Keywords
COVID-19 - SARS-CoV-2 infection - Genus Epidemicus - Homeopathy
Introduction
In December 2019, clusters of pneumonia cases were identified in Wuhan, China, caused
by a newly identified β-coronavirus, named as severe acute respiratory syndrome coronavirus
2 (SARS-CoV-2).[1]
The classical clinical presentation is a severe acute respiratory infection ranging
from a mild common cold-like illness to a severe viral pneumonia leading to potentially
fatal SARS.[2] Recent case reports suggest that coronavirus disorder 2019 (COVID-19) is a complex
systemic disorder with extra-pulmonary manifestations, possibly due to viral-induced
inflammation, affecting ACE2 (angiotensin-converting enzyme 2) receptors present in
tissues other than lungs.[3]
[4]
Although COVID-19 is a polymorphic disease, its severity is classified on the basis
of respiratory manifestations: mild (uncomplicated upper respiratory tract infection
without evidence of breathlessness or hypoxia; SpO2 >94%); moderate (pneumonia with no signs of severe disease, SpO2 <94% [90–94%] on room air, respiratory rate more than or equal to 24/min); severe
(clinical signs of pneumonia plus one of the following; respiratory rate >30 breaths/min,
severe respiratory distress, SpO2 <90%).[5]
COVID-19 has affected over 20 million individuals worldwide, causing a large number
of deaths and posing a serious threat to public health.[6] In India, as of July 13, 2020, nearly 0.9 million patients have tested positive,
of whom more than 0.1 million are from Delhi.[7]
This pandemic has led researchers and health care organizations to develop strategies
to combat this infectious disease through repurposed drugs, vaccines and control measures.[8] Evidence from laboratory, animal and clinical studies, and clinical trials on conventional
medicine drugs such as remdesivir,[9] lopinavir/ritonavir,[10] lopinavir/ritonavir with interferon β-1a,[11] chloroquine,[12]
[13] and hydroxychloroquine,[14] have been reported. Treatment with convalescent plasma has been proposed as a potential
treatment in severe cases.[15] To date, however, no anti-SARS-CoV-2 drug or vaccine has been officially approved
due to the absence of adequate evidence.[16] So far, the therapeutic strategies to deal with this pandemic are conservative,
with limited options in terms of treatment modalities.
The pandemic has uniquely challenged health care decision makers and the medical research
community worldwide due to the absence of a vaccine or proven therapy. There is a
potential role for a prudent strategy to integrate traditional medicine with conventional
medicine to combat the present situation.[17] A recent systematic review suggested that the integration of traditional Chinese
medicine with “western medicine” improved cure rate with better symptom amelioration
in COVID‐19.[18] Similarly, homeopathy could also be seen as a potential adjunct to conventional
medicine.
Homeopathy has a long-standing history in the management of epidemic diseases.[19] In terms of the evidence base, homoeopathy trials have pursued the following: tested
preventive homeopathic medicines, where the focus has been on finding an effective
universal prophylactic medicine[20]
[21]
[22]; or tested the efficacy of individualized homeopathic treatment for patients with
the disease[23]
[24]
[25]; or tested the adjunctive effectiveness of homeopathic treatment.[26]
[27] Testing one medicine as Genus Epidemicus (GE) does not appear to be appropriate
for the present pandemic due to its kaleidoscopic manifestation; nor has a potential
GE been discerned.[28]
The potential of homeopathic treatment on a large scale can be tested by following
a step-wise process. The first step is characterization of data of COVID-19-positive
patients and identification of probable effective remedies. The second step will be
to evaluate the efficacy of these remedies through a high-quality randomized controlled
trial (RCT). If a remedy or group of remedies is found to be efficacious, these can
then be integrated in the treatment protocols of COVID patients. The third step might
then be to explore the potential of these remedies in preventing the disease through
rigorous RCTs in high-risk population groups and disease hot spots.[29]
This article addresses the above first step: systematic characterization of the clinical
presentation of COVID-19 in Indian patients, and identification of corresponding homeopathic
medicines for incorporation in treatment regimens. It is expected to be a stepping-stone
for further studies for systematic validation.
Objectives
The primary objective was to identify the clinical presentation of laboratory-confirmed
COVID-19 patients and identify a group of indicated homeopathic remedies based on
their symptomatologic profile.
