COVID-19 and Outpatient Antibiotic Prescriptions in the United States: A County-Level Analysis.

Background: Declines in outpatient antibiotic prescribing were reported during the beginning of the coronavirus disease 2019 (COVID-19) pandemic in the United States; however, the overall impact of COVID-19 cases on antibiotic prescribing remains unclear. Methods: This was an ecological study using random-effects panel regression of monthly reported COVID-19 county case and antibiotic prescription data, controlling for seasonality, urbanicity, health care access, nonpharmaceutical interventions (NPIs), and sociodemographic factors. Results: Antibiotic prescribing fell 26.8% in 2020 compared with prior years. Each 1% increase in county-level monthly COVID-19 cases was associated with a 0.009% (95% CI, 0.007% to 0.012%; P < .01) increase in prescriptions per 100 000 population dispensed to all ages and a 0.012% (95% CI, -0.017% to -0.008%; P < .01) decrease in prescriptions per 100 000 children. Counties with schools open for in-person instruction were associated with a 0.044% (95% CI, 0.024% to 0.065%; P < .01) increase in prescriptions per 100 000 children compared with counties that closed schools. Internal movement restrictions and requiring facemasks were also associated with lower prescribing among children. Conclusions: The positive association of COVID-19 cases with prescribing for all ages and the negative association for children indicate that increases in prescribing occurred primarily among adults. The rarity of bacterial coinfection in COVID-19 patients suggests that a fraction of these prescriptions may have been inappropriate. Facemasks and school closures were correlated with reductions in prescribing among children, possibly due to the prevention of other upper respiratory infections. The strongest predictors of prescribing were prior years' prescribing trends, suggesting the possibility that behavioral norms are an important driver of prescribing practices.

The effect of the COVID-19 pandemic on routine childhood immunization coverage and timeliness in India: Retrospective analysis of the National Family Health Survey of 2019-2021 data.

Background: The COVID-19 pandemic has disrupted health systems globally. We estimated the effect of the pandemic on the coverage and timeliness of routine childhood immunization in India through April 2021. Methods: We used data from India's National Family Health Survey 2019-2021 (NFHS-5), a cross-sectional survey which collected immunization information of under-five children from a nationally representative sample of households between June 2019 and April 2021. We used a mother fixed-effects regression model - accounting for secular trends and confounding factors - to compare COVID-affected children with their COVID-unaffected siblings (n=59,144). Children who were eligible for a vaccine after January 30, 2020 (date of the first COVID case in India) were considered as the COVID-affected group and those eligible for a vaccine after this date were included in the COVID-unaffected group. Coverage of the following vaccine doses was considered-Bacillus Calmette-Guérin (BCG), hepatitis B birth dose (hepB0), DPT1 (diphtheria, pertussis, and tetanus, first dose), DPT2, DPT3, polio1, polio2, polio3, and measles first dose (MCV1). Indicators of vaccine coverage and vaccine timeliness (defined as receiving a dose within 45 days of minimum eligibility age) were separately examined. Findings: Immunization coverage was lower in COVID-affected children as compared with unaffected children, ranging from 2% lower for BCG and hepB0 to 9% for DPT3 and 10% for polio3. There was no significant difference in MCV1 coverage. Coverage reduction was greater for vaccines doses given at later age groups. The rate of timely receipt of polio and DPT vaccine doses was 3%-5% lower among COVID-affected children relative to unaffected children. Among population subgroups, COVID-affected male children and those from rural areas experienced the highest reduction in vaccine coverage. Interpretation: Children in India experienced lower routine immunization coverage and greater delays in immunization during the COVID-19 pandemic. Funding: The Bill & Melinda Gates Foundation.

SARS-CoV-2 testing strategies for outbreak mitigation in vaccinated populations.

