Clinical presentation and outcomes of COVID-19 compared with other respiratory virus infections and hospital populations

As of September 2022, more than 600 million cases of coronavirus disease 2019 (COVID-19) and 6.5 million deaths have been officially reported to the World Health Organization (WHO). The unfolding pandemic has exerted enormous strains on healthcare systems worldwide yet to be fully understood. The overarching aim of this thesis was to characterize clinical presentation and outcomes in adult patients hospitalized with COVID-19 and compare these with patients hospitalized with other respiratory virus infections as well as other hospital populations. Six retrospective cohort studies were conducted, all set in Stockholm Region in Sweden.

In study I, baseline characteristics, clinical presentation, and outcomes in patients hospitalized with COVID-19 were compared with patients hospitalized with influenza, respiratory syncytial virus (RSV) infection, and other respiratory virus infections. Despite being younger and having an overall better health status, adult patients hospitalized with COVID-19 had an increased risk of severe outcomes, in particular mortality, compared with the other infections. These risks were greater among the elderly and during the first months of the pandemic.

In study II, the prevalence of bacterial co-infections in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive community-acquired pneumonia (CAP) upon hospital admission was compared with patients hospitalized with influenza virus positive CAP and RSV positive CAP. The occurrence of detected bacterial co-infection upon hospital admission was substantially lower in the SARS-CoV-2 cohort compared with both the influenza and the RSV cohort.

In study III, we compared the occurrence of ventilator-associated lower respiratory tract infection (VA-LRTI) in patients mechanically ventilated with versus without COVID-19. The incidence rate was increased in the COVID-19 cohort when compared with influenza and other infectious diseases but decreased when compared with most of the non-infectious diseases. Further, the incidence rate was in the COVID-19 cohort increased during the second wave when compared with the first wave of the pandemic.

In study IV, the incidence rate and 30-day mortality rate of hospital-onset bacteraemia (HOB) were compared among patients hospitalized with COVID-19 and patients hospitalized without COVID-19 both before and during the pandemic. The incidence as well as mortality of HOB was increased for both COVID-19 and non-COVID-19 patients during the pandemic when compared with patients hospitalized before the pandemic.

In study V, we investigated one-year mortality among patients admitted to the intensive care unit (ICU) with versus without COVID-19. Furthermore, we compared the number of days alive and free from hospitalization during one year in those patients who were discharged alive from the ICU-associated hospitalization. An increased risk of acute mortality was observed in patients treated in the ICU with versus without COVID-19, primarily among the elderly. On the contrary, survivors of COVID-19 critical illness had compared with other critical illness survivors more days alive and free from further hospitalizations during the next year.

In study VI, we investigated the occurrence and characteristics of post COVID-19 condition (PCC) diagnosis across different severities of the acute COVID-19 episode. The occurrence of PCC diagnosis was substantially higher in individuals hospitalized versus not hospitalized during the acute COVID-19 episode. Associations between health status factors and PCC diagnosis differed by severity of the acute COVID-19 episode, with more and stronger associations among those not hospitalized during the acute infection. Increases in outpatient healthcare utilization up to one year after the acute infection indicated an incomplete recovery in individuals diagnosed with PCC.

Taken together, these studies contribute to our understanding of the clinical epidemiology of COVID-19, highlighting severe acute clinical outcomes in hospitalized patients as well as a different occurrence and trajectory of PCC across different severities of the acute infection. Given the life-saving rollout of COVID-19 vaccines and the evolving nature of the virus, the generalizability of these findings over time needs to be carefully considered. Further investigations of the acute and in particular long-term effects of COVID-19 are warranted. An improved understanding of how the pandemic has caused disruptions and backlogs in healthcare delivery is also necessary.

List of scientific papers

I. Clinical phenotypes and outcomes of SARS-CoV-2, influenza, RSV and seven other respiratory viruses: a retrospective study using complete hospital data. Pontus Hedberg, John Karlsson Valik, Suzanne Desirée van der Werff, Hideyuki Tanushi, Ana Requena Mendez, Fredrik Granath, Max Bell, Johan Mårtensson, Robert Dyrdak, Olof Hertting, Anna Färnert, Anders Ternhag, Pontus Nauclér. Thorax. 2022 Feb;77(2):154-163.
https://doi.org/10.1136/thoraxjnl-2021-216949

II. Bacterial co-infections in community-acquired pneumonia caused by SARS-CoV-2, influenza virus and respiratory syncytial virus. Pontus Hedberg, Niclas Johansson, Anders Ternhag, Lina Abdel-Halim, Jonas Hedlund, Pontus Nauclér. BMC Infect Dis. 2022 Jan 31;22(1):108.
https://doi.org/10.1186/s12879-022-07089-9

III. Ventilator-associated lower respiratory tract bacterial infections in COVID-19 compared with non-COVID-19 patients. Pontus Hedberg*, Anders Ternhag*, Christian Giske, Kristoffer Strålin, Volkan Özenci, Niclas Johansson, Carl Spindler, Jonas Hedlund, Johan Mårtensson, Pontus Nauclér. Crit Care Med. 2022 May 1;50(5):825-836. *Shared first authorship.
https://doi.org/10.1097/CCM.0000000000005462

IV. Impact of the COVID-19 pandemic on the incidence and mortality of hospital-onset bloodstream infection: a cohort study. John Karlsson Valik, Pontus Hedberg, Fredrik Holmberg, Suzanne Desirée van der Werff, Pontus Nauclér. BMJ Qual Saf. 2022 May;31(5):379-382.
https://doi.org/10.1136/bmjqs-2021-014243

V. One-year mortality and hospital-free days in COVID-19 versus non-COVID-19 critical illness. Pontus Hedberg, Nicholas Baltzer, Fredrik Granath, Michael Fored, Johan Mårtensson, Pontus Nauclér. [Manuscript]

VI. Post COVID-19 condition diagnosis: A population-based cohort study of occurrence, associated factors, and healthcare use by severity of acute infection. Pontus Hedberg, Fredrik Granath, Judith Bruchfeld, Johan Askling, Daniel Sjöholm, Michael Fored, Anna Färnert, Pontus Nauclér. [Submitted]