The secondary objective was to compare the collected data with those from similar
studies in order to inform the design of a suitable RCT.
Materials and Methods
Setting
Nehru Homeopathic Medical College and Hospital (NHMCH), Defense Colony, New Delhi,
was designated as a COVID Health Centre by the Department of Health and Family Welfare,
Government of NCT of Delhi, for the isolation and treatment of COVID-19-positive patients,
providing integrated care comprising conventional treatment (analgesic, anti-allergic,
anti-tussive, antibiotics) and adjunctive individualized homeopathic treatment.[30] Six homeopathic doctors, Junior Residents pursuing post-graduation and four conventional
doctors were deputed in a duty roster of 12 h. All infection control guidelines, including
use of appropriate personal protection equipment, were followed by the medical as
well as support staff.
Development of the protocol and study design, manuscript writing, and coordination
was done by doctors with 20 years of experience. The ethical clearance from the Institutional
Ethics Committee was obtained on June 2, 2020 for undertaking retrospective analysis
of patients admitted in the hospital.
Patients signed an informed consent form at the time of admission for add-on homeopathic
treatment and subsequent data analysis and publication. A patient case record form
(CRF) was used for case taking, based on the World Health Organization (WHO) format
for COVID-19.[31] The patient data were anonymized by removing direct identifier variables for the
analysis. The patients were jointly treated by this medical team and the work was
supervised by doctors with 35 years' experience each. Epidemiological history, demographic
data, clinical characteristics, laboratory data, treatment programs and outcome measures
were obtained from the patients' medical records. Homeopathic characteristic data
were obtained by daily follow-up during hospital stay. Initially the patients were
discharged only after two consecutive negative tests for RT-PCR; later on, patients
were discharged after complete recovery of symptoms, usually between 10 and 17 days
as per the government guidelines.
Participants
Laboratory confirmed COVID-19-positive (reported positive on RT-PCR testing) symptomatic
patients were admitted to NHMCH between April 29, 2020 and June 17, 2020.
Variables
These comprised demographic details and clinical symptoms of COVID-19-positive patients.
Data Sources
The CRFs of all admitted COVID-19-positive patients were analyzed retrospectively.
Patients having common and characteristic symptoms were identified.[32] Homeopathic medicines were prescribed to patients in addition to standard conventional
treatment.[33] Initially cases were prescribed after symptom repertorization, but later on, when
the symptoms of patients followed a commonly recognized pattern, the same remedy was
given. Prescribing indication(s) and the most prominent symptom(s) were specifically
recorded to assess potential effectiveness, despite concurrent use of a conventional
drug.
Results
A total of 196 patients were admitted during the time frame. Fifty-eight patients
did not give consent to receive add-on homeopathic treatment. The average age of patients
was 38.9 years (standard deviation, 16.3; range, 2–92 years); 54 (27.55%) were female
and 142 (72.45%) were male. The mean age of patients with mild symptoms was 38.6 ± 15.8
years. The mean age of patients with moderate symptoms was 66.0 ± 9.1 years. No patients
with severe symptoms were seen. Eighty-three (42.35%) patients had a positive contact
history, whilst the history was unknown for 113 (57.65%) patients ([Table 1]).
Table 1
Demographic details
|
Total
(n = 196)
|
Mild
(n = 178)
|
Moderate
(n = 18)
|
|
Age
|
|
|
Mean
|
38.9 ± 16.3
|
38.6 ± 15.8
|
66.0 ± 9.1
|
|
Median
|
35.5
|
35
|
68
|
|
Gender
|
|
|
Male
|
142
|
128
|
14
|
|
Female
|
54
|
50
|
4
|
The majority of patients (90.8%) were within the mild category (n = 178) and the rest (9.2%) were categorized as moderate (n = 18). A total of 153 (78%) patients were discharged after complete recovery of all
symptoms. Ten cases (5.1%) deteriorated due to persistent fever, breathlessness and
oxygen concentration <90%, and were then considered under the severe category. Remedies
were worked out after repertorization of these severe cases, but since the study hospital
setting did not have an intensive care unit to manage severe or critical cases, these
patients were transferred and could not be evaluated for outcome from the adjunctive
homeopathic medicines. The mean duration of stay of the 196 patients patients at NHMCH
was 13 days (10–17 days). The predominant symptoms of disease were cough (47.4%),
fever (43.4%) and sore throat (29.6%) ([Table 2]).
