key: cord-263521-kv3l41qz
authors: Haigh, Kathryn; Syrimi, Zoe Joanna; Irvine, Sharon; Blanchard, Tom J.; Pervaiz, Muhammad Sajid; Toth, Arpad G.; Ratcliffe, Libuse
title: Hyperinflammation with Covid-19: the key to patient deterioration?()()
date: 2020-05-24
journal: Clin Infect Pract
DOI: 10.1016/j.clinpr.2020.100033
sha: 
doc_id: 263521
cord_uid: kv3l41qz

BACKGROUND: The potential risk of cytokine storm in patients with coronavirus disease 2019 (Covid-19) has been described(1); we write to share our experience treating a 17-year-old male with haemophagocytic lymphohistiocytosis (HLH) secondary to Covid-19 infection. CASE REPORT: This patient presented with cough, sore throat, anorexia and pyrexia. On examination, he had gross cervical lymphadenopathy and palpable splenomegaly. Nose and throat swab for SARS-CoV-2 was positive and blood tests revealed pancytopaenia with very high ferritin, triglyceride and d-dimer levels. The patient’s HScore(2) was calculated at 220, suggesting probability of HLH of 93-96%. Considering Russell and colleagues’(3) comments about potential harm of corticosteroid use in patients with Covid-19 infection, the patient was commenced on treatment with the selective IL-1 receptor antagonist drug, Anakinra, and a two day course of intravenous immunoglobulin. RESULTS: The patient responded rapidly to treatment, becoming apyrexial after 24 hours. His lymph nodes and spleen began to normalise after the first 48 hours, at which time point the ferritin also started to decrease. He was discharged after 11 days feeling fit and well. CONCLUSION: This case certainly illustrates the importance of hyperinflammation syndromes in Covid-19. It also raises the question – is the severe pneumonitis seen in patients with Covid-19 an immunological phenomenon? We know that the viral load of patients with Covid-19 seems to peak in the early stages of illness(4, 5), however patients deteriorate later in the disease course, at around days 10-14. This patient, who had risk factors for deterioration (male, pancytopaenic), did not develop an oxygen requirement and clinically and biochemically improved rapidly on Anakinra with no adverse events. We might suggest Anakinra to the scientific community as a treatment option in Covid-19 infection.

The potential risk of cytokine storm in patients with coronavirus disease 2019 (Covid-19) has been described 1 ; we write to share our experience treating a 17-year-old male with haemophagocytic lymphohistiocytosis (HLH) secondary to Covid-19.

The patient had no past medical history and no regular medications. He was a non-smoker with no alcohol intake and a normal body mass index. He lived with his parents and there was no family history of haemophagocytic lymphohistiocytosis or other inflammatory disorders.

This patient presented with a six day history of cough, sore throat, anorexia and pyrexia (recorded at 39.1 o C). On examination, he had gross cervical lymphadenopathy with submandibular nodes more than 10 centimetres in diameter. There was palpable splenomegaly.

Investigations revealed pancytopaenia, hyponatraemia, hypocalcaemia and elevated alanine aminotransferase, lactate and c-reactive protein. Ferritin was 8197ug/l, triglycerides 5.1mmol/l, LDH 586u/l, d-dimer 3758ng/ml, fibrinogen 1.73g/l and reticulocytes 13%. to exclude primary HLH, given his young age.

In terms of antimicrobial treatment, oral amoxicillin-clavulanic acid 625 milligrams three times a day was commenced on admission to provide cover for bacterial infection. On day two, antimicrobial therapy was escalated to intravenous piperacillin-tazobactam 4.5 grams three times a day to provide cover for neutropaenic sepsis. After five days of piperacillintazobactam, intravenous meropenem 1 gram three times a day was started as his liver function tests had not yet stabilised and there was concern that the piperacillin-tazobactam The patient responded rapidly to treatment, becoming apyrexial after 24 hours of Anakinra.

His lymph nodes and spleen began to reduce in size after the first 48 hours, at which time point the ferritin also started to decrease. Liver function tests worsened over the first five days, with alanine aminotransferase peaking at 771u/l, but reduced thereafter. Once his ferritin had fallen to less than 1000ug/l, on day nine, Anakinra was discontinued. The patient was kept in hospital for a further three days to ensure that his ferritin continued to decrease following treatment. He was discharged on day 11 feeling fit and well, with a ferritin of 766ug/l and almost normal clotting and liver function tests. Outpatient follow up was arranged to allow for clinical and biochemical review.

This case certainly illustrates the importance of hyperinflammation syndromes in Covid-19. It also raises the questionis the severe pneumonitis seen in patients with Covid-19 an immunological phenomenon? We know that the viral load of patients with Covid-19 seems to peak in the early stages of illness 4,5 , however patients deteriorate later in the disease course, at around days 10-14. This patient, who had risk factors for deterioration (male, pancytopaenic), did not develop an oxygen requirement and clinically and biochemically improved rapidly on Anakinra with no adverse events. We might suggest Anakinra to the scientific community as a treatment option in Covid-19 infection, and we understand a clinical trial is indeed in progress 6 .

COVID-19: consider cytokine storm syndromes and immunosuppression

Development and validation of the HSCore, a score for the diagnosis of reactive hemophagocytic syndrome

Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury

Viral load of SARS-CoV-2 in clinical samples

SARS-CoV-2 viral load in upper respiratory specimens of infected patients

J o u r n a l P r e -p r o o f