Concurrent Infection with SARS-CoV-2 and Orientia tsutsugamushi during the COVID-19 Pandemic in the Maldives

Round 1

Reviewer 1 Report

The authors reported about a co-infection case of SARS CoV2 and Orientia tsutsugamushi case during the COVID-19 pandemic in the Maldives. The case report was well written and highlighted the importance of careful differential diagnosis and screening for endemic diseases even in the pandemic situation.

I have only two minor comments.

i. the standard values for aPTT (sec) and d-Dimer were not described in the table. I would recommend to add it.

ii. The authors described that Rickettsiosis is endemic in the area where the case was living but the detail situation of COVID19 in the region was not described. Even though the COVID19 diagnosis was confirmed by PCR, it will be informative for the readers to know the situation at the time of the reported case.

Author Response

Comments and Suggestions for Authors

The authors reported about a co-infection case of SARS CoV2 and Orientia tsutsugamushi case during the COVID-19 pandemic in the Maldives. The case report was well written and highlighted the importance of careful differential diagnosis and screening for endemic diseases even in the pandemic situation.

I have only two minor comments.

1. the standard values for aPTT (sec) and d-Dimer were not described in the table. I would recommend to add it.
2. The authors described that Rickettsiosis is endemic in the area where the case was living but the detail situation of COVID19 in the region was not described. Even though the COVID19 diagnosis was confirmed by PCR, it will be informative for the readers to know the situation at the time of the reported case.

We appreciate the reviewers time and welcome the suggestions.

 

In the revised manuscript, we have added the missing reference ranges to Table 1.

 

Day of illness (days)	Day 7	Day 8	Day 10	Day 15
Hospitalization (days)	Day 1	Day 2	Day 4	Follow up
Leukocytes (5000-10,000/µL)	12,800		12,200	9,400
Neutrophils (40-60%)	85.0		72.0	72.0
Lymphocytes (12.2 - 47.1%%)	9.0		23.0	22.0
Eosinophils (0.0 - 4.4%)	0.0		0.0	0.0
Basophils (0.0 - 0.7%)	0.0		0.0	0.0
Monocytes (4.4 - 12.3%)	6.0		5.0	6.0
Hemoglobin (11.9 - 15.4 g/dL)	12.0		12.2	12.6
Hematocrit (36.2 - 46.3%)	36.6		36.8	37.0
Platelets (151,000 - 304,000/µL)	75,000		123,000	176,000
Creatinine (0.7-1.2 mg/dL)	0.68		0.70	0.70
Urea (19.0-44.1 mg/dL)	8.0		10.0	10.0
Sodium (136-145 mmol/L)	135		137
Potassium (3.5-5.1 mmol/L)	3.8		3.7
Total Bilirubin (0.2-1.2 mg/dL)		2.9	1.3	0.7
Direct Bilirubin (0.0-0.5 mg/dL)		2.0	0.9	0.3
Albumin (35-5.2 g/dL)		2.4	2.8	3.2
Protein (6.4-8.3 g/dL)		5.3	5.8	6.2
Aspartate aminotransferase 5.0-34.0 IU/L)		156	93	35
Alanine aminotransferase (0.0-55.0 IU/L)		95	63	47
Alkaline phosphatase (40.0-150.0 IU/L)		347	270	156
Prothrombin time (11-13.5 sec)		12/1.0
aPTT (30-40 sec)		35
d-Dimer (≤0.50 mg/L FEU)		13.55	4.56
CRP (0.0-0.5 mg/dL)		26.0	13.8	2.3
LDH (140-280 IU/L)		726	510	256
Lactate (0.0-1.0mmol/L)		3.6
Ferritin (10-120 ng/mL)		4,887	4,165
Hepatitis B surface Ag		Negative
Anti-hepatitis B surface Ab		Negative
Anti-hepatitis C Ab		Negative
Anti-HIV Ag/Ab		Negative
Dengue NS1		Negative
Anti-dengue IgM		Negative
Anti-dengue IgG		Negative
SARS-CoV-2 RT-PCR		Positive
Scrub typhus IgM		Positive
Scrub typhus IgG		Positive
Blood culture		No growth
Sputum culture		No growth

aPTT: activated partial thromboplastin time, FEU: fibrinogen equivalent units, d-Dimer: domain dimer, CRP: c-reactive protein, LDH: lactate dehydrogenase, Ag: antigen, Ab: antibody, IgM: immunoglobulin M, IgG: immunoglobulin G, SARS-CoV-2: severe acute respiratory syndrome coronavirus 2, RT-PCR: real-time polymerase chain reaction.

 

 

We have also described a brief summary of situation of COVID-19 pandemic in the Maldives in the Introduction. The following sentence was added to the revised manuscript Lines 107-110.

 

“In the Maldives, there were 185,708 laboratory confirmed cases (33% of the population) out of which three hundred and eleven fatalities were recorded since the beginning of the pandemic. Presently, 86% of individuals above the age of 12 years have received at least two doses of vaccine against COVID-19”

Reviewer 2 Report

Authors have discussed about the  Concurrent infection with SARS-CoV-2 and Orientia tsutsugamushi during the COVID-19 pandemic in the Maldives. In the endemic region of  Orientia tsutsugamushi, co-infection can be possible and the physicians should keep in mind about the possible coinfections. To increase the impact authors can add a table about the coinfection of Orientia tsutsugamushi and COVID-19 reported around the world with comparing their clinical presentation and laboratory parameters.

