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Journal of Infection xxx (xxxx) xxx

Contents lists available at ScienceDirect

Journal of Infection
journal homepage: www.elsevier.com/locate/jinf

Clinical characteristics of severe acute respiratory syndrome


coronavirus 2 reactivation
Guangming Ye a,1, Zhenyu Pan b,1, Yunbao Pan a,1, Qiaoling Deng a, Liangjun Chen a, Jin Li a,
Yirong Li a,∗, Xinghuan Wang c,d,∗∗
a
Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, Hubei, China
b
Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, Hubei, China
c
Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
d
Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China

a r t i c l e i n f o s u m m a r y

Article history: Objectives: Previous studies on the pneumonia outbreak caused by the 2019 novel coronavirus disease
Accepted 5 March 2020 (COVID-19) were based on information from the general population. However, limited data was avail-
Available online xxx
able for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reactivation. This study aimed to
Keywords: evaluate the clinical characteristics of the SARS-CoV-2 reactivation.
SARS-CoV-2 Methods: Clinical records, laboratory results, and chest CT scans were retrospectively reviewed for 55 pa-
COVID-19 tients with laboratory-confirmed COVID-19 pneumonia (i.e., with throat swab samples that were positive
Laboratory medicine for SARS-CoV-2) who were admitted to Zhongnan Hospital of Wuhan University, Wuhan, China, from Jan.
CT scan 8 to Feb. 10, 2020.
Results: All 55 patients had a history of epidemiological exposure to COVID-19, and 5 (9%) patients who
discharged from hospital presented with SARS-CoV-2 reactivation. Among the 5 reactivated patients, other
symptoms were also observed, including fever, cough, sore throat, and fatigue. One of the 5 patients had
progressive lymphopenia (from 1.3 to 0.56 × 109 cells per L) and progressive neutrophilia (from 4.5 to
18.28 × 109 cells per L). All 5 reactivated patients presented normal aminotransferase levels. Throat swab
samples from the 5 reactivated patients were tested for SARS-CoV-2, indicating all positive for the virus.
Conclusions: Findings from this small group of cases suggested that there was currently evidence for
reactivation of SARS-CoV-2 and there might be no specific clinical characteristics to distinguish them.
© 2020 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Introduction induce symptoms including fever, dry cough, dyspnea, fatigue and
lymphopenia in patients, and might result in severe acute respira-
A novel human coronavirus which is a new strain of RNA tory syndrome (SARS) and even death in severe cases.1-3
viruses was recognized in Wuhan, China, in Dec. 2019. The novel SARS-CoV-2 belongs to the beta-coronavirus 2b lineage in
coronavirus is now officially named SARS-CoV-2 (Severe Acute Res- the phylogenetic tree and shares ∼80% identity sequencing with
piratory Syndrome Coronavirus-2) by International Committee on the Bat SARS-like coronavirus and the original SARS epidemic
Taxonomy of Viruses (ICTV). The pneumonia caused by SARS-CoV- virus.4 , 5 Currently, it remains to be determined the origins and
2 has been recently identified as COVID-19 (coronavirus disease possible intermediate animal vectors of SARS-CoV-2, as well as the
2019). COVID-19 spread quickly across Hubei Province and other mechanism that this virus spread among humans. Despite many
regions of China,1 , 2 also the global alert for COVID-19 has been is- reports have characterized the clinical, epidemiological, laboratory,
sued by the World Health Organization (WHO).1 , 2 COVID-19 could and radiological features, as well as treatment and clinical out-
comes of patients with COVID-19 pneumonia, the information of
the SARS-CoV-2 reactivation remains not reported. The curative

Corresponding author at: Department of Laboratory Medicine, Zhongnan Hospi- and eradicative therapy for COVID-19 is not currently available.
tal of Wuhan University, Wuhan, Hubei, China. Urgent questions that need to be addressed promptly include
∗∗
Corresponding author at: Center for Evidence-Based and Translational Medicine, whether patients with COVID-19 pneumonia will reactivate, and
Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
whether risk factors predict SARS-CoV-2 reactivation in patients.
E-mail addresses: [email protected] (Y. Li), [email protected] (X.
Wang). To prevent and control COVID-19 reactivation, we retrospectively
1
Thease authors contributed equally. collected and analyzed detailed clinical data from SARS-CoV-2

https://doi.org/10.1016/j.jinf.2020.03.001
0163-4453/© 2020 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Please cite this article as: G. Ye, Z. Pan and Y. Pan et al., Clinical characteristics of severe acute respiratory syndrome coronavirus 2
reactivation, Journal of Infection, https://doi.org/10.1016/j.jinf.2020.03.001
JID: YJINF
ARTICLE IN PRESS [m5G;March 20, 2020;10:14]

