The COVID pandemic was officially declared over more than 3 years ago. Today, 6 years after the identification of SARS-CoV-2 — the virus that brought much of the world to a near standstill — fear of infection seems to have all but disappeared. Although various aspects of the pandemic continue to be debated, COVID has largely faded from public consciousness as a potentially severe illness.

On the one hand, this is because nearly all subvariants currently circulating are descendants of the comparatively less pathogenic Omicron variant, and acute cases are therefore generally milder than those seen at the start of the pandemic. On the other hand, repeated exposure to the antigen has led to a high level of baseline immunity in the population as a whole. National health authorities have taken this changed situation into account and adjusted their vaccination recommendations. As a routine vaccination, immunization against COVID is now recommended only for older adults; as an indicated vaccination, it is recommended only for those with certain underlying medical conditions. Both are undoubtedly positive developments — but they also risk obscuring the ongoing presence of the virus, which has claimed 7.1 million confirmed lives. According to estimates from the World Health Organization, the actual number is likely to be far higher: SARS-CoV-2 may have caused 22 million deaths worldwide.

Those who, contrary to expectations, experience severe illness or continue to suffer from the aftereffects of infection are no longer the focus of media coverage. This is another reason why COVID is now perceived as little more than a mundane seasonal infectious disease and — similar to influenza — its potential health risk is underestimated. The likelihood of being hospitalized with COVID or dying from it may have fallen substantially. However, for many people, infection still leads to severe illness; inability to work and subsequent, long-lasting health limitations are not uncommon.

An assessment of the COVID situation in 2026 highlights two medical priorities: improving the treatment of COVID sequelae and evaluating the effectiveness of existing therapies for the prevention of long COVID and post-COVID syndrome (PCS).

Long COVID/PCS: The Long Shadow of the Pandemic

Long COVID and PCS refer to sequelae triggered by COVID that vary in intensity and duration. Although the two terms are often used interchangeably, they have now become established as distinct descriptions for symptoms that persist after a COVID infection. Long COVID is defined as postacute symptoms lasting more than 4 weeks, whereas PCS is defined as postacute health impairment lasting more than 12 weeks. Long COVID and PCS will continue to pose a significant public health challenge even after the pandemic has ended.

Based on the current state of research, it can be assumed that up to 10% of all symptomatic cases develop persistent symptoms. In recent years, the risk associated with new infections has decreased because strong immune protection is already in place and the circulating variants have become less pathogenic. For example, the British Virus Watch study shows that the risk for long-term COVID effects following infection with the wild-type virus and the Alpha, Delta, and Omicron BA.1 variants was significantly higher at 27%-34% than with later Omicron subvariants (11%-14%).

Worldwide, however, approximately 5 million people still suffer from sometimes severe physical and psychological exhaustion, as well as inflammation, cognitive impairment, pain, and dyspnea. Compounding the problem is the fact that the significant burden on those affected is often not fully recognized by those around them or is even downplayed, and therapeutic approaches are still largely in their infancy.

The duration of symptoms is prognostically significant. Several prospective cohort studies from recent years have shown that the longer a person suffers from the consequences of the disease, the poorer the prognosis. In particular, patients who meet the criteria for myalgic encephalomyelitis/chronic fatigue syndrome often show no significant improvement in their symptoms over a very long period of follow-up.

Medical care, support, and rehabilitation for patients with long-term illness also incur high costs. In April of this year, the Organisation for Economic Co-operation and Development (OECD) published a report on the direct and indirect economic impacts of long COVID and PCS. These impacts are enormous: Despite conservative estimates, OECD economists project an additional annual cost of USD 11 billion to healthcare systems over the next 10 years. According to their calculations, the annual gross domestic product of OECD member states could decline by 0.2% due to the burden of long COVID/PCS; they estimate the total economic burden at USD 135 billion per year.

To contain the “long shadow of the pandemic” — as the authors aptly describe the health and economic consequences of long COVID/PCS — there is one key area of focus: prevention.

Focus on Preventing Long-Term Effects

Current research efforts are primarily focused on treating long COVID and PCS but have not yet led to established therapies. Increasingly, however, attention is turning to medications that might prevent the development of long-term sequelae after COVID. Several candidates are currently being tested, and promising results are already available for some of them. Among these is the most commonly used COVID-specific acute medication, nirmatrelvir/ritonavir (Paxlovid).

