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\title{A Confusing case, leptospirosis during COVID-19 pandemic: A case report}



\author[1]{sara mohammadnia}%
\author[1]{Arefeh Babazadeh}%
\author[1]{Soheil Ebrahimpour}%
\author[2]{Zeinab Mohseni Afshar}%
\affil[1]{Babol University of Medical Science}%
\affil[2]{Kermanshah University of Medical Sciences}%


\vspace{-1em}



  
  \date{June 06, 2024}


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\textbf{Introduction}

since march 11, 2020 world health organization (WHO) reported a
worldwide pandemic occurring by Severe Acute Respiratory Syndrome
Coronavirus-2 (SARS-CoV-2) (1, 2). COVID-19 infections symptoms includes
a variation of fever, cough, dyspnea, headache, myalgia and abdominal
pain (3).Since then, there were reports of coinfections or misdiagnoses
of covid-19 with other infections which have the same clinical or
paraclinical symptoms (4, 5). Leptospirosis is a common infection in
Southeast Asia and is one of those infections which can have the same
symptoms as COVID-19 including cough and myalgia (6). In this study we
are reporting a case that was not surely a severe pulmonary
leptospirosis or covid-19.

\textbf{Case-report}

On August 22,2022, a 27-year-old man presented to emergency room with
severe abdominal pain, dyspnea, bloating and dyspepsia. The patient had
a history of going to paddy two days ago, and two days before
hospitalization he had experienced severe myalgia, headache and fever
and had taken Diclofenac suppositories each 8 hours to control his
fever. The day before hospitalization he had nausea and vomiting two
times so he got serum injections.

On admission, the patient's body Temperature was 38.2\selectlanguage{ngerman}°, with an oxygen
saturation at ambient air of 97\%, the Respiratory rate was 25
cycles/min, the pulse rate was 130 beats/minute and his Blood Pressure
was 120/80. The patient was not dyspneic while talking. In clinical
examination no unusual pulmonary sounds was heard, no rash, jaundice,
conjunctival pallor and conjunctival suffusion were seen. He could
answer questions consciously and was mentally normal.

Laboratory tests did not show any Leukocytosis at first (white blood
cell: 10000 lymphocytes/mm\textsuperscript{3}), but Thrombocytopenia was
seen at 71000 thrombocytes/mm\textsuperscript{3}, and a normal serum
creatinine level of 0.8 mg/dl (normal value,0.7-1.4 mg/dl). The
patient's Blood Urea Nitrogen level was 20 mmol/L, and Aspartate
aminotransferase and Alanine transferase were at 69 and 244 U/L. His
C-reactive protein was at 290 mg/L, and Troponin 1 was negative but the
B-type natriuretic peptide was high at 9641 pg/ml (Table 1).

On the second day of admission, SARS-CoV-2 reverse
transcription-polymerase chain reaction (RT-PCR) test was done on
nasopharyngeal sample and was negative but the D-dimer was high at
1585.7 ng/ml (normal value, 0-800 ng/ml). High-resolution computed
tomography (HRCT) of the chest was performed on admission and no unusual
pulmonary symptom was seen that could confirm the COVID-19 diagnosis.
(Figure 1)

At this time, there was no evidence of COVID-19 so he got serum
injections and pantoprazole (40 mg BD)for his abdominal pain. But 12
hours after admission, the patient's oxygen saturation at ambient air
decreased to 79\% and he developed dyspnea, requiring admission to the
intensive care unit (ICU) to increase the oxygen saturation. At this
time, the patient's general condition was not good enough for performing
CT-Scan but in portable sonography a thickening of the gallbladder wall,
low volume free liquid in pelvis interlope space and hepatitis was seen.
After improvements in patient's general condition a chest X-Ray was done
and patch like lesions was seen from the apex to the base of both lungs.
The administrated ICU treatment combined oxygen therapy with low-flow
oxygen therapy with reservoir bag and corticosteroid therapy with
dexamethasone (4mg stat and BID) and remdesivir (200mg stat and 100 mg
daily) was given as the COVID-19 pandemic was happening at the moment.
Another treatment that was given was ceftriaxone which was injected
intravenously (1G, BID) because of the probability of leptospirosis
which is a tropical infection that at the time was endemic in northern
areas of Iran and also the patient mentioning attempting to paddy
increasing the possibility of this infection. Leptospirosis could be the
reason of his pulmonary symptoms that can happen when multi-organ
failure happens by this infection so that hemorrhagic lesions in lungs
at chest X-Ray can be the presence of this infection in lungs.

But after some hours, because of the slow increase in oxygen saturation
at ambient air, because of the possibility of cytokine storm,
Baricitinib (4 mg daily) was given orally.

On day 3 of admission, Procalcitonin was high at 4.14 ng/mL which shows
sepsis or viral is likely that has affected kidney and a high N-terminal
pro b-type Natriuretic peptide (NT- proBNP) at 9641 pg/ml can be because
of the myocarditis caused by Covid-19 or leptospirosis infection, so
Furosemide was injected intravenously (40 mg BD).

At this stage, Leptospirosis serology was performed on day 6 with ELISA
(OneSite\textsuperscript{TM} Leptospira IgM/IgG Combo Rapid Test) and
reported the presence of anti-Leptospira IgMs at 5.8 NTU*(Negative
result\textless{}9 NTU) and IgGs at 4.6 NTU (Negative result\textless{}9
NTU).

