Of the initially 269 SARS-CoV-2 negative patients, 55 had been retested for ongoing clinical suspicion of COVID-19, 14 of these by PCR from bronchoalveolar fluid (BAL). Two of the retested ones revealed to be positive during retesting, so a total number of 267 SARS-CoV-2 negative patients were further analysed for their ICD main diagnosis group. Respiratory diseases (ICD 10 group J) were found in 42.7% (114/267) of cases, followed by 14.2% (38/267) infections of other origin (ICD 10 groups A/B), 11.2% (30/267) cardiovascular (ICD 10 group I), 9.0% (24/267) oncological (ICD 10 groups C/D), 6.7% (18/267) gastrointestinal (ICD 10 group K), 4.9% (13/267) urogenital (ICD 10 group N), 1.9% (5/267) neurological (ICD 10 group G) and 9.4% (25/267) miscellaneous diseases (all remaining ICD 10 groups ) (Fig. 3).
Further evaluation of the respiratory diseases group (n = 114) resulted in exclusion of 25 cases of non-infectious respiratory diseases (pulmonary edema, non-infectious exacerbation of COPD, pleural effusion, asthma, hypercapnic respiratory failure), so a total of 89 COVID-19 negative respiratory infections (50 pneumonia (J18.0-J18.9), 17 influenza/ viral pneumonia (J10.0, J10.1, J10.8, J12.1, J12.8), 6 upper respiratory tract infections (J06.8, J06.9), 16 acute bronchitis (J20.9, J22, J44.01, J44.09)) could be included.
A total of 136 patients (mean age 68 years ± 17.5 year.; 46 female (33.8%)) were included in the analysis. Baseline characteristics are summarized in Table 1. According to the MTS 14 patients were classified as “red” (10.3%), 12 patients as “orange” (8.8%), 50 patients as “yellow” (36.8%), 58 patients as “green” (42.6%) and 2 patients as “blue” (1.5%).
47 patients were tested positive for SARS-Cov-2.
Of all COVID-19 patients, 40% (19/47) reported dyspnea, while this clinical feature was present in 61% (54/89) of non COVID-19 patients (p = 0.024). Among the COVID-19 patients, 15% reported taste disorders (7/47), whereas only 2% (2/89) of the COVID-19 negative patients did so (p = 0.005). Significant differences between the two groups were not observed for other clinical features or vital parameters (table 2).
Patients with COVID-19 had significant less preexisting renal disorders (8.5% vs 24.7%; p = 0.025). No significant differences were observed for the presence of a preexisting cardiac or pulmonary disorder, previous thrombosis or pulmonary embolism and oncological diseases between COVID-19 positive and COVID-19 negative patients.
There were significantly more active smokers in the COVID-19 negative group than in the group with COVID-19 positive patients (16.9% vs 2.1%; p = 0.011). However, the number of patients with an unknown smoking status was, although not significantly, higher in the non-COVID-19 group than in the group tested positively (70.2% vs 58.4%; p = 0.177).
The mortality of COVID-19 patients admitted to our hospital via the ED was 19.1%, which was significantly higher than of the group admitted with similar symptoms but negative COVID-19 result (5.6%) (p = 0.014). The duration of hospital stay was longer among COVID-19 patients (9.0 vs. 5.6 days, p = 0.014) than among COVID-19 negative patients.
In the group of COVID-19 patients, mean levels of lactate dehydrogenase (LDH) were significantly higher (439.5 vs. 335.8 U/l, p = 0.025). The mean levels of procalcitonine tended to be higher in COVID-19 negative patients (6,74 versus 0.42 µg/l), but were not significantly different (p = 0.354).
We could not find any significant differences regarding to other laboratory values, vital parameters and treatment modes between the two groups (table 2)
Table 2: group comparison COVID-19 versus COVID-19 negative airway infections Discussion:
Early triage and differential diagnosis of patients presenting with typical clinical symptoms of COVID-19 remains very challenging but relevant. Our study had the following main findings:
-
Differential diagnosis of typical COVID-19 symptoms is very broad and comprises many common respiratory, infectious and cardiovascular diseases whereas respiratory diseases are the most frequent. Diseases from nearly every field of clinical medicine can mimic a clinical picture similar to that of COVID-19 with respiratory diseases being the most prevalent.
-
Patients with COVID-19 present with similar symptoms as COVID-19 negative respiratory infections so clinical discrimination is not reliable.
Dyspnea is less frequent found in our COVID-19 patients, whereas dysgeusia is significantly more prevalent. The latter finding has been described by other studies before and can be found in up to 44% of cases following meta-analysis (13). Whenever present, dysgeusia should rise a high suspicion for COVID-19, especially during pandemia.
Dyspnea is a typical symptom of COVID-19, which could be found in about 29% of cases in a study of 270.000 patients in the U.S.(9). Controversially, several authors described a specific phenomenon called “happy hypoxemia” in COVID-19 with a disconnect between the severity of hypoxemia and a relatively mild respiratory discomfort (14, 15). Therefore, dyspnea might be less frequent in our COVID-19 positive patients than in other respiratory infections.
Elevated levels of LDH have been described before (16) and were significantly higher among non-survivors in a case series from Wuhan (11) so this finding in our COVID-19 patients is in line with the more severe clinical course of this group. The tendency towards higher procalcitonine levels in COVID-19 negative patients may be explained by a higher rate of bacterial infections such as pneumonia, since elevated procalcitonine levels can usually only be found in advanced respectively complicated courses of COVID-19 (4). Case numbers might have been too small to reach significance here.
The significantly lower frequency of smokers in the COVID-19 group should be interpreted very cautiously since the rate of unknown smoking status is 70%, thwarting the attempt to draw any further conclusions.
Therefore, no clinical sign or symptom, nor any of the analysed laboratory values will be able to predict COVID-19 status in a reliable way. Only dysgeusia, when present, should raise a high suspicion of COVID-19 during pandemia. Strict isolation policy and frequent SARS-CoV-2 testing will remain the most important measures to keep control of the situation.
3. When inpatient treatment for respiratory infections is needed, COVID-19 patients seem to take a more severe clinical course.
The mortality of our COVID-19 positive inpatient patients is significantly higher than in the COVID-19 negative group. The mortality rate of 19.1% is comparable to those found by Petrilli et al (17), who reported a mortality of 24.1% among inpatients in New York City. The COVID negative group is a heterogeneous one, comprising different kinds of respiratory infections with pneumonia as the most frequent diagnosis (50/89). Inpatients with CAP showed a 30-day mortality of 11.9% in Europe in one study (18), so the lower mortality of the COVID negative group might be explainable hereby. A more severe course of disease can also explain the significantly higher time of admission (9.0 vs. 5.6 days, p = 0.014) among the COVID-19 positive patients in our study.
4. The false-negative rate of nasopharyngeal swab testing was low
55 patients were retested due to ongoing clinical suspicion of COVID-19, some even more than one time including bronchoalveolar specimens in 14 cases. Only 2 more positive cases (3.6%) could be found, both by BAL. This suggests that the false-negative rate is low whenever experienced and well-trained staff carries out a nasopharyngeal SARS-Cov2 swab. Previous research has reported rates of 11% for false negative PCR results in COVID-19 (19). Of note, all patients were symptomatic so that very early stages of disease who might carry a higher likelihood of false negative testing were scarce in our study.