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Posted Content•DOI•

Second wave mortality among patients hospitalised for COVID-19 in Sweden: a nationwide observational cohort study

Kristoffer Strålin1, Kristoffer Strålin2, Erik Wahlström3, Sten Walther4, Anna M Bennet-Bark3, Mona Heurgren3, Thomas Lindén3, Johanna B. Holm3, Håkan Hanberger4 •
Karolinska University Hospital1, Karolinska Institutet2, National Board of Health and Welfare3, Linköping University4
31 Mar 2021-medRxiv (Cold Spring Harbor Laboratory Press)-
TL;DR: In this article, the authors used Poisson regression to estimate the relative risk (RR) for death by month of admission, adjusting for age, sex, socioeconomic data, comorbidity, care dependency, and country of birth.
Abstract: Background During the first pandemic wave, a substantial decline in mortality was seen among hospitalized COVID-19 patients. We aimed to study if the decreased mortality continued during the second wave, using data compiled by the Swedish National Board of Health and Welfare. Method Retrospective nationwide observational study of all patients hospitalized in Sweden between March 1st and December 31st, 2020, with SARS-CoV-2 RNA positivity 14 days before to 5 days after admission and a discharge code for COVID-19. Outcome was 60-day all-cause mortality. Poisson regression was used to estimate the relative risk (RR) for death by month of admission, adjusting for age, sex, socioeconomic data, comorbidity, care dependency, and country of birth. Findings A total of 32 452 patients were included. December had the highest number of admissions/month (n=8253) followed by April (n=6430). The 60-day crude mortality decreased from 24.7% (95% CI, 23.0%-26.5%) for March to 10.4% (95% CI, 8.9%-12.1%) for July-September (as reported previously), later increased to 19.9% (95% CI, 19.1-20.8) for December. RR for 60-day death for December (reference) was higher than those for June to November (RR ranging from 0.74 to 0.89; 95% CI <1 for all months). SARS-CoV-2 variants of concern were only sporadically found in Sweden before January 2021. Interpretation The decreased mortality of hospitalized COVID-19 patients after the first wave turned and increased during the second wave.

Summary (3 min read)

Jump to: [Introduction] – [Study design and setting] – [Outcome] – [Covariate data] – [Statistical analyses] – [Ethics and Reporting] – [Study population] – [Overall mortality] – [Discussion] – [Contributors] and [Data sharing]

Introduction

  • During the first pandemic wave, a substantial decline in mortality was noted among patients hospitalised for COVID-19 in many countries, including Sweden [1-6], but not in all countries [7].
  • The decline in mortality was believed to be due to a combination of factors, including improved patient triage, decreased patient load, improvements in care and standard medication, and possibly changes in virus virulence [1-4].
  • Since the relative importance of these factors were unknown, no one could foresee how mortality would change during forthcoming waves.
  • The aim of the present study was to see how mortality among patients hospitalised for COVID-19 changed during the second pandemic wave.

Study design and setting

  • Nationwide observational cohort study on SARS-CoV-2-positive individuals treated for COVID-19 in Swedish hospitals, using data compiled by the Swedish National Board of Health and Welfare.
  • CC-BY-NC-ND 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
  • The copyright holder for this preprint this version posted March 31, 2021.
  • The study population was derived from cross-linked national population-based registers, using the same design and statistical methods described previously [1].
  • All patients hospitalised in Sweden between March 1st and December 31st, 2020 and reported to the National Patient Register, with SARS-CoV-2 RNA positivity 14 days before to 5 days after admission, and a discharge code for COVID-19, i.e. U07.1 or U07.2 according to the 10th International Statistical Classification of Diseases (ICD-10), were included.

Outcome

  • Study outcome was 60-day mortality, defined as death from any cause within 60 days of index hospital admission.
  • Mortality data (reporting is mandatory by law) were derived from the Swedish Tax Agency.

Covariate data

  • The authors main exposure of interest was time period of hospital admission.
  • Data on comorbidity (including Charlson Comorbidity Index; CCI), care dependency prior to admission, and ICU data were extracted as described previously [1].
  • The CCI was calculated according to a modified .
  • CC-BY-NC-ND 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
  • In the present study, the authors have added data on disposable income, education level and main income source, obtained from the Swedish Longitudinal Integrated Database for Health Insurance and Labour Market Studies (LISA database) held by Statistics Sweden.

Statistical analyses

  • Relative risk (RR) for death within 60 days was estimated using modified Poisson regression models [8] with month of admission as exposure variable of interest.
  • CC-BY-NC-ND 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
  • The copyright holder for this preprint this version posted March 31, 2021.
  • Patients were categorised as “ICU-treated” if they were ever ICU-treated during hospital stay or “non-ICU-treated” if they were never ICU-treated during hospital stay.
  • Additionally, when modelling interactions for Income source, all categories except “employed/student/caregiver” and “retired” were collapsed as “other” due to sparse data.