After getting treatments mentioned above, the patient started to get
better and was discharged after 10 days of hospitalization.\selectlanguage{english}
\begin{longtable}[]{@{}lllll@{}}
\toprule
Results & Day1 & Day 3 & Day7 & Day10\tabularnewline
\midrule
\endhead
Leukocytes & 10000 & 9500 & 30900 & 14000\tabularnewline
Neutrophils/mm3 & 90\% & 94\% & 80\% & 82\%\tabularnewline
Lymphocytes/mm\textsuperscript{3} & 10\% & 6\% & 15\% &
16\%\tabularnewline
Platelets/mm\textsuperscript{3} & 71000 & 5000 & 113000 &
49000\tabularnewline
C-reactive protein (mg/L) & 290 & 208 & 290 & 245\tabularnewline
Creatinine (\selectlanguage{greek}µ\selectlanguage{english}mol/L) & 0.8 & 1.1 & 0.9 & 0.6\tabularnewline
Blood urea nitrogen (mmol/L) & 20 & 25 & 27.9 & 36\tabularnewline
Aspartate aminotransferase (U/L) & 244 & 204 & 109 & 215\tabularnewline
Alanine aminotransferase (U/L) & 69 & 78 & 48 & 138\tabularnewline
Total Bilirubin (mmol/L) & ------ & ------ & 2.94 &
------\tabularnewline
NP SARS CoV-2 IgG and IgM (ELISA) & Negative & ------ & Negative &
------\tabularnewline
Serum Leptospira IgM and IgG (ELISA) & ------ & ------ & ------ &
Negative\tabularnewline
\bottomrule
\end{longtable}

*NTU: Nova Tech Units

Table 1: Laboratory tests\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

\end{center}
\end{figure}\selectlanguage{english}
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\includegraphics[width=0.70\columnwidth]{figures/image2/image2}

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Figure 1: HRCT

\textbf{Discussion}

Similarities in clinical presentation of pulmonary leptospirosis and
covid-19 such as flu-like symptoms, acute respiratory distress, and
CT-identified peripheral ground-glass opacities may cause misdiagnosis
while the ongoing covid-19 pandemic going on all around the world (5).
In order to confirm leptospirosis two tests' results are needed; IgM-
positive ELISA serology and a positive PCR (7). About 17.5\% of the
participants in a report who were positive in MAT were negative in
IgM-ELISA and calculated the specificity and sensitivity of IgM-ELISA as
78.8\% (8). That can be the reason why the IgM and IgM ELISA were
negative in this patient.

There are criteria for establishing the severity of leptospirosis
including: severe respiratory failure, initial renal injury with
hypokalemia and elevation of transaminases (5). In this case potassium
was always in a normal range but during the hospitalization it raised
from 3.5 to 4.3; but in a Urine Analysis that was done fourth day of
hospitalization showed proteinuria and 7-8 Red Blood Cells; the
transaminases AST and ALT were always high during this time. So, because
of these evidences severe leptospirosis infection can be considered for
this patient. COVID-19 can rise the amount of D-dimer, LDH, AST and ALT
(9), just like what was seen in this case.

A rise in the amount Procalcitonin (PCT) levels can happen in COVID-19.
In a study PCT level was over eight times higher in patients who had
more crucial appearance than in moderate patients (10) just like that,
in this case PCT level was almost eighty times higher than the upper
limit of the normal range.

Both COVID-19 and leptospirosis can cause Cytokine storms during the
infection (11).

Leptospira is reported to be highly susceptible to a lot of antibiotics.
Although Penicillin is the first choice for this infection, there are
other antibiotics such as doxycycline, cefotaxime and ceftriaxone that
are useful in treatment (12, 13). However, the treatments may be
affective in early onset of the infection. Leptospirosis have some
immune-mediated complications which can be controlled by adjuvant
steroids (13).

\textbf{Conclusion}

Although we didn't completely prove the type of microorganism in this
patient, this case-report may help clinicians consider pulmonary
leptospirosis along covid-19 infection, and recommends them to pay more
attention not to misdiagnose these two infections with each other and
also have both infections in their mind while approaching patients with
the same symptoms. In endemic areas for leptospirosis clinicians should
consider leptospirosis when they have negative SARS-CoV-2RT-PCR test;
Because early antibiotic therapy would be helpful in the prognosis.

\textbf{Acknowledgements}

The authors would like to thank the Clinical Research Development
Center, Imam Reza Hospital, Kermanshah University of Medical Sciences,
and the Department of infectious diseases, School of Medicine, Babol
University of Medical Sciences.

\textbf{Conflict of interest}

All authors have no relevant financial interests to be declared.

\textbf{Funding information}

None.

\textbf{Consent}

Written informed consent was obtained from the patient to publish the
current case report.

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2. Ochani R, Asad A, Yasmin F, Shaikh S, Khalid H, Batra S, et al.
COVID-19 pandemic: from origins to outcomes. A comprehensive review of
viral pathogenesis, clinical manifestations, diagnostic evaluation, and
management. Le infezioni in medicina. 2021;29(1):20-36.

3. Bolay H, G\selectlanguage{ngerman}ül A, Baykan B. COVID-19 is a Real Headache! Headache.
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4. Gupta N, Wilson W, Ravindra P, Raghu R, Saravu K. Coinfection of
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5. Turmel JM, Olive C, Bigeard B, Abel S, Banydeen R, Daoud L, et al.
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8. Araghian A, Elmi A, Farahbakhsh M, Hosseini S, Faezi S.
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11. Hu B, Huang S, Yin L. The cytokine storm and COVID\selectlanguage{english}-19. Journal of
medical virology. 2021;93(1):250-6.

12. Griffith ME, Hospenthal DR, Murray CK. Antimicrobial therapy of
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13. Turmel J-M, Olive C, Bigeard B, Abel S, Banydeen R, Daoud L, et al.
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American journal of tropical medicine and hygiene. 2022;107(1):97.

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