Molecular Determinants of Sensitivity to Polatuzumab Vedotin in Diffuse Large B Cell Lymphoma.

Polatuzumab Vedotin (Pola-V) is an antibody-drug conjugate directed to the CD79B subunit of the B cell receptor (BCR). When combined with conventional immunochemotherapy, Pola-V improves outcomes in DLBCL. To identify determinants of Pola-V sensitivity, we used CRISPR-Cas9 screening for genes that modulated Pola-V toxicity for lymphomas or the surface expression of its target, CD79B. Our results reveal the striking impact of CD79B glycosylation on Pola-V epitope availability on the lymphoma cell surface and on Pola-V toxicity. Genetic, pharmacological, and enzymatic approaches that remove sialic acid from N-linked glycans enhanced lymphoma killing by Pola-V. Pola-V toxicity was also modulated by KLHL6, an E3 ubiquitin ligase that is recurrently inactivated in germinal center derived lymphomas. We reveal how KLHL6 targets CD79B for degradation in normal and malignant germinal center B cells, thereby determining expression of the surface BCR complex. Our findings suggest precision medicine strategies to optimize Pola-V as a lymphoma therapeutic.

ZMIZ1 enhances ERα-dependent expression of E2F2 in breast cancer.

The estrogen receptor-α (ER) drives 75% of breast cancers. On activation, the ER recruits and assembles a 1-2 MDa transcriptionally active complex. These complexes can modulate tumour growth, and understanding the roles of individual proteins within these complexes can help identify new therapeutic targets. Here, we present the discovery of ER and ZMIZ1 within the same multi-protein assembly by quantitative proteomics, and validated by proximity ligation assay. We characterise ZMIZ1 function by demonstrating a significant decrease in the proliferation of ER-positive cancer cell lines. To establish a role for the ER-ZMIZ1 interaction, we measured the transcriptional changes in the estrogen response post-ZMIZ1 knockdown using an RNA-seq time-course over 24 h. Gene set enrichment analysis of the ZMIZ1-knockdown data identified a specific delay in the response of estradiol-induced cell cycle genes. Integration of ENCODE data with our RNA-seq results identified that ER and ZMIZ1 both bind the promoter of E2F2. We therefore propose that ER and ZMIZ1 interact to enable the efficient estrogenic response at subset of cell cycle genes via a novel ZMIZ1-ER-E2F2 signalling axis. Finally, we show that high ZMIZ1 expression is predictive of worse patient outcome, ER and ZMIZ1 are co-expressed in breast cancer patients in TCGA and METABRIC, and the proteins are co-localised within the nuclei of tumour cell in patient biopsies. In conclusion, we establish that ZMIZ1 is a regulator of the estrogenic cell cycle response and provide evidence of the biological importance of the ER-ZMIZ1 interaction in ER-positive patient tumours, supporting potential clinical relevance.

Ten Years Analysis of Parental Counselling-in-Continuum in Paediatric Surgery: Psychosocial and Medico-legal Outcome.

BACKGROUND: Parents are anxious and apprehensive about the health of their children. A standardised, reproducible and meticulous parental counselling is helpful to both the parents and the treating doctors, as well as markedly reduces instances of scrimmage and medico-legal litigations. The aim of this study is to assess the psychosocial and medico-legal outcomes of parental counselling-in-continuum (PCiC) in paediatric surgery. MATERIALS AND METHODS: The study was conducted at two government-run Tertiary Healthcare Centres in North India. The study design involves prospective feedback-based study. It included all the admitted paediatric surgery patients. Periodic multisession PCiC was done for each patient by three paediatric surgery teams from 2011 to 2021. At the time of discharge, feedback was taken to assess the psychosocial outcome of PCiC, and the medico-legal outcome was calculated based on the number of litigations. RESULTS: A total of 22,353 admissions were done in paediatric wards at these institutes. 1574 cases were managed conservatively and 20,779 patients who underwent surgeries were included in the study. 4758 (22.89%) were emergency procedures and 16,021 (77.11%) were elective procedures. Parents rated the counselling efforts excellent in 18,285 (81.80%), good in 3162 (14.14%), satisfactory in 876 (3.91%) and poor in 30 (0.13%) cases with zero medico-legal litigations and 12 incidents of scrimmage. CONCLUSIONS: PCiC, being a novel concept, should form a centerpiece of paediatric surgical management as it maximally enhances the patient satisfaction level and protects the treating paediatric surgical team from scrimmage and medico-legal litigations.