Ethics and Reporting

  • Ethical approval for the study was obtained from the Swedish Ethics Review Authority, Uppsala (Dnr 2020-04278).
  • The study conforms to the Reporting of Observational Studies in Epidemiology statement.

Study population

  • The peak in number of patients admitted for COVID-19 per month occurred in December, with 8 253 admissions .
  • CC-BY-NC-ND 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
  • Supplementary table S3 shows that the length of hospital stay was substantially longer for ICU-treated patients than for non-ICU-treated patients.

Overall mortality

  • A multivariable analysis of RR for death within 60 days is shown in figure 3, where sex, age, income, income source, education level, comorbidity, care dependency, country of birth, and month of admission, are modelled as main effects.
  • The copyright holder for this preprint this version posted March 31, 2021.
  • As can be seen in figure 4, the overall adjusted RR for death within 60 days for December was higher than RRs for June, July-September, October, and November, and was similar to the RR for May.

Discussion

  • The present nationwide study of patients hospitalised for COVID-19 in Sweden showed that the decrease in 60-day mortality after the first pandemic wave turned and increased significantly during the second wave.
  • CC-BY-NC-ND 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
  • Still, even after adjustment for baseline patient characteristics, the increased mortality remained and was seen in all age groups, regardless of comorbidities and care dependency .
  • During the first pandemic wave, management and care of patients with COVID19 changed considerably [1], and most likely these improvements were partly the reason for the decline in mortality during the first wave.
  • First, data on disease severity of non-ICU-treated patients and data on do-not-resuscitate orders were not available.

Contributors

  • All authors conceived and designed the study.
  • CC-BY-NC-ND 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
  • EW and JH drafted and finalised all tables and figures.
  • All authors had full access to data in the study and accept responsibility for submission for publication.

Data sharing

  • The data underlying this article cannot be shared publicly due to regulations under Swedish law.
  • According to the Swedish Ethics Review Act, the General Data Protection Regulation, the Public Access to Information and Secrecy Act, data can only be made available, after legal .
  • CC-BY-NC-ND 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
  • The copyright holder for this preprint this version posted March 31, 2021.
  • Requests regarding data in this paper may be made to the senior author.

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Figures (1)

