COVID-19 pandemic from an ophthalmology point of view.

Coronavirus disease 2019 (COVID-19) is caused by a highly contagious RNA virus termed as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Ophthalmologists are at high-risk due to their proximity and short working distance at the time of slit-lamp examination. Eye care professionals can be caught unaware because conjunctivitis may be one of the first signs of COVID-19 at presentation, even precluding the emergence of additional symptoms such as dry cough and anosmia. Breath and eye shields as well as N95 masks, should be worn while examining patients with fever, breathlessness, or any history of international travel or travel from any hotspot besides maintaining hand hygiene. All elective surgeries need to be deferred. Adults or children with sudden-onset painful or painless visual loss, or sudden-onset squint, or sudden-onset floaters or severe lid oedema need a referral for urgent care. Patients should be told to discontinue contact lens wear if they have any symptoms of COVID-19. Cornea retrieval should be avoided in confirmed cases and suspects, and long-term preservation medium for storage of corneas should be encouraged. Retinal screening is unnecessary for coronavirus patients taking chloroquine or hydroxychloroquine as the probability of toxic damage to the retina is less due to short-duration of drug therapy. Tele-ophthalmology and artificial intelligence should be preferred for increasing doctor-patient interaction.

Perception of college-going girls towards corneal donation in North India: A latent class analysis study.

Purpose: To assess the perception of college-going girls toward corneal donation in Northern India. Methods: An online survey with a pre-structured, pre-validated questionnaire was conducted on 1721 college-going girls in Northern India. The knowledge and attitude scores were regressed, and latent class analysis was carried out. Results: The average of scores for all participants was computed individually for the knowledge questions and the attitude questions, and based on this score, total participants were divided into two groups: Better corneal donation behaviors (BCDB) and poor corneal donation behaviors. The binomial logistic regression model of knowledge domain for predicting BCDB, age of the participant, their awareness about corneal donation, and willingness to discuss eye donation among family members were found significant. Similarly, for the attitude domain, awareness about corneal donation, knowledge about hours within which ideal eye donation needs to be undertaken, and knowledge about eye donation during coronavirus disease 2019 (COVID-19) pandemic were found to be significant. Latent class analysis identified one subset of participants having poorer knowledge and attitude scores and that they were more from a rural background, were having more than first order as birth order, were belonging to SC/ST classes, had illiterate or secondary education of father and mother, and were living in rented houses. Conclusion: The findings of the study significantly contribute to devising a mechanism to improve knowledge and influencing the attitude about eye donation among the youth, especially young women, who can act as counselors and motivators for the masses as well as their own families, in the generations to come.

Development of a multiomics model for identification of predictive biomarkers for COVID-19 severity: a retrospective cohort study.

BACKGROUND: COVID-19 is a multi-system disorder with high variability in clinical outcomes among patients who are admitted to hospital. Although some cytokines such as interleukin (IL)-6 are believed to be associated with severity, there are no early biomarkers that can reliably predict patients who are more likely to have adverse outcomes. Thus, it is crucial to discover predictive markers of serious complications. METHODS: In this retrospective cohort study, we analysed samples from 455 participants with COVID-19 who had had a positive SARS-CoV-2 RT-PCR result between April 14, 2020, and Dec 1, 2020 and who had visited one of three Mayo Clinic sites in the USA (Minnesota, Arizona, or Florida) in the same period. These participants were assigned to three subgroups depending on disease severity as defined by the WHO ordinal scale of clinical improvement (outpatient, severe, or critical). Our control cohort comprised of 182 anonymised age-matched and sex-matched plasma samples that were available from the Mayo Clinic Biorepository and banked before the COVID-19 pandemic. We did a deep profiling of circulatory cytokines and other proteins, lipids, and metabolites from both cohorts. Most patient samples were collected before, or around the time of, hospital admission, representing ideal samples for predictive biomarker discovery. We used proximity extension assays to quantify cytokines and circulatory proteins and tandem mass spectrometry to measure lipids and metabolites. Biomarker discovery was done by applying an AutoGluon-tabular classifier to a multiomics dataset, producing a stacked ensemble of cutting-edge machine learning algorithms. Global proteomics and glycoproteomics on a subset of patient samples with matched pre-COVID-19 plasma samples was also done. FINDINGS: We quantified 1463 cytokines and circulatory proteins, along with 902 lipids and 1018 metabolites. By developing a machine-learning-based prediction model, a set of 102 biomarkers, which predicted severe and clinical COVID-19 outcomes better than the traditional set of cytokines, were discovered. These predictive biomarkers included several novel cytokines and other proteins, lipids, and metabolites. For example, altered amounts of C-type lectin domain family 6 member A (CLEC6A), ether phosphatidylethanolamine (P-18:1/18:1), and 2-hydroxydecanoate, as reported here, have not previously been associated with severity in COVID-19. Patient samples with matched pre-COVID-19 plasma samples showed similar trends in muti-omics signatures along with differences in glycoproteomics profile. INTERPRETATION: A multiomic molecular signature in the plasma of patients with COVID-19 before being admitted to hospital can be exploited to predict a more severe course of disease. Machine learning approaches can be applied to highly complex and multidimensional profiling data to reveal novel signatures of clinical use. The absence of validation in an independent cohort remains a major limitation of the study. FUNDING: Eric and Wendy Schmidt.

