Treatment of Patients with Flu Like Syndrome - Case Series

Introduction

In last and current centuries so many new diseases have emerged. AIDS is potentially fatal, and others can be fatal with increase in severity. Amongst these newly emerged diseases almost all are variants of metabolic/ non communicable diseases/consequences or because of a genetic shift or drift in disease causing viruses¹ . Genetic shift and drift are frequently seen in common cold viruses. Almost every five-year NH virus undergoes a genetic shift or drift resulting in a new variant. The variant virus being new genetically and expression of new antigens is not recognized by the immune system easily. This lapse in the immune system makes the people susceptible to viral infection. All these factors lead to rapid spread, infection by variant virus and result in an epidemic or pandemic. In December 2019, one variant of corona virus appeared in Wuhan, China and from there it started spreading in an alarming pace and soon spread all over the world. Seeing the worldwide spread, World Health Organization, declared it a pandemic. Corona virus is a member of the Coronaviridae family² and its existence is known since long. It has always been the causative factor for seasonal common cold and in the past corona virus disease was considered as trivial and self-limiting because of its mild manifestations. It was dangerous only in debilitating individuals. The present variant of corona virus, COVID-19 is different from the past viruses antigenically and in virulence. After infection, very soon it involves the lung, and an atypical type of pneumonia sets in^3,4. This interferes with gaseous exchange and oxygen level falls drastically to dangerous levels. At this stage, the only hope is artificial respiration to maintain desirable oxygen levels. Usually, COVID-19 manifests as fever, sore throat, dry cough, headache, body ache and breathlessness⁵ . As the disease advances breathlessness increases and patient may collapse due to hypoxia. Death usually occurs because of respiratory failure.⁴ Recently, role of cytokines in the course of infection by corona virus has be identified and cytokines storm is responsible for multiple organ failure.⁴ The cytokine storm is considered an exaggerated response of the immune system to combat the virus. On the other hand, some researchers are observing failure of immune response in case of an infection with corona virus and they advocate immune boosting. Still no definitive treatment is available to fight against COVID-19⁶ . Trial and error with many drugs are going on and different countries are claiming that certain drugs are effective in combating COVID-19. Till now doxycycline, ivermectin, hydroxychloroquine, remdesivir, dexamethasone, other antibiotics and steroids have been reported effective^6,7. The final measure taken to rescue the patient is providing a ventilator for respiratory support and some of these patients succumb to hypoxia.

Unani system of medicine is amongst the oldest healing systems in the world. The vast description of epidemic diseases are listed under the heading Waba⁸ . Raziz was the first physician who differentiated between chickenpox and measles⁹ . Unani medicine recognizes epidemics because of toxic changes in the essence of air¹⁰. Recently, WHO declared COVID-19 as an air borne disease. Unani physicians have suggested fumigation as an effective way to purify the air from epidemic toxins¹¹. This step could contain further spread of the virus. Others preventive measures are directed towards susceptible individuals. Unani medicine believes that all individuals of a particular locality are not equally affected by the epidemic. Only the susceptible are affected and manifest the disease. To reduce the individual susceptibility certain measures are suggested which are mainly based on elimination of susceptible morbid matter from the body, or on protection from morbid matter from acquiring the infection. For protection from infection, prophylactic use of drugs that control infections is suggested. For example, Elva (Alove barbadensis), Murmaki (Commiphora myrrh), Zafran (Crocus sativus), Sirka (Vinegar), Gile makhtum (Marl, Sealing clay) and Gile armani (Armenian bole) etc^12,13. In one of the studies, combination of Elva, Murmaki and Zafran was found effective in reducing the frequency of infections in elderly¹⁴. At the same time, this formulation increases CD⁴ count.

For the diseased, various therapeutic regimens are suggested by physicians. On the basis of pharmacological actions and therapeutic uses of drugs, formulations can be tailor-made by physicians from a vast array of drugs. The drugs are selected based on the clinical manifestation, therapeutic use of drugs, action of drugs and experience of physicians. On these grounds, a decoction formulation of unani medicines has acquired fame for its effects in COVID-19 patients in Malegaon city, Maharashtra state, India. This decoction was formulated by the experts in Unani medicine for clinical use in patients with FLS. The same decoction was also used to prevent corona infection. On past clinical experience and on the basis of literature evidence, the formulation consisting of Unnab (Zizyphus vulgaris), Sapistan (Cordia latifolia), Injeer (Ficus carica), Mulethi (Glycyrrhiza glabra), Zanjabeel (Zingiber officinale) and Zoofa (Hyssopus officinalis) was administered to patients with FLS, irrespective of their COVID-19 status. The present study was not a formal clinical trial and did not follow a research protocol. Initially this formulation was administered to flu-like/COVID-like symptomatic patients in decoction form in the outpatient departments (OPD)/clinics across Mumbai. Only patients with mild and moderate severity visited the OPD. Progressive improvement in fever, sore throat, cough, difficulty in breathing, headache, weakness and insomnia were noted. Initially presumptive formulation proved unexpectedly effective in improving FLS. Because of good efficacy of the present formulation, the report of patients treated is presented as a case series.

Methodology

The present study was a trial and error design of treating patients and no control group or control conditions were a part of this study. Patients with FLS/COVID-19-like syndrome who visited the clinic were included and on their first visit apparent symptoms were recorded and they were advised to follow COVID-19 containment measure strictly as dictated by the Government and WHO. Recording their baseline symptoms, the decoction of drugs in packets was given to drink, twice a day. Method of preparation was explained. The patients were instructed to soak drugs in 3 cups of water, let it stand for at least 6 hours or overnight, boil until it is reduced to one cup and then let it to cool. Now squeeze the drugs to extract as much as extract water and the extracted water is consumed. The remnant drugs were again soaked in the same amount of fresh water and the same process was repeated the second time. The remnant drugs were disposed and a fresh packet of drug was soaked for further use. On follow up, which was on the third day, symptomatic relief was recorded.

