Changes in Population Immunity Against Infection and Severe Disease From Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Variants in the United States Between December 2021 and November 2022.

BACKGROUND: Although a substantial fraction of the US population was infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during December 2021-February 2022, the subsequent evolution of population immunity reflects the competing influences of waning protection over time and acquisition or restoration of immunity through additional infections and vaccinations. METHODS: Using a Bayesian evidence synthesis model of reported coronavirus disease 2019 (COVID-19) data (diagnoses, hospitalizations), vaccinations, and waning patterns for vaccine- and infection-acquired immunity, we estimate population immunity against infection and severe disease from SARS-CoV-2 Omicron variants in the United States, by location (national, state, county) and week. RESULTS: By 9 November 2022, 97% (95%-99%) of the US population were estimated to have prior immunological exposure to SARS-CoV-2. Between 1 December 2021 and 9 November 2022, protection against a new Omicron infection rose from 22% (21%-23%) to 63% (51%-75%) nationally, and protection against an Omicron infection leading to severe disease increased from 61% (59%-64%) to 89% (83%-92%). Increasing first booster uptake to 55% in all states (current US coverage: 34%) and second booster uptake to 22% (current US coverage: 11%) would increase protection against infection by 4.5 percentage points (2.4-7.2) and protection against severe disease by 1.1 percentage points (1.0-1.5). CONCLUSIONS: Effective protection against SARS-CoV-2 infection and severe disease in November 2022 was substantially higher than in December 2021. Despite this high level of protection, a more transmissible or immune evading (sub)variant, changes in behavior, or ongoing waning of immunity could lead to a new SARS-CoV-2 wave.

Population Immunity to Pre-Omicron and Omicron Severe Acute Respiratory Syndrome Coronavirus 2 Variants in US States and Counties Through 1 December 2021.

BACKGROUND: Both severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) vaccination contribute to population-level immunity against SARS-CoV-2. This study estimated the immunological exposure and effective protection against future SARS-CoV-2 infection in each US state and county over 2020-2021 and how this changed with the introduction of the Omicron variant. METHODS: We used a Bayesian model to synthesize estimates of daily SARS-CoV-2 infections, vaccination data and estimates of the relative rates of vaccination conditional on infection status to estimate the fraction of the population with (1) immunological exposure to SARS-CoV-2 (ever infected with SARS-CoV-2 and/or received ≥1 doses of a COVID-19 vaccine), (2) effective protection against infection, and (3) effective protection against severe disease, for each US state and county from 1 January 2020 to 1 December 2021. RESULTS: The estimated percentage of the US population with a history of SARS-CoV-2 infection or vaccination as of 1 December 2021 was 88.2% (95% credible interval [CrI], 83.6%-93.5%). Accounting for waning and immune escape, effective protection against the Omicron variant on 1 December 2021 was 21.8% (95% CrI, 20.7%-23.4%) nationally and ranged between 14.4% (13.2%-15.8%; West Virginia) and 26.4% (25.3%-27.8%; Colorado). Effective protection against severe disease from Omicron was 61.2% (95% CrI, 59.1%-64.0%) nationally and ranged between 53.0% (47.3%-60.0%; Vermont) and 65.8% (64.9%-66.7%; Colorado). CONCLUSIONS: While more than four-fifths of the US population had prior immunological exposure to SARS-CoV-2 via vaccination or infection on 1 December 2021, only a fifth of the population was estimated to have effective protection against infection with the immune-evading Omicron variant.

Changes in population immunity against infection and severe disease from SARS-CoV-2 Omicron variants in the United States between December 2021 and November 2022.

