Hospital mortality - A look at the current situation

A representative cohort study with data from more than 5000 hospitalized patients in Switzerland showed that compared with influenza A or B, the corona variant omicron was associated with a 1.5-fold increased risk of mortality. Prof. Dr. Christoph Spinner, Senior Physician for Clinical Infectiology at the Klinikum rechts der Isar of the Technical University of Munich, gives an overview of the current COVID situation with regard to hospital mortality [1].

Coronaviruses are named for the crown-like spines on their surface. They are enveloped, positive-stranded ribonucleic acid viruses (RNA viruses) that are correspondingly sensitive to environmental influences. Although, like all enveloped viruses, they cannot persist forever, human coronaviruses have played an important role as causative agents of seasonal respiratory infections for some time. They can cause clinical pictures associated with the general flu but also banal respiratory diseases. Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-1) were among the pathogens that first caused deep pneumonia with severe disease progression in 2012 and 2002, respectively. However, unlike SARS-CoV-2, which is also a member of the beta coronavirus family and was first observed in December 2019, these stopped on their own. In general, all coronaviruses have a natural host in which they can replicate significantly and to a relevant extent before translocating to intermediate hosts. To date, however, it has not been conclusively determined which intermediate host introduced the SARS-CoV-2 infections to humanity, thereby triggering the COVID-19 pandemic.

COVID-19 course (Omicron)

After the initial infection phase, as with all viral variants of SARS-CoV-2, there is a kind of latency period in the first few days. It is now known that the incubation period is on average a few days (three to five days) and that the disease is infectious even before the onset of symptoms. Camilla Rothe of the Tropical Institute described this phenomenon during the first patient outside of Asia in the spring of 2020. As known from other respiratory diseases, SARS-CoV-2 also showed infectivity after one to two days before symptom onset. After the initial latency and incubation period of about a few days to a week, there is usually a week-long symptomatology corresponding to a classic respiratory disease with general symptoms such as fever, muscle pain but also respiratory symptoms as is the case with other seasonal respiratory diseases. Infectivity persists for several days after symptoms subside. In addition, infections can also be passed from vaccinated individuals as likely as from unvaccinated individuals, making the transmissibility of SARS-CoV-2 a major problem to date, as the virus transmits much more easily than other respiratory diseases [2,3]. Data from Sweden show that unvaccinated individuals in particular were at relevant risk of severe COVID-19 with a probability of up to 37%, whereas vaccination generally resulted in a more marked credence of disease severity in the general population [4].

COVID-19 mortality significantly regressed during the course of the pandemic

A Financial Times account shows that COVID-19 mortality changed significantly during the pandemic. The mortality of COVID-19 disease at the start of the pandemic in July 2020 is still about 20 times that of influenza. By immunizing mainly so-called vulnerable groups, at the beginning of the availability of vaccination campaign from the end of 2020 and beginning of 2021, it was possible to reduce mortality to about a factor of five of influenza. In addition, the application of the booster campaign, which was necessary in the course of the campaign, succeeded in further reducing mortality, and the lower virulence of Omikron additionally caused COVID-19 to lose its terror and dangerousness. UK data show that COVID-19 mortality has now fallen significantly compared with influenza [5].

Comparison of COVID-19 mortality with vaccination coverage in three countries.

Mortality from COVID-19 was relevantly high at the beginning of the pandemic in the United States of America as well as in Germany and Japan. In the course of the pandemic, the mortality rate changed: While the mortality rate in the United States of America is still around 1% in mid-2023, it has fallen to well below 0.5% in Germany and even below 0.2% in Japan (Fig. 1) [6]. The reason for this is most likely the correlation between the proportion of vaccinated people in the population and the dangerousness of COVID-19, as over 80% of people in Japan, over 75% in Germany, and under 70% in the United States of America have received one or more COVID-19 vaccinations (Fig. 2) [6].

Comparison of COVID-19 hospitalizations in four countries.

A look at the hospitalization rate also shows clear differences in the respective countries. While relevant hospitalization with the increasing infections was observed in Switzerland and the United Kingdom of England already at the beginning of the pandemic in spring 2020, this was initially not the case in other countries. As the pandemic progressed, there were marked differences and so-called hospitalization waves that were often associated with cases of illness. Which means that SARS-CoV-2 is actually an outbreak-like disease associated with both mortality and hospitalizations (Fig. 3) [6].

A study was conducted to analyze COVID-19 omicron associated mortality compared to influenza associated mortality. This retrospective multicenter cohort study included data from patients admitted to one of 14 hospitals in Switzerland, including all five Swiss university hospitals. Seven centers continuously collected data for all adult patients hospitalized for influenza A/B. A total of another 14 centers collected data for all adult patients hospitalized for COVID-19. The primary endpoint was defined as all-cause in-hospital mortality. Secondary endpoint was admission to the intensive care unit. Other exploratory endpoints included cardiovascular, pulmonary, renal, or neurologic complications during hospitalization or length of stay and antibiotic treatment [7].

The study included 2843 patients from 14 acute care hospitals in Switzerland with a confirmed diagnosis of community-acquired COVID-19 hospitalized between February 19, 2020, and July 22, 2020. This represents 50% of all reported hospitalizations in Switzerland during this period. It also includes 1331 patients with community-acquired influenza A (96.4%) and 50 patients (3.6%) with community-acquired influenza B from seven centers in Switzerland who were hospitalized between October 26, 2018, and March 26, 2020. The majority of patients with COVID-19 (87%) and those with influenza A/B (97%) were referred directly to one of the participating hospitals. Patients with COVID-19 were younger (median 67 years) than patients with influenza A/B (median 74 years) and a greater percentage were male (61%) than female (48%) [7].

