Are omicron infections more frequently associated with bacterial co-infections?

ABSTRACT Are omicron infections more frequently associated with bacterial co-infections? Introduction: Clinical observations suggest that Omicron infections may pre- sent with different radiographic findings and be more frequently associated with bacterial co-infections, but there is a paucity of published data. This study aimed to compare the clinical and radiographic findings of patients hospitalized with Omicron versus alpha-delta infections. Materials and Methods: Between January 1, 2021 and June 30, 2021 (alpha and delta period) and between January 1, 2022 and July 31, 2022 (Omicron period), respectively 149 and 163 COVID-19 PCR-positive patients who were followed up in the COVID-19 ward and intensive care unit of a tertiary care center were included in the study. Clinical (presence of fever and purulent sputum), laboratory and radiologic findings of the two groups were com- pared. Sputum culture results and antibiotic use were also evaluated. Results: In the alpha/delta group, ground glass opacities were seen in 75.2% (112) of the patients, consolidation in 2.7% (4), and both findings together in 6.0% (9). In the Omicron group, ground glass was seen in 40.5% (66), con- solidation in 5.5% (9), and both ground glass and consolidation together in 8.7% (13) (p< 0.001). Procalcitonin levels were 0.25 µg/L or higher in 29.6% and 43.9% of the patients in the alpha/delta and Omicron groups, respec- tively. Mean PCT values were 0.36 µg/L and 1.93 µg/L, respectively (p> 0.05). CRP levels were similar in both groups. Mean LDH level in the Omicron group was 278 U/L and was significantly lower than the alpha/delta group (381 U/L) (p< 0.001). The proportion of patients requiring intensive care during hospitalization was higher in the alpha/delta group (36.2% vs 26.4%) (p= 0.06). Conclusion: Lower LDH levels, less need for intensive care and less frequent development of ARDS indicate that Omicron causes milder disease, while a higher rate of consolidation and higher procalcitonin levels suggest a higher frequency of bacterial co-infections. Key words: COVID-19; SARS-CoV-2; co-infections ÖZ Omicron enfeksiyonlarında bakteriyel koenfeksiyon riski daha yüksek mi? Giriş: Klinik gözlemler, Omicron enfeksiyonlarının farklı radyografik bulgularla ortaya çıkabileceğini ve bakteriyel koenfeksiyonlarla daha sık ilişkili olabileceğini düşündürmektedir, ancak yayımlanmış veri azdır. Bu çalışmanın amacı, Omicron ve alfa-delta enfeksiyon- ları ile hastaneye yatırılan hastaların klinik ve radyografik bulgularını karşılaştırmaktır. Materyal ve Metod: 1 Ocak 2021-30 Haziran 2021 tarihleri arasında (alfa ve delta dönemi) ve 1 Ocak 2022-31 Temmuz 2022 tarihleri arasında (Omicron dönemi) üçüncü basamak bir merkezin COVID-19 servisinde ve yoğun bakım ünitesinde takip edilen 149 ve 163 COVID-19 PCR-pozitif hasta çalışmaya dahil edilmiştir. İki grubun klinik (ateş ve pürülan balgam varlığı), laboratuvar ve rad- yolojik bulguları karşılaştırılmıştır. Balgam kültürü sonuçları ve antibiyotik kullanımı da değerlendirilmiştir. Bulgular: Alfa/delta grubunda hastaların %75,2 (112)’sinde buzlu cam opasiteleri, %2,7 (4)’sinde konsolidasyon ve %6,0 (9)’sında her iki bulgu birlikte görülmüştür. Omicron grubunda ise %40,5 (66)’inde buzlu cam, %5,5 (9)’inde konsolidasyon ve %8,7 (13)’sinde hem buzlu cam hem de konsolidasyon birlikte görüldü (p< 0,001). Prokalsitonin düzeyleri alfa/delta ve Omicron grupla- rında hastaların %29,6 ve %43,9’unda 0,25 µg/L veya üzerindeydi. İki gruptaki ortalama PCT değerleri sırasıyla 0,36 µg/L ve 1,93 µg/L idi (p> 0.05). CRP değerleri iki grupta da benzer düzeydeydi. Ortalama LDH düzeyi Omicron grubunda 278 U/L idi ve alfa/ delta grubuna (381 U/L) göre daha düşüktü (p< 0,001). Yoğun bakım gerektiren hasta oranı alfa/delta grubunda daha yüksekti (%36,2 vs 26,4) (p= 0,06). Sonuç: Daha düşük LDH seviyeleri, daha az yoğun bakım ünitesi ihtiyacı ve daha az ARDS gelişimi Omicron’un daha hafif hastalığa neden olduğunu gösterirken, daha yüksek konsolidasyon oranı ve daha yüksek prokalsitonin seviyeleri daha yüksek bakteriyel koen- feksiyon sıklığına işaret etmektedir. Anahtar kelimeler: COVID-19; SARS-CoV-2; bakteriyel koenfeksiyon


