key: cord-311948-3v311fnd authors: Ishiguro, Takashi; Takano, Kenji; Kagiyama, Naho; Hosoda, Chiaki; Kobayashi, Yoichi; Takaku, Yotaro; Takata, Naomi; Ueda, Miyuki; Morimoto, Yasuhiro; Kasuga, Keisuke; Ozawa, Ryota; Isono, Taisuke; Nishida, Takashi; Kawate, Eriko; Kobayashi, Yasuhito; Shimizu, Yoshihiko; Kurashima, Kazuyoshi; Yanagisawa, Tsutomu; Takayanagi, Noboru title: Clinical Course and Findings of 14 Patients with COVID-19 Compared with 5 Patients with Conventional Human Coronavirus Pneumonia date: 2020-08-27 journal: Respir Med Case Rep DOI: 10.1016/j.rmcr.2020.101207 sha: doc_id: 311948 cord_uid: 3v311fnd OBJECTIVE: To clarify what future problems must be resolved and how clinical findings of SARS-CoV-2 infection differ from those of cHCoV infection. METHODS: Patients and Methods Clinical characteristics of 14 patients with laboratory-confirmed Coronavirus disease 2019 (COVID-19) and 5 patients with cHCoV pneumonia admitted to our institution and treated up to March 8, 2020, were retrospectively analyzed. RESULTS: On admission, 10 patients had pneumonia, 5 of whom had pulmonary shadows detectable only via computed tomography (CT). During hospitalization, another patient with no pulmonary shadows on admission developed pneumonia. In total, 11 (78.6%) of the 14 patients developed pneumonia, indicating its high prevalence in COVID-19. During hospitalization, the patients’ symptoms spontaneously relapsed and resolved, and gastrointestinal symptoms were frequently found. C-reactive protein values showed correlation with the patients’ clinical courses. Ritonavir/lopinavir were administered to 5 patients whose respiratory conditions worsened during admission, all of whom improved. However, the pneumonia in the 6 other patients improved without antivirals. None of the 14 patients died, whereas 5 other patients with cHCoV pneumonia were in respiratory failure on admission, and one patient (20%) died. CONCLUSION: Both SARS-CoV-2 and cHCoV can cause severe pneumonia. Problems for future resolution include whether antiviral agents administered in cases of mild or moderate severity can reduce the number of severe cases, and whether antivirals administered in severe cases can reduce mortality. reviewed the X-rays and high-resolution computed tomography (CT) scans. These observers assessed the presence of 4 X-ray findings: consolidation, ground-glass opacities (GGOs), and nodules with their distribution (lung fields) and shape (patchy or broad), along with 16 CT findings: consolidation and GGOs with their distribution, halo sign, inverted halo sign, cavitation, centrilobular nodules, mass, tree-in-bud sign, intralobular reticulation, J o u r n a l P r e -p r o o f day 16, and he remains in stable condition. A 70-year-old man developed fatigue, red eyes, and fever of 38.5°C, followed by a cough that spontaneously improved. After positive PCR testing on day 10, he was transferred to our hospital. Admission chest X-ray was normal, but CT showed bilateral GGOs ( Figure 5 ). He remained stable during hospitalization and was discharged on day 38. Case 5: A 69-year-old woman developed appetite loss, nausea, fever of 37.5-37.8°C, cough, sputum, and diarrhea. PCR testing on day 5 was positive, and she was transferred to our hospital on day 7 ( Figure 6 ). Chest X-ray showed patchy consolidation in the left lower lung field. CT showed subpleural GGOs. Her dyspnea worsened, and blood gas analysis under ambient air on day 13 was pH 7.510, PaCO2 34.7 Torr, PaO2 58.8 Torr, and HCO3-27.1 mmol/L. Chest X-ray showed increased pulmonary shadows ( Figure 6 ). We started ritonavir/lopinavir and intravenous immunoglobulin (IVIg) therapy on day 15 along with high-flow nasal cannula (HFNC) therapy. The pulmonary shadows on chest X-ray continued to worsen until day 15 and then gradually improved. Her CRP peaked at 17.56 mg/dL on day Because she had no symptoms on admission, we followed her without antibiotics or antivirals. Her condition continued to be stable and she was discharged on day 28. A 54-year-old woman initially developed red eyes and then sore