Importance: While a substantial fraction of the US population was infected with SARS-CoV-2 during December 2021 - February 2022, the subsequent evolution of population immunity against SARS-CoV-2 Omicron variants reflects the competing influences of waning protection over time and acquisition or restoration of immunity through additional infections and vaccinations. Objective: To estimate changes in population immunity against infection and severe disease due to circulating SARS-CoV-2 Omicron variants in the United States from December 2021 to November 2022, and to quantify the protection against a potential 2022-2023 winter SARS-CoV-2 wave. Design setting participants: Bayesian evidence synthesis of reported COVID-19 data (diagnoses, hospitalizations), vaccinations, and waning patterns for vaccine- and infection-acquired immunity, using a mathematical model of COVID-19 natural history. Main Outcomes and Measures: Population immunity against infection and severe disease from SARS-CoV-2 Omicron variants in the United States, by location (national, state, county) and week. Results: By November 9, 2022, 94% (95% CrI, 79%-99%) of the US population were estimated to have been infected by SARS-CoV-2 at least once. Combined with vaccination, 97% (95%-99%) were estimated to have some prior immunological exposure to SARS-CoV-2. Between December 1, 2021 and November 9, 2022, protection against a new Omicron infection rose from 22% (21%-23%) to 63% (51%-75%) nationally, and protection against an Omicron infection leading to severe disease increased from 61% (59%-64%) to 89% (83%-92%). Increasing first booster uptake to 55% in all states (current US coverage: 34%) and second booster uptake to 22% (current US coverage: 11%) would increase protection against infection by 4.5 percentage points (2.4-7.2) and protection against severe disease by 1.1 percentage points (1.0-1.5). Conclusions and Relevance: Effective protection against SARS-CoV-2 infection and severe disease in November 2022 was substantially higher than in December 2021. Despite this high level of protection, a more transmissible or immune evading (sub)variant, changes in behavior, or ongoing waning of immunity could lead to a new SARS-CoV-2 wave. Key points: Question: How did population immunity against SARS-CoV-2 infection and subsequent severe disease change between December 2021, and November 2022?Findings: On November 9, 2022, the protection against a SARS-CoV-2 infection with the Omicron variant was estimated to be 63% (51%-75%) in the US, and the protection against severe disease was 89% (83%-92%).Meaning: As most of the newly acquired immunity has been accumulated in the December 2021-February 2022 Omicron wave, risk of reinfection and subsequent severe disease remains present at the beginning of the 2022-2023 winter, despite high levels of protection.

Reconstructing the course of the COVID-19 epidemic over 2020 for US states and counties: Results of a Bayesian evidence synthesis model.

Reported COVID-19 cases and deaths provide a delayed and incomplete picture of SARS-CoV-2 infections in the United States (US). Accurate estimates of both the timing and magnitude of infections are needed to characterize viral transmission dynamics and better understand COVID-19 disease burden. We estimated time trends in SARS-CoV-2 transmission and other COVID-19 outcomes for every county in the US, from the first reported COVID-19 case in January 13, 2020 through January 1, 2021. To do so we employed a Bayesian modeling approach that explicitly accounts for reporting delays and variation in case ascertainment, and generates daily estimates of incident SARS-CoV-2 infections on the basis of reported COVID-19 cases and deaths. The model is freely available as the covidestim R package. Nationally, we estimated there had been 49 million symptomatic COVID-19 cases and 404,214 COVID-19 deaths by the end of 2020, and that 28% of the US population had been infected. There was county-level variability in the timing and magnitude of incidence, with local epidemiological trends differing substantially from state or regional averages, leading to large differences in the estimated proportion of the population infected by the end of 2020. Our estimates of true COVID-19 related deaths are consistent with independent estimates of excess mortality, and our estimated trends in cumulative incidence of SARS-CoV-2 infection are consistent with trends in seroprevalence estimates from available antibody testing studies. Reconstructing the underlying incidence of SARS-CoV-2 infections across US counties allows for a more granular understanding of disease trends and the potential impact of epidemiological drivers.

Phylogeography and transmission of M. tuberculosis in Moldova: A prospective genomic analysis.

