Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 150
Filter
1.
Chest ; 2022.
Article in English | ScienceDirect | ID: covidwho-1814242

ABSTRACT

Mortality has historically been the primary outcome of choice for acute and critical care clinical trials. However, undue reliance on mortality can limit the scope of trials that can be performed. Large sample sizes are usually needed for trials powered for a mortality outcome and focusing solely on mortality fails to recognize the importance that reducing morbidity can have patients’ lives. The coronavirus disease 2019 (COVID-19) pandemic has highlighted the need for rapid, efficient trials to rigorously evaluate new therapies for hospitalized patients with acute lung injury. Oxygen-free days (OFDs) is a novel outcome for clinical trials that is a composite of mortality and duration of new supplemental oxygen use. It is designed to characterize recovery from acute lung injury in populations with a high prevalence of new hypoxemia and supplemental oxygen use. In these populations, OFDs captures two patient-centered consequences of acute lung injury, including mortality and hypoxemic lung dysfunction. Power to detect differences in OFDs is typically greater than that for other clinical trial outcomes such as mortality and ventilator-free days. OFDs is the primary outcome for the ACTIV-4 Host Tissue platform, which evaluates novel therapies targeting the host response to COVID-19 among adults hospitalized with COVID-19 and new hypoxemia. This manuscript outlines the rationale for use of OFDs as an outcome for clinical trials, proposes a standardized method for defining and analyzing OFDs, and provides a framework for sample size calculations using the OFD outcome.

2.
PLoS One ; 17(3): e0261508, 2022.
Article in English | MEDLINE | ID: covidwho-1793546

ABSTRACT

BACKGROUND: Accurate methods of identifying patients with COVID-19 who are at high risk of poor outcomes has become especially important with the advent of limited-availability therapies such as monoclonal antibodies. Here we describe development and validation of a simple but accurate scoring tool to classify risk of hospitalization and mortality. METHODS: All consecutive patients testing positive for SARS-CoV-2 from March 25-October 1, 2020 within the Intermountain Healthcare system were included. The cohort was randomly divided into 70% derivation and 30% validation cohorts. A multivariable logistic regression model was fitted for 14-day hospitalization. The optimal model was then adapted to a simple, probabilistic score and applied to the validation cohort and evaluated for prediction of hospitalization and 28-day mortality. RESULTS: 22,816 patients were included; mean age was 40 years, 50.1% were female and 44% identified as non-white race or Hispanic/Latinx ethnicity. 6.2% required hospitalization and 0.4% died. Criteria in the simple model included: age (0.5 points per decade); high-risk comorbidities (2 points each): diabetes mellitus, severe immunocompromised status and obesity (body mass index≥30); non-white race/Hispanic or Latinx ethnicity (2 points), and 1 point each for: male sex, dyspnea, hypertension, coronary artery disease, cardiac arrythmia, congestive heart failure, chronic kidney disease, chronic pulmonary disease, chronic liver disease, cerebrovascular disease, and chronic neurologic disease. In the derivation cohort (n = 16,030) area under the receiver-operator characteristic curve (AUROC) was 0.82 (95% CI 0.81-0.84) for hospitalization and 0.91 (0.83-0.94) for 28-day mortality; in the validation cohort (n = 6,786) AUROC for hospitalization was 0.8 (CI 0.78-0.82) and for mortality 0.8 (CI 0.69-0.9). CONCLUSION: A prediction score based on widely available patient attributes accurately risk stratifies patients with COVID-19 at the time of testing. Applications include patient selection for therapies targeted at preventing disease progression in non-hospitalized patients, including monoclonal antibodies. External validation in independent healthcare environments is needed.


Subject(s)
SARS-CoV-2
3.
Front Immunol ; 13: 850987, 2022.
Article in English | MEDLINE | ID: covidwho-1779942

ABSTRACT

Three COVID-19 vaccines have received FDA-authorization and are in use in the United States, but there is limited head-to-head data on the durability of the immune response elicited by these vaccines. Using a quantitative assay we studied binding IgG antibodies elicited by BNT162b2, mRNA-1273 or Ad26.COV2.S in an employee cohort over a span out to 10 months. Age and sex were explored as response modifiers. Of 234 subjects in the vaccine cohort, 114 received BNT162b2, 114 received mRNA-1273 and six received Ad26.COV2.S. IgG levels measured between seven to 20 days after the second vaccination were similar in recipients of BNT162b2 and mRNA-127 and were ~50-fold higher than in recipients of Ad26.COV2.S. However, by day 21 and at later time points IgG levels elicited by BNT162b2 were lower than mRNA-1273. Accordingly, the IgG decay curve was steeper for BNT162b2 than mRNA-1273. Age was a significant modifier of IgG levels in recipients of BNT162b2, but not mRNA-1273. After six months, IgG levels elicited by BNT162b2, but not mRNA-1273, were lower than IgG levels in patients who had been hospitalized with COVID-19 six months earlier. Similar findings were observed when comparing vaccine-elicited antibodies with steady-state IgG targeting seasonal human coronaviruses. Differential IgG decay could contribute to differences observed in clinical protection over time between BNT162b2 and mRNA-1273.