Table 2
Details of clinical characteristics of COVID-19 patients
|
Symptoms
|
n
|
%
|
|
Cough
|
93
|
47.45%
|
|
Fever
|
85
|
43.37%
|
|
Sore throat
|
58
|
29.59%
|
|
Headache
|
36
|
18.37%
|
|
Myalgia or arthralgia
|
35
|
17.86%
|
|
Fatigue
|
33
|
16.84%
|
|
Chest discomfort
|
27
|
13.78%
|
|
Shortness of breath
|
22
|
11.22%
|
|
Loss of taste
|
20
|
10.20%
|
|
Dryness of mouth
|
19
|
9.69%
|
|
Nasal coryza
|
17
|
8.67%
|
|
Constipation
|
16
|
8.16%
|
|
Diarrhea
|
13
|
6.63%
|
|
Abdominal pain
|
12
|
6.12%
|
|
Nausea
|
12
|
6.12%
|
|
Vomiting
|
10
|
5.10%
|
|
Nasal blockage
|
7
|
3.57%
|
|
Loss of smell
|
7
|
3.57%
|
|
Retrosternal burning
|
5
|
2.55%
|
|
Sneezing
|
5
|
2.55%
|
|
Hemoptysis
|
1
|
0.51%
|
Abbreviation: COVID-19, coronavirus disease 2019.
The detailed homeopathic clinical analysis of major symptoms revealed that fever was
predominantly low grade with prolonged heat stage (17.8%), with the concomitant symptom
of dryness of mouth (9.7%). Dry cough was reported in 50 (25.5%) patients, whilst
sputum during cough was reported in 43 (21.9%) patients. Amongst the 43 patients with
productive cough, it was observed that 28 (14.2%) had easy expectoration and 19 (9.6%)
had whitish sputum ([Table 3]).
Table 3
Detailed clinical analysis of chief symptoms
|
Chief complaint
|
Characteristic
|
|
Fever (n = 85) (43.3%)
|
Low grade (<37.5–38.3°C) (n = 62) (31.6%)
|
Chill (n = 18) (9.1%)
|
|
>38.3°C (n = 23) (11.7%)
|
Heat (n = 35) (17.8%)
|
|
Perspiration (n = 12) (6.1%)
|
|
Cough (n = 93) (47.4%)
|
Dry (n = 50) (25.5%)
|
Thirst increased (n = 30) (15.3%)
|
|
Productive (n = 43) (21.9%)
|
Expectoration:
|
|
Easy (n = 28) (14.2%)
|
|
Difficult (n = 8) (4.1%)
|
|
Color:
|
|
White (n = 19) (9.6%)
|
|
Yellow (n = 16) (8.1%)
|
|
Transparent (n = 3) (1.5%)
|
|
Bloody (n = 1) (0.5%)
|
Homeopathic treatment was provided to 138 patients alongside standard conventional
treatment. Cases were repertorized with Synthesis Repertory Radar Opus, with special
emphasis on characteristic symptoms. Repertorial analysis of the collective symptoms
of these patients indicated 28 medicines in total. Medicines were given in different
potencies (LM, 30C, 200C). The most frequently used medicines were Bryonia alba (33.3%), Arsenicum album (18.1%), Pulsatilla nigricans (13.8%), Nux vomica (8%), Rhus toxicodendron (7.2%), and Gelsemium sempervirens (5.8%). 30C was the most commonly used potency (n = 120) ([Table 4]).