Content maybe subject to copyright    Report

Second wave mortality among patients hospitalised for
COVID-19 in Sweden: a nationwide observational cohort
study
Kristoffer Strålin*,
1,2,3
Erik Wahlström*,
4
Sten Walther,
5,6,7
Anna M
Bennet-Bark,
4
Mona Heurgren,
4
Thomas Lindén,
4
Johanna Holm,
4
Håkan
Hanberger
8,9
* Equal contribution
Author affiliations:
1
Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden
2
Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden
3
National Programme Area for Infectious Diseases, National System for Knowledge-
Driven Management within Healthcare, Sweden’s Regions in Collaboration, Sweden
4
National Board of Health and Welfare, Sweden
5
Swedish Intensive Care Registry, Värmland County Council, Karlstad, Sweden
6
Department of Cardiothoracic and Vascular Surgery, Heart Centre, Linköping
University Hospital, Linköping, Sweden
7
Department of Health, Medicine, and Caring Sciences, Linköping University,
Linköping, Sweden
8
Division of Inflammation and Infection, Department of Biomedical and Clinical
Sciences, Faculty of Medicine and Health Sciences, Linköping University, Linköping,
Sweden
9
Department of Infectious Diseases, Linköping University Hospital, Linköping, Sweden
Corresponding author:
Prof Håkan Hanberger, MD, PhD
Department of Biomedical and Clinical Sciences, Faculty of Medicine
SE-581 83 Linköping, Sweden
Phone: +46 (0)101031367
Mobile: +46 (0)705797102
. CC-BY-NC-ND 4.0 International licenseIt is made available under a
is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted March 31, 2021. ; https://doi.org/10.1101/2021.03.29.21254557doi: medRxiv preprint
NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.
2
Research in context
Evidence before this study
During the first pandemic wave, a substantial decline in mortality was
seen among hospitalised COVID-19 patients in many countries. As the
reason for this decline has not been clarified, no one could foresee how
mortality would change during forthcoming waves.
Added value
This retrospective nationwide study of all patients hospitalised for
COVID-19 in Sweden from March to December 2020 showed that the
gradual decrease in mortality seen in the first pandemic wave was
followed by an increased crude and adjusted 60-day all-cause mortality
during the second wave. This increase in mortality occurred although the
standard-of-care recommendations for hospitalised COVID-19 patients
did not change in Sweden during the second half of 2020.
Implications of all the available evidence
While improved standard-of-care was believed to be an important factor for the
decrease in mortality during the first pandemic wave, the increasing mortality
during the second wave has no apparent explanation. As the currently known
virus variants of concern occurred only sporadically in Sweden before January
2021, they were most likely not involved. Focused research is urgent to describe
if this increase in mortality was caused by a high load of patients, management
and treatment factors, viral properties, or other circumstances.
. CC-BY-NC-ND 4.0 International licenseIt is made available under a
is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted March 31, 2021. ; https://doi.org/10.1101/2021.03.29.21254557doi: medRxiv preprint
3
ABSTRACT
Background During the first pandemic wave, a substantial decline in mortality
was seen among hospitalised COVID-19 patients. We aimed to study if the
decreased mortality continued during the second wave, using data compiled by
the Swedish National Board of Health and Welfare.
Method Retrospective nationwide observational study of all patients
hospitalised in Sweden between March 1
st
and December 31
st
, 2020, with SARS-
CoV-2 RNA positivity 14 days before to 5 days after admission and a discharge
code for COVID-19. Outcome was 60-day all-cause mortality. Poisson
regression was used to estimate the relative risk (RR) for death by month of
admission, adjusting for age, sex, socio-economic data, comorbidity, care
dependency, and country of birth.
Findings A total of 32 452 patients were included. December had the highest
number of admissions/month (n=8253) followed by April (n=6430). The 60-day
crude mortality decreased from 24·7% (95% CI, 23·0%-26·5%) for March to
10·4% (95% CI, 8·9%-12·1%) for July-September (as reported previously), later
increased to 19·9% (95% CI, 19·1-20·8) for December. RR for 60-day death for
December (reference) was higher than those for June to November (RR ranging
from 0·74 to 0·89; 95% CI <1 for all months). SARS-CoV-2 variants of concern
were only sporadically found in Sweden before January 2021.
Interpretation
The decreased mortality of hospitalised COVID-19
patients after the first wave turned and increased during the second wave.
. CC-BY-NC-ND 4.0 International licenseIt is made available under a
is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted March 31, 2021. ; https://doi.org/10.1101/2021.03.29.21254557doi: medRxiv preprint
4
Focused research is urgent to describe if this increase was caused by a
high load of patients, management and treatment, viral properties, or other
factors.
. CC-BY-NC-ND 4.0 International licenseIt is made available under a
is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted March 31, 2021. ; https://doi.org/10.1101/2021.03.29.21254557doi: medRxiv preprint
5
Introduction
During the first pandemic wave, a substantial decline in mortality was noted
among patients hospitalised for COVID-19 in many countries, including Sweden
[1-6], but not in all countries [7]. The decline in mortality was believed to be due
to a combination of factors, including improved patient triage, decreased patient
load, improvements in care and standard medication, and possibly changes in
virus virulence [1-4]. Since the relative importance of these factors were
unknown, no one could foresee how mortality would change during forthcoming
waves.
The aim of the present study was to see how mortality among patients
hospitalised for COVID-19 changed during the second pandemic wave.
Methods
Study design and setting
Nationwide observational cohort study on SARS-CoV-2-positive individuals
treated for COVID-19 in Swedish hospitals, using data compiled by the Swedish
National Board of Health and Welfare.
Participants
. CC-BY-NC-ND 4.0 International licenseIt is made available under a
is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted March 31, 2021. ; https://doi.org/10.1101/2021.03.29.21254557doi: medRxiv preprint
Citations
More filters
Journal Article•DOI•
Treatments, resource utilization, and outcomes of COVID-19 patients presenting to emergency departments across pandemic waves: an observational study by the Canadian COVID-19 Emergency Department Rapid Response Network (CCEDRRN)

[...]