The two components of this drug combination are protease inhibitors. While nirmatrelvir was specifically developed as an inhibitor of the main protease of SARS-CoV-2, ritonavir has been used for decades as part of antiviral combination therapies. The drug was an obvious candidate for closer investigation: Previous studies have shown that infections with Omicron subvariants rarely lead to severe illness or hospitalization, and that nirmatrelvir/ritonavir offers little benefit in this regard. However, treated patients have a lower viral load and recover more quickly from the illness.

It therefore made sense to investigate whether the two active ingredients could also reduce the incidence of long COVID. Evidence for this comes from a recently published, placebo-controlled clinical trial from Norway, PANORAMIC Norway. In this study, the authors showed that administering nirmatrelvir/ritonavir during the acute phase of infection can significantly reduce the risk of developing long COVID within 3 months and may therefore also be suitable for long-term prevention. This is consistent with findings from previous retrospective studies. However, due to the small study population in PANORAMIC Norway, further research is needed to confirm the potential preventive effect of nirmatrelvir/ritonavir in a large cohort.

Metformin, ivabradine, agomelatine, and vortioxetine are already being used off-label for the prevention of long COVID. They are available by prescription for this indication in Germany and many other European countries.

Continued Search for Effective Therapies

The treatment of patients who are already severely affected by long COVID/PCS must, of course, not be neglected. Two approaches are intended to ensure improved treatment options: In addition to the development of new drugs, already approved medications are also being evaluated for their potential efficacy. However, no true game-changers for long COVID have been identified so far.

Promising candidates for drug repurposing for long COVID included, among others, the antihistamines loratadine and famotidine, the gout medication colchicine, and the direct oral anticoagulant rivaroxaban. However, a large, randomized study published in The Lancet in July, which was conducted at 12 specialized long COVID clinics in the UK, failed to deliver convincing results. Participants in the phase 3 trial were randomized into four cohorts and, in addition to standard therapy, received 500 μg of colchicine twice daily, 10 mg of rivaroxaban once daily, 40 mg of famotidine once daily, and 10 mg of loratadine once daily — or no additional medication — for 12 weeks.

The primary endpoint was fatigue after 12 weeks; the secondary endpoint was fatigue after 24 weeks, both assessed using the Fatigue Assessment Scale, with a change of more than 10% considered clinically relevant.

An improvement in fatigue was observed after 12 weeks in all four groups, with slightly better results than in the control group for the colchicine and famotidine-loratadine groups. The benefits were lost again after the medications were discontinued. The study team concluded that long-term improvements with these medications will likely only be achievable in combination with other therapies. No additional improvement was achieved with rivaroxaban.

Despite these disappointing results, progress has been made in the treatment of patients with long COVID. Such progress is generally attributable to intensive multidisciplinary collaboration. For clinical practice, the European Respiratory Society has made its current clinical guideline on the prevention and treatment of long COVID available.

Controversy Over SARS-CoV-2 Origin Persists

SARS-CoV-2 has not only brought medical and public health challenges. Coping with the greatest health crisis in many decades has led to divisions in society, the effects of which have not yet fully subsided even after the pandemic was declared over. Discussions continue regarding the effectiveness of individual measures to contain the infection and how to evaluate the newly developed vaccines.

Many of these discussions are emotionally charged and lack a factual basis on social media. They are among the long shadows that the pandemic still casts — and for which no effective treatments yet exist.

Scientists who speak out against the political exploitation of fears stemming from the pandemic, against the denial of facts, and against targeted medical disinformation are increasingly subject to attacks. We see this particularly clearly in the US, where public health policy has, at times, shifted away from an evidence-based approach, contributing to confusion and diminished trust in government health organizations.

This strategy of confusion, misinformation, and personal defamation is aided by the fact that the origin of SARS-CoV-2 has not yet been clarified. The virus that triggered the pandemic lends itself to all kinds of conspiracy narratives as long as its origin remains unknown. This means that the so-called “lab theory” — which, in its most prevalent form, posits that the virus was engineered and escaped from a Chinese research lab — can repeatedly be turned into a political issue, despite all evidence to the contrary. Everything currently known about SARS-CoV-2 points instead to a natural origin, and that assessment remains unchanged.

Will the shadow cast by the most improbable theories about the virus’s origin eventually fade? Presumably only if, one day, a direct predecessor of SARS-CoV-2 is found in nature. The first SARS pandemic demonstrated just how difficult this search is — it took more than 10 years to find a very likely predecessor of SARS-CoV-1. The virus from which SARS-CoV-2 evolved most likely exists somewhere in a cave inhabited by bats — and it is to be hoped that it will be discovered at some point.

This story was translated from Univadis Germany, part of the Medscape Professional Network.