Transcutaneous Hitching Sutures in Paediatric Minimally Invasive Surgery: A Novel Technique of "Assistant Without Port".

BACKGROUND: Transcutaneous hitching sutures in paediatric minimally invasive surgery (MIS) is a unique and rare technique. This technique has been used previously in adult patients undergoing gastric resections and laparoscopic cholecystectomy; however, its use in paediatric population has never been reported in the world literature. The primary objective of this study was to bring out the advantages and feasibility of this technique in minimally invasive gastrointestinal, hepatobiliary, urological and thoracoscopic surgeries on paediatric patients. MATERIALS AND METHODS: This retrospective observational study was conducted on 167 paediatric patients who underwent MIS surgery for different indications between April 2016 and March 2020 at two paediatric surgery tertiary care centres. RESULTS: A total of 167 patients, including 91 boys and 76 girl patients between the age group of new-born period to 12 years were operated. The mean hospital stay was 4 days. Five out of 167 cases (3%) had post-operative surgical emphysema, which resolved spontaneously. At 6-month follow-up, parental satisfaction was 100%, and in 99% of patients, scars were imperceptible. CONCLUSION: This versatile technique is of exemplary utility, especially in paediatric patients where there is a paucity of working space at low intra-abdominal pressure, and eases the dissection even in narrow and closed spaces with a better functional and cosmetic outcome.

Comparable outcomes with low-dose and standard-dose horse anti-thymocyte globulin in the treatment of severe aplastic anemia.

BACKGROUND: The standard dose (SD) of horse anti-thymocyte globulin (hATG) ATGAM (Pfizer, USA) or its biosimilar thymogam (Bharat Serum, India) for the treatment of Aplastic Anemia (AA) is 40 mg/kg/day for 4 days in combination with cyclosporine. Data on the impact of hATG dose on long-term outcomes are limited. Here, we describe our comparative experience using 25 mg/kg/day (low-dose [LD]) hATG for 4 days with SD for the treatment of AA. METHODS: We retrospectively studied patients with AA (age > 12 years) who received two doses of hATG combined with cyclosporine. Among 93 AA patients who received hATG, 62 (66.7%) and 31 (33.3%) patients received LD and SD hATG with cyclosporine, respectively. Among these,seventeen(18.2%) patients also received eltrombopag with hATG and cyclosporine. Overall response rates [complete response (CR) and partial response (PR)] of LD and SD hATG groups at 3 months (50% vs. 48.4%; p = 0.88), 6 months (63.8% vs. 71.4%; p = 0.67), and 12 months (69.6% vs. 79.2%; p = 0.167) were comparable. The mean (Standard Deviation) 5-year Kaplan-Meier estimate of overall survival and event-free survival was 82.1 (4.6)% and 70.9 (5.5)% for the study population. The mean (standard deviation) 5-year Kaplan-Meier estimate of overall survival and event-free survival of those who received LD hATG versus SD hATG dose was 82.9 (5·3)% versus 74.8 (10·3)% (P = 0·439), and 75.2 (6.2)% versus 61.4(11.2)% (P = 0·441). CONCLUSION: Our study revealed that the response rates of patients with AA and LD were similar to those of patients with SD to hATG combined with cyclosporine in a real-world setting.

Determinants of polycystic ovary syndrome: A matched case-control study.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is a multifaceted endocrine disorder of women of reproductive age with a multifactorial aetiology. Despite much research, there is still inconclusive data on the impact of dietary, lifestyle and socio-economic factors on PCOS aetiology. Thus, the present study explored the association of PCOS with diet, eating behaviour, other lifestyle and socio-economic factors. METHODS: A matched-pair case-control study was conducted on 150 women with PCOS and 150 healthy controls. Information on diet, eating behaviour and physical activity, and also anthropometric and socio-economic data were collected through standard questionnaires. The adjusted odds ratios (AmOR) were calculated and reported using conditional multivariable logistic regression. RESULTS: The results showed low education level (AmOR = 8.44; 95% confidence interval [CI] = 1.63-43.68), high sugar consumption (AmOR = 11.61; 95% CI = 2.05-65.72) along with higher body mass index (BMI) and inactivity to be significantly associated with PCOS. Also, a significant protective effect was found for cognitive dietary restraint (AmOR = 0.79; 95% CI = 0.66-0.93), crude fibre (AmOR = 0.61; 95% CI = 0.45-0.82) and protein intake. CONCLUSIONS: Low education status may contribute to higher receptiveness to choosing unhealthy diets and lifestyles, resulting in adiposity and an increased risk of PCOS.