Subject(s)
COVID-19 , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Immunoglobulin G , SARS-CoV-2 , United States , Vaccination
4.
J Infect Dis ; 2022 Apr 06.
Article in English | MEDLINE | ID: covidwho-1778929

ABSTRACT

BACKGROUND: The study objective was to evaluate 2 and 3 dose COVID-19 mRNA vaccine effectiveness (VE) in preventing COVID-19 hospitalization among adult solid organ transplant (SOT) recipients. METHODS: 21-site case-control analysis of 10,425 adults hospitalized March-December 2021. Cases were hospitalized with COVID-19; controls were hospitalized for an alternative diagnosis (SARS-CoV-2 negative). Participants were classified as: SOT recipient (n=440), other immunocompromising condition (n=1684), or immunocompetent (n=8301). VE against COVID-19 associated hospitalization was calculated as 1-adjusted odds ratio of prior vaccination among cases compared with controls. RESULTS: Among SOT recipients, VE was 29% (95% CI: -19 to 58%) for 2 doses and 77% (95% CI: 48 to 90%) for 3 doses. Among patients with other immunocompromising conditions, VE was 72% (95% CI: 64 to 79%) for 2 doses and 92% (95% CI: 85 to 95%) for 3 doses. Among immunocompetent patients, VE was 88% (95% CI: 87 to 90%) for 2 doses and 96% (95% CI: 83 to 99%) for 3 doses. CONCLUSION: Effectiveness of COVID-19 mRNA vaccines was lower for SOT recipients than immunocompetent people and those with other immunocompromising conditions. Among SOT recipients, vaccination with 3 doses of an mRNA vaccine led to substantially greater protection than 2 doses.

5.
Sci Rep ; 12(1): 5729, 2022 Apr 06.
Article in English | MEDLINE | ID: covidwho-1778632

ABSTRACT

The Coronavirus disease 2019 (COVID-19) pandemic-caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)- has posed a global threat and presented with it a multitude of economic and public-health challenges. Establishing a reliable means of readily available, rapid diagnostic testing is of paramount importance in halting the spread of COVID-19, as governments continue to ease lockdown restrictions. The current standard for laboratory testing utilizes reverse transcription quantitative polymerase chain reaction (RT-qPCR); however, this method presents clear limitations in requiring a longer run-time as well as reduced on-site testing capability. Therefore, we investigated the feasibility of a reverse transcription looped-mediated isothermal amplification (RT-LAMP)-based model of rapid COVID-19 diagnostic testing which allows for less invasive sample collection, named SaliVISION. This novel, two-step, RT-LAMP assay utilizes a customized multiplex primer set specifically targeting SARS-CoV-2 and a visual report system that is ready to interpret within 40 min from the start of sample processing and does not require a BSL-2 level testing environment or special laboratory equipment. When compared to the SalivaDirect and Thermo Fisher Scientific TaqPath RT-qPCR testing platforms, the respective sensitivities of the SaliVISION assay are 94.29% and 98.28% while assay specificity was 100% when compared to either testing platform. Our data illustrate a robust, rapid diagnostic assay in our novel RT-LAMP test design, with potential for greater testing throughput than is currently available through laboratory testing and increased on-site testing capability.


Subject(s)
COVID-19 , COVID-19/diagnosis , COVID-19 Testing , Communicable Disease Control , Diagnostic Tests, Routine , Humans , Molecular Diagnostic Techniques/methods , Nucleic Acid Amplification Techniques/methods , RNA, Viral/analysis , RNA, Viral/genetics , SARS-CoV-2/genetics , Saliva/chemistry , Sensitivity and Specificity
6.
Lancet ; 2022 Apr 08.
Article in English | MEDLINE | ID: covidwho-1778513

