameters along with contributing factors was assessed. Design: Cross-sectional analytical study. Materials and Methods: One hundred and fifty consecutive patients with chronic illnesses attending medicine outpatient department during unlock down phase I were enrolled. A 5 point Likert scale was used to determine the effect on diet, exercise, pain, physical and psychological symptoms, and a personal interview to assess the contributing factors. Clinical examination and laboratory investigations were done to compare between pre and post lockdown status and appropriate statistical tests were used. Results: The mean age of the patients was 48.53 +/- 6.4 years with a female preponderance. Mean duration of illness was 8.93 +/- 2.4 years and majority had hypertension (21%), diabetes (19%) or both (12%), hypothyroidism (18%), and gastroesophageal reflux disease (8%). While physical symptoms and pain did not show a significant change, 41.3% had worsening of psychological symptoms, 53.3% diet, and 70.6% exercise noncompliance. Weight, blood pressure, lipids, serum thyroid-stimulating hormone showed little change. Glycemic control was deranged in 72.5% with HbA1c increasing from 6.47 +/- 1.9 to 8.1 +/- 2.4 (P = 0.007). Contributing factors, 52.3% reported lack of exercise, 40% financial problems, 36% transport difficulties, and 30% unavailability of medicines. Conclusion: Lockdown negatively affected the management of chronic diseases with significant worsening of psychological symptoms, diet, and exercise adherence. Glycemic control worsened in diabetics. Lack of transport and unavailability of medicines were the significant contributing factors.

Pre-Operative SARS CoV-2 Rapid Antigen Test and Reverse Transcription Polymerase Chain Reaction: A conundrum in surgical decision making.

PURPOSE: Since the eye is in close proximity to the oro-nasal cavity, transmission of SARS CoV-2 is higher during ophthalmic surgical procedures, it is vital to ensure the safety of the healthcare team by pre-operative Rapid Antigen Test (RAT) and real-time Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) for SARS CoV-2 viral RNA of all patients planned for elective or emergency surgery. Hence, understanding the profile of pre-operative RAT and real-time RT-PCR among patients planned for various ophthalmic procedures, will help us make better decisions for future guidelines, for optimal planning of ophthalmic elective or emergency surgeries, keeping in mind the current scenario. METHODS: This is a prospective descriptive study conducted on patients planned for elective or emergency ophthalmic surgeries, who had no COVID-19-related symptoms pre-operatively and were subjected to preoperative RAT and real-time RT-PCR of nasopharyngeal and throat swabs for SARS CoV-2 viral RNA. Data was compiled and statistically analysed. RESULTS: 204 patients underwent pre-operative RAT and RT-PCR testing; of which, 85 were females and 119 were males. Mean age of the study population was 51.44 ± 16.501 years. Among the 204, 2 tested positive for SARS CoV-2 with Rapid Antigen testing as well as RT-PCR and 10 patients tested positive via RT-PCR after a negative RAT result of the same sample. CONCLUSION: Pre-operative testing for COVID-19 disease is indispensable as there is a high chance of transmission from patient to healthcare workers. RAT has the advantage of quick results and may play a role in case of emergency procedures. However, it is prudent to perform the more sensitive real-time RT-PCR before any elective, non-emergency procedures or surgeries to avoid any undue risk to the healthcare team.

Fundus evaluation in COVID-19 positives with non-severe disease.

PURPOSE: The aim of this work was to study and document retinal changes in coronavirus disease-2019 (COVID-19) positive patients with nonsevere disease using a nonmydriatic handheld fundus camera. METHODS: A cross-sectional observational study was conducted on patients affected by COVID-19 who were admitted at our center. Our study included patients with no, mild, and moderate symptoms (nonsevere cases). Intensive care unit (ICU)-admitted patients were excluded considering the difficulty in procuring the fundus image by the handheld camera due to patients positioning. Patients with systemic conditions (diabetes, hypertension, and severe anemia) known to cause retinopathy were also excluded. Bedside anterior segment examination, fundus examination using indirect ophthalmoscopy and fundus imaging of each patient using a nonmydriatic handheld fundus camera was done by a trained ophthalmologist posted for COVID duty. RESULTS: In a cohort of 138 patients, 94 (68.1%) were men and 44 (31.9%) were women. A total of 276 eyes were evaluated. The mean age of the patients was 38.51 ± 14.4 years. Anterior segment evaluation showed no abnormality in any of the eyes. On fundus screening using nonmydriatic handheld camera, a single streak of superficial retinal hemorrhage was noted at the posterior pole of the fundus in the left eye of one patient (0.72%), which was away from fovea. Laboratory tests revealed low hemoglobin (between 10 and 10.9 g/dL falling under mild Anemia) in 12 patients, elevated total leucocyte count in 6 patients, raised LDH in majority of patients (323 ± 101 Units/L) and elevated CRP (14.6 ± 30.99 mg/L). Rest of the lab parameters were within the normal range. CONCLUSION: In our study, COVID patients with mild-to-moderate symptoms did not show any inflammatory/infective or vaso-occlusive lesions in the retina attributable to COVID-19 infection, except one patient who had a single streak hemorrhage in the macula away from fovea, probably incidental.

Ophthalmic manifestations in the COVID-19 clinical spectrum.

PURPOSE: The aim of this study was to determine the frequency and various types of ophthalmic manifestation of patients with COVID-19. METHODS: This is a prospective observational study conducted on patients with SARS-Co-V-2 infection, at a dedicated tertiary COVID-19 hospital in South India from April 1 to July 31, 2020. At the time of their admission to the COVID hospital, demographic data such as name, age, sex was recorded. A thorough history regarding the onset, duration, progression, nature of symptoms and its associated factors, medication history, treatment history were elicited and documented. Ocular examination was performed under torchlight by an ophthalmologist posted for COVID duty. Further investigations including imaging were sought for, depending on clinical indications. Serial follow-up examinations of all patients were carried out every 72 hours or when patients complained of any ocular symptoms whichever earlier, until discharge. All relevant data were compiled and statistically analyzed. RESULTS: A total of 2742 patients were examined. Of them, 1461 (53.28%) were males and 1281 (46.72%) were females. The mean age (±SD) was 39.46 ± 17.63 years. None of the patients in our study had any ocular symptoms or signs as the presenting complaint at the time of their admission. On subsequent follow-up, only 20 (0.72%) developed ocular manifestations, of which 19 (95%) had features suggestive of Bilateral viral conjunctivitis. However, 1 (5%) patient had orbital cellulitis secondary to pansinusitis. CONCLUSION: Ophthalmic manifestations in the clinical spectrum of COVID-19 infection are uncommon and unlikely to be the presenting clinical impression. However, it has broadened our view to a wider spectrum of COVID-19 presentations enhancing our clinical acumen for staunch detection of COVID-19 suspects in our daily practice, augmenting early diagnosis and management and also break the chain of transmission for the greater good of humanity.