A worker in PPE disinfects the inside of a passenger train after it was converted into an isolation facility, near Kolkata, April 2020. Photo: Reuters/Rupak De Chowdhuri.
India, which has a quarter of the global tuberculosis cases, faces the grim prospects of COVID-19 pandemic disrupting its already over-burdened healthcare system struggling with tuberculosis and HIV, and putting a spanner in the country’s efforts to eliminate TB by 2025.
Many of India’s 1.3 billion people resides in densely populated, resource-constrained settings, which puts them at risk for any emerging outbreak. In addition, the burden of chronic diseases such as tuberculosis (TB), HIV and malaria puts further pressure on the health system, say a team of Indian medical researchers in the International journal of Tuberculosis and Lung Disease (IJTLD). They include experts from the National Institute of Tuberculosis and Respiratory Diseases, Vallabhbhai Patel Chest Institute and AIIMS, all in New Delhi, and from institutes in Spain and France.
India, which confirmed its first case of COVID-19 on January 30, currently has the world’s third highest number of cases even following a lockdown, although the latter has been widely panned for being ill-planned and callous. The lockdown was also a major hurdle for TB patients seeking care and has resulted in delays in diagnosis and treatment, scientists cautioned in their correspondence to IJTLD. The lockdown has also forced many migrant workers to return to their homes, leading to interrupted treatment regimens, which medical experts fear will increase the incidence of multi-drug resistant TB.
The International Union Against Tuberculosis and Lung Disease is concerned about the impact of COVID-19 on TB services, says Grania Brigden, director of its department of tuberculosis. “It is vital that TB services continue and that people with TB are diagnosed and started on treatment.”
At present there is little data to conclude what kind of impact COVID-19 infection would have on TB patients. But should outcomes worsen, it is important to continue TB prevention activities and even scale them up to prevent any worse outcomes, she adds.
Some scientists elsewhere are making projections based on models. For example, a model developed Nimalan Arinamapthy’s and colleagues from Imperial College, London, predict that there could be a 70% reduction in TB testing lab capacity and availability of health care staff in India.
Arinamapathy cautioned in a webinar in June that even a moderate lockdown of two months followed by two months of recovery would result in “an escalation of TB burden for the next 2 years in India”.
“I am worried about how COVID-19 lockdown and travel ban might disrupt supply chain and production of ARVs and anti-TB medicines,” says Madhukar Pai, director of the McGill International TB Centre and of the McGill Global Health Programs. He suggests India must proactively protect drug supplies and make sure there are no major stock-outs of critical medicines – “not just for Indian patients, but for the whole world that relies on Indian generics.”
As the lockdown extended, there were reports of huge drop in TB notifications and people with TB symptoms are not care seeking, points out Pai. “What about known TB patients? Are they getting TB medicines? Can they be contacted via phone and supported via tele-consultations? Can we send them TB drugs via couriers or via local pharmacies that might be open? Can we give them medicines for at least two to three months, to ensure adherence? These are some practical things that could be done to prevent complete disruption of TB care.”
Adding to the problem are the fears of health care workers about the new infection whose knowledge is still evolving. A top microbiology expert who is overseeing management of cases in a leading public-funded hospital in India says that COVID19 is taking a heavy toll on all resources. Both HIV and TB are less infectious as compared to novel coronavirus. Meanwhile, as had happened in the early years of HIV out break and treatment in India, health care workers are mostly scared of managing COVID 19 patients as compared to any other disease. “Before this, I have seen this scare to only HIV patients,” he adds.
There are additional concerns over shortage of hospital beds and ventilators. The National Health Profile 2019 data indicates approximately 714,000 available government hospital beds, which works out to 0.55 beds per 1000 population. The Indian government has begun to mobilise beds for isolation and management of COVID-19 patients. However, this may lead to the reduced availability of beds for TB patients who are critically ill or require hospitalisation for management of adverse drug reactions.
Besides, TB facilities and services, a huge uncertainty is the impact of COVID-19 infections on TB patients with impaired lung health, and whether medications cross-react. While experts point out that, in the absence of specific treatment for COVID-19, it is too early to talk of cross-reactions between drugs given for the three conditions; but matters are not helped by paucity of data at this stage.