ABSTRACT

BACKGROUND: Timely, accurate, and comprehensive estimates of SARS-CoV-2 daily infection rates, cumulative infections, the proportion of the population that has been infected at least once, and the effective reproductive number (Reffective) are essential for understanding the determinants of past infection, current transmission patterns, and a population's susceptibility to future infection with the same variant. Although several studies have estimated cumulative SARS-CoV-2 infections in select locations at specific points in time, all of these analyses have relied on biased data inputs that were not adequately corrected for. In this study, we aimed to provide a novel approach to estimating past SARS-CoV-2 daily infections, cumulative infections, and the proportion of the population infected, for 190 countries and territories from the start of the pandemic to Nov 14, 2021. This approach combines data from reported cases, reported deaths, excess deaths attributable to COVID-19, hospitalisations, and seroprevalence surveys to produce more robust estimates that minimise constituent biases. METHODS: We produced a comprehensive set of global and location-specific estimates of daily and cumulative SARS-CoV-2 infections through Nov 14, 2021, using data largely from Johns Hopkins University (Baltimore, MD, USA) and national databases for reported cases, hospital admissions, and reported deaths, as well as seroprevalence surveys identified through previous reviews, SeroTracker, and governmental organisations. We corrected these data for known biases such as lags in reporting, accounted for under-reporting of deaths by use of a statistical model of the proportion of excess mortality attributable to SARS-CoV-2, and adjusted seroprevalence surveys for waning antibody sensitivity, vaccinations, and reinfection from SARS-CoV-2 escape variants. We then created an empirical database of infection-detection ratios (IDRs), infection-hospitalisation ratios (IHRs), and infection-fatality ratios (IFRs). To estimate a complete time series for each location, we developed statistical models to predict the IDR, IHR, and IFR by location and day, testing a set of predictors justified through published systematic reviews. Next, we combined three series of estimates of daily infections (cases divided by IDR, hospitalisations divided by IHR, and deaths divided by IFR), into a more robust estimate of daily infections. We then used daily infections to estimate cumulative infections and the cumulative proportion of the population with one or more infections, and we then calculated posterior estimates of cumulative IDR, IHR, and IFR using cumulative infections and the corrected data on reported cases, hospitalisations, and deaths. Finally, we converted daily infections into a historical time series of Reffective by location and day based on assumptions of duration from infection to infectiousness and time an individual spent being infectious. For each of these quantities, we estimated a distribution based on an ensemble framework that captured uncertainty in data sources, model design, and parameter assumptions. FINDINGS: Global daily SARS-CoV-2 infections fluctuated between 3 million and 17 million new infections per day between April, 2020, and October, 2021, peaking in mid-April, 2021, primarily as a result of surges in India. Between the start of the pandemic and Nov 14, 2021, there were an estimated 3·80 billion (95% uncertainty interval 3·44-4·08) total SARS-CoV-2 infections and reinfections combined, and an estimated 3·39 billion (3·08-3·63) individuals, or 43·9% (39·9-46·9) of the global population, had been infected one or more times. 1·34 billion (1·20-1·49) of these infections occurred in south Asia, the highest among the seven super-regions, although the sub-Saharan Africa super-region had the highest infection rate (79·3 per 100 population [69·0-86·4]). The high-income super-region had the fewest infections (239 million [226-252]), and southeast Asia, east Asia, and Oceania had the lowest infection rate (13·0 per 100 population [8·4-17·7]). The cumulative proportion of the population ever infected varied greatly between countries and territories, with rates higher than 70% in 40 countries and lower than 20% in 39 countries. There was no discernible relationship between Reffective and total immunity, and even at total immunity levels of 80%, we observed no indication of an abrupt drop in Reffective, indicating that there is not a clear herd immunity threshold observed in the data. INTERPRETATION: COVID-19 has already had a staggering impact on the world up to the beginning of the omicron (B.1.1.529) wave, with over 40% of the global population infected at least once by Nov 14, 2021. The vast differences in cumulative proportion of the population infected across locations could help policy makers identify the transmission-prevention strategies that have been most effective, as well as the populations at greatest risk for future infection. This information might also be useful for targeted transmission-prevention interventions, including vaccine prioritisation. Our statistical approach to estimating SARS-CoV-2 infection allows estimates to be updated and disseminated rapidly on the basis of newly available data, which has and will be crucially important for timely COVID-19 research, science, and policy responses. FUNDING: Bill & Melinda Gates Foundation, J Stanton, T Gillespie, and J and E Nordstrom.

8.
MMWR Morb Mortal Wkly Rep ; 71(12): 459-465, 2022 Mar 25.
Article in English | MEDLINE | ID: covidwho-1761302

ABSTRACT

COVID-19 mRNA vaccines (BNT162b2 [Pfizer-BioNTech] and mRNA-1273 [Moderna]) are effective at preventing COVID-19-associated hospitalization (1-3). However, how well mRNA vaccines protect against the most severe outcomes of these hospitalizations, including invasive mechanical ventilation (IMV) or death is uncertain. Using a case-control design, mRNA vaccine effectiveness (VE) against COVID-19-associated IMV and in-hospital death was evaluated among adults aged ≥18 years hospitalized at 21 U.S. medical centers during March 11, 2021-January 24, 2022. During this period, the most commonly circulating variants of SARS-CoV-2, the virus that causes COVID-19, were B.1.1.7 (Alpha), B.1.617.2 (Delta), and B.1.1.529 (Omicron). Previous vaccination (2 or 3 versus 0 vaccine doses before illness onset) in prospectively enrolled COVID-19 case-patients who received IMV or died within 28 days of hospitalization was compared with that among hospitalized control patients without COVID-19. Among 1,440 COVID-19 case-patients who received IMV or died, 307 (21%) had received 2 or 3 vaccine doses before illness onset. Among 6,104 control-patients, 4,020 (66%) had received 2 or 3 vaccine doses. Among the 1,440 case-patients who received IMV or died, those who were vaccinated were older (median age = 69 years), more likely to be immunocompromised* (40%), and had more chronic medical conditions compared with unvaccinated case-patients (median age = 55 years; immunocompromised = 10%; p<0.001 for both). VE against IMV or in-hospital death was 90% (95% CI = 88%-91%) overall, including 88% (95% CI = 86%-90%) for 2 doses and 94% (95% CI = 91%-96%) for 3 doses, and 94% (95% CI = 88%-97%) for 3 doses during the Omicron-predominant period. COVID-19 mRNA vaccines are highly effective in preventing COVID-19-associated death and respiratory failure treated with IMV. CDC recommends that all persons eligible for vaccination get vaccinated and stay up to date with COVID-19 vaccination (4).