BACKGROUND: The incidence of multidrug-resistant tuberculosis (MDR-TB) remains critically high in countries of the former Soviet Union, where >20% of new cases and >50% of previously treated cases have resistance to rifampin and isoniazid. Transmission of resistant strains, as opposed to resistance selected through inadequate treatment of drug-susceptible tuberculosis (TB), is the main driver of incident MDR-TB in these countries. METHODS AND FINDINGS: We conducted a prospective, genomic analysis of all culture-positive TB cases diagnosed in 2018 and 2019 in the Republic of Moldova. We used phylogenetic methods to identify putative transmission clusters; spatial and demographic data were analyzed to further describe local transmission of Mycobacterium tuberculosis. Of 2,236 participants, 779 (36%) had MDR-TB, of whom 386 (50%) had never been treated previously for TB. Moreover, 92% of multidrug-resistant M. tuberculosis strains belonged to putative transmission clusters. Phylogenetic reconstruction identified 3 large clades that were comprised nearly uniformly of MDR-TB: 2 of these clades were of Beijing lineage, and 1 of Ural lineage, and each had additional distinct clade-specific second-line drug resistance mutations and geographic distributions. Spatial and temporal proximity between pairs of cases within a cluster was associated with greater genomic similarity. Our study lasted for only 2 years, a relatively short duration compared with the natural history of TB, and, thus, the ability to infer the full extent of transmission is limited. CONCLUSIONS: The MDR-TB epidemic in Moldova is associated with the local transmission of multiple M. tuberculosis strains, including distinct clades of highly drug-resistant M. tuberculosis with varying geographic distributions and drug resistance profiles. This study demonstrates the role of comprehensive genomic surveillance for understanding the transmission of M. tuberculosis and highlights the urgency of interventions to interrupt transmission of highly drug-resistant M. tuberculosis.

Population immunity to pre-Omicron and Omicron SARS-CoV-2 variants in US states and counties through December 1, 2021.

Prior infection and vaccination both contribute to population-level SARS-CoV-2 immunity. We used a Bayesian model to synthesize evidence and estimate population immunity to prevalent SARS-CoV-2 variants in the United States over the course of the epidemic until December 1, 2021, and how this changed with the introduction of the Omicron variant. We used daily SARS-CoV-2 infection estimates and vaccination coverage data for each US state and county. We estimated relative rates of vaccination conditional on previous infection status using the Census Bureau’s Household Pulse Survey. We used published evidence on natural and vaccine-induced immunity, including waning and immune escape. The estimated percentage of the US population with a history of SARS-CoV-2 infection or vaccination as of December 1, 2021, was 88.2% (95%CrI: 83.6%-93.5%), compared to 24.9% (95%CrI: 18.5%-34.1%) on January 1, 2021. State-level estimates for December 1, 2021, ranged between 76.9% (95%CrI: 67.6%-87.6%, West Virginia) and 94.4% (95%CrI: 91.2%-97.3%, New Mexico). Accounting for waning and immune escape, the effective protection against the Omicron variant on December 1, 2021, was 21.8% (95%CrI: 20.7%-23.4%) nationally and ranged between 14.4% (95%CrI: 13.2%-15.8%, West Virginia), to 26.4% (95%CrI: 25.3%-27.8%, Colorado). Effective protection against severe disease from Omicron was 61.2% (95%CrI: 59.1%-64.0%) nationally and ranged between 53.0% (95%CrI: 47.3%-60.0%, Vermont) and 65.8% (95%CrI: 64.9%-66.7%, Colorado). While over three-quarters of the US population had prior immunological exposure to SARS-CoV-2 via vaccination or infection on December 1, 2021, only a fifth of the population was estimated to have effective protection to infection with the immune-evading Omicron variant. Significance: Both SARS-CoV-2 infection and COVID-19 vaccination contribute to population-level immunity against SARS-CoV-2. This study estimates the immunity and effective protection against future SARS-CoV-2 infection in each US state and county over 2020-2021. The estimated percentage of the US population with a history of SARS-CoV-2 infection or vaccination as of December 1, 2021, was 88.2% (95%CrI: 83.6%-93.5%). Accounting for waning and immune escape, protection against the Omicron variant was 21.8% (95%CrI: 20.7%-23.4%). Protection against infection with the Omicron variant ranged between 14.4% (95%CrI: 13.2%-15.8%%, West Virginia) and 26.4% (95%CrI: 25.3%-27.8%, Colorado) across US states. The introduction of the immune-evading Omicron variant resulted in an effective absolute increase of approximately 30 percentage points in the fraction of the population susceptible to infection.

Reconstructing the course of the COVID-19 epidemic over 2020 for US states and counties: results of a Bayesian evidence synthesis model.