Treatment challenges in the management of difficult-to-treat gram-positive infections: A consensus view apropos therapeutic role of novel anti-MRSA antibiotics, levonadifloxacin (IV) and alalevonadifloxacin (oral).

PURPOSE: Treatment of antibiotic-resistant Gram-positive infections (GPIs), including methicillin-resistant Staphylococcus aureus (MRSA) is becoming increasingly difficult, particularly in patients with multiple co-morbidities who require antibiotics with greater safety and a consistent pharmacokinetic/pharmacodynamic (PK/PD) profile. Such difficult-to-treat GPIs are often associated with poor outcomes, extended hospital stay and increased expenditure. This can be partly attributed to the limited safety and aberrant PK/PD profile of existing anti-MRSA antibiotics. In this context, intravenous levonadifloxacin and its oral prodrug alalevonadifloxacin are novel anti-MRSA antibiotics that have significant advantages over conventional anti-Gram-positive antibiotics. The purpose of this paper was to generate a consensus on the optimal use of levonadifloxacin and alalevonadifloxacin for tackling resistant Gram-positive infections in patients with multiple co-morbidities. METHOD: Using a modified Delphi approach that combines critical appraisal of evidence and expert opinion, therapeutic use of levonadifloxacin and alalevonadifloxacin in various clinical scenarios and specific unmet conditions was deliberated. Fifteen expert members from medicine, critical-care, emergency, microbiology, and intensive-care disciplines participated and voted on 11 pre-conceived statements. When there was at least 70 % agreement, a consensus was reached. RESULTS: Following the voting, agreements were reached on 10 out of the 11 statements. Broadly, a consensus was reached in defining the therapeutic role of levonadifloxacin and alalevonadifloxacin in the treatment of various clinical indications involving resistant Gram-positive pathogens, including MRSA, in patients with co-morbidities, such as co-existing or increased risk for kidney dysfunction or hepatic disease and/or immunosuppression; also, in therapeutically challenging conditions caused by Gram-positive bacteria such as bacteraemia, bone and joint infection, diabetic foot infection, febrile neutropenia, and hospital-acquired pneumonia. CONCLUSIONS: This consensus supports the therapeutic use of levonadifloxacin and alalevonadifloxacin in the treatment of antibiotic-resistant GPIs, including those caused by MRSA and certain polymicrobial infections, in patients with multiple co-morbidities requiring drug with adequate safety and consistent efficacy.

Proteomic profiling of centrosomes across multiple mammalian cell and tissue types by an affinity capture method.

Centrosomes are the major microtubule-organizing centers in animals and play fundamental roles in many cellular processes. Understanding how their composition varies across diverse cell types and how it is altered in disease are major unresolved questions, yet currently available centrosome isolation protocols are cumbersome and time-consuming, and they lack scalability. Here, we report the development of centrosome affinity capture (CAPture)-mass spectrometry (MS), a powerful one-step purification method to obtain high-resolution centrosome proteomes from mammalian cells. Utilizing a synthetic peptide derived from CCDC61 protein, CAPture specifically isolates intact centrosomes. Importantly, as a bead-based affinity method, it enables rapid sample processing and multiplexing unlike conventional approaches. Our study demonstrates the power of CAPture-MS to elucidate cell-type-dependent heterogeneity in centrosome composition, dissect hierarchical interactions, and identify previously unknown centrosome components. Overall, CAPture-MS represents a transformative tool to unveil temporal, regulatory, cell-type- and tissue-specific changes in centrosome proteomes in health and disease.

PLK1 inhibition dampens NLRP3 inflammasome-elicited response in inflammatory disease models.