Higher in-hospital mortality with COVID-19 compared with influenza.

Although previous data have shown that COVID-19 associated mortality has progressively decreased over time, this study still shows a relevant difference in univariate analysis. This is because the intra-hospital mortality of SARS-CoV-2 Omicron is significantly higher at 7% compared to influenza at 4.4%. A further look at the data shows that the median length of hospitalization with COVID-19 is slightly shorter than with influenza A/B infection, and there are no relevant differences in the overall study population with respect to COVID-19-related or influenza-related ICU admission. Nevertheless, the complication rate of influenza A/B infections is significantly higher compared to COVID-19 and if one takes a more detailed look into the distribution of in-hospital mortality for COVID-19 compared to influenza, a so-called cause-specific hazard ratio (csHR) for in-hospital death due to COVID-19 compared to influenza of 1.93 can be identified [7].

Further studies showed, among other things, an indication of a higher daily probability of death by COVID-19, so mixed analyses that included age, sex, and hospital context were performed accordingly. Here, a so-called adjusted hazard ratio (sdHR) analysis for in-hospital death from COVID-19 compared with influenza showed a 1.54-fold increased risk of death during hospital treatment with COVID-19 Omicron compared with influenza [7].

Significantly increased mortality and higher ICU admission rates among those hospitalized for (rather than with) COVID-19.

Subgroup analyses of those hospitalized for (rather than with) COVID-19 and influenza A/B show a significantly higher proportion hospitalized for COVID-19 (49.6%) compared with influenza (24%). In addition, this was the first case to show that the probability of intensive care admission with COVID-19 omicron and associated hospitalization was also significantly higher than the probability of intensive care transfer for and with influenza infection [7].

Subsequent consideration of the sdHR for in-hospital death due to COVID-19 compared with those hospitalized for influenza A/B, showed a significantly higher likelihood with a 2.86-fold increased mortality risk for in-hospital death compared with the general study population, and the likelihood of intensive care transfer due to COVID-19 hospitalized was also relevantly increased by a factor of 1.69 compared with those hospitalized for influenza. Additional subgroup analyses restricting the observation in this subgroup during the same period, i.e., from January 15 to March 15, can reproduce these results shown in the subgroups [7].

Take-Home Messages

The study presented showed an approximately 1.5-fold increased risk of in-hospital mortality for COVID-19 omicron compared with influenza A/B patients, with shorter hospitalization with COVID-19.
Subgroup analyses in those hospitalized for (and not with) COVID-19 and influenza A/B show even greater differences in up to 2.5-fold increased mortality, confirming the overall population finding.
The rate of intensive care unit (ICU) admissions was generally not different, although a subgroup analysis showed hospitalized for (rather than with) COVID-19 were approximately 1.7 times more likely to be transferred to an ICU.
While mortality was as high as 13% with the alpha variant at the beginning of the pandemic [8], increasing immunity after vaccination and infection (approximately 98% in Switzerland) led to markedly declining mortality, while virulence continued to fall with omicron.
The study presented provides evidence that intra-hospital mortality (in at-risk groups) remains elevated with COVID-19 omicron , so specific COVID-19 therapeutics (such as nirmatrelvir, remdesivir, o.a.) may(t) provide additional benefit.

Literature:

Spinner C: Covid-19. hospital mortality – A look at the current situation. Available at: https://medizinonline.com/krankenhaussterblichkeit-aufgrund-von-covid-19-ein-blick-in-die-aktuelle-situation.
Jørgensen SB, et al: Secondary attack rates for Omicron and Delta Variants of SARS-CoV-2 in Norwegian Households. JAMA 2022;
doi: 10.1001/jama.2022.3780.
Liu Y, Rocklöv J: The effective reproductive number of the Omicron variant of SARS-CoV-2 is several times relative to Delta. Journal of Travel Medicine 2022; doi: https://doi.org/10.1093/jtm/taac037.
Kahn F, et al: Risk of severe COVID-19 from the Delta and Omicron variants in relation to vaccination status, sex, age and comorbidities – surveillance results from southern Sweden, July 2021 to January 2022. Euro Surveillance 2022; doi: 10.2807/1560-7917.ES.2022.27.9.2200121.
Burn-Murdoch J, Barnes O: Vaccines and Omicron mean Covid now less deadly than flu in England. The Financial Times 2022. Available at:
www.ft.com/content/e26c93a0-90e7-4dec-a796-3e25e94bc59b.
Available at: https://ourworldindata.org/coronavirus
Portmann L, et al: Hospital Outcomes of Community-Acquired SARS-CoV-2 Omicron Variant Infection Compared With Influenza Infection in Switzerland. JAMA 2023; doi: 10.1001/jamanetworkopen.2022.55599.
Fröhlich GM, et al: Hospital outcomes of community-acquired COVID-19 versus influenza: Insights from the Swiss hospital-based surveillance of influenza and COVID-19. Euro Surveillance 2022; doi: www.eurosurveillance.org/content/10.2807/1560-7917.ES.2022.27.1.2001848.