Among the more sobering moments at the UK Covid-19 inquiry over the past few weeks was the palpable dismay and affront shown by the mild-mannered NHS respiratory consultant Prof Chris Brightling, when he noted that Boris Johnson’s response to a Department of Health briefing on long Covid was to write “bollocks” across it in large letters. Brightling said he was “deeply saddened” and made “extremely angry” by the comment. “Does he mean bollocks to the science?” he mused, or “is it bollocks to the patients?” For the millions of sufferers whose lives, careers and finances have been shattered by the disease, it may be hard to disengage from the idea that this opinion fed into the disease being wilfully ignored. The inquiry is a reminder that even as public (and policy) attention span for all things Covid has inevitably waned, it is worth looking at the state of play for the many millions of patients, advocates and researchers around the world still very much grappling with long Covid. From where I sit – somewhere between the international long Covid medical research community, the patient support groups, and those running long Covid clinical services – I’d describe it as a rather bleak period, with a continuing crisis of confidence for all concerned. In each of these spheres there has come the stark realisation that the initial momentum (and with it, much of the funding) has fallen off the cliff edge. There have been incredible scientific advances in our understanding of the disease, but we are also learning how little we actually know. Gez Medinger, my colleague and co-author, has described the initial research as being like a huge jigsaw puzzle with some of the easy bits in place around the edge, and everyone trying to guess if the picture in the middle is of a horse or a steam engine. Some thousands of peer-reviewed publications later, many more pieces are in place and the edge of the jigsaw is going well, but we’ve come to realise that the disease – the way it works, and its symptoms – is so heterogeneous that we may actually have mixed up several jigsaws of horses, steam engines and sunsets, yet are trying to solve a single one from the jumbled pieces. This is similar to the state of diabetes diagnoses, before we stratified them into type 1 and type 2 and several states in between. It may be that someday what we now call “long Covid” will be stratified into several different disease entities. For researchers working in the many medical areas that appear to be affected by long Covid – such as blood coagulation, autoimmune disease, viral persistence, organ damage, or any number of others – the big picture remains challenging. How can these areas be pulled together in such a way as to make a real clinical difference? A new study published in Cell gives us a sense of the problem, as it reports intriguing new information about how long Covid may work, but also complicates our overall understanding. The results show that persistent coronavirus infection in the gut triggers an inflammatory response, impairing the gut’s ability to take in the amino acid tryptophan. This matters because tryptophan is needed to make the neurotransmitter serotonin – which can have an effect on everything from neurocognition and depression to vasoconstriction. This suggests long Covid may in time be helped by treatments such as tryptophan supplements, or drugs targeting serotonin signalling. It offers a new avenue for exploration, yet further complicates the big picture, as it adds a new effect and possible treatment approach to the many already being studied. In terms of long Covid clinics, sufferers elsewhere look at the UK with some envy in terms of an agreed and costed masterplan for ongoing national provision. However, services are uneven across the country, and many long Covid sufferers express their frustration at what they perceive as the lack of a substantive care pathway or therapeutic options to get them back up to speed. The comprehensive package of research programmes put into place by the National Institute for Health and Care Research (NIHR) in July 2021 will soon come to a hard stop. They have offered many important insights for future directions, but unsurprisingly – given how long medical research takes to deliver – no substantive answers that have yet cured anybody. Discussions in the world of long Covid sufferers now often turn to the incredibly harsh realities of terminated work contracts, medical retirement, or the search for part-time work from home. And evidence from those who suffered the closely related long-Sars after the 2003-04 outbreak is that the more severe cases may never return to their former lives and employment. In the US, there has been a call for a new “moonshot” of $1bn a year over the next decade for long Covid research. While it’s unlikely there’s the political appetite in the UK for such an approach, we have a track record, having led the world in the globally game-changing Recovery clinical trials for treating acute Covid-19 during the pandemic. With an estimated 3% of our workforce currently pushed out of the economy by long Covid, a fitting rebuttal to the “bollocks” comment would surely be to lead a programme of clinical trials that might get those people their lives back, with all this entails for boosting the economy. Danny Altmann is a professor of immunology at Imperial College London who contributed advice to the Cabinet Office on long Covid