This retrospective cohort study examined the characteristics and clinical outcomes of hospitalized patients with sCoV infection compared to patients with COVID-19. Patients with COVID-19 presented a higher case fatality rate and an almost 4-fold increased risk of death than patients with sCoV. Interestingly, the rates of ICU admission and IMV use were not significantly different. However, more patients with sCoV were extubated and were more likely discharged from the ICU than patients with COVID-19. Seasonal coronaviruses are usually associated with mild upper respiratory illness in adults and are not a considerable public health burden [14]. Though, elderly individuals and immunocompromised hosts can sometimes develop life-threatening bronchiolitis, pneumonia, and even neurological infection (hCoV-OC43) [2]. In one study of community-acquired pneumonia requiring hospitalization among U.S. adults, the incidence of coronaviruses in individuals 80 years of age or older was similar to that of Streptococcus pneumoniae [21]. Besides, previous studies have linked common respiratory viruses, including sCoV, with COPD exacerbations, asthma exacerbations, and worsening cardiovascular disease [22–25]. In our cohort, patients admitted with sCoV were found to be initially admitted due to exacerbation of a pre-existing condition, namely heart failure exacerbation and COPD or asthma exacerbation, and later found to have a sCoV infection, where coronaviruses were likely responsible for disease aggravation, as demonstrated by the significantly higher proportions of patients with sCoV infection and underlying cardiovascular disease, obstructive pulmonary disease, and immunodeficiency in comparison to patients with COVID-19. In contrast, most patients with SARS-CoV-2 infection were merely admitted due to COVID-19 and its complications.
The clinical spectrum of hospitalized patients with SARS-CoV-2 infection has been mainly compared to SARS, MERS, and other pandemic viruses [26, 27]; nevertheless, our data shows significant differences with these viruses and important similarities with hospitalized patients with sCoV infection. For instance, although all coronaviruses can affect persons in all age groups, hospitalized patients with COVID-19 and sCoV infection were found to be older (median age 69 and 74 years, respectively). In contrast, previous series reported younger populations affected by SARS and MERS (median age 39 and 56 years, respectively) [28–33]. COVID-19 and MERS affected more male patients, while sCoV and SARS affected predominately female patients. Overall, SARS series reported fewer patients with pre-existing underlying conditions (10 to 30%) [28–30], while in MERS series, 50 to 96% of patients were reported to have at least one underlying condition [31–33]. Similar to MERS series, more than 80% of hospitalized patients with sCoV and COVID-19 had two or more underlying comorbidities in our cohorts. For COVID-19, sCoV, and MERS, the most common presenting symptoms included fever, cough, and shortness of breath, while in SARS series, fever and cough were more prominent relative to shortness of breath [28–33]. Leukopenia on admission was less common in our cohort of patients with sCoV (6.3%) and COVID-19 (9.5%) compared to previous MERS (14–42%) and SARS (25–35%) series [32, 33], whereas lymphopenia rates were similar in patients with sCoV (71.6%), COVID-19 (78.9%), and SARS (68–85%) in comparison to MERS (34%) [33]. As expected, rates of bilateral or multifocal infiltrates at admission were overall higher in patients with COVID-19 (61.6%), SARS (29–45%), and MERS (26-80.3%) than in patients with sCoV infection (30.5%) [28–30, 31–32]. The rates of ICU admission among patients with sCoV (35.3%) and COVID-19 (32.1%) in our cohorts were higher than in SARS series (20–26%) but lower than in MERS series (78–89%) [28–30, 31, 33]. Overall, the rates of IMV were higher in MERS series (24.5–80%), followed by our cohort of patients with COVID-19 (19.5%), SARS series (13.8–21%), and our cohort of patients with sCoV infection (14.2%) [28–33]. Case fatality rates were higher in series of hospitalized patients with MERS (20.4–65%), followed by our cohort of hospitalized patients with COVID-19 (34.7%), SARS series (3.6–13.6%), and our cohort of hospitalized patients with sCoV infection (11.6%) [28–33]. Considering all patients, including outpatients and inpatients, the estimated case-fatality rate of COVID-19 is around 1–3%, 9.5–15% for SARS, and 34.4% for MERS. The overall case-fatality rate for seasonal coronaviruses is not well described [26.27]. However, using data from the Underlying Cause of Death tool in the CDC Wide-ranging ONline Data for Epidemiologic Research (CDC WONDER) Online Database and the National Respiratory and Enteric Virus Surveillance System (NREVS), we estimated a rough case fatality rate of 0.0027% (108 deaths from unspecified coronavirus illness reported between the years 2014–2017 in the CDC WONDER Online Database and 39 588 cases of HCoV reported to the NREVSS during the same period) [6, 34].
With the expansion of SARS-CoV-2 worldwide, the emergence of new, more transmissible variants [35, 36], and the variable effectiveness of current vaccines against those variants [37], there is little hope for eliminating the virus from the human population. Unlike SARS-CoV and MERS-CoV, which were locally contained, SARS-CoV-2 will likely transition to endemicity and continued circulation with the other sCoVs [14]. Seasonal coronaviruses have annual circulation peaks in the winter months in the U.S., and individual species show variable circulation from year to year [6]. The most recent data from the NREVSS showed that during the 2019-20 winter season, HCoV-HKU1 was the most common sCoV circulating in the U.S., followed by HCoV-NL63. In comparison, during the 2020-21 winter season, HCoV-OC43 was the most common sCoV circulating in the U.S., again followed by HCoV-NL63 [38]. In our cohort, encompassing nine years, the most common isolated sCoV was HCoV-OC42, followed by HCoV-HKU1. Although it is not clear whether COVID-19 will become a chronic seasonal disease, numerous epidemiological studies and models have explored the relationship between COVID-19 transmission and meteorological factors and shown that infectivity of SARS-CoV-2 and mortality of COVID-19 are both more substantial in colder climates and that COVID-19 seasonality is more pronounced at higher latitudes where larger seasonal amplitudes of environmental indicators are observed [13, 39].
This study has several limitations. First, this was a retrospective cohort study, and clinical data were retrospectively collected through electronic medical records and manual chart review. Therefore, a degree of inter-rater variability is expected. Second, the present study was observational and included populations of patients distributed at different points in time, and thus, unknown risk factors and bias might have been unequally distributed between the two groups in the analysis. Third, the subjects with COVID-19 included for analysis encompass a series of consecutively admitted patients early in the pandemic before using steroids as the standard of care and the development of standardized, evidence-based management guidelines, which have shown to impact the inpatient case-fatality rate. On the other hand, the cohort of subjects with sCoV infection included patients from a period of 9 years, during which progress in medical knowledge and patient care are expected; hence, the crude case-fatality ratio must be taken with caution. Finally, the analyzed population was limited to one Integrated-Delivery Health system in the Chicago metropolitan area and may have limited external generalizability.
In conclusion, the clinical spectrum of hospitalized patients with COVID-19 is more similar to SARS and MERS in terms of illness severity and case-fatality rate than hospitalized patients with sCoV infection. However, the demographics and baseline characteristics of patients hospitalized with COVID-19 and sCoV infection are more in alignment, affecting older populations with many underlying conditions. Further population studies will elucidate the endemicity and seasonality of SARS-CoV-2, the effect of the vaccines in the severity of the illness, and the ecological interactions between SARS-CoV-2 and sCoVs.