Although COVID-19 vaccines are globally available, waning immunity and emerging vaccine-evasive variants of concern have hindered the international response and transition to a post-pandemic era. Testing to identify and isolate infectious individuals remains the most proactive strategy for containing an ongoing COVID-19 outbreak. We developed a stochastic, compartmentalized model to simulate the impact of using Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) assays, rapid antigen tests, and vaccinations on SARS-CoV-2 spread. We compare testing strategies across an example high-income country (the United States) and low- and middle-income country (India). We detail the optimal testing frequency and coverage in the US and India to mitigate an emerging outbreak even in a vaccinated population: overall, maximizing testing frequency is most important, but having high testing coverage remains necessary when there is sustained transmission. A resource-limited vaccination strategy still requires high-frequency testing to minimize subsequent outbreaks and is 16.50% more effective in reducing cases in India than the United States. Tailoring testing strategies to transmission settings can help effectively reduce disease burden more than if a uniform approach were employed without regard to epidemiological variability across locations.

All-cause mortality during the COVID-19 pandemic in Chennai, India: an observational study.

BACKGROUND: India has been severely affected by the ongoing COVID-19 pandemic. However, due to shortcomings in disease surveillance, the burden of mortality associated with COVID-19 remains poorly understood. We aimed to assess changes in mortality during the pandemic in Chennai, Tamil Nadu, using data on all-cause mortality within the district. METHODS: For this observational study, we analysed comprehensive death registrations in Chennai, from Jan 1, 2016, to June 30, 2021. We estimated expected mortality without the effects of the COVID-19 pandemic by fitting models to observed mortality time series during the pre-pandemic period, with stratification by age and sex. Additionally, we considered three periods of interest: the first 4 weeks of India's first lockdown (March 24 to April 20, 2020), the 4-month period including the first wave of the pandemic in Chennai (May 1 to Aug 31, 2020), and the 4-month period including the second wave of the pandemic in Chennai (March 1 to June 30, 2021). We computed the difference between observed and expected mortality from March 1, 2020, to June 30, 2021, and compared pandemic-associated mortality across socioeconomically distinct communities (measured with use of 2011 census of India data) with regression analyses. FINDINGS: Between March 1, 2020, and June 30, 2021, 87 870 deaths were registered in areas of Chennai district represented by the 2011 census, exceeding expected deaths by 25 990 (95% uncertainty interval 25 640-26 360) or 5·18 (5·11-5·25) excess deaths per 1000 people. Stratified by age, excess deaths numbered 21·02 (20·54-21·49) excess deaths per 1000 people for individuals aged 60-69 years, 39·74 (38·73-40·69) for those aged 70-79 years, and 96·90 (93·35-100·16) for those aged 80 years or older. Neighbourhoods with lower socioeconomic status had 0·7% to 2·8% increases in pandemic-associated mortality per 1 SD increase in each measure of community disadvantage, due largely to a disproportionate increase in mortality within these neighbourhoods during the second wave. Conversely, differences in excess mortality across communities were not clearly associated with socioeconomic status measures during the first wave. For each increase by 1 SD in measures of community disadvantage, neighbourhoods had 3·6% to 8·6% lower pandemic-associated mortality during the first 4 weeks of India's country-wide lockdown, before widespread SARS-CoV-2 circulation was underway in Chennai. The greatest reductions in mortality during this early lockdown period were observed among men aged 20-29 years, with 58% (54-62) fewer deaths than expected from pre-pandemic trends. INTERPRETATION: Mortality in Chennai increased substantially but heterogeneously during the COVID-19 pandemic, with the greatest burden concentrated in disadvantaged communities. Reported COVID-19 deaths greatly underestimated pandemic-associated mortality. FUNDING: National Institute of General Medical Sciences, Bill & Melinda Gates Foundation, National Science Foundation. TRANSLATION: For the Hindi translation of the abstract see Supplementary Materials section.

SARS-CoV-2 infection and mortality during the first epidemic wave in Madurai, south India: a prospective, active surveillance study.