Reported COVID-19 cases and deaths provide a delayed and incomplete picture of SARS-CoV-2 infections in the United States (US). Accurate estimates of both the timing and magnitude of infections are needed to characterize viral transmission dynamics and better understand COVID-19 disease burden. We estimated time trends in SARS-CoV-2 transmission and other COVID-19 outcomes for every county in the US, from the first reported COVID-19 case in January 13, 2020 through January 1, 2021. To do so we employed a Bayesian modeling approach that explicitly accounts for reporting delays and variation in case ascertainment, and generates daily estimates of incident SARS-CoV-2 infections on the basis of reported COVID-19 cases and deaths. The model is freely available as the covidestim R package. Nationally, we estimated there had been 49 million symptomatic COVID-19 cases and 400,718 COVID-19 deaths by the end of 2020, and that 27% of the US population had been infected. The results also demonstrate wide county-level variability in the timing and magnitude of incidence, with local epidemiological trends differing substantially from state or regional averages, leading to large differences in the estimated proportion of the population infected by the end of 2020. Our estimates of true COVID-19 related deaths are consistent with independent estimates of excess mortality, and our estimated trends in cumulative incidence of SARS-CoV-2 infection are consistent with trends in seroprevalence estimates from available antibody testing studies. Reconstructing the underlying incidence of SARS-CoV-2 infections across US counties allows for a more granular understanding of disease trends and the potential impact of epidemiological drivers.

Estimation of Excess Deaths Associated With the COVID-19 Pandemic in the United States, March to May 2020.

Importance: Efforts to track the severity and public health impact of coronavirus disease 2019 (COVID-19) in the United States have been hampered by state-level differences in diagnostic test availability, differing strategies for prioritization of individuals for testing, and delays between testing and reporting. Evaluating unexplained increases in deaths due to all causes or attributed to nonspecific outcomes, such as pneumonia and influenza, can provide a more complete picture of the burden of COVID-19. Objective: To estimate the burden of all deaths related to COVID-19 in the United States from March to May 2020. Design, Setting, and Population: This observational study evaluated the numbers of US deaths from any cause and deaths from pneumonia, influenza, and/or COVID-19 from March 1 through May 30, 2020, using public data of the entire US population from the National Center for Health Statistics (NCHS). These numbers were compared with those from the same period of previous years. All data analyzed were accessed on June 12, 2020. Main Outcomes and Measures: Increases in weekly deaths due to any cause or deaths due to pneumonia/influenza/COVID-19 above a baseline, which was adjusted for time of year, influenza activity, and reporting delays. These estimates were compared with reported deaths attributed to COVID-19 and with testing data. Results: There were approximately 781 000 total deaths in the United States from March 1 to May 30, 2020, representing 122 300 (95% prediction interval, 116 800-127 000) more deaths than would typically be expected at that time of year. There were 95 235 reported deaths officially attributed to COVID-19 from March 1 to May 30, 2020. The number of excess all-cause deaths was 28% higher than the official tally of COVID-19-reported deaths during that period. In several states, these deaths occurred before increases in the availability of COVID-19 diagnostic tests and were not counted in official COVID-19 death records. There was substantial variability between states in the difference between official COVID-19 deaths and the estimated burden of excess deaths. Conclusions and Relevance: Excess deaths provide an estimate of the full COVID-19 burden and indicate that official tallies likely undercount deaths due to the virus. The mortality burden and the completeness of the tallies vary markedly between states.

Estimating the early death toll of COVID-19 in the United States.

BACKGROUND: Efforts to track the severity and public health impact of the novel coronavirus, COVID-19, in the US have been hampered by testing issues, reporting lags, and inconsistency between states. Evaluating unexplained increases in deaths attributed to broad outcomes, such as pneumonia and influenza (P&I) or all causes, can provide a more complete and consistent picture of the burden caused by COVID-19. METHODS: We evaluated increases in the occurrence of deaths due to P&I above a seasonal baseline (adjusted for influenza activity) or due to any cause across the United States in February and March 2020. These estimates are compared with reported deaths due to COVID-19 and with testing data. RESULTS: There were notable increases in the rate of death due to P&I in February and March 2020. In a number of states, these deaths pre-dated increases in COVID-19 testing rates and were not counted in official records as related to COVID-19. There was substantial variability between states in the discrepancy between reported rates of death due to COVID-19 and the estimated burden of excess deaths due to P&I. The increase in all-cause deaths in New York and New Jersey is 1.5-3 times higher than the official tally of COVID-19 confirmed deaths or the estimated excess death due to P&I. CONCLUSIONS: Excess P&I deaths provide a conservative estimate of COVID-19 burden and indicate that COVID-19-related deaths are missed in locations with inadequate testing or intense pandemic activity.