Subject(s)
COVID-19/prevention & control , Respiration, Artificial , COVID-19/mortality , Hospital Mortality , Humans , United States/epidemiology
9.
Ann Intern Med ; 175(2): 234-243, 2022 02.
Article in English | MEDLINE | ID: covidwho-1753917

ABSTRACT

BACKGROUND: In a randomized, placebo-controlled, clinical trial, bamlanivimab, a SARS-CoV-2-neutralizing monoclonal antibody, given in combination with remdesivir, did not improve outcomes among hospitalized patients with COVID-19 based on an early futility assessment. OBJECTIVE: To evaluate the a priori hypothesis that bamlanivimab has greater benefit in patients without detectable levels of endogenous neutralizing antibody (nAb) at study entry than in those with antibodies, especially if viral levels are high. DESIGN: Randomized, placebo-controlled trial. (ClinicalTrials.gov: NCT04501978). SETTING: Multicenter trial. PATIENTS: Hospitalized patients with COVID-19 without end-organ failure. INTERVENTION: Bamlanivimab (7000 mg) or placebo. MEASUREMENTS: Antibody, antigen, and viral RNA levels were centrally measured on stored specimens collected at baseline. Patients were followed for 90 days for sustained recovery (defined as discharge to home and remaining home for 14 consecutive days) and a composite safety outcome (death, serious adverse events, organ failure, or serious infections). RESULTS: Among 314 participants (163 receiving bamlanivimab and 151 placebo), the median time to sustained recovery was 19 days and did not differ between the bamlanivimab and placebo groups (subhazard ratio [sHR], 0.99 [95% CI, 0.79 to 1.22]; sHR > 1 favors bamlanivimab). At entry, 50% evidenced production of anti-spike nAbs; 50% had SARS-CoV-2 nucleocapsid plasma antigen levels of at least 1000 ng/L. Among those without and with nAbs at study entry, the sHRs were 1.24 (CI, 0.90 to 1.70) and 0.74 (CI, 0.54 to 1.00), respectively (nominal P for interaction = 0.018). The sHR (bamlanivimab vs. placebo) was also more than 1 for those with plasma antigen or nasal viral RNA levels above median level at entry and was greatest for those without antibodies and with elevated levels of antigen (sHR, 1.48 [CI, 0.99 to 2.23]) or viral RNA (sHR, 1.89 [CI, 1.23 to 2.91]). Hazard ratios for the composite safety outcome (<1 favors bamlanivimab) also differed by serostatus at entry: 0.67 (CI, 0.37 to 1.20) for those without and 1.79 (CI, 0.92 to 3.48) for those with nAbs. LIMITATION: Subgroup analysis of a trial prematurely stopped because of futility; small sample size; multiple subgroups analyzed. CONCLUSION: Efficacy and safety of bamlanivimab may differ depending on whether an endogenous nAb response has been mounted. The limited sample size of the study does not allow firm conclusions based on these findings, and further independent trials are required that assess other types of passive immune therapies in the same patient setting. PRIMARY FUNDING SOURCE: U.S. government Operation Warp Speed and National Institute of Allergy and Infectious Diseases.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Neutralizing/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Adenosine Monophosphate/adverse effects , Adenosine Monophosphate/therapeutic use , Aged , Alanine/adverse effects , Alanine/therapeutic use , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Neutralizing/adverse effects , Antibodies, Neutralizing/blood , Antigens, Viral/blood , Antiviral Agents/adverse effects , Biomarkers/blood , COVID-19/blood , COVID-19/virology , Double-Blind Method , Drug Therapy, Combination , Female , Humans , Male , Medical Futility , Middle Aged , RNA, Viral/blood , SARS-CoV-2 , Treatment Failure
11.
Blood Cancer Discov ; 2022 Mar 09.
Article in English | MEDLINE | ID: covidwho-1736169

ABSTRACT

Patients with B-lymphoid malignancies have been consistently identified as a population at high risk of severe COVID-19. Whether this is exclusively due to cancer-related deficits in humoral and cellular immunity, or whether risk of severe COVID-19 is increased by anti-cancer therapy, is uncertain. Using data derived from the COVID-19 and Cancer Consortium (CCC19), we show that patients treated for B-lymphoid malignancies have an increased risk of severe COVID-19 compared to control populations of patients with non-B-lymphoid hematologic malignancies. Among patients with B-lymphoid malignancies, those who received anti-cancer therapy within 12 months of COVID-19 diagnosis experienced increased COVID-19 severity compared to patients with B-lymphoid malignancies off therapy, after adjustment for cancer status and several other prognostic factors. Our findings suggest that patients recently treated for a B-lymphoid malignancy are at uniquely high risk for severe COVID-19.

