Associations of the COVID-19 pandemic with the reported incidence of important endemic infectious disease agents and syndromes in Pakistan.

BACKGROUND: Persons in Pakistan have suffered from various infectious diseases over the years, each impacted by various factors including climate change, seasonality, geopolitics, and resource availability. The COVID-19 pandemic is another complicating factor, with changes in the reported incidence of endemic infectious diseases and related syndromes under surveillance. METHODS: We assessed the monthly incidence of eight important infectious diseases/syndromes: acute upper respiratory infection (AURI), viral hepatitis, malaria, pneumonia, diarrhea, typhoid fever, measles, and neonatal tetanus (NNT), before and after the onset of the COVID-19 pandemic. Administrative health data of monthly reported cases of these diseases/syndromes from all five provinces/regions of Pakistan for a 3-year interval (March 2018-February 2021) were analyzed using an interrupted time series approach. Reported monthly incidence for each infectious disease agent or syndrome and COVID-19 were subjected to time series visualization. Spearman's rank correlation coefficient between each infectious disease/syndrome and COVID-19 was calculated and median case numbers of each disease before and after the onset of the COVID-19 pandemic were compared using a Wilcoxon signed-rank test. Subsequently, a generalized linear negative binomial regression model was developed to determine the association between reported cases of each disease and COVID-19. RESULTS: In late February 2020, concurrent with the start of COVID-19, in all provinces, there were decreases in the reported incidence of the following diseases: AURI, pneumonia, hepatitis, diarrhea, typhoid, and measles. In contrast, the incidence of COVID was negatively associated with the reported incidence of NNT only in Punjab and Sindh, but not in Khyber Pakhtunkhwa (KPK), Balochistan, or Azad Jammu & Kashmir (AJK) & Gilgit Baltistan (GB). Similarly, COVID-19 was associated with a lowered incidence of malaria in Punjab, Sindh, and AJK & GB, but not in KPK and Balochistan. CONCLUSIONS: COVID-19 was associated with a decreased reported incidence of most infectious diseases/syndromes studied in most provinces of Pakistan. However, exceptions included NNT in KPK, Balochistan and AJK & GB, and malaria in KPK and Balochistan. This general trend was attributed to a combination of resource diversion, misdiagnosis, misclassification, misinformation, and seasonal patterns of each disease.

Antimicrobial resistance (AMR) in COVID-19 patients: a systematic review and meta-analysis (November 2019-June 2021).

BACKGROUND: Pneumonia from SARS-CoV-2 is difficult to distinguish from other viral and bacterial etiologies. Broad-spectrum antimicrobials are frequently prescribed to patients hospitalized with COVID-19 which potentially acts as a catalyst for the development of antimicrobial resistance (AMR). OBJECTIVES: We conducted a systematic review and meta-analysis during the first 18 months of the pandemic to quantify the prevalence and types of resistant co-infecting organisms in patients with COVID-19 and explore differences across hospital and geographic settings. METHODS: We searched MEDLINE, Embase, Web of Science (BioSIS), and Scopus from November 1, 2019 to May 28, 2021 to identify relevant articles pertaining to resistant co-infections in patients with laboratory confirmed SARS-CoV-2. Patient- and study-level analyses were conducted. We calculated pooled prevalence estimates of co-infection with resistant bacterial or fungal organisms using random effects models. Stratified meta-analysis by hospital and geographic setting was also performed to elucidate any differences. RESULTS: Of 1331 articles identified, 38 met inclusion criteria. A total of 1959 unique isolates were identified with 29% (569) resistant organisms identified. Co-infection with resistant bacterial or fungal organisms ranged from 0.2 to 100% among included studies. Pooled prevalence of co-infection with resistant bacterial and fungal organisms was 24% (95% CI 8-40%; n = 25 studies: I2 = 99%) and 0.3% (95% CI 0.1-0.6%; n = 8 studies: I2 = 78%), respectively. Among multi-drug resistant organisms, methicillin-resistant Staphylococcus aureus, carbapenem-resistant Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa and multi-drug resistant Candida auris were most commonly reported. Stratified analyses found higher proportions of AMR outside of Europe and in ICU settings, though these results were not statistically significant. Patient-level analysis demonstrated > 50% (n = 58) mortality, whereby all but 6 patients were infected with a resistant organism. CONCLUSIONS: During the first 18 months of the pandemic, AMR prevalence was high in COVID-19 patients and varied by hospital and geography although there was substantial heterogeneity. Given the variation in patient populations within these studies, clinical settings, practice patterns, and definitions of AMR, further research is warranted to quantify AMR in COVID-19 patients to improve surveillance programs, infection prevention and control practices and antimicrobial stewardship programs globally.