BACKGROUND: SARS-CoV-2 has spread substantially within India over multiple waves of the ongoing COVID-19 pandemic. However, the risk factors and disease burden associated with COVID-19 in India remain poorly understood. We aimed to assess predictors of infection and mortality within an active surveillance study, and to probe the completeness of case and mortality surveillance. METHODS: In this prospective, active surveillance study, we used data collected under expanded programmatic surveillance testing for SARS-CoV-2 in the district of Madurai, Tamil Nadu, India (population of 3 266 000 individuals). Prospective testing via RT-PCR was done in individuals with fever or acute respiratory symptoms as well as returning travellers, frontline workers, contacts of laboratory-confirmed COVID-19 cases, residents of containment zones, patients undergoing medical procedures, and other risk groups. Standardised data collection on symptoms and chronic comorbid conditions was done as part of routine intake. Additionally, seroprevalence of anti-SARS-CoV-2 immunoglobulin G was assessed via a cross-sectional survey recruiting adults across 38 clusters within Madurai District from Oct 19, 2020, to Nov 5, 2020. We estimated adjusted odds ratios (aORs) for positive RT-PCR results comparing individuals by age, sex, comorbid conditions, and aspects of clinical presentation. We estimated case-fatality ratios (CFRs) over the 30-day period following RT-PCR testing stratified by the same variables, and adjusted hazard ratios (aHRs) for death associated with age, sex, and comorbidity. We estimated infection-fatality ratios (IFRs) on the basis of age-specific seroprevalence. RESULTS: Between May 20, 2020, and Oct 31, 2020, 13·5 diagnostic tests were done per 100 inhabitants within Madurai, as compared to 7·9 tests per 100 inhabitants throughout India. From a total of 440 253 RT-PCR tests, 15 781 (3·6%) SARS-CoV-2 infections were identified, with 8720 (5·4%) of 160 273 being positive among individuals with symptoms, and 7061 (2·5%) of 279 980 being positive among individuals without symptoms, at the time of presentation. Estimated aORs for symptomatic RT-PCR-confirmed infection increased continuously by a factor of 4·3 from ages 0-4 years to 80 years or older. By contrast, risk of asymptomatic RT-PCR-confirmed infection did not differ across ages 0-44 years, and thereafter increased by a factor of 1·6 between ages 45-49 years and 80 years or older. Seroprevalence was 40·1% (95% CI 35·8-44·6) at age 15 years or older by the end of the study period, indicating that RT-PCR clinical testing and surveillance testing identified only 1·4% (1·3-1·6%) of all infections in this age group. Among RT-PCR-confirmed cases, older age, male sex, and history of cancer, diabetes, other endocrine disorders, hypertension, other chronic circulatory disorders, respiratory disorders, and chronic kidney disease were each associated with elevated risk of mortality. The CFR among RT-PCR-confirmed cases was 2·4% (2·2-2·6); after age standardisation. At age 15 years or older, the IFR based on reported deaths was 0·043% (0·039-0·049), with reported deaths being only 11·0% (8·2-14·5) of the expected count. INTERPRETATION: In a large-scale SARS-CoV-2 surveillance programme in Madurai, India, we identified equal risk of asymptomatic infection among children, teenagers, and working-age adults, and increasing risk of infection and death associated with older age and comorbidities. Establishing whether surveillance practices or differences in infection severity account for gaps between observed and expected mortality is of crucial importance to establishing the burden of COVID-19 in India. FUNDING: The Bill & Melinda Gates Foundation, the National Science Foundation, and the National Institute of General Medical Sciences. TRANSLATION: For the Hindi translation of the abstract see Supplementary Materials section.

Key considerations on the potential impacts of the COVID-19 pandemic on antimicrobial resistance research and surveillance.