Some patients discontinued treatment as soon as their symptoms were relieved. Some patients continued treatment till they recovered completely. Progress was recorded on every visit, day wise. Since the present study was not a formal clinical trial, a strict protocol of randomized control trial (RCT) was not followed. Sampling was purely purposive and sample size calculation was not performed. All patients visited the clinic with flu or COVID-19-like symptoms, tested positive or no, with comorbid condition or no and with mild to moderate severity of symptoms were included in this study. The proposed formulation consisted of Unnab (Zizyphus vulgaris)-5 numbers, Sapistan (Cordia latifolia)-7 numbers, Injeer (Ficus carica)-3 numbers, Mulethi (Glycyrrhiza glabra)-6 gm, Zanjabeel (Zingiber officinale)-6 gm and Zoofa (Hyssopus officinalis)-6 gm in decoction form.

Dose Schedule

Twice a day on empty stomach for a maximum 10 days.

Results

The focus was on achieving symptomatic relief in patients visiting the clinic with flu or COVID-19-like symptoms. Symptoms observed were fever, cough, sore throat, headache, difficulty in breathing, weakness, anosmia and running nose. On follow up after 3 days, patients reported ≥50% relief in symptoms. Treatment was started on the first visit (Day 1) and continue until symptomatic relief. Symptoms observed in each case are presented as tables (Table 1-20).

Discussion

The studied formulation proved unexpectedly effective in improving COVID-19 or flu-like symptoms in the studied subjects. The studied formulation was a presumptive combination and was based on therapeutic uses of included drugs and on clinical experience. The included drugs are frequently used to treat cough, cold, throat pain, chest congestion and difficulty in breathing. These drugs have soothing, liquifying, expectorating, dissolving and anticough properties11,15. Unnab (Zizyphus vulgaris), Injeer (Ficus carica), and Zoofa (Hyssopus officinalis) are frequently used in the treatment of chest diseases and they are very effective in relieving difficulty in breathing16. Unnab (Zizyphus vulgaris), Sapistan (Cordia latifolia), Mulethi (Glycyrrhiza glabra) and Zanjabeel (Zingiber officinale) are effective in relieving throat swelling, calming irritative cough and in liquifying thick secretions in the respiratory tract^{16,17,18,19,20,21,22}. Injeer (Ficus carica), Mulethi (Glycyrrhiza glabra), Zanjabeel (Zingiber officinale) and Zoofa (Hyssopus officinalis) are effective in dissolving swelling, cleaning the respiratory tract, dilating the bronchus and relieving throat swelling^{23,24,25,26,27,28}. Unnab (Zizyphus vulgaris), Sapistan (Cordia latifolia) and Mulethi (Glycyrrhiza glabra) are frequently used to treat fever and they indirectly relieve fever by reducing swelling and morbid matter^29,30.

Fever was present in almost all patients on the first day and subsided in most of the patients by 6th day of treatment. This effect of prescribed formulation is significant. As without taking any conventional antipyretics, fever did not rise during treatment and declined from the 2nd day of treatment. This effect of formulation not only increased confidence but also a feeling of well-being in patients. Dry cough and throat pain were the major complaints in these patients. These complaints started to decline after taking two doses of the decoction and were relieved in all patients on 10th day of treatment. This formulation proved itself most effective in relieving dry cough, throat pain and swelling. Mild to moderate breathlessness was present in 19 patients and they were not able to walk comfortably. This problem started to improve approximately from the 4th day of treatment. On 10th day of treatment all patients were relieved of breathlessness. This effect was significant as it prevents hospitalization and ventilation. Maximum patients of flu-like syndrome or COVID-19-like symptoms died of respiratory failure and this aspect of the disease is most threatening to patients and their family members. This problem also poses a burden on the state health facility. Improvement in breathlessness prevents patients from going to the hospital for respiratory support and in this way reduces the burden on the health facility and they can be treated in the OPD. Similarly, improvement in other symptoms started from the second day of treatment and all patients completely recovered from FLS/ COVID19-like symptoms on the10th day of treatment. This was the maximum duration of treatment observed with this formulation. It has been observed that anosmia persists for a month or more in recovered patients, but with this formulation along with other symptoms anosmia was also relieved completely and patients were comfortable with their nasal functions. Running nose was not a problem in most patients, while one patient visited the clinic with this complaint and nasal secretions dried up on the 5th day of treatment.

Conclusions

The present study is a case series from Mumbai, India. This formulation was given to patients presenting with COVID-19 or flu-like symptoms, at clinics. It was a presumptive formulation and expected to relieve FLS. The drugs for formulation were chosen on the basis of experience ann therapeutic activity of the drugs included. Surprisingly, this formulation proved very effective in relieving symptoms. All patients who visited the clinics and consumed the drugs as per advice, were relieved of COVID-19-like or flu-like symptoms on the 10th day of treatment. The efficacy was marked in patients with mild to moderate severity. The tested formulation prevents disease progression and improves symptoms as early as the second day of treatment. No patients were hospitalized after starting the prescribed formulation.

Conflicts of interest

The authors declare no conflict of interests.

Funding

This study did not receive any grant from funding agencies in the public, commercial or not-for-profit sectors.