Response to SARS-CoV-2 vaccination in immune mediated inflammatory diseases: Systematic review and meta-analysis.

OBJECTIVES: The treatment for COVID-19 often utilizes immune-modulating drugs. These drugs are also used in immune mediated inflammatory diseases (IMIDs). We performed a systematic review about seroconversion after SARS-CoV-2 vaccination in patients with IMIDs and impact of various drugs on seroconversion rates. METHODS: Electronic databases were searched to identify relevant studies reporting seroconversion rates following SARS-CoV-2 vaccination in IMIDs. We calculated the pooled seroconversion rates after a single or two doses of vaccination, pooled seroconversion rates in patients with specific IMIDs, and rates in patients on various drugs/drug classes. RESULTS: Twenty-five studies were included in the systematic review. The pooled seroconversion rates after two doses of mRNA vaccination were higher (83.1, 95%CI: 74.9-89.0, I2 = 90%) as compared to a single dose (69.3, 52.4-82.3, I2 = 95%). The odds of seroconversion were lower in IMIDs as compared to healthy controls (0.05, 0.02-0.13, I2 = 21%). The seroconversion rates in patients with inflammatory bowel disease (95.2, 95%CI: 92.6-96.9, I2 = 0%), spondyloarthropathy (95.6, 95% CI: 83.4-98.9, I2 = 35%), and systemic lupus erythematosus (90.7, 95%CI: 85.4-94.2, I2 = 0%) were higher as compared to rheumatoid arthritis (79.5, 95% CI: 65.1-88.9, I2 = 85%), and vasculitis (70.5, 95% CI: 52.9-83.5, I2 = 51%). The seroconversion rates following double dose of mRNA were excellent (>90%) in those on anti-tumour necrosis factor (TNF), anti-integrin (vedolizumab), anti-IL 17 (secukinumab), anti-IL6 (Tocilizumab) and anti-IL12/23 (Ustekinumab) therapies but attenuated (<70%) in patients on anti-CD20 (Rituximab) or anti-cytotoxic T lymphocyte associated antigen (CTLA-4) therapies (Abatacept). The seroconversion rates were good (70-90%) with steroids, hydroxychloroquine, JAK inhibitors, mycophenolate mofetil and leflunomide. Combination of anti-TNF with immunomodulators (azathioprine, 6-meracptopurine, methotrexate) resulted in an attenuated vaccine response as compared to anti-TNF monotherapy. CONCLUSION: Seroconversion rates after SARS-CoV-2 vaccination are lower in patients with IMIDs. Certain therapies (anti-TNF, anti-integrin, anti-IL 17, anti-IL6, anti-12/23) do not impact seroconversion rates while others (anti-CD20, anti-CTLA-4) result in poorer responses.

System for administering and monitoring hydroxychloroquine prophylaxis for COVID-19 in accordance with a national advisory: preliminary experience of a tertiary care institute in India.

