Clinical differentiation of severe acute respiratory syndrome coronavirus 2 pneumonia using the Japanese guidelines

The coronavirus disease 2019 (COVID-19) pandemic, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a sudden and substantial increase in hospitalizations for pneumonia worldwide.1 Although the reverse transcription PCR assay is a commonly used tool for the diagnosis of COVID-19, the sensitivity of PCR is not high using oropharyngeal and nasopharyngeal swab specimens and depends on the time of collection and the collector.2, 3 The Japanese Respiratory Society (JRS) scoring system, consisting of six parameters, is a useful tool for the early presumptive diagnosis of mild-to-moderate atypical pneumonia, mainly Mycoplasma pneumoniae pneumonia.4 These parameters were: (1) age < 60 years, (2) no or minor comorbid illness, (3) presence of stubborn cough, (4) absence of chest adventitious sounds, (5) no sputum or no identified aetiological agent by rapid diagnostic tests (Gram staining, urinary antigen tests and nasopharyngeal antigen test) and (6) a peripheral white blood cell (WBC) count of <10,000/μl. We evaluated whether the JRS scoring system could be adapted to the diagnosis of mild-to-moderate SARS-CoV-2 pneumonia.

This study was conducted at five institutions between February 2020 and June 2021, and assessed a total of 823 patients with SARS-CoV-2 pneumonia (335 had lineage B.1.1.7., also known as the Alpha variant; Table 1) and 202 patients with bacterial pneumonia. COVID-19 was diagnosed with positive PCR results from sputum or nasopharyngeal swab specimens according to the protocol recommended by the National Institute of Infectious Diseases, Japan.

TABLE 1. Underlying conditions and clinical findings in patients with SARS-CoV-2 pneumonia in the non-Alpha variant and Alpha variant groups at the first examination Variables Non-Alpha variant Alpha variant p-value No. of patients 488 335 Median age (IQR), years 65 (46–76) 64 (51–74) 0.387 No. of males/females 302/186 227/108 0.889 No. (%) of patients with comorbid illnesses Diabetes mellitus 100 (20.5) 65 (19.4) 0.723 Chronic lung disease 55 (11.3) 43 (12.8) 0.512 Chronic heart disease 38 (7.8) 23 (6.9) 0.685 Cerebrovascular disease 32 (6.6) 20 (6.0) 0.772 Chronic renal disease 31 (6.4) 24 (7.2) 0.671 Neoplastic disease 30 (6.1) 14 (4.2) 0.269 Chronic liver disease 15 (3.1) 9 (2.7) 0.834 Autoimmune disease 15 (3.1) 7 (2.1) 0.510 No. (%) of patients with the following clinical signs and symptoms History of fever (≥37.0°C) 413 (84.6) 295 (88.1) 0.183 Cough 249 (51.0) 209 (62.4) 0.001 Fatigue 167 (35.9) 110 (32.8) 0.707 Shortness of breath 132 (27.0) 109 (32.5) 0.101 Sore throat 97 (19.9) 68 (20.3) 0.929 Loss of taste 65 (13.3) 55 (16.4) 0.228 Anosmia 54 (11.1) 49 (14.6) 0.134 Headache 54 (11.1) 33 (9.9) 0.644 Diarrhoea 51 (10.5) 27 (8.1) 0.276 Sputum production 49 (10.0) 54 (16.1) 0.013 Runny nose 36 (7.4) 24 (7.2) >0.999 Joint pain 28 (5.7) 14 (4.2) 0.338 Chest pain 18 (3.7) 5 (1.5) 0.083 Muscle ache 17 (3.5) 4 (1.2) 0.044 Nausea or vomiting 16 (3.3) 14 (4.2) 0.571 Abdominal pain 6 (1.2) 1 (0.3) 0.250 Laboratory findings, median (IQR) White blood cell count, /μl 5100 (4295–6400) 5400 (4400–7350) 0.242 No. (%) of patients with each pneumonia severity scorea 0 197 (40.4) 57 (17.0) <0.001 1 128 (26.2) 134 (40.0) <0.001 2 110 (22.5) 88 (26.3) 0.245 3 52 (10.7) 56 (16.7) 0.015 Positive cases/no. (%) for the presumptive diagnosis of atypical pneumonia in different age groups 20–29 years 41/41 (100) 29/29 (100) >0.999 30–39 years 54/54 (100) 15/15 (100) >0.999 40–49 years 41/42 (97.6) 37/37 (100) >0.999 50–59 years 53/63 (84.1) 52/56 (92.9) 0.164 60–69 years 46/96 (47.9) 30/71 (42.3) 0.531 70–79 years 29/112 (25.9) 23/90 (25.6) >0.999 ≥80 years 23/80 (28.8) 7/37 (18.9) 0.363 Note: Continuous values are presented as medians and IQRs and categorical/binary values as counts and percentages. Abbreviations: IQR, interquartile range; JRS, Japanese Respiratory Society; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2. a The severity of pneumonia was evaluated using predictive rules via the A-DROP system (a 5-point scoring system) proposed by the JRS guidelines: age over 70 years in men and over 75 years in women, dehydration, respiratory failure, orientation disturbance and low blood pressure. An A-DROP score of 0–3 points was classified as mild-to-moderate pneumonia.