Unabated activation of the NLR family pyrin domain-containing 3 (NLRP3) inflammasome is linked with the pathogenesis of various inflammatory disorders. Polo-like kinase 1 (PLK1) has been widely studied for its role in mitosis. Here, using both pharmacological and genetic approaches, we demonstrate that PLK1 promoted NLRP3 inflammasome activation at cell interphase. Using an unbiased proximity-dependent biotin identification (Bio-ID) screen for the PLK1 interactome in macrophages, we show an enhanced proximal association of NLRP3 with PLK1 upon NLRP3 inflammasome activation. We further confirmed the interaction between PLK1 and NLRP3 and identified the interacting domains. Mechanistically, we show that PLK1 orchestrated the microtubule-organizing center (MTOC) structure and NLRP3 subcellular positioning upon inflammasome activation. Treatment with a selective PLK1 kinase inhibitor suppressed IL-1ß production in in vivo inflammatory models, including LPS-induced endotoxemia and monosodium urate-induced peritonitis in mice. Our results uncover a role of PLK1 in regulating NLRP3 inflammasome activation during interphase and identify pharmacological inhibition of PLK1 as a potential therapeutic strategy for inflammatory diseases with excessive NLRP3 inflammasome activation.

Assessment of quality of life in patients having Poly-Cystic Ovarian Syndrome: A cross-sectional facility-based study.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is a complex and heterogeneous disorder affecting various body organs. Menstrual irregularity, anovulation, and many cosmetic issues faced by PCOS patients endanger the essence of being a woman and may have a deleterious impact on their health-related quality of life (HRQOL). This study aimed to assess HRQOL in patients with PCOS and to identify the clinical and socio-demographic factors that might predict poor HRQOL. MATERIALS AND METHODS: This cross-sectional study was carried out in the tertiary care hospital in India. A total of 275 women visiting the same setting and diagnosed with PCOS were included. The participants' quality of life was studied using a disease-specific HRQOL questionnaire. Information regarding clinical and socio-demographics was collected using the interviewer schedule. For evaluating the predictors of HRQOL in PCOS subjects, analysis of variance and independent t-test was applied. For subgroup analysis, the post hoc (Gabriel) test was applied. RESULTS: The average total score of HRQOL of the study participants was 125.41 ± 29.1. The lowest weighted mean score was for menstrual problems. Among the socio-demographic variables, age and educational level influenced the HRQOL scores. Highly educated women reported the poorest HRQOL. The analysis of variance also indicated a significant variation in HRQOL scores among body mass index categories [F (4,270) = 5.09, P = <.001] and hirsutism status [F (2,272) = 14.222, P =<.001]. CONCLUSIONS: Menstrual irregularity, hirsutism, increased body mass index, educational status, and age are critical in altering HRQOL in PCOS cases. Clinicians should inquire about the HRQOL of patients with severe clinical manifestations and appropriate support must be provided during patient care.

Treatment seeking behavior among patients with polycystic ovarian syndrome (PCOS)-A cross-sectional study from Northern India.

BACKGROUND: Polycystic ovarian syndrome (PCOS) has now become a common problem among adolescent girls and young women in India. However, little is known about the treatment and satisfaction incurred from it. Our study aimed to assess the treatment-seeking behaviour among patients with PCOS. MATERIALS AND METHODS: The cross-sectional study was carried out in gynecology OPD of PGIMER, Chandigarh. Women with PCOS, 275, visiting the gynecology OPD were included. The treatment-seeking behavior for PCOS was elucidated among cases using a questionnaire. This included parameters like healthcare consulted, preferred system of medicine, referral pattern, treatment efficacy, and expenses incurred. Univariate descriptive analysis was used to present the results. RESULTS: The majority (68%) of the study participants were less than 25 years of age. The average weight was 66.78 (±13.0) Kg. Half of the participants were students. More than 70% belonged to the upper or upper-middle class. The study participants were diagnosed with PCOS at an average age of 21.4 (±4.7) years. The minimum age reported at diagnosis was 11 years, and the maximum age of diagnosis was 36 years. Most respondents preferred Allopathic treatment followed by homeopathy and Ayurveda. Few also opted for other treatment choices like diet therapy, yoga & meditation, weight loss supplements, and home remedies. Treatment efficacy ranged between 17.3%-34.2%. The majority of respondents reported the treatment to be moderately expensive. Most respondents (58.91%) were hardly influenced, while 16% were quite influenced by PCOS medicine or treatment advertisements. CONCLUSION: PCOS patients opt for different treatment options but generally find the treatment less effective and expensive.

Electrochemical behavior, antimicrobial activities, and effect of temperature on micellization of imidazolium monomeric surfactants.