throat, dry cough, headache, and myalgia. Her PCR test on day 6 was positive, and she was transferred to our hospital on day 8. On admission, her chest X-ray and CT showed no abnormal shadows ( Figure 8 ), and we followed her without antibiotics and antivirals. Her appetite loss and cough continued after admission, and her CRP gradually increased. On day 17, although a chest X-ray appeared normal, CT showed subpleural consolidation and bilateral GGOs. We started ceftriaxone plus clarithromycin, and she became afebrile 3 days later. Her CRP gradually decreased and became negative, and she was discharged on day 38. A 64-year-old man developed fever, cough, and sputum, and after a positive PCR test, he was transferred to our hospital. On admission, he was afebrile, but his SpO2 under ambient air was 93% and blood gases under ambient air showed hypoxemia. Chest X-ray showed bilateral consolidation mainly distributed in the bilateral lower lung fields. CT showed bilateral GGOs ( Figure 9 ). After admission, his SpO2 decreased to 89%, and we started IVIg, ritonavir/lopinavir, and clarithromycin. A chest X-ray the next day showed improvement. His SpO2 also improved, and on day 21, he was in stable condition, and laboratory testing showed a CRP of 0.06 mg/dL. A 26-year-old man developed cough and sputum. PCR testing was positive on day 5, J o u r n a l P r e -p r o o f and he was transferred to our hospital on day 8. Chest X-ray showed left-sided patchy GGOs, and CT showed patchy bilateral GGOs ( Figure 10 ). We started ceftriaxone plus clarithromycin, and his condition gradually improved. On day 19, he was in stable condition, and laboratory testing showed a CRP of 0.06 mg/dL. He was discharged on day 20. A-56-year-old woman developed a fever and dyspnea on the day following. PCR testing was positive, and she was transferred to our hospital on day 3. Because her symptoms, laboratory data, and radiological findings were mild with patchy GGOs detectable only by CT ( Figure 11 ), we did not administer antibiotics or antivirals, and she remained in stable condition during hospitalization. Her CRP was 0.14 mg/dL, and she was discharged on day 16. A 65-year-old woman developed sore throat and was transferred to our hospital for follow-up because COVID-21 was strongly suspected. She developed diarrhea, and her CRP remained slightly increased after admission. On day 11, her SpO2 decreased, and blood gas analysis under ambient air was pH 7.420, PaCO2 37.2 Torr, PaO2 64.8 Torr, and HCO3-23.6 mmol/L. Chest X-ray showed left-sided consolidation. Chest CT showed consolidation and GGOs in the left lower lobe, and we started ritonavir/lopinavir, IVIg, and oxygen therapy. Her PCR test turned positive on day 12. Her symptoms and chest X-ray had improved on day 14. All pneumonia associated with SARS-CoV-2 was primary viral pneumonia. The SARS-CoV-2 pneumonia patients included 4 men and 7 women, whereas the cHCoV pneumonia patients comprised 5 men (Table 1) . Three patients with SARS-CoV-2 pneumonia had underlying respiratory diseases, one with COPD plus asthma and two with asthma. Seven patients had underlying non-respiratory diseases. Only one patient smoked. The patients with cHCoV pneumonia included 3 smokers, 2 with underlying respiratory diseases (asthma, asthma and COPD), and 4 with underlying non-respiratory diseases (diabetes mellitus, congestive heart failure, atrial fibrillation, hypertension, and chronic kidney disease). The 11 SARS-CoV-2 pneumonia patients were admitted from 3 to 8 days after initial symptoms onset, and 3 patients developed pneumonia >10 days from symptom onset. Five patients (45.5%) developed diarrhea, and 6 (54.5%) developed nausea and vomiting (Table 2) . Only one of the SARS-CoV-2 pneumonia patients was in severe condition on admission (Table 3) , but 5 patients worsened during hospitalization, and one patient (Case 5) required HFNC therapy. Overall, 3 patients were classified as having severe disease. Contrastingly, all of the cHCoV pneumonia patients were in respiratory failure on admission. Elevated CRP values were present