12.
BMJ ; 376: e069761, 2022 03 09.
Article in English | MEDLINE | ID: covidwho-1736045

ABSTRACT

OBJECTIVES: To characterize the clinical severity of covid-19 associated with the alpha, delta, and omicron SARS-CoV-2 variants among adults admitted to hospital and to compare the effectiveness of mRNA vaccines to prevent hospital admissions related to each variant. DESIGN: Case-control study. SETTING: 21 hospitals across the United States. PARTICIPANTS: 11 690 adults (≥18 years) admitted to hospital: 5728 with covid-19 (cases) and 5962 without covid-19 (controls). Patients were classified into SARS-CoV-2 variant groups based on viral whole genome sequencing, and, if sequencing did not reveal a lineage, by the predominant circulating variant at the time of hospital admission: alpha (11 March to 3 July 2021), delta (4 July to 25 December 2021), and omicron (26 December 2021 to 14 January 2022). MAIN OUTCOME MEASURES: Vaccine effectiveness calculated using a test negative design for mRNA vaccines to prevent covid-19 related hospital admissions by each variant (alpha, delta, omicron). Among patients admitted to hospital with covid-19, disease severity on the World Health Organization's clinical progression scale was compared among variants using proportional odds regression. RESULTS: Effectiveness of the mRNA vaccines to prevent covid-19 associated hospital admissions was 85% (95% confidence interval 82% to 88%) for two vaccine doses against the alpha variant, 85% (83% to 87%) for two doses against the delta variant, 94% (92% to 95%) for three doses against the delta variant, 65% (51% to 75%) for two doses against the omicron variant; and 86% (77% to 91%) for three doses against the omicron variant. In-hospital mortality was 7.6% (81/1060) for alpha, 12.2% (461/3788) for delta, and 7.1% (40/565) for omicron. Among unvaccinated patients with covid-19 admitted to hospital, severity on the WHO clinical progression scale was higher for the delta versus alpha variant (adjusted proportional odds ratio 1.28, 95% confidence interval 1.11 to 1.46), and lower for the omicron versus delta variant (0.61, 0.49 to 0.77). Compared with unvaccinated patients, severity was lower for vaccinated patients for each variant, including alpha (adjusted proportional odds ratio 0.33, 0.23 to 0.49), delta (0.44, 0.37 to 0.51), and omicron (0.61, 0.44 to 0.85). CONCLUSIONS: mRNA vaccines were found to be highly effective in preventing covid-19 associated hospital admissions related to the alpha, delta, and omicron variants, but three vaccine doses were required to achieve protection against omicron similar to the protection that two doses provided against the delta and alpha variants. Among adults admitted to hospital with covid-19, the omicron variant was associated with less severe disease than the delta variant but still resulted in substantial morbidity and mortality. Vaccinated patients admitted to hospital with covid-19 had significantly lower disease severity than unvaccinated patients for all the variants.


Subject(s)
COVID-19 Vaccines , COVID-19/prevention & control , COVID-19/virology , SARS-CoV-2 , Case-Control Studies , Hospitalization , Humans , Immunization Schedule , Prospective Studies , Severity of Illness Index , United States
13.
Am J Crit Care ; 31(2): 146-157, 2022 03 01.
Article in English | MEDLINE | ID: covidwho-1737135

ABSTRACT

BACKGROUND: Understanding COVID-19 epidemiology is crucial to clinical care and to clinical trial design and interpretation. OBJECTIVE: To describe characteristics, treatment, and outcomes among patients hospitalized with COVID-19 early in the pandemic. METHODS: A retrospective cohort study of consecutive adult patients with laboratory-confirmed, symptomatic SARS-CoV-2 infection admitted to 57 US hospitals from March 1 to April 1, 2020. RESULTS: Of 1480 inpatients with COVID-19, median (IQR) age was 62.0 (49.4-72.9) years, 649 (43.9%) were female, and 822 of 1338 (61.4%) were non-White or Hispanic/Latino. Intensive care unit admission occurred in 575 patients (38.9%), mostly within 4 days of hospital presentation. Respiratory failure affected 583 patients (39.4%), including 284 (19.2%) within 24 hours of hospital presentation and 413 (27.9%) who received invasive mechanical ventilation. Median (IQR) hospital stay was 8 (5-15) days overall and 15 (9-24) days among intensive care unit patients. Hospital mortality was 17.7% (n = 262). Risk factors for hospital death identified by penalized multivariable regression included older age; male sex; comorbidity burden; symptoms-to-admission interval; hypotension; hypoxemia; and higher white blood cell count, creatinine level, respiratory rate, and heart rate. Of 1218 survivors, 221 (18.1%) required new respiratory support at discharge and 259 of 1153 (22.5%) admitted from home required new health care services. CONCLUSIONS: In a geographically diverse early-pandemic COVID-19 cohort with complete hospital folllow-up, hospital mortality was associated with older age, comorbidity burden, and male sex. Intensive care unit admissions occurred early and were associated with protracted hospital stays. Survivors often required new health care services or respiratory support at discharge.


