Hyperpyrexia in a Healthy Pregnant Female With COVID Pneumonia

Abstract and Introduction

Abstract

Background: Infection due to the SARS-CoV-2 virus can have a wide range of presentations from asymptomatic/mildly symptomatic to severe disease with multiorgan failure. Fever is a common symptom. But hyperpyrexia defined as temperature > 41.5 °C is not usual in COVID-19.

Case Presentation: A 24-year-old previously well Sri Lankan female in the 24th week of gestation of her first pregnancy presented with fever and shortness of breath. She was confirmed to have coronavirus disease-2019 (COVID-19). History was suggestive of late presentation on approximately the eighth day of the illness. She had rapidly deteriorating hypoxia due to COVID pneumonia requiring mechanical ventilation two days after the admission. There was evidence of cytokine storm without any secondary bacterial infection. She received glucocorticoids, tocilizumab, and intravenous antibiotics. Although she initially showed mild improvements, she subsequently developed high-grade fever with the axillary temperature rising to 41.7 °C starting from the seventh day of admission. There were no causative medicines or risk factors to explain hyperpyrexia. She died on the ninth day of admission.

Conclusions: There are no reports of patients developing this complication during pregnancy. The pathophysiology of this rare life-threatening complication remains elusive. Detailed reporting and in-depth analysis of such patients will facilitate the understanding of the associations and successful management of these patients.

Table 1. Summary of investigations and their progress during the hospital stay
Investigation	Reference range	At the time of admission (day 1)	Day 4	At the time of hyperpyrexia (D7)	Before death (day 8)
White cell count (× 10⁹/L)	4–10	6.31	15.59	14.17	25.84
Neutrophils (× 10⁹/L)	2–7	5.62	13.88	9.92	19.64
Lymphocytes (× 10⁹/L)	1–3	0.59	1.09	3.12	3.1
Haematocrit (%)	36–46	31.6	42	31.3	38.4
Platelet count (× 10⁹/L)	150–410	169	313	232	137
C-reactive protein (mg/L)	< 3	147	46.1	4	2.1
Procalcitonin (ng/mL)	< 0.05	< 0.05	0.15	0.26	84.78
Lactate dehydrogenase (U/L)	135–250	342		970	2881
Ferritin (ng/mL)	15–150	137		438	9153
Arterial blood pH	7.35–7.45	7.32	7.41	7.36	7.21
Arterial bicarbonate (mmol/L)	22–26	20.2	26.4	29	18.3
PaO₂/FiO₂ (mmHg)		49.4	243	80	215
Arterial PCO₂ (mmHg)	35–45	38.2	41	52	45.3
AST (U/L)	< 32	25	15	70	572
ALT (U/L)	< 45	9	46	33	207
Total Bilirubin (mg/dL)	0.1–1.2	0.2	0.2	0.9	2
Albumin (g/L)	35–52	34.3	35.3	30.8	28.5
Creatinine (mg/dL)	0.51–0.95	0.79	0.8	0.72	2.32
Sodium (mmol/L)	136–145	137	143	149	150
Potassium (mmol/L)	3.5–5.1	3.8	4.4	4.6	5.1
CPK (U/L)	20–180				1410
Blood culture		No growth		No growth
Urine culture		No growth		No growth

Table 1. Summary of investigations and their progress during the hospital stay

Investigation

Reference range

At the time of admission (day 1)

Day 4

At the time of hyperpyrexia (D7)

Before death (day 8)

White cell count (× 10⁹/L)

4–10

6.31

15.59

14.17

25.84

Neutrophils (× 10⁹/L)

2–7

5.62

13.88

9.92

19.64

Lymphocytes (× 10⁹/L)

1–3

0.59

1.09

3.12

3.1

Haematocrit (%)

36–46

31.6

31.3

38.4

Platelet count (× 10⁹/L)

150–410

169

313

232

137

C-reactive protein (mg/L)

< 3

147

46.1

2.1

Procalcitonin (ng/mL)

< 0.05

0.15

0.26

84.78

Lactate dehydrogenase (U/L)

135–250

342

970

2881

Ferritin (ng/mL)

15–150

137

438

9153

Arterial blood pH

7.35–7.45

7.32

7.41

7.36

7.21

Arterial bicarbonate (mmol/L)

22–26

20.2

26.4

18.3

PaO₂/FiO₂ (mmHg)

49.4

243

215

Arterial PCO₂ (mmHg)

35–45

38.2

45.3

AST (U/L)

< 32

572

ALT (U/L)

< 45

207

Total Bilirubin (mg/dL)

0.1–1.2

0.2

0.9

Albumin (g/L)

35–52

34.3

35.3

30.8

28.5

Creatinine (mg/dL)

0.51–0.95

0.79

0.8

0.72

2.32

Sodium (mmol/L)

136–145

137

143

149

150

Potassium (mmol/L)

3.5–5.1

3.8

4.4

4.6

5.1

CPK (U/L)