2 G. Ye, Z. Pan and Y. Pan et al. / Journal of Infection xxx (xxxx) xxx

reactivated patients. In the study, we presented clinical features of Discussion


SARS-CoV-2 reactivated patients and discussed the potential risk
factors of SARS-CoV-2 reactivation. We confirmed that in a significantly proportion of COVID-19 pa-
tients, SARS-CoV-2 reactivation developed after discharging from
Material and methods hospital (9%). We reported clinical data from 5 patients with
SARS-CoV-2 reactivation. The clinical characteristics of these pa-
Study design and patients tients with SARS-CoV-2 reactivation were similar to those of non-
reactivated patients with COVID-19 infection. None of the 5 pa-
We retrospectively recruited 55 patients who were diagnosed tients developed severe pneumonia or died, as of Feb. 24, 2020.
as COVID-19 pneumonia at the Zhongnan Hospital of Wuhan Notably, based on our findings in these 5 patients, there is cur-
University from Jan. 8, 2020 to Feb. 10, 2020. The patients com- rently evidence to suggest that a proportion of recovered COVID-19
prised 19 males and 36 females with a median age of 37 (range patients could reactivate.
22–67 years). Diagnosis of COVID-19 pneumonia was based on The reactivated patients included 1 asymptomatic patient and 4
the New Coronavirus Pneumonia Prevention and Control Program. symptomatic patients, which suggests the reactivation potential of
All patients with COVID-19 pneumonia were tested positively for asymptomatic or minimally symptomatic patients. The time from
SARS-CoV-2 by use of quantitative RT-PCR on samples from the SARS-CoV-2 negative to positive ranged from 4 to 17 days, suggest-
respiratory tract. This study was reviewed and approved by the ing that recovered patients still may be virus carriers and require
Ethical Committee of Zhongnan Hospital of Wuhan University. additional round of viral detection and isolation.
Written informed consent was waived by the Ethics Commission We need better data to determine risk factors and mechanisms
for emerging infectious diseases. that cause SARS-CoV-2 reactivation. The timing of onset of SARS-
CoV-2 reactivation can be variable depending upon the host fac-
tors, underlying disease and the type of immunosuppressive thera-
Data collection
pies. In our study, the recovered patients had positive RT-PCR test
results 4–17 days later. The key risk factors for reactivation would
We reviewed clinical records, laboratory findings, and chest CT
include 3 categories: (1) host status, (2) virologic factors and (3)
scans for all patients. Two study investigators independently re-
type and degree of immunosuppression. Host factors may include
viewed the data. Throat swab samples were collected and tested
sex, older age, type of disease needing immunosuppression. Al-
for SARS-CoV-2, following WHO guidelines for qRT-PCR.6 , 7
though we could not identify risk factors for these host factors
in the current study, the potential requires further large cohort
Statistical analysis confirmation. The virologic factors associated with increased risk
of reactivation include high baseline SARS-CoV-2 load and vari-
Statistical analysis was done with SPSS, version 22.0. Continu- able genotype. SARS-CoV-2 viral load would also linked to treat-
ous variables were directly expressed as a range. Categorical vari- ment response, disease severity and progression.8 The association
ables were expressed as number (%). of SARS-CoV-2 genotypes and viral load with SARS-CoV-2 reac-
tivation will be an important question to address. In our study,
Results all the patients received antiviral therapy (Oseltamivir or Arbidol).
These cases suggest that SARS-CoV-2 reactivation may occur what-
At presentation, all 55 patients had a history of epidemiolog- ever the antiviral therapy used. These host and virologic factors
ical exposure to COVID-19, and 5 (9%) patients who discharged are important considerations that may further increase the likeli-
from hospital presented SARS-CoV-2 reactivation. The age range hood of SARS-CoV-2 reactivation. Therefore, the assessment of host
of the SARS-CoV-2 reactivated patients was 27–42 years. None of as well as virologic risk factors should be important caveats to
the reactivated patients had underlying diseases such as diabetes, help decide whether to initiate prophylactic therapy and immuno-
chronic hypertension, or cardiovascular disease. One patient, how- suppression. Immunosuppressive therapies are the commonly used
ever, had history of tuberculosis in the mediastinal lymph node in causative agents. These agents have a general mechanism that in-
2009. Additionally, all the reactivated patients excluded influenza hibits many immune functions. For example, steroid inhibits cell-
virus and H7 avian influenza virus infection upon admission to mediated immunity by suppressing interleukins production which
hospital. is important for T and B cell proliferation.9 It is thus not surpris-
Four of the 5 patients presented with a fever without chills, one ing that these general immunosuppressive effects result in broad
had a high fever (39.3 °C). Patients’ body temperatures fluctuated immune dysfunctions and potential SARS-CoV-2 reactivation.
within a range from 36.2 to 39.3 °C. One patient showed normal SARS-CoV-2 reactivation will be a vexing and persistent prob-
body temperature. Other symptoms of an upper respiratory tract lem. Considering numerous patients infected or previously exposed
infection were also observed: one patient had cough, one had sore to the virus, such a problem poses a major public health burden in
throat, all patients reported fatigue (Table 1). Additionally, one pa- terms of global morbidity and possibly mortality. Currently, we did
tient showed constipation. However, none of the 5 patients devel- not find reliable markers in predicting the risk of SARS-CoV-2 re-
oped severe pneumonia, requiring mechanical ventilation, or died activation, nor there are any validated tests to determine whether
of COVID-19 pneumonia, as of Feb. 24, 2020. a particular drug or therapy is associated with SARS-CoV-2 reacti-
All the 5 reactivated patients were given empirical antibiotic vation. The latter point was often determined by our empirical ex-
treatment and were administered antiviral therapy (Table 1). Data perience. Although decades of the experiences helped us to iden-
from laboratory tests showed that one patient had progressive tify important drugs and to manage these situations appropriately,
lymphopenia (from 1.3 to 0.56 × 109 cells per L) and progres- we could not accurately evaluate the risk of the drugs prior to its
sive elevated neutrophilia (from 4.5 to 18.28 × 109 cells per L). clinical application.
Two patients had elevated concentrations of C-reactive protein Considering the significance of this ongoing global public health
(> 18 mg/L). All the 5 patients had normal alanine aminotrans- emergency, although our conclusions are limited by the small sam-
ferase (ALT) and aspartate aminotransferase (AST). All 5 patients ple size, we believe that the findings are important to understand
had chest CT scan. All patients showed typical findings of chest CT the clinical characteristics and SARS-CoV-2 reactivation potential in
images-multiple patchy ground-glass shadows in lungs (Fig. 1). COVID-19 patients.