INTRODUCTION
As of today, SARS-CoV-2 infections have led to more than 17 million documented cases and more than 101.492deaths in Türkiye according to the official sources (1,2).Different variants originating from mutations along the course of the disease have been observed.The most prevalent and concerning ones have been the alpha, delta and Omicron variants.The World Health Organization announced on November 24, 2021 that a new variant (B.1.1.529)was active and labeled it as Omicron.When compared with the previous variants, Omicron was observed to be more infectious (3).Omicron variant has been diagnosed in Türkiye starting from December 2021.There was a rapid increase in the number of infected cases, which was associated with a relatively weak increase in hospitalizations and mortality (2,4).Chronologically, the alpha variant became the dominant strain in November 2020 and its activity lasted till April 2021.Then, delta activity started and became the dominant strain in a short period.Since December 2021, Omicron activity has been mainly observed Eris, or EG.5.1, the current dominant strain, is considered to be an Omicron subvariant (5).
In a meta-analysis of studies performed during the period when alpha and delta variants were dominant (2020 and 2021), the most frequently observed CT finding was bilateral, subpleural, multifocal ground glass opacities (6).Besides, the frequency of bacterial co-infections associated with COVID-19 during the same period was reported to be 5-11% (7,8).In contrast, we observed in patients who presented to our hospital during the Omicron period that the radiographic findings were somewhat different and antibiotics were more frequently used in relation with the laboratory and radiographic features.
There are scant data on the clinical and radiographic findings of Omicron infections.The aim of this study was to define the radiographic features of and the frequency of bacterial co-infections in Omicron infections in comparison with the alpha and delta variant infections.

Study Population
Between January 1, 2021 and June 30, 2021 (alpha and delta period) and between January 1, 2022 and July 31, 2022 (Omicron period), respectively 149 and 163 COVID-19 PCR-positive patients who were followed up in the COVID-19 ward and intensive care unit of the Department of Chest Diseases, Ege University Faculty of Medicine were included in the study.

Parameters Assessed for the Comparison of the Two Periods
Clinical (presence of fever and purulent sputum), laboratory (serum CRP, procalcitonin, LDH levels, leukocyte and neutrophil counts) and radiologic findings (presence of ground glass opacities and consolidation) of the two groups were compared.High fever was defined as a temperature of 37.5 °C or higher as determined by an ear thermometer.Sputum culture results and antibiotic use were also evaluated.

Statistical Analysis
Descriptive statistics were used for demographic data.The conformity of the variables to normal distribution was examined using visual (histogram and probability graphs) and analytical methods (Kolmogorov-Smirnov / Shapiro-Wilk tests).For nonnormally distributed variables, median and interquartile range were used (using frequency tables for ordinal variables).For normally distributed variables, mean and standard deviation were used.Chi-square and Mann-Whitney U tests were used to compare independent groups for non-normally distributed data and ordinal and nominal data, and Student's t test was used to compare normally distributed data.Univariate logistic regression and multivariate logistic regression analysis were used to determine independent variables associated with mortality.Results were considered significant when the p value was below 0.05.

RESULTS
In the alpha-delta and Omicron periods, 51.7% (77) and 56.4% (92) of the patients were males, respectively (p> 0.05).The demographic features and comorbidities of the two study groups are shown in Table .At the time of hospitalization, 66.4% (99) of the patients were hospitalized in the ward and 33.6% (50) in the intensive care unit in 2021, whereas in 2022, 82.8% (135) were hospitalized in the ward and 17.2% (28) in the intensive care unit (p< 0.001).

Clinical Findings at Admission
Upon admission, 24.8% (37) of the patients in the alpha/delta group and 9.8% (16) of the patients in the Omicron group had high fever (p< 0.001).
There was no difference in the oxygenation status of the patients at admission; 73.2% (109) in the alphadelta group and 71.2% (116) in the Omicron group needed oxygen.

CT Findings
In the alpha/delta group, ground glass opacities were seen in 75.2% (112) of the patients, consolidation in 2.7% (4), and both findings together in 6.0% (9).In the Omicron group, ground glass was seen in 40.5% (66), consolidation in 5.5% (9), and both ground glass and consolidation together in 8.7% (13) (p< 0.001).No radiographic lung involvement was observed in 6.7% (10) of the patients in the alpha/ delta group and 1.8% (3) in the Omicron group.

Antibiotic Treatment
Antibiotic treatment was given to 45.6% (68) patients in the alpha/delta group and 67.5% (110) patients in the Omicron group (p< 0.001).
In the alpha/delta group, 85.2% (127) and in the Omicron group, 87.7% (143) of the patients were discharged after completion of treatment.Of the patients, 14.8% (22) and 12.3% (20) died due to different causes during treatment, respectively (p> 0.05).
Mean length of hospital stay was similar in both groups (8.8 and 9.3 days, respectively).

Table 2 .
Comparison of markers of infection and inflammation *p< 0.001.