Antibiotic use in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients during the COVID-19 pandemic has exceeded the incidence of bacterial coinfections and secondary infections, suggesting inappropriate and excessive prescribing. Even in settings with established antimicrobial stewardship (AMS) programmes, there were weaknesses exposed regarding appropriate antibiotic use in the context of the pandemic. Moreover, antimicrobial resistance (AMR) surveillance and AMS have been deprioritised with diversion of health system resources to the pandemic response. This experience highlights deficiencies in AMR containment and mitigation strategies that require urgent attention from clinical and scientific communities. These include the need to implement diagnostic stewardship to assess the global incidence of coinfections and secondary infections in COVID-19 patients, including those by multidrug-resistant pathogens, to identify patients most likely to benefit from antibiotic treatment and identify when antibiotics can be safely withheld, de-escalated or discontinued. Long-term global surveillance of clinical and societal antibiotic use and resistance trends is required to prepare for subsequent changes in AMR epidemiology, while ensuring uninterrupted supply chains and preventing drug shortages and stock outs. These interventions present implementation challenges in resource-constrained settings, making a case for implementation research on AMR. Knowledge and support for these practices will come from internationally coordinated, targeted research on AMR, supporting the preparation for future challenges from emerging AMR in the context of the current COVID-19 pandemic or future pandemics.

Antimicrobial resistance research in a post-pandemic world: Insights on antimicrobial resistance research in the COVID-19 pandemic.

Antimicrobial resistance must be recognised as a global societal priority - even in the face of the worldwide challenge of the COVID-19 pandemic. COVID-19 has illustrated the vulnerability of our healthcare systems in co-managing multiple infectious disease threats as resources for monitoring and detecting, and conducting research on antimicrobial resistance have been compromised during the pandemic. The increased awareness of the importance of infectious diseases, clinical microbiology and infection control and lessons learnt during the COVID-19 pandemic should be exploited to ensure that emergence of future infectious disease threats, including those related to AMR, are minimised. Harnessing the public understanding of the relevance of infectious diseases towards the long-term pandemic of AMR could have major implications for promoting good practices about the control of AMR transmission.

Economic and Behavioral Influencers of Vaccination and Antimicrobial Use.

Despite vast improvements in global vaccination coverage during the last decade, there is a growing trend in vaccine hesitancy and/or refusal globally. This has implications for the acceptance and coverage of a potential vaccine against COVID-19. In the United States, the number of children exempt from vaccination for "philosophical belief-based" non-medical reasons increased in 12 of the 18 states that allowed this policy from 2009 to 2017 (1). Meanwhile, the overuse and misuse of antibiotics, especially in young children, have led to increasing rates of drug resistance that threaten our ability to treat infectious diseases. Vaccine hesitancy and antibiotic overuse exist side-by-side in the same population of young children, and it is unclear why one modality (antibiotics) is universally seen as safe and effective, while the other (vaccines) is seen as potentially hazardous by some. In this review, we consider the drivers shaping the use of vaccines and antibiotics in the context of three factors: individual incentives, risk perceptions, and social norms and group dynamics. We illustrate how these factors contribute to the societal and individual costs of vaccine underuse and antimicrobial overuse. Ultimately, we seek to understand these factors that are at the nexus of infectious disease epidemiology and social science to inform policy-making.

Epidemiology and transmission dynamics of COVID-19 in two Indian states.

Although most cases of coronavirus disease 2019 (COVID-19) have occurred in low-resource countries, little is known about the epidemiology of the disease in such contexts. Data from the Indian states of Tamil Nadu and Andhra Pradesh provide a detailed view into severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission pathways and mortality in a high-incidence setting. Reported cases and deaths have been concentrated in younger cohorts than would be expected from observations in higher-income countries, even after accounting for demographic differences across settings. Among 575,071 individuals exposed to 84,965 confirmed cases, infection probabilities ranged from 4.7 to 10.7% for low-risk and high-risk contact types, respectively. Same-age contacts were associated with the greatest infection risk. Case fatality ratios spanned 0.05% at ages of 5 to 17 years to 16.6% at ages of 85 years or more. Primary data from low-resource countries are urgently needed to guide control measures.