Please cite this article as: G. Ye, Z. Pan and Y. Pan et al., Clinical characteristics of severe acute respiratory syndrome coronavirus 2
reactivation, Journal of Infection, https://doi.org/10.1016/j.jinf.2020.03.001
JID: YJINF
ARTICLE IN PRESS [m5G;March 20, 2020;10:14]

G. Ye, Z. Pan and Y. Pan et al. / Journal of Infection xxx (xxxx) xxx 3

Table 1
Clinical and laboratory characteristics.

Clinical characteristics Patient 1 Patient 2 Patient 3 Patient 4 Patient 5

Date of admission Jan. 3 Jan. 13 Jan. 27 Jan. 22 Jan. 20


Sex Male Male Female Female Female
Age (years) 30 42 32 27 31
Epidemiological history Yes Yes Yes Yes Yes
SARS-CoV-2 negative to positive (days) 4 8 17 15 9
Complications None None None None None
Signs and symptoms
Fever on admission Yes Yes Yes No Yes
Cough No Yes No No No
Dyspnoea No No No No No
Sore throat No No Yes No No
Fatigue Yes Yes Yes Yes Yes
Laboratory characteristics
White blood cell count (× 109 cells per L) 5.9 7.1 4.4 6.5 4.5
Neutrophil count (× 109 cells per L) 3.5 4.5 1.8 4.1 2.6
Lymphocyte count (× 109 cells per L) 1.7 1.3 1.7 1.7 1.4
Monocyte count (× 109 cells per L) 0.63 1.24 0.75 0.58 0.4
Eosinophil count (× 109 cells per L) 0.13 0.05 0.02 0.09 0
Basophile count (× 109 cells per L) 0.02 0.04 0.03 0.02 0.02
C-reactive protein (mg/L) 18.7 23.7 NA <0.50 NA
Elevated ALT (>45 U/L) or AST (>35 U/L) No No No No No
ALT (U/L) 40 16 11 9 10
AST(U/L) 32 19 20 13 22
Confirmatory test (SARS-CoV-2 PCR) Yes Yes Yes Yes Yes
CT evidence of pneumonia
Typical signs of viral infection Yes Yes Yes Yes Yes
Treatment
Antiviral therapy Yes Yes Yes Yes Yes
Antibiotic therapy Yes Yes Yes Yes Yes
Use of corticosteroid Yes Yes No No Yes

NA=not applicable. ALT=alanine transaminase. AST=aspartate transaminase.

Fig. 1. Chest CT scans of the 5 patients.

Funding/support Statement of patient consent

This study was supported in part by grants from Medical Sci- All patients provided written informed consent. All study pro-
ence Advancement Program (Clinical Medicine) of Wuhan Univer- cedures were performed in accordance with the ethical standards
sity (TFLC2018002). of the Institutional Ethics Review Committee.

Role of the funders/sponsors


Declaration of Competing Interest
The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript. None.

Please cite this article as: G. Ye, Z. Pan and Y. Pan et al., Clinical characteristics of severe acute respiratory syndrome coronavirus 2
reactivation, Journal of Infection, https://doi.org/10.1016/j.jinf.2020.03.001
JID: YJINF
ARTICLE IN PRESS [m5G;March 20, 2020;10:14]