Matching rates to the six parameters of the JRS scoring system were identical in both non-Alpha variant and Alpha variant groups, and high matching rates were observed in the following parameters: absence of chest adventitious sounds, 71.6% (non-Alpha variant group, 73.2%; Alpha variant group, 69.3%); no sputum or no identified aetiological agent by rapid diagnostic tests, 87.1% (90.0% and 83.0%); and a peripheral WBC count of <10,000/μl, 97.6% (98.2% and 96.7%). The matching rates of the other three parameters were as follows: age < 60 years, 42.2% (43.0% and 40.9%); no or minor comorbid illness, 57.8% (57.8% and 57.9%); and presence of stubborn cough, 10.4% (9.4% and 11.9%). The sensitivity and specificity for the diagnosis of atypical pneumonia in patients with SARS-CoV-2 pneumonia based on four or more parameters were 58.3% (58.8% in the non-Alpha variant group and 57.6% in the Alpha variant group, respectively) and 92.2%, respectively.

When the diagnostic sensitivity was analysed for different ages stratified into the 10-year groups, the diagnostic sensitivity of patients in both the non-Alpha variant and Alpha variant groups was highest in the 20–39-year age group and decreased in order from the youngest to the oldest age group (Table 1). There was a clear difference between elderly (aged ≥60 years) and non-elderly (aged <60 years) patients with SARS-CoV-2 pneumonia. The diagnostic sensitivity for SARS-CoV-2 pneumonia was 95.5% for non-elderly patients and 32.5% for elderly patients.

Our results demonstrated that the JRS scoring system is a useful tool for distinguishing between SARS-CoV-2 pneumonia and bacterial pneumonia in patients aged <60 years, but not in patients aged ≥60 years.

AUTHOR CONTRIBUTION

Conceptualization: Naoyuki Miyashita (lead), Yasushi Nakamori (equal), Makoto Ogata (supporting), Naoki Fukuda (supporting), Akihisa Yamura (supporting), Yoshihisa Ishiura (supporting), Shosaku Nomura (supporting). Data curation: Naoyuki Miyashita (lead), Yasushi Nakamori (lead), Makoto Ogata (supporting), Naoki Fukuda (supporting), Akihisa Yamura (supporting), Yoshihisa Ishiura (supporting), Shosaku Nomura (supporting). Formal analysis: Makoto Ogata (lead), Naoki Fukuda (equal). Funding acquisition: Yoshihisa Ishiura (lead), Shosaku Nomura (equal). Investigation: Naoyuki Miyashita (lead), Yasushi Nakamori (equal), Makoto Ogata (supporting), Naoki Fukuda (supporting), Akihisa Yamura (supporting), Yoshihisa Ishiura (supporting), Shosaku Nomura (supporting). Methodology: Makoto Ogata (lead), Naoki Fukuda (equal). Project administration: Naoyuki Miyashita (lead), Yasushi Nakamori (equal), Yoshihisa Ishiura (supporting), Shosaku Nomura (supporting). Resources: Naoyuki Miyashita (lead), Yasushi Nakamori (equal), Yoshihisa Ishiura (supporting), Shosaku Nomura (supporting). Software: Naoyuki Miyashita (lead), Yasushi Nakamori (equal), Yoshihisa Ishiura (supporting), Shosaku Nomura (supporting). Supervision: Naoyuki Miyashita (lead), Yasushi Nakamori (equal), Yoshihisa Ishiura (supporting), Shosaku Nomura (supporting). Validation: Yoshihisa Ishiura (lead), Shosaku Nomura (equal). Visualization: Makoto Ogata (lead), Naoki Fukuda (equal). Writing – original draft: Naoyuki Miyashita (lead), Yasushi Nakamori (equal). Writing – review & editing: Naoyuki Miyashita (lead), Yasushi Nakamori (equal), Makoto Ogata (supporting), Naoki Fukuda (supporting), Akihisa Yamura (supporting), Yoshihisa Ishiura (supporting), Shosaku Nomura (supporting).

HUMAN ETHICS APPROVAL STATEMENT

The study protocol was approved by the Ethics Committee of Kansai Medical University and all participating facilities (approval number 2020319). Informed consent was obtained from all individual participants in the study.

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