Initial COVID Hydroxychloroquine Failure Responds to Interferon and Tocilizumab

Currently there is no established treatment protocol for SARS-2 (CoVid-19). Proponents of hydroxychloroquine (HCQ) argue that early intervention may sufficiently prevent replication of the virus and avoid the need for hospitalization. In instances where viral replication continues and the patient develops CoViD pneumonia (CVP), such patients – particularly with comorbidities – are prone to develop an InflammoThrombotic response similar to cytokine release syndrome (CRS). We present one such patient who failed HCQ treatment and was subsequently treated successfully with an interleukin-6 inhibitor and interferon.


Abstract
Currently there is no established treatment protocol for SARS-2 (CoVid-19). Proponents of hydroxychloroquine (HCQ) argue that early intervention may su ciently prevent replication of the virus and avoid the need for hospitalization. In instances where viral replication continues and the patient develops CoViD pneumonia (CVP), such patients -particularly with comorbidities -are prone to develop an In ammoThrombotic response similar to cytokine release syndrome (CRS). We present one such patient who failed HCQ treatment and was subsequently treated successfully with an interleukin-6 inhibitor and interferon.

Clinical Case
A 73-year old obese (170 cm, 95.4 kg) Cuban male (E.G.) developed fatigue, hyposmia, and dyspnea. He was not aware of any exposure to individuals with CoVid-19. His medical history revealed no other comorbidities other than his age and weight. He was taking no medications. A nasal swab for PCR was obtained and he was started on hydroxchloroquine (HCQ) 200 mg po BID along with 50 mg po elemental zinc daily.
He returned 4-days later with worsening dyspnea and was admitted following FMTVDM [1] imaging to evaluate the severity of corona virus pneumonia (CVP) in ammation. The initial quanti cation revealed two speci c areas in the right lung elds ( Figure 1) where an in ammatory response was present.
Following measurements, he was admitted and started on Tocilizumab 762.2 mg IV repeated one time 8hours later (Treatment arm 7), Interferon alpha-2b 5 million units per nebulizer BID (Treatment arm 9), Atrovent nebulizer treatments q 4-hours, and SQ heparin 5000 Unit q 12-hours per NCT04349410. The patient was initially positioned in the prone position with O2 monitoring. His initial IL-6 level was 16 pg/ml [2], and ferritin 379 ng/ml, with a normal range brinogen level.
During the rst 48-hours he reported improvement in breathing and was repositioned to a supine position.
Following 72-hours of treatment he underwent repeat FMTVDM (Figure 1) imaging which showed improvement in CVP in ammation, matching his improved symptoms, and follow up blood tests including an IL-6 of 10 pg/ml and ferritin of 224 ng/ml. The initial PCR test for SARS-2 returned positive.

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The patient continued to improve and was discharged on the 8 th day post admission. Discussion SARS-2 attaches to human cells through a variety of receptors including ACE-2. Respiratory cells are particularly vulnerable and evidence indicates that su cient viral replication has occurred within 96-hours to become clinically signi cant [3].
HCQ proponents have argued that initiation of HCQ must begin immediately once the clinician thinks the patient has SARS-2. Arguably treatment may have been started too late for HCQ to provide clinical bene t or the patient might have bene tted from a combination of HCQ and interferon in the prehospital setting [4].
Viruses including SARS-2 are one of many factors involved in In ammoThrombotic reactions produced by the immune system [5] resulting in in ammation and blood clots [6] that have proven to be associated with deaths in SARS-2 patients.
Measurement of this In ammoThrombotic response [1] makes it possible to determine treatment response in SARS-2 patients. In this instance, the patient was evaluated and admitted for treatment following failure of HCQ. This treatment consisted of prone positioning, use of beta-2 bronchdilator nebulizer treatment, administration of low dose heparin to reduce the potential formation of thrombi, and the initiation of both interferon (IFN) and interleukin-6 inhibitor (IL6-I) treatments.
Treatment with IFN is common in Cuba and when combined with an IL6-I appears to be promising.
Currently only 100 deaths from CoVid have been reported in Cuba and this may represent the bene t of using IFN and IL6-I's. While this represents only one such case example, it emphasizes the importance of objectively evaluating CoVid-19 patients and initiating treatment intervention early.