Disability-adjusted life years (DALYs) due to the direct health impact of COVID-19 in India, 2020.

COVID-19 has affected all countries. Its containment represents a unique challenge for India due to a large population (> 1.38 billion) across a wide range of population densities. Assessment of the COVID-19 disease burden is required to put the disease impact into context and support future pandemic policy development. Here, we present the national-level burden of COVID-19 in India in 2020 that accounts for differences across urban and rural regions and across age groups. Input data were collected from official records or published literature. The proportion of excess COVID-19 deaths was estimated using the Institute for Health Metrics and Evaluation, Washington data. Disability-adjusted life years (DALY) due to COVID-19 were estimated in the Indian population in 2020, comprised of years of life lost (YLL) and years lived with disability (YLD). YLL was estimated by multiplying the number of deaths due to COVID-19 by the residual standard life expectancy at the age of death due to the disease. YLD was calculated as a product of the number of incident cases of COVID-19, disease duration and disability weight. Scenario analyses were conducted to account for excess deaths not recorded in the official data and for reported COVID-19 deaths. The direct impact of COVID-19 in 2020 in India was responsible for 14,100,422 (95% uncertainty interval [UI] 14,030,129-14,213,231) DALYs, consisting of 99.2% (95% UI 98.47-99.64%) YLLs and 0.80% (95% UI 0.36-1.53) YLDs. DALYs were higher in urban (56%; 95% UI 56-57%) than rural areas (44%; 95% UI 43.4-43.6) and in men (64%) than women (36%). In absolute terms, the highest DALYs occurred in the 51-60-year-old age group (28%) but the highest DALYs per 100,000 persons were estimated for the 71-80 years old age group (5481; 95% UI 5464-5500 years). There were 4,815,908 (95% UI 4,760,908-4,924,307) DALYs after considering reported COVID-19 deaths only. The DALY estimations have direct and immediate implications not only for public policy in India, but also internationally given that India represents one sixth of the world's population.

Differential Co-Expression Network Analysis Reveals Key Hub-High Traffic Genes as Potential Therapeutic Targets for COVID-19 Pandemic.

Background: The recent emergence of COVID-19, rapid worldwide spread, and incomplete knowledge of molecular mechanisms underlying SARS-CoV-2 infection have limited development of therapeutic strategies. Our objective was to systematically investigate molecular regulatory mechanisms of COVID-19, using a combination of high throughput RNA-sequencing-based transcriptomics and systems biology approaches. Methods: RNA-Seq data from peripheral blood mononuclear cells (PBMCs) of healthy persons, mild and severe 17 COVID-19 patients were analyzed to generate a gene expression matrix. Weighted gene co-expression network analysis (WGCNA) was used to identify co-expression modules in healthy samples as a reference set. For differential co-expression network analysis, module preservation and module-trait relationships approaches were used to identify key modules. Then, protein-protein interaction (PPI) networks, based on co-expressed hub genes, were constructed to identify hub genes/TFs with the highest information transfer (hub-high traffic genes) within candidate modules. Results: Based on differential co-expression network analysis, connectivity patterns and network density, 72% (15 of 21) of modules identified in healthy samples were altered by SARS-CoV-2 infection. Therefore, SARS-CoV-2 caused systemic perturbations in host biological gene networks. In functional enrichment analysis, among 15 non-preserved modules and two significant highly-correlated modules (identified by MTRs), 9 modules were directly related to the host immune response and COVID-19 immunopathogenesis. Intriguingly, systemic investigation of SARS-CoV-2 infection identified signaling pathways and key genes/proteins associated with COVID-19's main hallmarks, e.g., cytokine storm, respiratory distress syndrome (ARDS), acute lung injury (ALI), lymphopenia, coagulation disorders, thrombosis, and pregnancy complications, as well as comorbidities associated with COVID-19, e.g., asthma, diabetic complications, cardiovascular diseases (CVDs), liver disorders and acute kidney injury (AKI). Topological analysis with betweenness centrality (BC) identified 290 hub-high traffic genes, central in both co-expression and PPI networks. We also identified several transcriptional regulatory factors, including NFKB1, HIF1A, AHR, and TP53, with important immunoregulatory roles in SARS-CoV-2 infection. Moreover, several hub-high traffic genes, including IL6, IL1B, IL10, TNF, SOCS1, SOCS3, ICAM1, PTEN, RHOA, GDI2, SUMO1, CASP1, IRAK3, HSPA5, ADRB2, PRF1, GZMB, OASL, CCL5, HSP90AA1, HSPD1, IFNG, MAPK1, RAB5A, and TNFRSF1A had the highest rates of information transfer in 9 candidate modules and central roles in COVID-19 immunopathogenesis. Conclusion: This study provides comprehensive information on molecular mechanisms of SARS-CoV-2-host interactions and identifies several hub-high traffic genes as promising therapeutic targets for the COVID-19 pandemic.