Corinne M. Hohl, Rhonda J. Rosychuk, Jeffrey P. Hau, Jake Hayward, Megan Landes, Justin W. Yan, Daniel K. Ting, Michelle Welsford, Patrick Archambault, Eric Mercier, Kavish Chandra, P. Davis, Samuel Vaillancourt, Murdoch Leeies, Serena S Small, Laurie J. Morrison 
01 Jun 2022-Canadian Journal of Emergency Medicine
TL;DR: In this paper , the authors compared treatments, acute care utilization, and outcomes of COVID-19 patients presenting to emergency departments (ED) across pandemic waves, and found increased rates of ED discharges and lower hospital and critical care resource use over time.
Abstract: Treatment for coronavirus disease 2019 (COVID-19) evolved between pandemic waves. Our objective was to compare treatments, acute care utilization, and outcomes of COVID-19 patients presenting to emergency departments (ED) across pandemic waves.This observational study enrolled consecutive eligible COVID-19 patients presenting to 46 EDs participating in the Canadian COVID-19 ED Rapid Response Network (CCEDRRN) between March 1 and December 31, 2020. We collected data by retrospective chart review. Our primary outcome was in-hospital mortality. Secondary outcomes included treatments, hospital and ICU admissions, ED revisits and readmissions. Logistic regression modeling assessed the impact of pandemic wave on outcomes.We enrolled 9,967 patients in 8 provinces, 3,336 from the first and 6,631 from the second wave. Patients in the second wave were younger, fewer met criteria for severe COVID-19, and more were discharged from the ED. Adjusted for patient characteristics and disease severity, steroid use increased (odds ratio [OR] 7.4; 95% confidence interval [CI] 6.2-8.9), and invasive mechanical ventilation decreased (OR 0.5; 95% CI 0.4-0.7) in the second wave compared to the first. After adjusting for differences in patient characteristics and disease severity, the odds of hospitalization (OR 0.7; 95% CI 0.6-0.8) and critical care admission (OR 0.7; 95% CI 0.6-0.9) decreased, while mortality remained unchanged (OR 0.7; 95% CI 0.5-1.1).In patients presenting to cute care facilities, we observed rapid uptake of evidence-based therapies and less use of experimental therapies in the second wave. We observed increased rates of ED discharges and lower hospital and critical care resource use over time. Substantial reductions in mechanical ventilation were not associated with increasing mortality. Advances in treatment strategies created health system efficiencies without compromising patient outcomes.Clinicaltrials.gov, NCT04702945.RéSUMé: CONTEXTE: Le traitement de la maladie à coronavirus 2019 (COVID-19) a évolué entre les vagues pandémiques. Notre objectif était de comparer les traitements, l'utilisation des soins aigus et les résultats des patients atteints de la maladie COVID-19 se présentant aux urgences à travers les vagues de pandémie. MéTHODES: Cette étude observationnelle a recruté des patients COVID-19 éligibles consécutifs se présentant à 46 services d'urgence participant au Réseau canadien de réponse rapide aux services d'urgence COVID-19 (CCEDRRN) entre le 1er mars et le 31 décembre 2020. Nous avons recueilli des données au moyen d’un examen rétrospectif des dossiers. Notre principal résultat a été la mortalité à l’hôpital. Les résultats secondaires incluaient les traitements, les admissions à l'hôpital et aux soins intensifs, les revisites aux urgences et les réadmissions. La modélisation par régression logistique a évalué l'impact de la vague de pandémie sur les résultats. RéSULTATS: Nous avons recruté 9 967 patients dans 8 provinces, 3 336 de la première vague et 6 631 de la deuxième vague. Les patients de la deuxième vague étaient plus jeunes, moins nombreux à répondre aux critères de gravité de la COVID-19 et plus nombreux à quitter les urgences. Après ajustement en fonction des caractéristiques des patients et de la gravité de la maladie, le recours aux stéroïdes a augmenté (rapport de cotes [RC] 7.4 ; intervalle de confiance à 95 % [IC] 6.2–8.9) et la ventilation mécanique invasive a diminué (RC 0.5 ; IC à 95 % 0.4–0.7) lors de la deuxième vague par rapport à la première. Après ajustement pour tenir compte des différences dans les caractéristiques des patients et la gravité de la maladie, les probabilités d'hospitalisation (RC 0.7 ; IC à 95 % 0.6–0.8) et d'admission en soins intensifs (RC 0.7 ; IC à 95 % 0.6–0.9) ont diminué, tandis que la mortalité est restée inchangée (RC 0.7 ; IC à 95 % 0.5–1.1). INTERPRéTATION: Chez les patients se présentant dans les établissements de soins de santé, nous avons observé une adoption rapide des thérapies fondées sur des données probantes et un moindre recours aux thérapies expérimentales lors de la deuxième vague. Nous avons observé une augmentation des taux de sortie des services d'urgence et une diminution de l'utilisation des ressources hospitalières et des soins intensifs au fil du temps. Les réductions substantielles de la ventilation mécanique n'étaient pas associées à une augmentation de la mortalité. Les progrès réalisés dans les stratégies de traitement ont permis d'améliorer l'efficacité des systèmes de santé sans compromettre les résultats pour les patients.

8 citations

Posted Content•DOI•
Treatments, resource utilization, and outcomes of covid-19 patients presenting to emergency departments across pandemic waves: an observational study by the canadian covid-19 emergency department rapid response network (ccedrrn)

[...]