20–180

1410

Blood culture

No growth

Urine culture

No growth

Table 2. Summary of the six articles describing patients with hyperpyrexia and COVID-19
Author, year	Patient details	Highest temperature reported	Cause of hyperpyrexia as indicated by the authors	Additional complications	Clinical outcome	Notes
Czepiel, 2020 [7]	60-year-old female, 43-year-old female, 46-year-old male (all three had additional co-morbidities)	42.4 °C (108.3 °F) 42 °C (107.6 °F) 42 °C (107.6 °F)	High dose dexmedetomidine	Acute hypoxic respiratory failure needing intubation and ventilation (Rhabdomyolysis in the second patient)	Hyperpyrexia resolved after discontinuing dexmedetomidine (first patient died subsequently due to multiorgan failure)	Temporally associated with dexmedetomidine
Jeon, 2020 [8]	58-year-old female	41.6 °C	Hyperinflammatory syndrome of COVID (No mention about additional risk factors, was treated with lopinavir, ritonavir, glucocorticoids)	Acute hypoxic respiratory failure needing intubation and ventilation, heart failure, shock (CPK not mentioned)	Recovered	Treated with therapeutic temperature modulation and extracorporeal membrane oxygenation
Singhal, 2020 [9]	42-year-old male with diabetes mellitus	107 °F (41.7 °C)	Cytokine storm (Treated with fentanyl, midazolam, and atracurium. No mention about additional risk factors)	Acute hypoxic respiratory failure needing intubation and ventilation, elevated CPK, later multiorgan failure	Died	Pre-print
Suwanwongse, 2020 [10]	Six patients (four females), 54–62 years, five had multiple medical co-morbidities	107.2 °F (41.8 °C) − 109.7 °F (43.2 °C)	Brain injury, exuberant immune response, and thrombus formation related to COVID	All had hypoxic respiratory failure requiring intubation and ventilation (No muscle rigidity or rhabdomyolysis)	All six patients died	No exposure to presumably causative medicines
Nuckchady, 2021 [11]	20 years, female with history of asthma	44 °C	Not discussed	COVID pneumonia with hypoxia needing intubation and ventilation, initial respiratory acidosis, and subsequent metabolic alkalosis. (CPK not mentioned)	Died	Letter to the editor
Chiba, 2021 [12]	36 years, previously healthy male	41.5 °C	Malignant hyperthermia due to COVID-19, (Treated with favipiravir, midazolam, fentanyl and rocuronium. No family history of malignant hyperpyrexia, dexmedetomidine started after high fever spike)	Pneumonia with refractory hypoxia requiring mechanical ventilation, rhabdomyolysis, muscle rigidity, Systemic inflammatory response syndrome	Recovered	Improvement observed after starting treatment with dantrolene

Table 2. Summary of the six articles describing patients with hyperpyrexia and COVID-19

Author, year

Patient details

Highest temperature reported

Cause of hyperpyrexia as indicated by the authors

Additional complications

Clinical outcome

Notes

Czepiel, 2020 [7]

60-year-old female, 43-year-old female, 46-year-old male (all three had additional co-morbidities)

42.4 °C (108.3 °F)
42 °C (107.6 °F)
42 °C (107.6 °F)

High dose dexmedetomidine

Acute hypoxic respiratory failure needing intubation and ventilation (Rhabdomyolysis in the second patient)

Hyperpyrexia resolved after discontinuing dexmedetomidine (first patient died subsequently due to multiorgan failure)

Temporally associated with dexmedetomidine

Jeon, 2020 [8]

58-year-old female

41.6 °C

Hyperinflammatory syndrome of COVID (No mention about additional risk factors, was treated with lopinavir, ritonavir, glucocorticoids)

Acute hypoxic respiratory failure needing intubation and ventilation, heart failure, shock (CPK not mentioned)

Recovered

Treated with therapeutic temperature modulation and extracorporeal membrane oxygenation

Singhal, 2020 [9]

42-year-old male with diabetes mellitus

107 °F (41.7 °C)

Cytokine storm (Treated with fentanyl, midazolam, and atracurium. No mention about additional risk factors)

Acute hypoxic respiratory failure needing intubation and ventilation, elevated CPK, later multiorgan failure

Died

Pre-print

Suwanwongse, 2020 [10]

Six patients (four females), 54–62 years, five had multiple medical co-morbidities

107.2 °F (41.8 °C) − 109.7 °F (43.2 °C)

Brain injury, exuberant immune response, and thrombus formation related to COVID

All had hypoxic respiratory failure requiring intubation and ventilation (No muscle rigidity or rhabdomyolysis)

All six patients died

No exposure to presumably causative medicines

Nuckchady, 2021 [11]

20 years, female with history of asthma

44 °C

Not discussed

COVID pneumonia with hypoxia needing intubation and ventilation, initial respiratory acidosis, and subsequent metabolic alkalosis. (CPK not mentioned)

Died

Letter to the editor

Chiba, 2021 [12]

36 years, previously healthy male

41.5 °C

Malignant hyperthermia due to COVID-19, (Treated with favipiravir, midazolam, fentanyl and rocuronium. No family history of malignant hyperpyrexia, dexmedetomidine started after high fever spike)

Pneumonia with refractory hypoxia requiring mechanical ventilation, rhabdomyolysis, muscle rigidity, Systemic inflammatory response syndrome

Recovered

Improvement observed after starting treatment with dantrolene