Meta-analysis and adjusted estimation of COVID-19 case fatality risk in India and its association with the underlying comorbidities.

Management of coronavirus disease 2019 (COVID-19) in India is a top government priority. However, there is a lack of COVID-19 adjusted case fatality risk (aCFR) estimates and information on states with high aCFR. Data on COVID-19 cases and deaths in the first pandemic wave and 17 state-specific geodemographic, socio-economic, health and comorbidity-related factors were collected. State-specific aCFRs were estimated, using a 13-day lag for fatality. To estimate country-level aCFR in the first wave, state estimates were meta-analysed based on inverse-variance weighting and aCFR as either a fixed- or random-effect. Multiple correspondence analyses, followed by univariable logistic regression, were conducted to understand the association between aCFR and geodemographic, health and social indicators. Based on health indicators, states likely to report a higher aCFR were identified. Using random- and fixed-effects models, cumulative aCFRs in the first pandemic wave on 27 July 2020 in India were 1.42% (95% CI 1.19%-1.70%) and 2.97% (95% CI 2.94%-3.00%), respectively. At the end of the first wave, as of 15 February 2021, a cumulative aCFR of 1.18% (95% CI 0.99%-1.41%) using random and 1.64% (95% CI 1.64%-1.65%) using fixed-effects models was estimated. Based on high heterogeneity among states, we inferred that the random-effects model likely provided more accurate estimates of the aCFR for India. The aCFR was grouped with the incidence of diabetes, hypertension, cardiovascular diseases and acute respiratory infections in the first and second dimensions of multiple correspondence analyses. Univariable logistic regression confirmed associations between the aCFR and the proportion of urban population, and between aCFR and the number of persons diagnosed with diabetes, hypertension, cardiovascular diseases and stroke per 10,000 population that had visited NCD (Non-communicable disease) clinics. Incidence of pneumonia was also associated with COVID-19 aCFR. Based on predictor variables, we categorised 10, 17 and one Indian state(s) expected to have a high, medium and low aCFR risk, respectively. The current study demonstrated the value of using meta-analysis to estimate aCFR. To decrease COVID-19 associated fatalities, states estimated to have a high aCFR must take steps to reduce co-morbidities.

Public health interventions slowed but did not halt the spread of COVID-19 in India.

The government of India implemented social distancing interventions to contain the COVID-19 epidemic. However, effects of these interventions on epidemic dynamics are yet to be understood. Rates of laboratory-confirmed COVID-19 infections per day and effective reproduction number (Rt ) were estimated for 7 periods (Pre-lockdown, Lockdown Phases 1 to 4 and Unlock 1-2) according to nationally implemented interventions with phased relaxation. Adoption of these interventions was estimated using Google mobility data. Estimates at the national level and for 12 Indian states most affected by COVID-19 are presented. Daily case rates ranged from 0.03 to 285.60/10 million people across 7 discrete periods in India. From 18 May to 31 July 2020, the NCT of Delhi had the highest case rate (999/10 million people/day), whereas Madhya Pradesh had the lowest (49/10 million/day). Average Rt was 1.99 (95% CI 1.93-2.06) and 1.39 (95% CI 1.38-1.40) for the entirety of India during the period from 22 March 2020 to 17 May 2020 and from 18 May 2020 to 31 July 2020, respectively. Median mobility in India decreased in all contact domains during the period from 22 March 2020 to 17 May 2020, with the lowest being 21% in retail/recreation, except home which increased to 129% compared to the 100% baseline value. Median mobility in the 'Grocery and Pharmacy' returned to levels observed before 22 March 2020 in Unlock 1 and 2, and the enhanced mobility in the Pharmacy sector needs to be investigated. The Indian government imposed strict contact mitigation, followed by a phased relaxation, which slowed the spread of COVID-19 epidemic progression in India. The identified daily COVID-19 case rates and Rt will aid national and state governments in formulating ongoing COVID-19 containment plans. Furthermore, these findings may inform COVID-19 public health policy in developing countries with similar settings to India.