Corinne M. Hohl1, Corinne M. Hohl2, Rhonda J. Rosychuk3, Jeffrey P. Hau2, Jeffrey P. Hau1, Jake Hayward3, Megan Landes4, Megan Landes5, Justin W. Yan6, Justin W. Yan7, Daniel K. Ting1, Michelle Welsford8, Michelle Welsford9, Patrick Archambault10, Eric Mercier10, Kavish Chandra11, Kavish Chandra12, Philip J. Davis13, Samuel Vaillancourt5, Samuel Vaillancourt4, Murdoch Leeies14, Serena Small1, Serena Small2, Laurie J. Morrison5, Laurie J. Morrison15 •
University of British Columbia1, Vancouver Coastal Health2, University of Alberta3, University Health Network4, University of Toronto5, University of Western Ontario6, London Health Sciences Centre7, Hamilton Health Sciences8, McMaster University9, Laval University10, Dalhousie University11, Saint John Regional Hospital12, University of Saskatchewan13, University of Manitoba14, St. Michael's GAA, Sligo15
01 Aug 2021-medRxiv
TL;DR: In this paper, the authors compared treatments, acute care resource utilization, and outcomes of COVID-19 patients presenting to Emergency Departments across two pandemic waves, and used logistic regression modeling to assess the impact of pandemic wave on outcomes.
Abstract: Background Treatment strategies for coronavirus disease 2019 (COVID-19) evolved between pandemic waves. Our objective was to compare treatments, acute care resource utilization, and outcomes of COVID-19 patients presenting to Emergency Departments across two pandemic waves. Methods This observational study enrolled consecutive eligible COVID-19 patients presenting to 46 Emergency Departments participating in the Canadian COVID-19 Emergency Department Rapid Response Network (CCEDRRN) between March 1 and December 31, 2020. We collected data by retrospective chart review. Our primary outcome was in-hospital mortality. We used logistic regression modeling to assess the impact of pandemic wave on outcomes. Results We enrolled 9,967 patients in 8 provinces, 3,336 from the first and 6,631 from the second wave. Patients in the second wave were younger, fewer met criteria for severe COVID-19, and more were discharged from the Emergency Department. Adjusted for patient characteristics and disease severity, steroid use increased (odds ratio [OR] 8.0; 95% confidence interval [CI] 6.4 – 10.0), while the use of invasive mechanical ventilation decreased (OR 0.5; 95%CI 0.4 – 0.6) in the second wave. After adjusting for differences in patient characteristics and disease severity, the odds of hospitalization (OR 0.7; 95%CI 0.6 – 0.8) and critical care admission (OR 0.6; 95%CI 0.4 – 0.7) decreased, while mortality remained unchanged (OR 1.0; 95%CI 0.7-1.4). Interpretation In patients presenting to Canadian acute care facilities, rapid uptake of steroid therapy was evident. Mortality was stable despite lower critical care utilization in the second wave. Trial Registration Clinicaltrials.gov, NCT04702945

3 citations

Posted Content•DOI•
Long-lasting humoral immunity in Covid-19 infected patients at a University Hospital Clinic in Östergötland County Council during 2020-2021

[...]

Mohammad Azharuddin1, Daniel Aili1, Robert Selegård1, Sajjad Naeimipour1, Sunnerhagen M1, Patra H2, Sjöberg Ks1, Niward K1, Hanberger H1, Åse Östholm-Balkhed1, Jorma Hinkula1 •
Linköping University1, University College London2
27 Apr 2021-bioRxiv
TL;DR: In this paper, the presence of serum IgG and IgA against SARS-CoV-2 antigens (S1-spike, nucleocapsid and NSP3) was analyzed.
Abstract: Longitudinal serum samples and nasopharyngeal/nasal swab samples were collected from forty-eight individuals (median age 66yrs) with Covid-19 PCR-positive test results at Linkoping University Hospital. Samples were collected from initial visit and for 6 months follow up. Presence of serum IgG and IgA against SARS-CoV-2 antigens (S1-spike, nucleocapsid and NSP3) were analyzed. Nasal swabs were tested for presence of IgA against the outer envelope S1 spike protein. Ninety-two percent of participants were seropositive against SARS-CoV-2 recombinant proteins at day 28 from study entry and all (100%) were seropositive from samples collected at 2 months or later. The most common antibody responses (both serum IgG, mainly IgG1 and IgA) were detected against the S1-spike protein and the nucleoprotein. In samples collected from nasal tissues considerably lower frequencies of IgA-positive reactivities were detected. Sixteen to 18 percent of study participants showed detectable IgA levels in nasal samples, except at day 60 when 36% of tested individuals showed presence of IgA against the S1-spike protein. The study suggests that the absolute majority of studied naturally infected Covid-19 patient in the Linkoping, Ostergotland health region develop over 6 months lasting detectable levels of serum IgG and IgA responses towards the SARS-CoV-2 S1-spike protein as well as against the nucleoprotein, but not against the non-structural protein 3.
References
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Journal Article•DOI•
A Modified Poisson Regression Approach to Prospective Studies with Binary Data

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Guangyong Zou1•
Robarts Research Institute1
01 Apr 2004-American Journal of Epidemiology
TL;DR: Results from a limited simulation study indicate that this approach is very reliable even with total sample sizes as small as 100, and the method is illustrated with two data sets.
Abstract: Relative risk is usually the parameter of interest in epidemiologic and medical studies. In this paper, the author proposes a modified Poisson regression approach (i.e., Poisson regression with a robust error variance) to estimate this effect measure directly. A simple 2-by-2 table is used to justify the validity of this approach. Results from a limited simulation study indicate that this approach is very reliable even with total sample sizes as small as 100. The method is illustrated with two data sets.