BACKGROUND: Hydroxychloroquine (HCQ) was one of the earliest drugs to be recommended for tackling the COVID-19 threat leading to its widespread usage. We provide preliminary findings of the system, established in a tertiary care academic center for the administration of HCQ prophylaxis to healthcare workers (HCW) based on Indian Council of Medical Research (ICMR) advisory. METHODS: A dedicated clinical pharmacology and internal medicine team screened for contraindications, administered informed consent, maintained compliance and monitored for adverse events. RESULTS: Among the 194 HCWs screened for ruling out contraindications for prophylaxis, 9 were excluded and 185 were initiated on HCQ. A total of 55 adverse events were seen in 38 (20.5%) HCWs out of which 70.9%, 29.1% were mild and moderate & none were severe. Before the completion of therapy, a total of 23 participants discontinued. Change in QTc interval on day 2 was 5 (IQR: -3.75, 11) ms and the end of week 1 was 15 ms (IQR: 2, 18). Out of the 5 HCW who turned positive for COVID-19, 2 were on HCQ. CONCLUSION: HCQ prophylaxis was found to be safe and well tolerated in HCW when administered after appropriate screening and with monitoring for adverse events.

Risk and outcomes of coronavirus disease in patients with inflammatory bowel disease: A systematic review and meta-analysis.

BACKGROUND: The risk of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infection and clinical outcomes of coronavirus disease (COVID-19) in inflammatory bowel disease are unclear. METHODS: We searched PubMed and Embase with the keywords: inflammatory bowel disease, Crohn's disease, ulcerative colitis and COVID-19, novel coronavirus and SARS-CoV-2. We included studies reporting the frequency of COVID-19 infection and outcomes (hospitalisation, need for intensive care unit care and mortality) in patients with inflammatory bowel disease. We estimated the pooled incidence of COVID-19 in inflammatory bowel disease and comparative risk vis-a-vis the general population. We also estimated the pooled frequency of outcomes and compared them in patients who received and did not receive drugs for inflammatory bowel disease. RESULTS: Twenty-four studies were included. The pooled incidence rate of COVID-19 per 1000 patients of inflammatory bowel disease and the general population were 4.02 (95% confidence interval [CI, 1.44-11.17]) and 6.59 [3.25-13.35], respectively, with no increase in relative risk (0.47, 0.18-1.26) in inflammatory bowel disease. The relative risk of the acquisition of COVID-19 was not different between ulcerative colitis and Crohn's disease (1.03, 0.62-1.71). The pooled proportion of COVID-19-positive inflammatory bowel disease patients requiring hospitalisation and intensive care unit care was 27.29% and 5.33% while pooled mortality was 4.27%. The risk of adverse outcomes was higher in ulcerative colitis compared to Crohn's disease. The relative risks of hospitalisation, intensive care unit admission and mortality were lower for patients on biological agents (0.34, 0.19-0.61; 0.49, 0.33-0.72 and 0.22, 0.13-0.38, respectively) but higher with steroids (1.99, 1.64-2.40; 3.41, 2.28-5.11 and 2.70, 1.61-4.55) or 5-aminosalicylate (1.59, 1.39-1.82; 2.38, 1.26-4.48 and 2.62, 1.67-4.11) use. CONCLUSION: SARS-CoV-2 infection risk in patients with inflammatory bowel disease is comparable to the general population. Outcomes of COVID-19-positive inflammatory bowel disease patients are worse in ulcerative colitis, those on steroids or 5-aminosalicylates but outcomes are better with biological agents.

Clinical presentation of COVID-19 in patients with inflammatory bowel disease: a systematic review and meta-analysis.

BACKGROUND/AIMS: Coronavirus disease 2019 (COVID-19) is recognized to have variable clinical manifestations. The clinical presentation of patients with inflammatory bowel disease (IBD) having COVID-19 is unclear. METHODS: We identified articles reporting about the clinical presentation of COVID-19 in those with underlying IBD from PubMed and Embase. The studies, irrespective of design or language, were included. The overall pooled frequency of various symptoms was estimated. Joanna Briggs Institute Critical appraisal checklist was used to assess the quality of studies. RESULTS: Eleven studies, including 1,325 patients, were included in the pooled analysis. The pooled estimates for clinical presentation were; fever: 67.53% (95% confidence interval [CI], 45.38-83.88), cough: 59.58% (95% CI, 45.01-72.63), diarrhea: 27.26% (95% CI, 19.51-36.69), running nose: 27% (95% CI, 15.26-43.19) and dyspnea: 25.29% (95% CI, 18.52-33.52). The pooled prevalence rates for abdominal pain, nausea and vomiting were 13.08% (95% CI, 9.24-18.19), 10.08% (95% CI, 5.84-16.85) and 8.80% (95% CI, 4.43-16.70) per 100 population, respectively. CONCLUSIONS: The clinical presentation of COVID-19 in IBD patients is similar to the general population.