in the cHCoV pneumonia patients, but procalcitonin values were low in all patients (Table 4) . Chest X-ray and CT findings obtained when pneumonia developed are listed in Tables 5 and 6 . Abnormal X-ray shadows were not detectable in 4 (36.3%) of the 11 SARS-CoV-2 pneumonia patients throughout their course, but abnormal shadows were found in the other patients on admission or during hospitalization. Chest X-ray findings worsened during days 6-16 from initial symptoms onset. Chest X-ray findings were worst on death in the non-surviving cHCoV pneumonia patient but worse at 3 weeks after onset in the other patients. Five of the 11 SARS-CoV-2 pneumonia patients received antivirals (ritonavir/lopinavir) (Table 7) Complications of SARS-CoV-2 pneumonia include acute respiratory distress syndrome, acute renal injury, and septic shock, but our patients did not experience them.(8) Seven of our 11 (63.6%) patients with SARS-CoV-2 pneumonia had gastrointestinal symptoms, which seems high when compared with the frequency reported elsewhere (8.0%). (9) One patient in our study initially showed negative PCR results that later became positive. Sensitivity of the PCR test for SARS-CoV-2 is reported to be 30-60%. 10 Abnormal shadows were not detected on initial chest X-ray in 5 of our 11 patients with SARS-CoV-2 pneumonia. X-ray shadows may not be detectable or are unilateral in the early phase8. X-ray findings worsened from 6 to 14 days after onset. In a previous study of CT scanning separated by a 4-day interval, maximum lung involvement peaked at approximately 10 days from initial symptoms onset,(11) as in our experience. Although the frequency of these findings differ when CT was performed, characteristic CT findings in SARS-CoV-2 pneumonia are reported to be bilateral GGOs. (12, 13, 14) Our SARS-CoV-2 pneumonia patients frequently showed bilateral and peripheral distribution of GGOs and relatively little consolidation compared with GGOs, as in previous reports. (13) Pulmonary shadows found on admission in Case 1 improved, but other shadows developed elsewhere, indicating a wandering course. Wandering shadows of short duration have been reported previously in patients with SARS-CoV-2 pneumonia. (11) We administered ritonavir/lopinavir to 5 of the 11 SARS-CoV-2 pneumonia patients, and chest X-ray findings gradually began to improve 3 days after the initiation of these agents in 3 patients. Although the efficacy of these antivirals remains unclear,(15) they appeared to us to be effective. However, 6 of the 11 patients with stable subjective feelings, respiratory conditions, and chest X-ray findings improved without these agents. Further studies need to clarify the characteristics of the patients who require such therapy. The cHCoV pneumonia patients had acute progressive interstitial lung diseases and received corticosteroids rather than antiviral therapy. The efficacy of corticosteroids for viral pneumonia is controversial. One (20%) of 5 patients with primary cHCoV pneumonia died. Mortality rates of pneumonia due to cHCoV have not been fully investigated. Among 10 Hong Kong patients with pneumonia due to HoV-HKU1, 2 (20.0%) died,(16) whereas none of 9 patients with pneumonia due to HCoV-NL63 died. (17) In Spain, none of 5 patients with coronavirus-229E or OC43 died.(5) The mortality rates of pneumonia due to SARS-CoV and MERS-CoV are reported to be 9.6% and 34.5%, respectively.(18) Mortality rates of pneumonia due to SARS-CoV-2 were initially reported to be 15% (19) and 11%,(8) whereas another study reported a rate of 4.3%. (20) None of our patients died, but we treated only 11 patients. Recently, the mortality rate of SARS-CoV-2 infections (COVID-19) was reported as 2% by WHO, but the rate may include patients with other than pneumonia. A previous study suggested that the true number of exposed cases in Wuhan may be vastly underestimated. This study has several limitations. We found a high prevalence of pneumonia in the SARS-CoV-2-infected patients. Abnormal CT shadows in some patients could be found only by CT, which led to a diagnosis of