Subject(s)
COVID-19 , Aged , COVID-19/therapy , Female , Hospital Mortality , Hospitalization , Humans , Intensive Care Units , Male , Middle Aged , Pandemics , Respiration, Artificial , Retrospective Studies , SARS-CoV-2
14.
Wang, Haidong, Paulson, Katherine R.; Pease, Spencer A.; Watson, Stefanie, Comfort, Haley, Zheng, Peng, Aravkin, Aleksandr Y.; Bisignano, Catherine, Barber, Ryan M.; Alam, Tahiya, Fuller, John E.; May, Erin A.; Jones, Darwin Phan, Frisch, Meghan E.; Abbafati, Cristiana, Adolph, Christopher, Allorant, Adrien, Amlag, Joanne O.; Bang-Jensen, Bree, Bertolacci, Gregory J.; Bloom, Sabina S.; Carter, Austin, Castro, Emma, Chakrabarti, Suman, Chattopadhyay, Jhilik, Cogen, Rebecca M.; Collins, James K.; Cooperrider, Kimberly, Dai, Xiaochen, Dangel, William James, Daoud, Farah, Dapper, Carolyn, Deen, Amanda, Duncan, Bruce B.; Erickson, Megan, Ewald, Samuel B.; Fedosseeva, Tatiana, Ferrari, Alize J.; Frostad, Joseph Jon, Fullman, Nancy, Gallagher, John, Gamkrelidze, Amiran, Guo, Gaorui, He, Jiawei, Helak, Monika, Henry, Nathaniel J.; Hulland, Erin N.; Huntley, Bethany M.; Kereselidze, Maia, Lazzar-Atwood, Alice, LeGrand, Kate E.; Lindstrom, Akiaja, Linebarger, Emily, Lotufo, Paulo A.; Lozano, Rafael, Magistro, Beatrice, Malta, Deborah Carvalho, Månsson, Johan, Mantilla Herrera, Ana M.; Marinho, Fatima, Mirkuzie, Alemnesh H.; Misganaw, Awoke Temesgen, Monasta, Lorenzo, Naik, Paulami, Nomura, Shuhei, O'Brien, Edward G.; O'Halloran, James Kevin, Olana, Latera Tesfaye, Ostroff, Samuel M.; Penberthy, Louise, Reiner Jr, Robert C.; Reinke, Grace, Ribeiro, Antonio Luiz P.; Santomauro, Damian Francesco, Schmidt, Maria Inês, Shaw, David H.; Sheena, Brittney S.; Sholokhov, Aleksei, Skhvitaridze, Natia, Sorensen, Reed J. D.; Spurlock, Emma Elizabeth, Syailendrawati, Ruri, Topor-Madry, Roman, Troeger, Christopher E.; Walcott, Rebecca, Walker, Ally, Wiysonge, Charles Shey, Worku, Nahom Alemseged, Zigler, Bethany, Pigott, David M.; Naghavi, Mohsen, Mokdad, Ali H.; Lim, Stephen S.; Hay, Simon I.; Gakidou, Emmanuela, Murray, Christopher J. L..
Lancet ; 2022 Mar 10.
Article in English | MEDLINE | ID: covidwho-1735067

ABSTRACT

BACKGROUND: Mortality statistics are fundamental to public health decision making. Mortality varies by time and location, and its measurement is affected by well known biases that have been exacerbated during the COVID-19 pandemic. This paper aims to estimate excess mortality from the COVID-19 pandemic in 191 countries and territories, and 252 subnational units for selected countries, from Jan 1, 2020, to Dec 31, 2021. METHODS: All-cause mortality reports were collected for 74 countries and territories and 266 subnational locations (including 31 locations in low-income and middle-income countries) that had reported either weekly or monthly deaths from all causes during the pandemic in 2020 and 2021, and for up to 11 year previously. In addition, we obtained excess mortality data for 12 states in India. Excess mortality over time was calculated as observed mortality, after excluding data from periods affected by late registration and anomalies such as heat waves, minus expected mortality. Six models were used to estimate expected mortality; final estimates of expected mortality were based on an ensemble of these models. Ensemble weights were based on root mean squared errors derived from an out-of-sample predictive validity test. As mortality records are incomplete worldwide, we built a statistical model that predicted the excess mortality rate for locations and periods where all-cause mortality data were not available. We used least absolute shrinkage and selection operator (LASSO) regression as a variable selection mechanism and selected 15 covariates, including both covariates pertaining to the COVID-19 pandemic, such as seroprevalence, and to background population health metrics, such as the Healthcare Access and Quality Index, with direction of effects on excess mortality concordant with a meta-analysis by the US Centers for Disease Control and Prevention. With the selected best model, we ran a prediction process using 100 draws for each covariate and 100 draws of estimated coefficients and residuals, estimated from the regressions run at the draw level using draw-level input data on both excess mortality and covariates. Mean values and 95% uncertainty intervals were then generated at national, regional, and global levels. Out-of-sample predictive validity testing was done on the basis of our final model specification. FINDINGS: Although reported COVID-19 deaths between Jan 1, 2020, and Dec 31, 2021, totalled 5·94 million worldwide, we estimate that 18·2 million (95% uncertainty interval 17·1-19·6) people died worldwide because of the COVID-19 pandemic (as measured by excess mortality) over that period. The global all-age rate of excess mortality due to the COVID-19 pandemic was 120·3 deaths (113·1-129·3) per 100 000 of the population, and excess mortality rate exceeded 300 deaths per 100 000 of the population in 21 countries. The number of excess deaths due to COVID-19 was largest in the regions of south Asia, north Africa and the Middle East, and eastern Europe. At the country level, the highest numbers of cumulative excess deaths due to COVID-19 were estimated in India (4·07 million [3·71-4·36]), the USA (1·13 million [1·08-1·18]), Russia (1·07 million [1·06-1·08]), Mexico (798 000 [741 000-867 000]), Brazil (792 000 [730 000-847 000]), Indonesia (736 000 [594 000-955 000]), and Pakistan (664 000 [498 000-847 000]). Among these countries, the excess mortality rate was highest in Russia (374·6 deaths [369·7-378·4] per 100 000) and Mexico (325·1 [301·6-353·3] per 100 000), and was similar in Brazil (186·9 [172·2-199·8] per 100 000) and the USA (179·3 [170·7-187·5] per 100 000). INTERPRETATION: The full impact of the pandemic has been much greater than what is indicated by reported deaths due to COVID-19 alone. Strengthening death registration systems around the world, long understood to be crucial to global public health strategy, is necessary for improved monitoring of this pandemic and future pandemics. In addition, further research is warranted to help distinguish the proportion of excess mortality that was directly caused by SARS-CoV-2 infection and the changes in causes of death as an indirect consequence of the pandemic. FUNDING: Bill & Melinda Gates Foundation, J Stanton, T Gillespie, and J and E Nordstrom.