Diagnostic accuracy of CT and radiographic findings for novel coronavirus 2019 pneumonia: Systematic review and meta-analysis.

PURPOSE: To evaluate pooled prevalence, sensitivity, and specificity of chest computed tomography (CT) and radiographic findings for novel coronavirus-2019 (COVID-19) pneumonia. METHODS: We performed systematic literature search in PubMed and Embase to identify articles reporting baseline imaging findings of COVID-19 pneumonia. The quality of the articles was assessed using NIH quality assessment tool for case series studies. The pooled prevalence, sensitivity, specificity, and diagnostic odds ratio of imaging findings were calculated. RESULTS: Fifty-six studies (6007 patients, age, 2.1-70 years, 2887 females, 5762 CT, 396 radiographs,) were included. The mean interval between onset of symptoms and CT acquisition was 1-8 days. On CT, the pooled prevalence of ground glass opacities (GGO), GGO plus consolidation, and consolidation only was 66.9% (95% CI 60.8-72.4%), 44.9% (38.7-51.3%), and 32.1 (23.6-41.9%) respectively. Pooled sensitivity and specificity of GGO on CT was 73% (71%-80%) and 61% (41%-78%), respectively. For GGO plus consolidation and consolidation only, the pooled sensitivities/ specificities were 58% (48%-68%)/ 58% (41%-73%) and 49% (20%-78%)/ 56% (30%-78%), respectively. The pooled prevalence of GGO and consolidation on chest radiograph was 38.7% (22.2%-58.3%) and 46.9% (29.7%-64.9%), respectively. The diagnostic accuracy of radiographic findings could not be assessed due to small number of studies. CONCLUSION: GGO on CT has the highest diagnostic performance for COVID-19 pneumonia, followed by GGO plus consolidation and consolidation only. However, the moderate to low sensitivity and specificity suggest that CT should not be used as the primary tool for diagnosis. Chest radiographic abnormalities are seen in half of the patients.

Hydroxychloroquine and QTc prolongation in patients with COVID-19: A systematic review and meta-analysis.

BACKGROUND: Among many drugs that hold potential in COVID-19 pandemic, chloroquine (CQ), and its derivative hydroxychloroquine (HCQ) have generated unusual interest. With increasing usage, there has been growing concern about the prolongation of QTc interval and Torsades de Pointes (TdP) with HCQ, especially in combination with azithromycin. AIMS: This meta-analysis is planned to study the risk of QTc prolongation and Torsades de pointes (TdP) by a well-defined criterion for HCQ, CQ alone, and in combination with Azithromycin in patients with COVID-19. METHODS: A comprehensive literature search was made in two databases (PubMed, Embase). Three outcomes explored in the included studies were frequency of QTc > 500 ms (ms) or ΔQTc > 60 ms (Outcome 1), frequency of QTc > 500 ms (Outcome 2) and frequency of TdP (Outcome 3). Random effects method with inverse variance approach was used for computation of pooled summary and risk ratio. RESULTS: A total of 13 studies comprising of 2138 patients were included in the final analysis. The pooled prevalence of outcome 1, outcome 2 and outcome 3 for HCQ, CQ with or without Azithromycin were 10.18% (5.59-17.82%, I2 - 92%), 10.22% (6.01-16.85%, I2 - 79%), and 0.72% (0.34-1.51, I2 - 0%) respectively. The prevalence of outcome 2 in subgroup analysis for HCQ and HCQ + Azithromycin was 7.25% (3.22-15.52, I2 - 59%) and 8.61% (4.52-15.79, I2 - 76%), respectively. The risk ratio (RR) for outcome 1 and outcome 2 between HCQ + Azithromycin and HCQ was 1.22 (0.77-1.93, I2 - 0%) & 1.51 (0.79-2.87, I2 - 13%), respectively and was not significant. Heterogeneity was noted statistically as well clinically (regimen types, patient numbers, study design, and outcome definition). CONCLUSION: The use of HCQ/CQ is associated with a high prevalence of QTc prolongation. However, it is not associated with a high risk of TdP.

