The present study was a retrospective study, conducted in Department of Microbiology, Atal Bihari Vajpayee Institute of Medical Sciences, Dr. Ram Manohar Lohia Hospital, New Delhi, Hospital which is a tertiary care centre in North India. The data was collected from 15^th September 2020 to 15^th January 2021 from the entries included in the department record registers, which incorporates all the samples received for testing by the department along with the appropriate patient credentials. The data was analysed in the month of February 2021.

Inclusion criteria: Patients more than 18 years of age, either sex were included in the study.

Exclusion criteria: Extrapulmonary samples and samples received from patients <18 years of age were excluded from the study.

Sputum/endotracheal aspirate or bronchoalveolar lavage samples received from non COVID-19 (n=1094) and COVID-19 ward (n=150) for MTBC detection by Cartridge Based Nucleic Acid Amplification Test (CBNAAT) by Cepheid^®, a molecular based method, were included in the study. All the samples included, were from admitted patients who presented with complaints of Influenza Like Illness (ILI) and Severe Acute Respiratory Illnesses (SARI) such as cough, fever, chest pain, breathlessness. Considering the ongoing pandemic, nasopharyngeal and oropharyngeal swabs were collected and RT-PCR was done to detect Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-COV-2) infection in all patients prior to the ward admission by commercially available RT-PCR kits. The patients detected for SARS-COV-2 were admitted in COVID-19 ward and those who were negative for SARS-COV-2 were admitted in non COVID-19 ward.

The data entry was done in the Microsoft Excel spreadsheet and the final analysis was done with the use of SPSS software version 21.0. Two by two contingency table was used for calculating the Odd’s ratio.

A total of 1094 samples were received from non COVID-19 ward and 150 from COVID-19 ward during the study period. Out of 1094 (age distribution 18-76 years), 601 were males and 493 were females. The mean age in males was 45.25 years and in females was 38.76 years. Similarly, out of the 150 COVID-19 positive patients (age distribution 19-85 years), 80 were males and 70 were females. Mean age in males was 40.24 years and mean age in females was 35.67 years.

Distribution of MTBC positive status in the COVID-19 vs non COVID-19 patients is shown in [Table/Fig-1]. The Odd’s ratio/RR of TB infection in COVID-19 infected patients was 3.08, (CI) 95%.

Of the 98 non COVID-19, MTB infected patients, 58 were males (mean age 35.63 years) 40 were females (mean age 36.22 years) (male:female 1.45:1). Of the 30 TB/COVID-19 co-infected patients, 20 were males (mean age 32.76 years) and 10 females (mean age 28.34 years) (male:female 2:1). All were newly diagnosed cases of active TB. Only two (both females) had Multidrug Resistance (MDR) TB. Three (10%), (two males and one female) succumbed to the diseases and rest 27 (90%) were discharged.

In September 2020, the Indian Ministry of Health and Family Welfare (MoHFW) stated that due to the COVID-19 pandemic there was an overall decline by 26% in TB notification during the period of January to June 2020, when compared to previous year [8]. It is noteworthy that apart from impact of COVID-19 on the NTEP, studies have also stated that active as well as latent TB is an important risk factor for SARS-CoV-2 infection, which results in increased susceptibility, development of severe symptoms and rapid disease progression associated with poor outcomes.

In present study, authors have compared the positivity of TB in COVID-19 group vs the non COVID-19 group. It was observed to be more than twice when compared to the non COVID-19 group (20% vs 8.96%). The odds ratio calculated was 3.08. This was similar to reports by other studies [9]. This can be justified by the temporary immunosuppression induced by TB, which may increase the susceptibility of patients to COVID-19, and vice-versa [10]. In other words, immunologically the TB/COVID-19 co-infection has the potential to converge into a "perfect storm". This immunomodulation disturbance induced by each pathogen leads to a conducive unchecked inflammatory response, which worsens the morbidity and mortality [7].

There was no gender preponderance observed in the COVID-19 positive group (80 males and 70 females). This was similar to the data of a brief report published by World Health Organisation (WHO) which shows a relatively even distribution of COVID-19 infections between women and men (47% versus 51%, respectively) [11]. However, in the present study it was found that the co-infection of TB and COVID-19 was more in males as compared to females (2:1). This finding was similar to a recently published review article in January 2021, in which many included studies have has stated co-infection more in males than females [7]. Similarly, the TB in non COVID-19 patients was more in males than females (1.45:1). In our setting this can be explained by the fact that in India, TB infection/LTBI is more common in males than in females.

The mortality was 10% in present study, which was comparable to studies by Tadolini M et al., and Motta I et al., which reported respectively 12.3% and 11.6%, mortality in patients co-infected with TB and COVID-19 [12,13]. None of the demised COVID-19 infected patients had any other co-morbidities than TB. Also, all three were infected by a Rifampicin sensitive TB strain. A recent review article published by Mousquer GT et al., has stated that higher mortality in TB/COVID-19 co-infection is due to an acute, secondary abuse in a previously compromised TB [7]. Amongst COVID-19 patients in India, around 2.3% mortality rate has been witnessed including patients with co-morbidities such as hypertension, diabetes and malignancy [14]. This was observed to be much higher in patients co-infected by TB. An observational study from Wuhan, found Mycobacterium tuberculosis infection to be a more common co-morbidity for COVID-19 (36%) and suggested that individuals with latent or active TB were more susceptible to SARS-CoV-2 infection [15].

Tuberculosis and COVID-19 have certain similarities- both present with fever, cough and breathlessness and they mainly invade susceptible population through droplet transmission [16]. Understanding the nature of the interactions between Mycobacterium tuberculosis and SARS-CoV-2 will be crucial for the development of therapeutic strategies against co-infection. Therefore, it is important that all LRTI patients are investigated for both SARS-COV-2 and TB as per the bi-directional TB/COVID-19 screening NTEP guidelines. A recent press release from MoHFW, January 2021, stated “The fight against TB needs to be made into a Jan Andolan, a people’s movement”. The release stated that an effective approach is required which should mainly aim at reaching the maximum population; should supplement the existing strategies of preventive, diagnostic and curative aspects of TB management; should work towards demand generation; ensuring mass-media coverage; and with special spotlight on community participation and mobilisation [17].

Due to substantial burden in both COVID-19 RT-PCR and CBNAAT for TB samples, bidirectional testing for all the samples could not be done which is need of the hour. Further prospective studies are required to generate structured algorithms for diagnosis and management of COVID-19- TB co-infection and its outcome.

Amidst the rising number of cases and deaths due to COVID-19, it is imperative to not forget TB. Authors have observed that the chance of contracting TB with COVID-19 infection is increased by three times (RR-3.08, CI-95%). Hence, it is important that all LRTI patients should be investigated for both SARS-COV-2 and TB.