15.
Clin Infect Dis ; 2022 Feb 26.
Article in English | MEDLINE | ID: covidwho-1713627

ABSTRACT

BACKGROUND: Open-label platform trials and a prospective meta-analysis suggest efficacy of anti-IL-6R therapies in hospitalized patients with COVID-19 receiving corticosteroids. This study evaluated the efficacy and safety of sarilumab, an anti-IL-6R monoclonal antibody, in the treatment of hospitalized patients with COVID-19. METHODS: In this adaptive, phase 2/3, randomized, double-blind, placebo-controlled trial, adults hospitalized with COVID-19 (ClinicalTrials.gov: NCT04315298) received intravenous sarilumab or placebo. The phase 3 primary analysis population included patients with critical COVID-19 receiving mechanical ventilation randomized to sarilumab 400 mg or placebo. The primary outcome was proportion of patients with ≥1-point improvement in clinical status from baseline to day 22. RESULTS: There were 457 and 1365 patients randomized and treated in phases 2 and 3, respectively. In phase 3, patients with critical COVID-19 receiving mechanical ventilation (n = 298; 28.2% on corticosteroids), the proportion with ≥1-point improvement in clinical status (alive, not receiving mechanical ventilation) at day 22 was 43.2% in sarilumab and 35.5% in placebo (risk difference +7.5%; 95% CI, -7.4 to 21.3; P = .3261), a relative risk improvement of 21.7%. In post-hoc analyses pooling phase 2 and 3 critical patients receiving mechanical ventilation, the hazard ratio for death in sarilumab versus placebo was 0.76 (95% CI, .51-1.13) overall and 0.49 (95% CI, .25-.94) in patients receiving corticosteroids at baseline. CONCLUSIONS: This study did not establish the efficacy of sarilumab in hospitalized patients with severe/critical COVID-19. Post-hoc analyses were consistent with other studies that found a benefit of sarilumab in patients receiving corticosteroids.

16.
J Infect Dis ; 2021 Dec 21.
Article in English | MEDLINE | ID: covidwho-1704377

ABSTRACT

In a multi-state network, vaccine effectiveness (VE) against COVID-19 hospitalizations was evaluated among immunocompetent adults (≥18-years) during March-August 2021 using a case-control design. Among 1669 hospitalized COVID-19 cases (11% fully vaccinated) and 1950 RT-PCR-negative controls (54% fully vaccinated), VE was higher at 96% (95% CI: 93-98%) among patients with no chronic medical conditions than patients with ≥3 categories of conditions (83% [95% CI: 76-88%]). VE was similar between those aged 18-64 years vs ≥65 years (p>0.05). Vaccine effectiveness against severe COVID-19 was very high among adults without chronic conditions and lessened with increasing burden of comorbidities.

17.
Clin Infect Dis ; 2021 Aug 06.
Article in English | MEDLINE | ID: covidwho-1700456

ABSTRACT

BACKGROUND: As SARS-CoV-2 vaccination coverage increases in the United States (US), there is a need to understand the real-world effectiveness against severe Covid-19 and among people at increased risk for poor outcomes. METHODS: In a multicenter case-control analysis of US adults hospitalized March 11-May 5, 2021, we evaluated vaccine effectiveness to prevent Covid-19 hospitalizations by comparing odds of prior vaccination with an mRNA vaccine (Pfizer-BioNTech or Moderna) between cases hospitalized with Covid-19 and hospital-based controls who tested negative for SARS-CoV-2. RESULTS: Among 1212 participants, including 593 cases and 619 controls, median age was 58 years, 22.8% were Black, 13.9% were Hispanic, and 21.0% had immunosuppression. SARS-CoV-2 lineage B.1.1.7 (Alpha) was the most common variant (67.9% of viruses with lineage determined). Full vaccination (receipt of two vaccine doses ≥14 days before illness onset) had been received by 8.2% of cases and 36.4% of controls. Overall vaccine effectiveness was 87.1% (95% CI: 80.7 to 91.3%). Vaccine effectiveness was similar for Pfizer-BioNTech and Moderna vaccines, and highest in adults aged 18-49 years (97.4%; 95% CI: 79.3 to 99.7%). Among 45 patients with vaccine-breakthrough Covid hospitalizations, 44 (97.8%) were ≥50 years old and 20 (44.4%) had immunosuppression. Vaccine effectiveness was lower among patients with immunosuppression (62.9%; 95% CI: 20.8 to 82.6%) than without immunosuppression (91.3%; 95% CI: 85.6 to 94.8%). CONCLUSION: During March-May 2021, SARS-CoV-2 mRNA vaccines were highly effective for preventing Covid-19 hospitalizations among US adults. SARS-CoV-2 vaccination was beneficial for patients with immunosuppression, but effectiveness was lower in the immunosuppressed population.