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Nicholas G Davies1, Christopher I Jarvis1, W. John Edmunds1, Nicholas P. Jewell1, Karla Diaz-Ordaz1, Ruth H. Keogh1 •
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TL;DR: In this paper, the authors analyzed a dataset that links 2.245,263 positive SARS-CoV-2 community tests and 17,452 deaths associated with COVID-19 in England from 1 November 2020 to 14 February 2021.
Abstract: SARS-CoV-2 lineage B.1.1.7, a variant that was first detected in the UK in September 20201, has spread to multiple countries worldwide. Several studies have established that B.1.1.7 is more transmissible than pre-existing variants, but have not identified whether it leads to any change in disease severity2. Here we analyse a dataset that links 2,245,263 positive SARS-CoV-2 community tests and 17,452 deaths associated with COVID-19 in England from 1 November 2020 to 14 February 2021. For 1,146,534 (51%) of these tests, the presence or absence of B.1.1.7 can be identified because mutations in this lineage prevent PCR amplification of the spike (S) gene target (known as S gene target failure (SGTF)1). On the basis of 4,945 deaths with known SGTF status, we estimate that the hazard of death associated with SGTF is 55% (95% confidence interval, 39–72%) higher than in cases without SGTF after adjustment for age, sex, ethnicity, deprivation, residence in a care home, the local authority of residence and test date. This corresponds to the absolute risk of death for a 55–69-year-old man increasing from 0.6% to 0.9% (95% confidence interval, 0.8–1.0%) within 28 days of a positive test in the community. Correcting for misclassification of SGTF and missingness in SGTF status, we estimate that the hazard of death associated with B.1.1.7 is 61% (42–82%) higher than with pre-existing variants. Our analysis suggests that B.1.1.7 is not only more transmissible than pre-existing SARS-CoV-2 variants, but may also cause more severe illness. Analysis of community-tested cases of SARS-CoV-2 indicates that the B.1.1.7 variant is not only more transmissible than pre-existing variants, but may also cause more severe illness, and is associated with a higher risk of death.

731 citations

Journal Article•DOI•
Factors Associated With Death in Critically Ill Patients With Coronavirus Disease 2019 in the US

