What does covid have to answer for

The Longterm consequences of Covid

RNfinity | 11-09-2022

Long covid has left many people suffering in its wake, but when you see your favourite blogger complaining of long covid symptoms, having contracted it 2 weeks ago, whilst they swan around a swimming pool on a gifted trip, you can be forgiven for rolling your eyes a little.

Covid 19 is fast catching up with HIV as the most studied disease of all time, having racked up 100,000s research publications in the space of 2.5 years. It is primarily a respiratory illness, but infective diseases can spread throughout the body and cause multi-system effects.

Viral infections can also reside for many years within the cells of the body. Examples of this being HIV which can be controlled with antivirals, but not yet eradicated, and Hepatitis C which is now curable in up to 90% of patients. The problem arises in interpreting numerous patient symptoms in a new, potentially chronic, potentially multisystem infection. How does the scientific process discern between vague symptoms that could be caused by colds, flus, chronic fatigue anxiety and depression which may have been caused by the upheaval of lockdowns. In a rapidly developing pandemic, there is an urgent need for new information and there has been huge media interest, amplified by unprecedented global connectivity and at times sensational reporting; where human experiences can be propagated as memes and entrenched as social media groups. So what does peer reviewed science say about the long-term effects of covid?

Here we take a look. A meta-analysis (collation) of studies on Covid 19 which analyzed 15 studies selected from 18251 papers with had more than 100 study patients lists fatigue, headache, attention disorder, hair loss, stomach acidity, as the 5 most common symptoms (Sandra Lopez Leon et al 2021). A problem with these studies are variable definitions, lack of characterization of the patients pre covid and collection of other associated patient characteristics which predict the progress of covid such as age and previous medical conditions. Many researchers were limited in their study design; the pre disease data was largely unavailable, and most of the studies had to be retrospective as many aspects of the pandemic could not be predicted. Despite this, there is a picture of the constellation of symptoms that characterize long Covid as emerged.

There are also many objective disease markers which are prolonged in Covid-19; abnormalities on CT radiographs, for example, may persist in one third of patients beyond 60-100 days after hospitalisation. Hair loss can be a very emotive subject for both genders. A further study has documented that about 25% of patients post covid 19 infection reported hair loss (Askoy et al 2021). Although there are no controls (patients who did not have covid 19), this seems a lot higher than the expected and was also found to be higher in hospitalised versus non hospitalized patients. Erectile dysfunction seem to be associated with covid 19 (Kadir Karkin et al 2021). In this paper, pre diseases testosterone and self-reported erectile dysfunctions scores were recorded- which is a good study design- to assess patient for which there was already relevant pre-existing data . Covid 19 infection was associated with a significant reduction in testosterone levels and erectile dysfunction scores. The reduction was worse in patients who were admitted to intensive care. Interestingly low testosterone seemed to be a predictor of intensive care admission, though this could be confounded by an increased age. Erectile dysfunction is associated with metabolic syndrome (obesity, diabetes) and can be a precursor to heart disease, it may also be a predictor of severity of covid infection as well as a sequalae to covid 19 infection. As one Italian group put it “Mask up to keep it Up” (Sansone et al 2021) as a potential campaign to promote mask wearing in a subgroup of patient. There is evidence that covid 19 infection impacts on semen quality with some studies indicating a decline with a subsequent return to normality with time. Most studies do not have measurements of pre-covid semen analysis. One report from India where pre-covid semen parameters were measured indicate that abnormalities persisted four months after infection (Mannur et al 2021) but this is not a consistent finding in other studies (Aitken 2022).

Abnormalities in the menstrual cycle seem more common amongst women who had covid 19, with reports of decreased cycle length and decreased menstrual volume which could be related to the stress of illness (Phelan et al 2021). Abnormalities of sex hormones seem to be associated with covid 19, with raised pituitary hormones working to push the ovaries which are suppressed, actually a not dissimilar picture to that noted in men, where more severe diseases may be associated with androgen suppression, however in men the relationship between hormonal function and fitness differs do that in women, hormone reduction is largely related to the menopause rather than metabolic syndrome.

Weight gain versus weight loss, which is it? A PubMed (medical article database) search will lead to 681 articles investigating weight loss and 431 articles investigating weight gain. So is it neither or both? There are multiple factors at play and the pandemic and lockdown means different things in different countries. Weight loss could be associated with severe diseases, depression, and poverty, whilst weight gain could be associated with reduced physical activity, work or depression. Weight gain and weigh loss are interesting symptom, in that weight is a continuum and its gain and loss could be viewed as either negative or positive depending on the starting weight and the context, however all the articles investigating weight gain regarded weight gain as negative consequence and all the articles investigating weight loss regarded weight loss as a negative consequence.

By contrast most of the other articles on long Covid symptoms, are investigating some loss of function, for example hair loss or reduced mood. I could not find any articles reporting hair gain or improved mood. It may be that looking through a certain negative lens does not give the best sense of perspective. Even with the best study design, meaningful results are not possible if we are not asking the right questions. The most useful investigations are those which lead to universal answers; that lead to some truth that is applicable to everyone across the planet and whilst I am sure they will be many further investigations into Covid-19 weight change, I am not sure they will lead to any meaningful understanding of the condition as there seems to be no universal answers here.

Covid-19 was a terrible event, which sadly took many lives and will have lasting health consequences, from which the world is only just recovering. The challenges of adversity can lead to positive responses. In some ways there has been a unifying effect; people could empathize with the experiences of others across the globe and communicate their thoughts rapidly. The image of people wearing mask was universal throughout the globe, as were the words ‘stay safe’ which was incorporated into every marketing email, regardless of what was being promoted. There has been international collaboration, widespread policy changes, and vaccine rollouts that have saved millions of lives, together with enormous financial support to individuals and businesses. It has given some people time and space to reflect on their lives, perhaps know their neighbours better, spend more time with their family or less time, it has changed the way we work and communicate and collaborate, perhaps in ways that place less environmental and energy demands.

An interesting aspect of Lockdown is that that economy was restricted to core activity- food, energy, transport and healthcare, with vast numbers of people working reduced hours or not working at all, yet there was no change to the fundamentals, everyone had food and water and kept their homes, hospital and transport continued- in essence we had everything we needed. Off course there was an economic downturn with increased national debt, but there were no repossessions as per the credit crunch. This undoubtedly made people wonder what they were working for, and could this situation continue indefinitely? Were their jobs just to turn the wheels of an economy based on inessential (but perhaps desirable) goods and services and did this work and its associated stress serve themselves and society in the broadest sense?

Whilst we may have been fettered at home during lockdown, we may have developed some new goals, perhaps improve our core muscle strength, to quote Iliza Shlesinger, learn a new language via video classes, or finish writing a book. All this pales in significance to the work of Isaac Newton between 1665 and 1666 where he was quarantined in Woolsthorpe to escape the plague. During that period, he is purported to have discovered the laws of motion and calculus, though he only published his work in 1887 and this was likely a continuous process of discovery over many more years. Many people have said that the time of the pandemic years seem to drag on forever. This could be due to boredom but in some cases, this could be due to breaking routine and gaining new experiences. It all depends on how we chose to use our time, if we were in a fortunate position.

As far as publishing is concerned, many opportunities were created for those in medicine, however there were also pitfalls created by huge public interest and constraints on study design, given the rapidly evolving situation, and pressure on researchers and journals to disseminate information quickly. Some of this led to scandal and work being redacted, even in high-ranking journals. As far as long Covid goes, more research needs to be focused on its mechanisms of action and treatment. It may give us an insight into potentially similar conditions such as chronic fatigue or ME (myalgia encephalomyelitis).