The lung infection caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), also known as COVID-19 pneumonia, is a major life-threatening complication of moderate to severe COVID-19 infection, which develops rapidly and would prove lethal if not addressed timely. Since the start of the pandemic in late 2019, it has been observed that SARS-CoV-2 tends to develop variants with variation in the clinical course and health impact, leading to infection waves across the globe. Many countries are going through a third wave of infection leading not only to human morbidity and mortality [1] but also crippling the global economy [2]. The ultimate solution to this problem is considered mass vaccination; however, the development as well as distribution of the vaccines remain slow and are affected by various complex factors [3]. In this situation, it is highly important that effective drug treatment must also be made available to the masses to reduce the impact of the pandemic. Although few drugs such as remdesivir and ritonavir have been approved for use in COVID-19, heavy treatment costs have increased the burden on the already compromised socioeconomic condition of society by and large [4], thus not being very propitious. Hence, it remains as relevant as the beginning of the pandemic to repurpose existing drugs to treat masses within the community. Drug repurposing helps to treat a patient at a low cost, with confidence in the safety profile of the drug and a shorter timeline for establishing therapeutic benefits if any [5]. An example of drug repurposing is azidothymidine, which was developed for the treatment of cancer but was beneficial in the treatment of human immunodeficiency virus. Similarly, ivermectin has been increasingly tried and tested in COVID-19 with promising results [6]. Traditionally, drug repurposing occurred in serendipity, now it has garnered the attention of researchers and is done with rationality [7].

At the start of the pandemic, hydroxychloroquine and azithromycin (AZI) were used and advocated for the treatment of COVID-19 but later it was known that these did not improve the clinical outcome [8,9]. However, other drugs would still require to be tested and trialed appropriately to explore their therapeutic benefits in COVID-19 infection.

One such drug is antibacterial teicoplanin, known for its ability to inhibit entry of coronaviruses in host cells [10] and this property can be useful to treat COVID-19 patients. In fact, it has shown in vitro activity against SARS-CoV-2, and other viruses such as Ebola, Flavivirus, and Hepatitis C virus [11]. Here, we report our experience of using teicoplanin to treat proven cases of COVID-19 pneumonia and discuss its potential for being used in this pandemic.

As the morbid situation struck the economy in a bad way, we have to find options that are readily available, cost-effective, and provide better results thus reducing the morbidity and the mortality of patients. Among the antibiotics most readily used was AZI, further options were tried in case of resistance is suspected.

This is a pilot case-control study conducted from March 2020 to April 2021. The research was conducted in accordance with the Declaration of Helsinki and national and institutional standards. The Ethical Review Committee of our institution approved the study with reference no. 00045/20. The diagnostic investigations included polymerase chain reaction testing for SARS-CoV-2, immunoglobulin titers against SARS-CoV-2, pulmonary radiological features [plain radiography and/or high resolution CT scan (HRCT) scan] inflammatory markers, such as C reactive protein (CRP), and additional investigations depending upon the presenting clinical picture and comorbidities. The mild-to-moderate COVID-19 patients who received AZI 500 mg PO daily for 7 days, were considered as the control group, while the cases comprised of moderate-to-severe COVID-19 pneumonia patients who received teicoplanin 400 mg 12 hourly on day 1 and then 400 mg daily for additional 9 days.

The general and clinical data of all patients were collected by a questionnaire that included age, gender, history of recent travel or COVID-19 exposure, and significant medical history. A total of 39 patients were included in the study.

The primary and secondary outcomes of the study are described previously [6]. Briefly, the primary outcomes included the limitations on activity due to illness, the need for hospitalization, the need for supplemental oxygen therapy, and/or ventilation by the 14th day of starting treatment. While the secondary outcomes included the same parameters recorded on an interim basis by the 7th day of starting treatment.

The groups were compared using the chi-square test or Student’s t-test where applicable. Odds ratios with a 95% confidence interval were computed for primary and secondary outcomes. In all analyses, only a p-value <0.05 was considered significant.

Further all symptoms were assessed for efficacy and chi square was applied to denote differences.