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Shruti Gupta1, Salim S. Hayek2, Wei Wang1, Lili Chan3, Kusum S. Mathews3, Michal L. Melamed4, Samantha K. Brenner5, Amanda K. Leonberg-Yoo6, Edward J. Schenck7, Jared Radbel5, Jochen Reiser8, Anip Bansal9, Anand Srivastava10, Yan Zhou11, Anne Sutherland5, Adam E. Green12, Alexandre M. Shehata13, Nitender Goyal14, Anitha Vijayan15, Juan Carlos Q. Velez16, Juan Carlos Q. Velez17, Shahzad Shaefi1, Chirag R. Parikh18, Justin Arunthamakun19, Ambarish M. Athavale, Allon N. Friedman20, Samuel A.P. Short21, Zoe A. Kibbelaar22, Samah Abu Omar1, Andrew J Admon2, John P. Donnelly2, Hayley B. Gershengorn4, Hayley B. Gershengorn23, Miguel A. Hernán1, Miguel A. Hernán24, Matthew W. Semler25, David E. Leaf1 •
Harvard University1, University of Michigan2, Icahn School of Medicine at Mount Sinai3, Yeshiva University4, Rutgers University5, University of Pennsylvania6, Cornell University7, Rush University Medical Center8, Anschutz Medical Campus9, Northwestern University10, Medical College of Wisconsin11, Rowan University12, Hackensack University Medical Center Mountainside13, Tufts University14, Washington University in St. Louis15, University of Queensland16, Ochsner Health System17, Johns Hopkins University18, Baylor University Medical Center19, Indiana University – Purdue University Indianapolis20, University of Vermont21, Boston University22, University of Miami23, Massachusetts Institute of Technology24, Vanderbilt University25
01 Nov 2020-JAMA Internal Medicine
TL;DR: This study identified demographic, clinical, and hospital-level risk factors that may be associated with death in critically ill patients with COVID-19 and can facilitate the identification of medications and supportive therapies to improve outcomes.
Abstract: Importance: The US is currently an epicenter of the coronavirus disease 2019 (COVID-19) pandemic, yet few national data are available on patient characteristics, treatment, and outcomes of critical illness from COVID-19. Objectives: To assess factors associated with death and to examine interhospital variation in treatment and outcomes for patients with COVID-19. Design, Setting, and Participants: This multicenter cohort study assessed 2215 adults with laboratory-confirmed COVID-19 who were admitted to intensive care units (ICUs) at 65 hospitals across the US from March 4 to April 4, 2020. Exposures: Patient-level data, including demographics, comorbidities, and organ dysfunction, and hospital characteristics, including number of ICU beds. Main Outcomes and Measures: The primary outcome was 28-day in-hospital mortality. Multilevel logistic regression was used to evaluate factors associated with death and to examine interhospital variation in treatment and outcomes. Results: A total of 2215 patients (mean [SD] age, 60.5 [14.5] years; 1436 [64.8%] male; 1738 [78.5%] with at least 1 chronic comorbidity) were included in the study. At 28 days after ICU admission, 784 patients (35.4%) had died, 824 (37.2%) were discharged, and 607 (27.4%) remained hospitalized. At the end of study follow-up (median, 16 days; interquartile range, 8-28 days), 875 patients (39.5%) had died, 1203 (54.3%) were discharged, and 137 (6.2%) remained hospitalized. Factors independently associated with death included older age (≥80 vs <40 years of age: odds ratio [OR], 11.15; 95% CI, 6.19-20.06), male sex (OR, 1.50; 95% CI, 1.19-1.90), higher body mass index (≥40 vs <25: OR, 1.51; 95% CI, 1.01-2.25), coronary artery disease (OR, 1.47; 95% CI, 1.07-2.02), active cancer (OR, 2.15; 95% CI, 1.35-3.43), and the presence of hypoxemia (Pao2:Fio2<100 vs ≥300 mm Hg: OR, 2.94; 95% CI, 2.11-4.08), liver dysfunction (liver Sequential Organ Failure Assessment score of 2 vs 0: OR, 2.61; 95% CI, 1.30-5.25), and kidney dysfunction (renal Sequential Organ Failure Assessment score of 4 vs 0: OR, 2.43; 95% CI, 1.46-4.05) at ICU admission. Patients admitted to hospitals with fewer ICU beds had a higher risk of death (<50 vs ≥100 ICU beds: OR, 3.28; 95% CI, 2.16-4.99). Hospitals varied considerably in the risk-adjusted proportion of patients who died (range, 6.6%-80.8%) and in the percentage of patients who received hydroxychloroquine, tocilizumab, and other treatments and supportive therapies. Conclusions and Relevance: This study identified demographic, clinical, and hospital-level risk factors that may be associated with death in critically ill patients with COVID-19 and can facilitate the identification of medications and supportive therapies to improve outcomes.

706 citations

Journal Article•DOI•
Risk of mortality in patients infected with SARS-CoV-2 variant of concern 202012/1: matched cohort study.

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Robert Challen1, Ellen Brooks-Pollock2, Jonathan M. Read3, Louise Dyson4, Krasimira Tsaneva-Atanasova1, Krasimira Tsaneva-Atanasova5, Leon Danon •
University of Exeter1, University of Bristol2, Lancaster University3, University of Warwick4, The Turing Institute5
10 Mar 2021-BMJ
TL;DR: In this article, a matched cohort study was conducted to establish whether there is any change in mortality from infection with a new variant of SARS-CoV-2, designated a variant of concern (VOC-202012/1) in December 2020, compared with circulating SARS CoV-19 variants.
Abstract: Objective To establish whether there is any change in mortality from infection with a new variant of SARS-CoV-2, designated a variant of concern (VOC-202012/1) in December 2020, compared with circulating SARS-CoV-2 variants. Design Matched cohort study. Setting Community based (pillar 2) covid-19 testing centres in the UK using the TaqPath assay (a proxy measure of VOC-202012/1 infection). Participants 54 906 matched pairs of participants who tested positive for SARS-CoV-2 in pillar 2 between 1 October 2020 and 29 January 2021, followed-up until 12 February 2021. Participants were matched on age, sex, ethnicity, index of multiple deprivation, lower tier local authority region, and sample date of positive specimens, and differed only by detectability of the spike protein gene using the TaqPath assay. Main outcome measure Death within 28 days of the first positive SARS-CoV-2 test result. Results The mortality hazard ratio associated with infection with VOC-202012/1 compared with infection with previously circulating variants was 1.64 (95% confidence interval 1.32 to 2.04) in patients who tested positive for covid-19 in the community. In this comparatively low risk group, this represents an increase in deaths from 2.5 to 4.1 per 1000 detected cases. Conclusions The probability that the risk of mortality is increased by infection with VOC-202012/01 is high. If this finding is generalisable to other populations, infection with VOC-202012/1 has the potential to cause substantial additional mortality compared with previously circulating variants. Healthcare capacity planning and national and international control policies are all impacted by this finding, with increased mortality lending weight to the argument that further coordinated and stringent measures are justified to reduce deaths from SARS-CoV-2.