18.
Gigascience ; 112022 02 16.
Article in English | MEDLINE | ID: covidwho-1692222

ABSTRACT

BACKGROUND: The Public Health Alliance for Genomic Epidemiology (PHA4GE) (https://pha4ge.org) is a global coalition that is actively working to establish consensus standards, document and share best practices, improve the availability of critical bioinformatics tools and resources, and advocate for greater openness, interoperability, accessibility, and reproducibility in public health microbial bioinformatics. In the face of the current pandemic, PHA4GE has identified a need for a fit-for-purpose, open-source SARS-CoV-2 contextual data standard. RESULTS: As such, we have developed a SARS-CoV-2 contextual data specification package based on harmonizable, publicly available community standards. The specification can be implemented via a collection template, as well as an array of protocols and tools to support both the harmonization and submission of sequence data and contextual information to public biorepositories. CONCLUSIONS: Well-structured, rich contextual data add value, promote reuse, and enable aggregation and integration of disparate datasets. Adoption of the proposed standard and practices will better enable interoperability between datasets and systems, improve the consistency and utility of generated data, and ultimately facilitate novel insights and discoveries in SARS-CoV-2 and COVID-19. The package is now supported by the NCBI's BioSample database.


Subject(s)
COVID-19 , SARS-CoV-2 , Genomics , Humans , Metadata , Public Health , Reproducibility of Results
19.
SSRN;
Preprint in English | SSRN | ID: ppcovidwho-326533

ABSTRACT

Background: Transmission of SARS-CoV-2 from humans to other mammals, including pet animals, has been reported. However, with the exception of farmed mink, there is no previous documentation that these infected animals can infect humans, nor of further onward spread among humans. Following a confirmed SARS-CoV-2 infection of a pet store worker, animals in the store and the warehouse supplying it were tested for evidence of SARS-CoV-2 infection. Methods: Viral swabs and blood samples from pet animals were collected in a pet shop and the warehouse supplying it and tested by SARS-CoV-2 RT-PCR and serological assays, respectively. SARS-CoV-2 RT-PCR positive samples were studied by full genome sequencing analysis. Findings: Over 50% of individually tested Syrian hamsters in the pet shop (8/16) and warehouse (7/12) were positive for SARS-CoV-2 infection in RT-PCR or serological tests. None of dwarf hamsters (n=77), rabbits (n=246), Guinea pigs (n=66), chinchilla (n=116) and mice (n=2) were confirmed positive in RT-PCR tests. SARS-CoV-2 viral genomes deduced from human and hamster cases in this incident all belong to Delta variant of concern (AY.127) that had not been circulating locally prior. These sequences are highly similar, but distinct. The viral genomes obtained from hamsters are phylogenetically related with some sequence heterogeneity and phylogenetic dating suggest infection in these hamsters occurred around 21 November 2021. Two separate transmission events to humans are documented, one leading to onward household spread. Interpretation: Pet hamsters can be naturally infected in “real-life” settings. The virus can circulate within hamsters and lead to human infections. Both genetic and epidemiological results strongly suggest that there were two independent hamster-to-human transmission and that such events can lead to onward human transmission. Importation of infected hamsters was the most likely source of virus infection.

20.
Lancet Healthy Longev ; 3(3): e143-e152, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1683812

ABSTRACT

Background: Older age is associated with poorer outcomes of SARS-CoV-2 infection, although the heterogeneity of ageing results in some older adults being at greater risk than others. The objective of this study was to quantify the association of a novel geriatric risk index, comprising age, modified Charlson comorbidity index, and Eastern Cooperative Oncology Group performance status, with COVID-19 severity and 30-day mortality among older adults with cancer. Methods: In this cohort study, we enrolled patients aged 60 years and older with a current or previous cancer diagnosis (excluding those with non-invasive cancers and premalignant or non-malignant conditions) and a current or previous laboratory-confirmed COVID-19 diagnosis who reported to the COVID-19 and Cancer Consortium (CCC19) multinational, multicentre, registry between March 17, 2020, and June 6, 2021. Patients were also excluded for unknown age, missing data resulting in unknown geriatric risk measure, inadequate data quality, or incomplete follow-up resulting in unknown COVID-19 severity. The exposure of interest was the CCC19 geriatric risk index. The primary outcome was COVID-19 severity and the secondary outcome was 30-day all-cause mortality; both were assessed in the full dataset. Adjusted odds ratios (ORs) and 95% CIs were estimated from ordinal and binary logistic regression models. Findings: 5671 patients with cancer and COVID-19 were included in the analysis. Median follow-up time was 56 days (IQR 22-120), and median age was 72 years (IQR 66-79). The CCC19 geriatric risk index identified 2365 (41·7%) patients as standard risk, 2217 (39·1%) patients as intermediate risk, and 1089 (19·2%) as high risk. 36 (0·6%) patients were excluded due to non-calculable geriatric risk index. Compared with standard-risk patients, high-risk patients had significantly higher COVID-19 severity (adjusted OR 7·24; 95% CI 6·20-8·45). 920 (16·2%) of 5671 patients died within 30 days of a COVID-19 diagnosis, including 161 (6·8%) of 2365 standard-risk patients, 409 (18·5%) of 2217 intermediate-risk patients, and 350 (32·1%) of 1089 high-risk patients. High-risk patients had higher adjusted odds of 30-day mortality (adjusted OR 10·7; 95% CI 8·54-13·5) than standard-risk patients. Interpretation: The CCC19 geriatric risk index was strongly associated with COVID-19 severity and 30-day mortality. Our CCC19 geriatric risk index, based on readily available clinical factors, might provide clinicians with an easy-to-use risk stratification method to identify older adults most at risk for severe COVID-19 as well as mortality. Funding: US National Institutes of Health National Cancer Institute Cancer Center.

SELECTION OF CITATIONS
SEARCH DETAIL