In the present study, we herein report the conductance behavior, effect of temperature, and chain-length of two environmentally friendly imidazolium cationic capric and stearic surfactants. The conductance behavior has been carried out in aqueous solvent (H2O) at four different temperatures such as 24 °C, 29 °C, 34 °C, and 39 °C. The normal micelles were formed in an aqueous solvent and critical micelle concentration (CMC) can be estimated through conductivity parameters. The expected dependency of the CMC on the alkyl chain length of the 3-(2-(decanoyloxy)ethyl)-1-methyl-1H-imidazol-3-ium-bromide and 3-(2-(octadecanoyloxy)ethyl)-1-methyl-1H-imidazol-3-ium-bromide was demonstrated. It was observed that the graphs of molar conduct activity v/s square root were not linear, which specifies that the synthesized surfactants behave as weak electrolytes in the dilute solutions. The electrochemical characterization of capric and stearic surfactant modified SPCE was studied in 1mM K3FeCN6 solution. The CS/SPCE and SS/SPCE were shown elevated sensitivity, high stability, and excellent conductivity. Moreover, the antimicrobial behaviors of the synthesized imidazolium cationic surfactants versus various microbial strains were evaluated. Results showed that capric surfactant demonstrated high antibacterial activity against Escherichia coli (MIC > 31.5 µg/mL).

CRISPR-Cas9 genetic screen leads to the discovery of L-Moses, a KAT2B inhibitor that attenuates Tunicamycin-mediated neuronal cell death.

Accumulation of aggregated and misfolded proteins, leading to endoplasmic reticulum stress and activation of the unfolded protein response, is a hallmark of several neurodegenerative disorders, including Alzheimer's and Parkinson's disease. Genetic screens are powerful tools that are proving invaluable in identifying novel modulators of disease associated processes. Here, we performed a loss-of-function genetic screen using a human druggable genome library, followed by an arrayed-screen validation, in human iPSC-derived cortical neurons. We identified and genetically validated 13 genes, whose knockout was neuroprotective against Tunicamycin, a glycoprotein synthesis inhibitor widely used to induce endoplasmic reticulum stress. We also demonstrated that pharmacological inhibition of KAT2B, a lysine acetyltransferase identified by our genetic screens, by L-Moses, attenuates Tunicamycin-mediated neuronal cell death and activation of CHOP, a key pro-apoptotic member of the unfolded protein response in both cortical and dopaminergic neurons. Follow-up transcriptional analysis suggested that L-Moses provided neuroprotection by partly reversing the transcriptional changes caused by Tunicamycin. Finally, L-Moses treatment attenuated total protein levels affected by Tunicamycin, without affecting their acetylation profile. In summary, using an unbiased approach, we identified KAT2B and its inhibitor, L-Moses, as potential therapeutic targets for neurodegenerative diseases.

Multi-omics analyses demonstrate a critical role for EHMT1 methyltransferase in transcriptional repression during oogenesis.

EHMT1 (also known as GLP) is a multifunctional protein, best known for its role as an H3K9me1 and H3K9me2 methyltransferase through its reportedly obligatory dimerization with EHMT2 (also known as G9A). Here, we investigated the role of EHMT1 in the oocyte in comparison to EHMT2 using oocyte-specific conditional knockout mouse models (Ehmt2 cKO, Ehmt1 cKO, Ehmt1/2 cDKO), with ablation from the early phase of oocyte growth. Loss of EHMT1 in Ehmt1 cKO and Ehmt1/2 cDKO oocytes recapitulated meiotic defects observed in the Ehmt2 cKO; however, there was a significant impairment in oocyte maturation and developmental competence in Ehmt1 cKO and Ehmt1/2 cDKO oocytes beyond that observed in the Ehmt2 cKO. Consequently, loss of EHMT1 in oogenesis results, upon fertilization, in mid-gestation embryonic lethality. To identify H3K9 methylation and other meaningful biological changes in each mutant to explore the molecular functions of EHMT1 and EHMT2, we performed immunofluorescence imaging, multi-omics sequencing, and mass spectrometry (MS)-based proteome analyses in cKO oocytes. Although H3K9me1 was depleted only upon loss of EHMT1, H3K9me2 was decreased, and H3K9me2-enriched domains were eliminated equally upon loss of EHMT1 or EHMT2. Furthermore, there were more significant changes in the transcriptome, DNA methylome, and proteome in Ehmt1/2 cDKO than Ehmt2 cKO oocytes, with transcriptional derepression leading to increased protein abundance and local changes in genic DNA methylation in Ehmt1/2 cDKO oocytes. Together, our findings suggest that EHMT1 contributes to local transcriptional repression in the oocyte, partially independent of EHMT2, and is critical for oogenesis and oocyte developmental competence.