617 citations

Journal Article•DOI•
SARS-CoV-2 detection, viral load and infectivity over the course of an infection.

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Kieran A. Walsh, Karen Jordan, Barbara Clyne1, Daniela Rohde, Linda Drummond, Paula Byrne, Susan Ahern, Paul G Carty, Kirsty K O'Brien, Eamon O'Murchu, Michelle O'Neill, Susan M Smith1, Máirín Ryan2, P. Harrington •
Royal College of Surgeons in Ireland1, Trinity College, Dublin2
29 Jun 2020-Journal of Infection
TL;DR: There is a relatively consistent trajectory of SARS-CoV-2 viral load over the course of COVID-19 from respiratory tract samples, however the duration of infectivity remains uncertain.

563 citations

Related Papers (5)
The high volume of patients admitted during the SARS-CoV-2 pandemic has an independent harmful impact on in-hospital mortality from COVID-19.

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28 Jan 2021-PLOS ONE
Alessandro Soria, Stefania Galimberti, Giuseppe Lapadula, F Visco, Agata Ardini, Maria Grazia Valsecchi, Paolo Bonfanti 
Trends in Patient Characteristics and COVID-19 In-Hospital Mortality in the United States During the COVID-19 Pandemic.

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13 Jul 2021-Critical Care Medicine
John M Dennis, Andrew McGovern, Nicholas J. Thomas, Harrison Wilde, Sebastian J. Vollmer, Bilal A. Mateen 
Changes in in-hospital mortality in the first wave of COVID-19: a multicentre prospective observational cohort study using the WHO Clinical Characterisation Protocol UK.

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14 May 2021
Annemarie B Docherty, Rachel H Mulholland, Nazir I Lone, Christopher P Cheyne, Daniela De Angelis, Karla Diaz-Ordaz, Cara Donegan, Thomas M Drake, Jake Dunning, Sebastian Funk, Marta García-Fiñana, Michelle Girvan, Hayley E Hardwick, Janet Harrison, Antonia Ho, David M Hughes, Ruth H. Keogh, Peter Kirwan, Gary Leeming, Jonathan S Nguyen Van-Tam, Riinu Pius, Clark D Russell, Rebecca G Spencer, Brian D. M. Tom, Lance Turtle, Peter J. M. Openshaw, J Kenneth Baillie, Ewen M Harrison, Malcolm G Semple 
Changes in COVID-19 in-hospital mortality in hospitalised adults in England over the first seven months of the pandemic: An observational study using administrative data

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30 Apr 2021
William K. Gray, Annakan Victor Navaratnam, Jamie Day, Julia Wendon, Tim W.R. Briggs, Tim W.R. Briggs 
Frequently Asked Questions (12)
Q1. What are the contributions in "Second wave mortality among patients hospitalised for covid-19 in sweden: a nationwide observational cohort study" ?

It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. 

In studies from the first wave, a high load of hospitalised patients was considered to be associated with a high mortality [7, 14, 15], motivating actions to flatten-the-curve to reduce the pressure on hospitals [16]. 

The SARS-CoV-2 virus variant of concern (B.1.1.7), which was first detected in the United Kingdom has been associated with an enhanced mortality among out-patients with SARSCoV-2 infection [19, 20]. 

as virus variants of concern occurred only sporadically in Sweden before January 2021 [21], they were most likely not involved in the increased second wave mortality that was noted in this study. 

The present nationwide study of patients hospitalised for COVID-19 in Sweden showed that the decrease in 60-day mortality after the first pandemic wave turned and increased significantly during the second wave. 

The 60-day crude mortality decreased from 24·7% (95% CI, 23·0%-26·5%) for March to 10·4% (95% CI, 8·9%-12·1%) for July-September (as reported previously), later increased to 19·9% (95% CI, 19·1-20·8) for December. 

32 452 patients admitted for COVID-19 to Swedish hospitals MarchDecember 2020 were studied, including 15 839 during the first wave (MarchJune), 1365 during the inter-wave period (July-September), and 15 248 during the second wave (October-December; figure 1). 

Among Swedish ICU-treated patients, however, crude mortality followed a U-shaped curve, with a maximum of 36% in March declining to 20% during the summer, increasing again to 35% in December (figure 2B). 

Another reason for the relationship between high mortality and peak in admission rate could be high exposure to circulating virus in the community, leading to heavier viral inoculates, perhaps causing more severe disease [18]. 

According to the Swedish Ethics ReviewAct, the General Data Protection Regulation, the Public Access toInformation and Secrecy Act, data can only be made available, after legal. 

2Evidence before this studyDuring the first pandemic wave, a substantial decline in mortality was seen among hospitalised COVID-19 patients in many countries. 

While improved standard-of-care was believed to be an important factor for the decrease in mortality during the first pandemic wave, the increasing mortality during the second wave has no apparent explanation.