Author Response

Comments and Suggestions for Authors

Authors have discussed about the  Concurrent infection with SARS-CoV-2 and Orientia tsutsugamushi during the COVID-19 pandemic in the Maldives. In the endemic region of  Orientia tsutsugamushi, co-infection can be possible and the physicians should keep in mind about the possible coinfections. To increase the impact authors can add a table about the coinfection of Orientia tsutsugamushi and COVID-19 reported around the world with comparing their clinical presentation and laboratory parameters.

reported case.

We are thankful for the reviewers time and appreciate the suggestion.

 

In the manuscript in the Discussion, we have already compared similar cases and tabulated the summary in TableS1 (Lines 284)

 

 

Table S1. Summary of cases in the literature and the present case that were co-infected with SARS-CoV-2 and Orientia tsutsugamushi

 

 

Clinical findings	Present case	Other cases
		Case I	Case II	Case III	Case IV
Patient’s characteristics	40-year-old female from Maldives	14-year-old girl from Nepal	§ 70-year-old lady from south India	§ 55-year-old man from central India	§  35-year-old man from north central India
Presenting complaints, symptoms and signs of illness	§ Fever § Body aches § Fatigue § Cough § Dyspnea	§ Fever § Headache § Myalgia § Arthralgia § Cough § Dyspnea	§ Fever § Fatigue § Myalgia	§ Fever § Cough § Dyspnea § Altered sensorium	§  Fever §  Cough §  Dyspnea §  Altered sensorium
Onset of symptoms prior to presentation	§ 10 days	§ 7 days	§ 3 days	§ unrecorded	§  7 days
Vital signs and finding supporting of clinical diagnosis	§ Temperature: 38.0°C § BP: 80/50mmHg § PR: 108 beats per min § RR: 28 breaths per min § SPO2: 92% (room air) § Eschar: on the right antecubital fossa § Crackles audible on auscultation of both lung fields	§ Temperature: 38.3°C § BP: 108/72 mmHg § PR: 112 beats per min § RR: § SPO2: 95% (room air) § Eschar: unreported	§ Temperature: § BP: 120/80mmHg § PR: 80 beats per min. § RR: 20 breaths per min. § SpO2: 99% (room air) § Eschar: on the left infra-axillary region	§ Temperature: unrecorded § BP: 100/58 mmHg § PR: 54 beats per min. § RR: 20 breaths per min. § SPO2: 100% (room air) § Eschar: not found	§ Temperature: unrecorded §  BP: 130/90 mmHg §  PR: 140 beats per min. §  RR: 38 breaths per min. §  SPO2: 50% (room air) §  Eschar: not found
Hematological and biochemical abnormalities and findings on imaging.	§ Thrombocytopenia § Transaminitis § Leukocytosis § Lymphopenia § Hypoalbuminemia § Ferritinemia § Chest x-ray: interstitial involvement	§ Thrombocytopenia § Transaminitis § Leukocytopenia       § Chest x-ray and computer tomography: dextrocardia	§ Thrombocytopenia   Leukocytosis	No thrombocytopenia Transaminitis Leukocytosis § Lymphopenia § Hypoalbuminemia § Elevated IL-6 § Ferrintinemia	No thrombocytopenia §  Transaminitis §  Leukocytosis §    §  Hypoalbuminemia
Laboratory confirmation: scrub typhus/ COVID-19	§ SARS-CoV-2 RT-PCR: +ve § Scrub typhus IgM/IgG antibodies: +ve	§ SARS-CoV-2 RT-PCR: +ve § Scrub typhus IgM/IgG antibodies: +ve	§ SARS-CoV-2 RT-PCR: +ve § Scrub typhus qPCR: +ve	§ SARS-CoV-2 RT-PCR: +ve § Scrub typhus IgM ELISA: +ve	§ RT-PCR for COVID-19: + ve § IgM ELISA: +ve
Complications	§ ARDS	§ Unreported	§ Unreported	§ Meningoencephalitis	§ ARDS and MODS
Antimicrobial therapy	§ Ceftriaxone § Remdesivir § Doxycycline	§ Unreported	§ Doxycycline	§ Ceftriaxone § Vancomycin § Doxycycline	§  Hydroxychloroquine §  Piperacillin/tazobactam §  Meropenem §  Doxycycline
Outcomes	§ Recovered	§ Unreported	§ Recovered	§ Recovered	§  Fatal

 

BP: blood pressure, PR: pulse rate, RR: respiratory rate, SpO₂ : oxygen saturation, IL-6: interleukin 6, SARS-CoV-2; severe acute respiratory syndrome associated virus 2, RT-PCR; reverse transcriptase polymerase chain reaction, IgM: immunoglobulin M, IgG: immunoglobulin G, ELISA: enzyme linked immunosorbent assay, COVID-19; coronavirus disease 2019.

 

 

 

Author Response File: Author Response.docx