pneumonia. Accordingly, the high frequency of pneumonia may be due to the high use of CT. In conclusion, the patients with COVID-19 easily developed gastrointestinal symptoms and pneumonia, which could be detected only by CT. Three (27%) patients developed pneumonia 10 or more days after initial symptoms onset. All pneumonia associated with SARS-CoV-2 was primary viral pneumonia. We administered ritonavir/lopinavir to 5 patients with SARS-CoV-2 pneumonia when their condition worsened and hypoxemia ensued, with apparent good effect. We report this result to further the accumulation of treatment results following the use of antiviral agents. Future problems to resolve include whether antiviral J o u r n a l P r e -p r o o f agents administered in cases of mild or moderate severity can reduce the number of severe cases, and whether antivirals administered in severe cases can reduce mortality. Future studies should also clarify which patients will require CT as the rates of COVID-19 increase. saturation measured by pulse oximeter; FiO 2 = fraction of inspired oxygen; PaO 2 = partial pressure of oxygen in arterial blood, PaCO 2 = partial pressure of carbon dioxide in arterial blood. Etiology and factors contributing to severity and mortality of community-acquired pneumonia Viral pneumonia requiring differentiation from acute and progressive diffuse lung diseases Coronavirus Disease 2019 (COVID-19): a perspective from China Predictive factors for pneumonia development and progression to respiratory failure in MERS-CoV Incidence and characteristics of viral community-acquired pneumonia in adults Viral infection in patients with severe pneumonia requiring intensive care unit admission Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study Clinical characteristics of novel coronavirus cases in tertiary hospitals in Evaluating the accuracy of different respiratory specimens in the laboratory diagnosis and monitoring the viral shedding of 2019-nCoV infections Changes of CT findings in a 2019 novel coronavirus (2019-nCoV)) pneumonia patient Chest CT findings in 2019 novel coronavirus (2019-nCoV) infections from Wuhan, China: key points for the radiologist Time course of lung changes on chest CT during recovery from 2019 novel coronavirus (COVID-19) pneumonia. Radiology. 2020 Chest CT findings in coronavirus disease-19 (COVID-19): relationship to duration of infection Zhongnan Hospital of Wuhan University Novel Coronavirus Management and Research Team, Evidence-Based Medicine Chapter of China International Exchange and Promotive Association for Medical and Health Care (CPAM).. A rapid advice guideline for the diagnosis and treatment of Clinical and molecular epidemiological features of coronavirus HKU1-associated community-acquired pneumonia Epidemiology of human coronavirus NL63 infection among hospitalized patients with pneumonia in Taiwan Nowcasting and forecasting the potential domestic and international spread of the 2019-nCoV outbreak originating in Wuhan, China: a modelling study Clinical features of patients infected with 2019 novel coronavirus in Wuhan Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China 2019-novel coronavirus (2019-nCoV): estimating the case-fatality rate -a word of caution Clinical manifestations, laboratory findings, and treatment outcomes of SARS patients Analysis of factors associated with disease outcomes in hospitalized patients with 2019 novel coronavirus Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia We thank Akiko Osawa and Megumi Kimura, Department of Nursery of Saitama Cardiovascular and Respiratory Center for their cooperation for infection control. Severe SARS-CoV-2 = severe acute respiratory syndrome coronavirus-2; HCoV = human coronavirus; F, female; M, male; COPD = chronic obstructive pulmonary disease; ILD = interstitial lung disease; HT = hypertension; DM = diabetes mellitus; CKD = chronic kidney disease; CHF = congestive heart failure; Af = atrial fibrillation. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 Hospital day 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26