4 G. Ye, Z. Pan and Y. Pan et al. / Journal of Infection xxx (xxxx) xxx

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(2019-nCoV) by real-time RT-PCR. Euro Surveil Bull Eur Maladies Transm = Eur
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monia in China, 2019. N Engl J Med 2020;382(8):727–33. 7. WHO. Laboratory testing for 2019 novel coronavirus (2019-nCoV) in sus-
2. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 pected human cases. Interim guidance. https://wwwwhoint/publications-detail/
novel coronavirus in Wuhan, China. Lancet 2020;395(10223):497–506. laboratory- testing- for- 2019- novel- coronavirus- in- suspected- human- cases-
3. Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 20200117 (Accessed 4 February 2020). 2020.
cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. 8. Zou L, Ruan F, Huang M, et al. SARS-CoV-2 viral load in upper respiratory speci-
Lancet 2020;395(10223):507–13. mens of infected patients. N Engl J Med 2020.
4. Lu R, Zhao X, Li J, et al. Genomic characterisation and epidemiology of 2019 9. Lowenberg M, Verhaar AP, van den Brink GR, Hommes DW. Glucocorticoid sig-
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5. Zhou P, Yang XL, Wang XG, et al. A pneumonia outbreak associated with a new
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Please cite this article as: G. Ye, Z. Pan and Y. Pan et al., Clinical characteristics of severe acute respiratory syndrome coronavirus 2
reactivation, Journal of Infection, https://doi.org/10.1016/j.jinf.2020.03.001
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up to your Harding reputations, as far as I can see—Babbie the
Butterfly, Madeline the Bohemian, Betty a Benevolent Adventurer.”
“And the moral of that is,” put in Babbie quickly, “what you are at
home, that you will be abroad.”
“Unless you drop all your individuality and become a Tourist, with
a capital T,” added Roberta.
“Or change your spots and turn from a man-hater into a fiancée,”
suggested Bob.
“That’s not changing your spots,” declared Mary wisely. “It’s just
making up your mind, isn’t it, Babe?”
“How in the world did you know that, Mary Brooks?” demanded
Babe in such awe-struck tones that her friends shrieked with
laughter, and Dr. Hinsdale came out from his study to ask about the
joke.
The girls had intended to leave early the next afternoon, but
when Georgia Ames appeared, hovering in the Belden House hall,
before dinner was over, and announced that she was giving a
gargoyle party for them that evening, why of course there was
nothing to do but insist that the gargoyle party should be a “small
and early,” and rush to the station to countermand orders for
carriages, and find out about making connections with sleepers at
the junction.
“For we’re not so young as we were once,” said Roberta, hugging
Betty. “We don’t have to be met at Harding by the registrar, and we
may travel at night if we like, as long as two go one way and three
the other.”
The gargoyle party was as mysterious as Mary Brooks’s historic
hair-raising had been. Mary almost wept when Georgia asked her,
and she was obliged to decline because of a previous dinner
engagement—not to mention the dignity of her position. She solaced
herself by making an elaborate costume for Eugenia Ford, a pretty
little freshman who, when Georgia asked her to the party, thanked
her gravely and explained that if gargoyles had anything to do with
gargles she wouldn’t come, because she never could manage to do
it—her throat must be queer. Most of the other guests professed
hapless ignorance of what a gargoyle might be, but Georgia referred
them easily to Bob’s cherished imp, which she had borrowed for the
occasion, together with some post-cards of other grotesque figures.
“Just run in any time this afternoon, and look them over,” she
urged, “and come in costume to-night, if you can. If not, it doesn’t
matter. Mrs. Hinsdale is going to offer a prize for the best one,