Table 4
Homeopathic medicines prescribed (n = 138)
|
Homeopathic medicine
|
n
|
%
|
|
Bryonia alba
|
46
|
33.33%
|
|
30 C
|
32
|
|
|
200 C
|
14
|
|
|
Arsenicum album
|
25
|
18.12%
|
|
30 C
|
24
|
|
|
200 C
|
1
|
|
|
Pulsatilla nigricans
|
19
|
13.77%
|
|
30 C
|
17
|
|
|
200 C
|
2
|
|
|
Nux vomica
|
11
|
7.97%
|
|
30 C
|
8
|
|
|
200 C
|
3
|
|
|
Rhus toxicodendron
|
10
|
7.25%
|
|
30 C
|
9
|
|
|
200 C
|
1
|
|
|
Gelsemium sempervirens
|
8
|
5.79%
|
|
30 C
|
6
|
|
|
200 C
|
2
|
|
|
Sulphur
|
7
|
5.07%
|
|
30 C
|
2
|
|
|
200 C
|
5
|
|
|
Spongia tosta
|
5
|
3.62%
|
|
30 C
|
3
|
|
|
200 C
|
2
|
|
|
Hepar sulphuricum
|
3
|
2.17%
|
|
30 C
|
2
|
|
|
200 C
|
1
|
|
|
Phosphorus 30 C
|
3
|
2.17%
|
|
Lycopodium clavatum 30 C
|
2
|
1.45%
|
|
Ammonium carbonicum 30 C
|
1
|
0.72%
|
|
Calcarea phosphorica 30C
|
1
|
0.72%
|
|
Carbo vegetabilis 30 C
|
1
|
0.72%
|
|
Coccus cacti 30 C
|
1
|
0.72%
|
|
Ferrum metallicum 30 C
|
1
|
0.72%
|
|
Ferrum phoshorica 30 C
|
1
|
0.72%
|
|
Ipecacuanha 30 C
|
1
|
0.72%
|
|
Sanguinaria canadensis 30 C
|
1
|
0.72%
|
|
Stannum metallicum 30 C
|
1
|
0.72%
|
|
Aconitum napellus 200 C
|
1
|
0.72%
|
|
Belladonna 200 C
|
1
|
0.72%
|
|
Calcarea carbonica 200 C
|
1
|
0.72%
|
|
Camphora 200 C
|
1
|
0.72%
|
|
Cinchona officinalis 200 C
|
1
|
0.72%
|
|
Hyoscyamus 200 C
|
1
|
0.72%
|
|
Justicia adhatoda Q
|
1
|
0.72%
|
|
Baptisia tinctoria Q
|
1
|
0.72%
|
Subsequently, patients' expression (symptoms) and signs (objective clinical features)
of disease were extracted from CRFs. These were converted into rubrics (group keywords)
using a dictionary-based approach (repertory). This information was compiled for the
top six medicines: namely Bryonia alba, Arsenicum album, Pulsatilla nigricans, Nux vomica, Rhus toxicodendron,
and Gelsemium sempervirens ([Table 5]).
Table 5
Prescribing indications of remedies based on repertorial totality
|
Medicine
|
Rubrics
|
No. of cases observed
|
|
Bryonia alba
|
General: slow manifestation
|
46
|
|
Cough: dry, fever during
|
37
|
|
Stomach: thirst, large quantities, for
|
23
|
|
Stool: constipation
|
16
|
|
Generals: pain, bones, as if broken
|
16
|
|
Mouth: dryness
|
14
|
|
Fever: night, dry burning
|
11
|
|
Head: pain, cough during
|
10
|
|
Throat: dryness
|
9
|
|
Mind: irritability, during headache
|
8
|
|
Throat: pain, swallowing, agg.
|
6
|
|
Cough, motion aggravates
|
6
|
|
Head: pain, bursting
|
5
|
|
Head: pain, pressure ameliorate
|
5
|
|
Mouth: taste, bitter
|
5
|
|
Arsenicum album
|
General: weakness, fever during
|
21
|
|
Stomach: thirst, small quantities for
|
15
|
|
General: warm applications ameliorate
|
13
|
|
Fever with chill
|
13
|
|
Throat: pain, warm drinks ameliorate
|
12
|
|
Chest: pain, burning
|
10
|
|
Mind: anxiety, lying
|
6
|
|
Chill: morning
|
6
|
|
Extremities: pain, feet, soles, burning
|
5
|
|
Chill, alternating with perspiration
|
5
|
|
Pulsatilla nigricans
|
Mouth: taste, wanting, loss of taste
|
14
|
|
Stomach: thirstless
|
13
|
|
Expectoration, thick
|
11
|
|
Expectoration, yellow
|
11
|
|
Abdomen: pain, stool before
|
8
|
|
Nose: smell, wanting
|
5
|
|
Mouth: dryness, thirstless
|
5
|
|
Expectoration: difficult
|
5
|
|
Nux vomica
|
Chills: morning
|
8
|
|
Throat: pain, warm drinks ameliorate
|
8
|
|
Chill: violent
|
7
|
|
Mouth: taste, bitter
|
6
|
|
Chest: pain, burning
|
6
|
|
Rectum: constipation, ineffectual urging and straining
|
6
|
|
Mouth: taste, wanting, loss of taste
|
5
|
|
Stomach: vomiting, eating after, agg.