Cross-sectional analysis of whole-brain microstructural changes in adult patients with bipolar and unipolar depression by diffusion kurtosis imaging.

RATIONALE AND OBJECTIVES: More than half of the bipolar depression (BD) subjects are misdiagnosed as unipolar depression (UD) due to lack of objective diagnostic criteria. We aimed to identify microstructural neuronal changes differentiating BD from UD groups using diffusion kurtosis imaging (DKI). The objective of the study is to identify an objective neuro-imaging marker to differentiate BD from UD. MATERIALS AND METHODS: A prospective, cross-sectional study included total of 62 subjects with diagnosis of bipolar depression (n = 21), unipolar depression (n = 21), and healthy controls (n = 20). All subjects underwent diffusion-weighted imaging (b = 0,1000,2000) of the whole brain on 3-Tesla MR scanner. DKI data was analyzed using 189 region whole-brain atlas. Eight diffusion and kurtosis metrics including mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), fractional anisotropy (FA), mean kurtosis (MK), axial kurtosis (AK), radial kurtosis (RK), and kurtosis fractional anisotropy (FKA) were measured against these 189 regions. Principle component analysis (PCA) was utilized to identify the most significant regions of the brain. ANOVA with post hoc tests was used for analyzing these regions. RESULTS: BD group showed increased MD, RD, decreased AK at the left amygdala and decreased MK and RK at the right hemi-cerebellum. UD group showed increased MK and RK at the right external capsule; and increased AK, MK, and RK at the right amygdala. CONCLUSION: The right and left amygdala, right external capsule, and right hemi-cerebellum showed microstructural abnormalities capable of differentiating BD and UD groups. Diffusion imaging especially DKI can aid in management of depression patients.

Utility of the Comprehensive Health and Stringency Indexes in Evaluating Government Responses for Containing the Spread of COVID-19 in India: Ecological Time-Series Study.

BACKGROUND: Many nations swiftly designed and executed government policies to contain the rapid rise in COVID-19 cases. Government actions can be broadly segmented as movement and mass gathering restrictions (such as travel restrictions and lockdown), public awareness (such as face covering and hand washing), emergency health care investment, and social welfare provisions (such as poor welfare schemes to distribute food and shelter). The Blavatnik School of Government, University of Oxford, tracked various policy initiatives by governments across the globe and released them as composite indices. We assessed the overall government response using the Oxford Comprehensive Health Index (CHI) and Stringency Index (SI) to combat the COVID-19 pandemic. OBJECTIVE: This study aims to demonstrate the utility of CHI and SI to gauge and evaluate the government responses for containing the spread of COVID-19. We expect a significant inverse relationship between policy indices (CHI and SI) and COVID-19 severity indices (morbidity and mortality). METHODS: In this ecological study, we analyzed data from 2 publicly available data sources released between March 2020 and October 2021: the Oxford Covid-19 Government Response Tracker and the World Health Organization. We used autoregressive integrated moving average (ARIMA) and seasonal ARIMA to model the data. The performance of different models was assessed using a combination of evaluation criteria: adjusted R2, root mean square error, and Bayesian information criteria. RESULTS: implementation of policies by the government to contain the COVID-19 crises resulted in higher CHI and SI in the beginning. Although the value of CHI and SI gradually fell, they were consistently higher at values of >80% points. During the initial investigation, we found that cases per million (CPM) and deaths per million (DPM) followed the same trend. However, the final CPM and DPM models were seasonal ARIMA (3,2,1)(1,0,1) and ARIMA (1,1,1), respectively. This study does not support the hypothesis that COVID-19 severity (CPM and DPM) is associated with stringent policy measures (CHI and SI). CONCLUSIONS: Our study concludes that the policy measures (CHI and SI) do not explain the change in epidemiological indicators (CPM and DPM). The study reiterates our understanding that strict policies do not necessarily lead to better compliance but may overwhelm the overstretched physical health systems. Twenty-first-century problems thus demand 21st-century solutions. The digital ecosystem was instrumental in the timely collection, curation, cloud storage, and data communication. Thus, digital epidemiology can and should be successfully integrated into existing surveillance systems for better disease monitoring, management, and evaluation.