though.”
So the chosen few cast English Lit. papers and a possible—nay,
probable—written review in Psych. to the winds, journeyed down-
town to buy masks and draperies, and preëmpted all the desirable
perches in Georgia’s room, marking them with big “Engaged” signs,
which came loose when the wind blew in next time the door was
opened, and gave the room a disconcerting air of having been
snowed under, when Georgia got back to it just before tea.
“But we had to do it,” Eugenia Ford explained, as she helped
Georgia put things to rights for the evening, “because the whole
point of a gargoyle is that it stands somewhere. Lucile Merrifield said
so. And the way you put on your costume makes a difference about
where you are to sit. No, the other way around.”
“Conversely, you mean, my child,” amended Georgia, pleasantly,
putting Mary’s five-pound box of Huyler’s on the chiffonier.
“But that’s got to be cleared off,” objected Eugenia. “That’s Miss
Bob Parker’s place. We all wanted it, but she got it tagged first.
Belden House Annie promised her a step-ladder to climb up by, but
she said a chair would do.”
Georgia sighed and dumped the ornaments of the dresser top,
cover and all, into her upper drawer. “A gargoyle party is a thing that
grows on your hands,” she said sadly. “Let’s go and eat. If there’s
anything else to clear off, we’ll do it later.”
When the gargoyle party opened it was certain that, whether or
not it had grown on Georgia’s hands, it was every bit her room could
hold. Betty and Babbie, who had been too busy enjoying Harding to
bother about costumes, were the only guests who were not wearing
some sort of fantastic disguise. Bob had bought a box of paints and
made her own mask, modeling it and her drapery of brown denim
after the imp that the “B. A.’s Abroad” had given her. Eugenia Ford
was a gryphon,—or at least Mary Brooks said so,—with the most
beautiful pair of wings that had ever appeared at a Harding party.
Polly Eastman was the elephant that sits on the tower of Notre
Dame. Georgia had planned to be the other half of the elephant, in
accordance with Harding usage in the matter of elephants and other
four-footed creatures. But at the last minute she discovered that the
Notre Dame elephant wasn’t four-footed.
“Gargoyles never are,” said Lucile wisely—it was she who had
pointed out the mistake. “But never mind, Georgia. You can be one
of my two heads. I was going to be a two-headed beast if I could.
Only Vesta White changed her mind afterward and wanted to be an
eagle.”
There were other gargoyles, as impossible to classify as the real
ones, and they squatted in rows on Georgia’s bed and her big
window-box, popped up mysteriously from behind her desk, or
lounged in strange attitudes in her easy chairs. Bob Parker actually
did get up on the chiffonier, off the edge of which she hung in such
realistic gargoyle style that the judges, Babbie and Betty,
unhesitatingly awarded her the prize.
“Not a bit fair,” objected young Eugenia, flapping her beautiful
gryphon’s wings disconsolately. “We should all have looked a lot
grander on chiffoniers.”
“But you weren’t all clever enough to grab the one there was,” put
in Georgia pacifically.
“Having a gargoyle of your own makes you notice the attitudes
more,” declared Bob proudly. “Never mind, Miss Ford. The prize is
candy, and we’ll pass it around while we wait for Georgia’s
refreshments to materialize.”
“You haven’t forgotten your Harding manners, Bob,” said Betty
severely.
“No, you don’t any of you act a bit like alums,” declared a tall
junior, taking off her mask to breathe.
“You lovely thing!” cried Bob, scrambling down from the chiffonier
to give the appreciative junior first choice of the prize candy.
And then the gargoyles had a dance and a parade, and delicious
“eats,” on which Georgia had rashly spent all that was left of her
month’s allowance. And after that, when the five 19—’s were having