|
5
|
|
Abdomen: pain, burning
|
5
|
|
Nose: smell, wanting
|
4
|
|
Rhus toxicodendron
|
Extremities: pain, joints, chill during
|
8
|
|
Generals: pain, sore
|
6
|
|
Cough: warm drinks ameliorate
|
6
|
|
Mouth: taste, altered
|
5
|
|
Back: pain, sore
|
5
|
|
Throat: pain, warmth ameliorates
|
4
|
|
Extremities: pain, shoulders
|
4
|
|
Abdomen: pain, walking ameliorates
|
4
|
|
Gelsemium sempervirens
|
General: slow manifestation [of symptoms]
|
8
|
|
Stomach: thirstless during fever
|
7
|
|
General: weakness, fever during
|
7
|
|
Sleep: sleepiness, heat during
|
5
|
|
Head: heaviness
|
5
|
|
Head: pain, forehead, lying agg.
|
4
|
|
Head: pain, occiput, dull pain
|
4
|
|
Mind: quiet, wants to be, during chill
|
4
|
Discussion
The full-recovery rate of COVID-19-positive patients was 78% and the average duration
of stay in the hospital was 13 days. The condition of 5.1% patients deteriorated during
the study and they were referred to a tertiary care center with ventilator support.
Though improvement and recovery were observed in most cases, further studies are needed
to evaluate the outcome from homeopathic medicines on variables such as time to clinical
improvement and laboratory parameters.
Homeopathic medicines were given in conjunction with standard conventional treatment
and it was observed that most of the patients under this hybrid system (standard protocol
plus homeopathy) recovered without major complications. The effectiveness of the homeopathy
element of this combined protocol might be explored in subsequent studies by comparing
conventional treatment plus homeopathic treatment with conventional treatment plus
placebo.
Datasets from clinical studies conducted at various hospitals internationally were
compiled to compare their clinical and demographic features with those of Indian COVID-19
patients. Most of the top-ranking symptoms observed in this study were also found
in an observational study by Guan et al, except for much greater prevalence of sore
throat in the current study.[4] Similar comparison with data reported in a cohort study of 41 patients undertaken
by Huang et al in Wuhan underscores that finding.[34] Another similar study reported that Bryonia alba and Arsenicum album are the most frequently prescribed medicines (in 30C potency) for symptomatic COVID-19-positive
patients treated by homeopathic physicians in Italy.[35] Others reported that Bryonia alba and Gelsemium sempervirens were the most commonly prescribed medicines in 18 mild COVID-19 cases in Hong Kong.[36]
The current study has paved a way to conduct a multi-center, prospective, randomized
double-blind controlled trial of homeopathic medicines for COVID-19 patients using
the identified medicines.
COVID-19 has presented a challenge for the scientific community in terms of size of
dataset and heterogeneity. The homeopathy community is facing similar challenges in
terms of fragmented initiatives, lack of high-quality clinical data, unavailability
of trained manpower, issues with data collection, and lack of high quality observational
and controlled studies. Artificial intelligence systems such as “machine learning”
(ML) can play an important role in addressing these challenges.[37]
[38]
[39]
[40]
[41] Future studies in ML can provide data-driven clinical decision-making for improving
treatment outcomes, consistency in prescribing, identification of a set of medicines
useful in COVID-19, and identification of repurposed existing drugs. When large datasets
become available, ML algorithms will be used and reported in a future publication
from our research group.
Study Limitations
Although the majority of cases improved and were discharged, the positive outcome
cannot be solely attributed to homeopathic medicines since patients were also given
conventional drugs. This disease is also known for its self-limiting course of 5 to
14 days in mild cases, and there was no control arm to assess the effectiveness. The
institute had limited laboratory resources and no radiology support.
Conclusion
Data from the current study in New Delhi reveal that Arsenicum album, Bryonia alba, Pulsatilla nigricans, Nux vomica, Rhus toxicodendron and Gelsemium sempervirens were the most frequently indicated homeopathic medicines. It is desirable that randomized
controlled clinical trials are instituted using these medicines and their identified
indications.