A total of 39 patients, including 12 females and 27 males diagnosed with COVID-19 were included in this study, who had received antibacterial drugs AZI (n=19) or teicoplanin (n=20) as part of the treatment. The baseline characteristics as well as therapeutic outcomes are given in Table 1 and Figure 1. Table 2 shows the symptoms and days of admission with changes in symptoms. The patients presented with typical syndrome including fever, body ache, lethargy, loss of smell sensation, and respiratory complaints. Since AZI was given to COVID patients suffering from mild disease and teicoplanin to patients suffering from moderate disease, both groups differed in their oxygen saturation, shortness of breath, need for oxygen therapy, total leukocyte count, as well as plasma levels of CRP, lactate dehydrogenase (LDH), and ferritin. The laboratory parameters are shown in Table 3. Despite this difference, the teicoplanin group had a consistent and significantly lower prevalence of fever on days 7, 10, and 15, showing recovery from their febrile illness earlier than the mild disease. Despite suffering from a severe form of the disease and established pulmonary involvement, the teicoplanin group showed a more rapid resolution of their cough as well as improvement in dyspnea. Teicoplanin group also showed rapid weaning off supplemental oxygen, with a strong coefficient value (R²=0.67), thus, suggesting a beneficial effect of teicoplanin in COVID pneumonia and a recovery rate better than the mild disease. Similarly, they had a significantly quicker tendency to recover from the loss of smell sensation by day 15.

This pilot study shows that teicoplanin use is associated with reduced duration of febrile illness in COVID-19 pneumonia and a quicker recovery from COVID-19 infection. It is interesting to note that the control group had a similar presentation but a relatively milder clinical course, thus making it a relevant comparison. Interestingly, despite having a severe form of the disease, the recovery was better and quicker as evidenced by the resolution of febrile illness, improvement of clinical symptoms, and reduction in biochemical markers of inflammation and tissue damage in the teicoplanin group, which could only be explained by a clinical antiviral activity of the drug, as AZI has failed to show a definite antiviral activity in COVID-19.

Teicoplanin and other glycoprotein antibiotics have been proposed as potential antiviral drugs for COVID-19 [11]. However, the clinical data is very limited and only at a preliminary stage. A small European study showed that teicoplanin use could clinically improve severe COVID-19 patients hospitalized in an intensive care unit, although, no statistical significance was achieved [12]. However, their study had several limitations and failed to show any therapeutic benefits. Thus, the present study provides an improved design and forms the basis of larger and prospective studies in this regard.

There are several advantages of this study. This study included a more homogenous group of patients suffering from COVID-19 pneumonia presenting at a single center. All had proven pulmonary involvement as evidenced by an HRCT scan or chest X-ray and documented molecular evidence of acute COVID-19 infection. Their clinical course was relatively stable and that made the cohort very useful in avoiding being a mixed population of patients which could lead to serious statistical bias. It was possible to have markers of tissue damage and systemic inflammation at specified intervals making it possible to see any trends of improvement as shown in Figure 1. Teicoplannin could become the drug of choice in COVID-19 infections, as stated because of its efficacy in treating the infection. Teicoplannin stops the replication of the virus and stops the super imposed infections [13]. Various drug therapeutics have been investigated and used to attain therapeutic benefits in treating COVID-19. Various vaccines are also tried to attain cost effectiveness [14]. Hurt stated the use of antibodies in therapeutics of COVID-19, they also reviewed resistance to new anti-viral regimens [15].

During the pandemic, we used various combinations to achieve therapeutic benefits. Certain drugs proved better than others in terms of response, cost-effectiveness, and availability.

There are some limitations of this study such as a case-control design and small sample size. The absence of severely ill or hospitalized patients in the control group is another limitation but since the result clearly shows a potential advantage in COVID-19 pneumonia, the effects of this limitation are minimal. Adequately designed randomized trials are needed to validate the results of this study and provide evidence for the clinical use of teicoplanin in COVID-19 infection.

In conclusion, the glycopeptide antibacterial drug teicoplanin used in COVID-19 infection seems to be a safe and well-tolerated drug that could shorten the duration of febrile illness in moderate-to-severe COVID-19 patients. The results of this pilot study should be verified through a well-designed randomized controlled trial to establish the efficacy of teicoplanin in coronavirus infections among patients who have various levels of disease severity.

A preprint version of this manuscript is available at ResearchGate and can be accessed at DOI: 10.13140/RG.2.2.17778.63683.

There is nothing to declare.

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