the very best time of all, just sitting around talking and realizing what
a dear, dear place Harding was, it was time to pull Bob out of her
beloved costume and rush for trains.
Later in the evening the five classmates sat in the station at the
junction, Babe and Betty waiting to go west, Bob, Babbie and
Roberta bound for New York.
Babbie looked critically at Babe and Betty. “I shall tell mother that
it worked,” she said. “You went to bed at three, and got up at seven
this morning to go canoeing. You’ve eaten four meals to-day and as
many ices. You’ve been horseback and trolley-riding. You’ve made
dozens of calls. It’s now ten p. m., and you’re fresh as the daisies in
Oban. How’s that for the Harding cure?”
“Don’t you feel exactly as if it was some June?” demanded Bob.
“Not last June, but a regular June, you know, and we were all just
going home for the summer.”
“Exactly,” agreed everybody, and then a sleepy silence settled
upon the group.
“What were those things we had in the ‘Rise of the Drama’
course?” asked Betty Wales suddenly. “Not intervals, but something
like that.”
“You mean Interludes, don’t you?” asked Roberta. “They came
right after the Moralities.”
Betty nodded. “That’s what this summer has been—an Interlude.”
“With Babe for the fascinating heroine,” put in Babbie.
“Yes,” agreed Betty hastily. “And when I get home to-morrow the
real business of life is going to begin.”
“Act I, Scene I, Life of Betty Wales, B. A.,” said Roberta. “Doesn’t
that sound serious? But it won’t be. You’ll play tennis with Nan, and
go to dances with your brother and other people’s brothers, and
amuse that darling little sister of yours, and be nice to everybody
who needs it, just as you always have, except that you won’t be
home on a snippy little vacation.”
“Oh, I hope so,” said Betty, laughing at Roberta’s choice of
details. “But then I want to do something that counts, too.”
“You’re always doing things that count,” Babe declared, giving
her a loving little squeeze.
“That was just fun,” Betty reminded her for the hundredth time at
least.
“But if fun counts, it counts,” declared Roberta. “Just ask
Madeline Ayres if it doesn’t. If you can make fun out of hard work,
then, according to Madeline, you really know how to live.”
“But we’re not the working contingent,” objected Babbie. “K. and
Rachel and Helen are the workers.”
“They are!” breathed Bob indignantly. “Just try taking care of
certain fresh-air youngsters for two weeks.”
“Or typewriting most particular briefs for your most particular
father, who always wants things in a terrific hurry,” added Roberta.
Betty considered. “I’ve helped in little ways of course, but I never
did any one big thing. I’m going to now, though.”
“Here’s to a winter of hard work!” cried Babe. “I shall have to sew,
and I hate it.”
“But you must make fun out of it all the same,” Betty told her, with
the flash of gay courage in her eyes that had won over Mr. Morton. “I
shall, no matter what happens, and whatever we do, think of the fun
we’ll have talking it over when we all get together again. Oh, is that
our train, Babe?” And with her curls flying and her eyes dancing with
eagerness Betty Wales turned merrily from her happy summer’s
Interlude to “the real business of life.”
THE END
Transcriber’s Notes:
Minor corrections (addition or deletion) of double quote marks have been made on pages
188, 196, 230 and 317, to conform to accepted usage.
Splended, on page 153, has been changed to splendid.
Cooperation, on page 218, has been changed to coöperation, to conform to other
occurrences in this e-book.
On page 270, Louxembourg has been changed to Luxembourg.
All other hyphenation and variant and archaic spellings have been retained as typeset.
Illustrations have been moved to avoid interrupting paragraphs.
*** END OF THE PROJECT GUTENBERG EBOOK BETTY WALES,
B. A.: A STORY FOR GIRLS ***

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