“Given that COVID-19 affects the lungs, we are concerned that co-infection in people with TB could cause worse outcomes either with regards to the severity of the COVID-19 infection but also their TB infection,” says Brigden. “The Union is also concerned about the impact of COVID-19 on TB survivors who are often left with residual lung damage following their TB disease,” she says. “We believe it is important that data are collected on people’s previous medical history so we can establish if this group of people needs additional protection against COVID-19.”
“There is nothing published at this point, but we know that TB and HIV are immune-suppressive diseases, and that might increase vulnerability to COVID-19,” says Pai. TB patients often have lung damage, and it is possible that they might have poorer outcomes if they also developed pneumonia due to coronavirus.
Another worrisome issue is that TB patients often have additional conditions or risk factors such as malnutrition, diabetes, HIV, smoking, and homelessness. These might also increase the risk of adverse outcomes after COVID-19, according to Pai.
Brigden says that at the moment, there is little data on the impact of COVID-19 on TB or of TB on COVID-19. But there is “very early data from China showing people with TB appeared to be more susceptible to COVID-19 and had a more severe COVID-19 infection.”
“It is of vital importance that we continue to collect data on the TB status of people with COVID-19 to gather more evidence on the risk of co-infection,” as such scientific evidence is paramount in guiding policy making, she adds.
Microbiologists do not expect any interaction between drugs for TB and those given to treat COVID-19 patients, mainly antipyretic agents (like paracetamol) to bring the fever down, and anti-allergens. Neither are preventive medicines such as the anti-malaria drug hydroxyl chloroquine (HCQ) and the antibiotic azithromycin expected to interact with drugs given to treat HIV and TB.
That said, people on ARVs or MDR-TB medicines often have adverse effects, such as liver toxicity, “and we don’t know if they will tolerate COVID-19 treatment less well because of that,” says Pai. Although it is hypothesised that anti-retrovirals might have a beneficial effect on coronavirus, this is not proven, he says. One trial reported that hospitalised adult patients with severe COVID-19 had no benefit with lopinavir-ritonavir treatment.
“Indirectly though, the COVID19 epidemic might have a significant impact on TB,” says a top Indian microbiologist. It is expected to have a positive impact on TB incidence (due to mass masking, and improved hand hygiene and cough and sneezing etiquette), but because most of the health delivery system is busy in COVID19, a negative impact might be seen on the outcome of multi-drug resistant (MDR) and extensively drug resistant (XDR) cases.”
But others, like Pai, point out that since coronavirus infection has no specific drug treatment at present, one nedn’t worry about drug-drug interactions. “But people on ARVs or MDR-TB medicines often have adverse effects such as liver toxicity and we don’t know if they will tolerate COVID-19 treatment less well because of that,” he says. Although researchrs have hypothesised that anti-retrovirals might have a beneficial effect on coronavirus, this is not proven. One trial reported that hospitalised adult patients with severe COVID-19 had no benefit with lopinavir-ritonavir treatment.
As with TB, there is little data on the impact of COVID-19 on people living with HIV. “At present, there is no evidence to suggest that there is an increased risk of infection and increased severity of illness for people living with HIV, provided that they are not immunosuppressed or have no other co-infections or co-morbidities,” says Brigden.
In theory, based on previous coronavirus outbreaks – including SARS and MERS – researchers argue that people living with HIV who are on treatment have a high CD4 count and low viral load. They should, therefore, not be at increased risk, and will be affected by COVID-19 in a similar way to what a person not living with HIV would be, says Brigden.
It is likely that those whose HIV status is unknown or are not on treatment with suppressed immunity will be more at risk, says Brigden. “But again the evidence is not known,” she adds. People living with HIV who are not on treatment or who are not virally suppressed may have a compromised immune system – measured by a low CD4 count – that makes them vulnerable to opportunistic infections and more severe illnesses.
As the COVID-19 pandemic extends into high-burden TB and HIV countries, more data and evidence on the effects on these populations will become known.
T.V. Padma is a freelance science journalist.