The trend of cutaneous lesions during COVID-19 pandemic: lessons from a meta-analysis and systematic review.

BACKGROUND: Besides predominant respiratory and gastrointestinal manifestations, reports on cutaneous manifestations in COVID-19 patients are being noted increasingly. OBJECTIVES: To estimate the prevalence of cutaneous manifestations in COVID-19 patients. METHODS: This study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. A detailed literature search was done in PubMed and Embase from December 1, 2019, till May 1, 2020. Studies reporting cutaneous manifestations in COVID-19 patients were included. Irrespective of the heterogeneity of data, a random effects model with inverse-variance approach was used for pooling the prevalence using meta package in R version 3.6.2. RESULTS: Out of 15,143 articles, 2086 articles were selected for full-text read. Forty-three articles were selected for qualitative analysis, of which 10 articles (N = 1682) were included for meta-analysis. The pooled prevalence of overall cutaneous lesions was 5.69 (95% confidence interval [CI]: 1.87-15.98; I2 88%). The pooled prevalence of other outcome parameters were as follows: viral exanthem-like presentation 4.15 (95% CI: 1.33-12.23; I2 88%), maculopapular rash 3.81 (95% CI: 1.02-13.18; I2 87%), vesiculobullous lesions 1.67 (95% CI: 0.70-3.96; I2 0%). CONCLUSION: The estimated prevalence of cutaneous manifestations in COVID-19 was 5.69%. Other manifestations were urticaria, chilblain-like lesions, livedo reticularis, and finger/toe gangrene. Although it is premature to conclude the prevalence of the cutaneous manifestations during this ongoing pandemic, our report may be a stimulating factor for the physicians to perform further vigilant streamlined reporting of cutaneous manifestations in COVID-19 patients to estimate the final prevalence.

Coronavirus disease (COVID-19) and the liver: a comprehensive systematic review and meta-analysis.

BACKGROUND: Liver function derangements have been reported in coronavirus disease (COVID-19), but reported rates are variable. METHODS: We searched PubMed and Embase with terms COVID and SARS-COV-2 from December 1, 2019 till April 5, 2020. We estimated overall prevalence, stratified prevalence based on severity, estimated risk ratio (RR), and estimated standardized mean difference (SMD) of liver function parameters in severe as compared to non-severe COVID. Random effect method utilizing inverse variance approach was used for pooling the data. RESULTS: In all, 128 studies were included. The most frequent abnormalities were hypoalbuminemia [61.27% (48.24-72.87)], elevations of gamma-glutamyl transferase (GGT) [27.94% (18.22-40.27)], alanine aminotransferase (ALT) [23.28% (19.92-27.01)], and aspartate aminotransferase (AST) [23.41% (18.84-28.70)]. Furthermore, the relative risk of these abnormalities was higher in the patients with severe COVID-19 when compared to non-severe disease [Hypoalbuminemia-2.65 (1.38-5.07); GGT-2.31 (1.6-3.33); ALT-1.76 (1.44-2.15); AST-2.30 (1.82-2.90)]. The SMD of hypoalbuminemia, GGT, ALT, and AST elevation in severe as compared to non-severe were - 1.05 (- 1.27 to - 0.83), 0.76 (0.40-1.12), 0.42 (0.27-0.56), and 0.69 (0.52-0.86), respectively. The pooled prevalence and RR of chronic liver disease as a comorbidity was 2.64% (1.73-4) and 1.69 (1.05-2.73) respectively. CONCLUSION: The most frequent abnormality in liver functions was hypoalbuminemia followed by derangements in gamma-glutamyl transferase and aminotransferases, and these abnormalities were more frequent in severe disease. The systematic review was, however, limited by heterogeneity in definitions of severity and liver function derangements. Graphical depiction of the summary of meta-analytic findings a) pooled prevalence of abnormalities b) Risk ratio of abnormality in severe versus non-severe COVID-19 c) standardized mean difference (SMD) between severe and non-severe group and d) pooled prevalence for parameters based on severity stratification for bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), albumin, globulin and acute hepatic injury (AHI) . Also estimates for overall/total liver disease (TLD) and chronic liver disease (CLD) amongst COVID-19 patients are depicted in a, b, d. For d) In addition to severity stratification, Overall (all studies for a particular estimate) and combined (only those studies which reported severity) estimates are provided.