key: cord-252818-1gms4zw3
authors: Bouayed, Jaouad; Bohn, Torsten
title: Behavioural manipulation ‐ key to the successful global spread of the new Coronavirus SARS‐Cov‐2?
date: 2020-08-19
journal: J Med Virol
DOI: 10.1002/jmv.26446
sha: 
doc_id: 252818
cord_uid: 1gms4zw3

Human‐ SARS‐CoV‐2 interaction can have an array of various outcomes – it could be mortal, morbid or merely carrying minor health consequences. The very rapid global spread has raised the issue whether there are further multi‐dimensional consequences of SARS‐CoV‐2 infection on human behaviour, the key of its transmission. During the coronavirus crisis, odd, abnormal, and irresponsible behaviour has been reported in COVID‐19 individuals, particularly in super‐spreaders, i.e. persons with a high viral load, thus constituting also super‐emitters. Indeed, cases of infected persons ignoring self‐confinement orders, intentionally disregarding physical distancing and multiplying social interactions, or even deliberately sneezing, spitting or coughing were reported. While it is known that some other viruses such as rabies and even influenza do change human behaviour, this remains unclear for SARS‐CoV‐2. In this perspective, we highlight the possibility that COVID‐19 is facilitated by altered human social behaviour that benefits SARS‐CoV‐2 transmission, through showcasing similar virus‐induced changed behaviour by other pathogens and relating this to reports from the grey literature. This article is protected by copyright. All rights reserved.

The devastating numbers of COVID-19 cases (over 20 million cases worldwide as of August 11, 2020) raised the question as to whether SARS-CoV-2 employs a more sophisticated strategy to ensure its rapid spread over the globe, by modulating human behaviour, the key of pathogenic spread. Understanding any such strategy is paramount to keep viral spread in check. Beyond its basic strategy to hijack our cell machinery, does SARS-CoV-2 influence our behaviour to make it more likely to spread?

It has been debated that the COVID-19 spread depends on clusters, in which superspreaders are playing a key role in the impressive rapid transmission of the novel coronavirus. 1 In Wuhan, it was estimated that undiagnosed asymptomatic individuals or those with only mild-symptoms were responsible for up to 79% of viral infections. 2 It is remarkable that most of the infected people did not spread the virus at all, 1 though it has been postulated that super-spreaders may carry rather high viral loads. 3, 4 Exhaled viruscontaining aerosols (and also droplets >5 µm to 10 µm) from super-emitters, during breathing, speaking, singing, vocalizing, coughing, and sneezing, constitute the key factor for the spread, 2,3 even if other means of transmission may exist, such as via hand contact. However, this is the first time that behavioural changes, especially in superspreaders, are presented as a plausible key to the successful global spread of the new coronavirus. Indeed, behavioural aspects can be considered as the first line of defence, resulting in either avoidance or exposure to the virus. This hypothesis is perhaps less farstretched as it may appear on a first glance. It should be kept in mind that a variety of intracellular obligate parasites, including viruses, have been reported to exactly do this, as exemplified in the following. Furthermore, grey literature has been increasingly adding to the body of evidence of strange abnormal behavioural patterns during COVID-19, in line with virus-induced altered mannerism. In the following, we briefly emphasize the possibility of COVID-19 instigated behaviour, contributing to the rapid spread of the virus we observe.

Parasite-induced behavioural manipulation is a multi-dimensional process impacting host behavioural decisions in a manner that benefits pathogen transmission. 5, 6 This is corroborated by the grey literature around COVID-19. During the coronavirus crisis, the international media have highlighted, in several parts of the world, peculiar cases of men and women intentionally ignoring physical distancing, deliberately sneezing or coughing in public places or on money, or even spitting on door handles, elevator buttons, shopping carts, credit cards, into people's faces, etc. 7, 8 Defying coronavirus health warnings by licking and kissing holy shrines in Iranian mausoleums was also observed.

Disregarding social distancing, benefitting SARS-CoV-2 transmission, was reported during anti-lockdown movements in both US and Germany, among other countries. Cell phone data suggested that anti-lockdown participants may have widely spread the virus in the US, as some of them did move hundreds of miles across states. Patients with COVID-19 escaping from hospitals were reported in several countries including Spain, where several cases leaving hospitals before they were formally discharged were recorded, resulting in being tracked down, as well as their close contacts, by the police.

Cases of infected individuals deliberately behaving to spread the novel coronavirus e.g. in bars were also reported. Certain governments consider deliberate transmission of COVID-19 as an offence under the general criminal laws. Indeed, individuals intentionally spreading the novel coronavirus could be charged as terrorists in the US, 9 and risk imprisonment for life, the ultimate penalty, in Australia. 8 In this context, deliberate HIV transmission for reasons of personal vengeance or frustration, was already reported and this type of behaviour was criminalised by several governments.

Stunningly, vaccinating humans with an influenza vaccine 10 significantly increased the number of interactions post-immunization compared to before, i.e. in the 48 h pre-symptomatic period prior to the expected onset of symptoms or sickness. In case of a real infection, this would contribute to a rapid spread of the virus. Unlike the precedent SARS-CoV, where its transmission originated from patients with more severe symptoms, 11 the SARS-CoV-2 is further transmissible by asymptomatic individuals or those with only mild-symptoms. 2, 3, 11 It is believed that a large portion of the spread of COVID-19 has been occurring through airborne transmission by asymptomatic individuals, particularly in indoor conditions, 2,3 where aerosols can remain airborne for hours, accumulate over time and follow air flows over distances further than 2 m 2 .

Moreover, the swine flu virus (H1N1) has been demonstrated to cause a variety of neuropsychiatric disorders, 12 including mood disorder and schizophrenia. Thus, the possibility of host-pathogen interactions toward a more active phenotype following infection must be considered. Indeed, host-parasite interactions constitute a well-known dynamic concept leading to abnormal behavioural patterns in the host, which are advantageous either to the host -such as employing defensive behaviour -or to the parasite, as a manipulative behaviour. 5, 6 However, from a co-evolutionary point of view, it is unclear how such behavioural changes can be produced by viruses which have been only interacting with humans for a short time, but they appear to occur, at least for individuals with influenza, and also certain AIDS patients.

Such irresponsible behaviour has been reported to result in an impressive number of cases of contamination in a single night -over 170 -by one individual who visited several clubs (termed "the nightclub's patient zero"), with thousands of potential contacts. 1 As a consequence, South Korean authorities warned of a pandemic's second wave. Interestingly, the first pandemic wave in South Korea was attributed to a single super-spreader known as Patient 31, the 31 st confirmed COVID-19 case. Until then, SARS-CoV-2 was under control and the number of patients was stable, with 30 confirmed cases. Instead of self-quarantine, the patient 31 (a female), had rather multiple social interactions, with thousands of contacts, a demeanour that turned South Korea's virus situation into an epidemic crisis. Indeed, on March 18, at least 60% of all cases in South Korea could be attributed to Patient 31. 13 Undoubtedly, travelling has been a major determining factor for the international spread of the novel coronavirus. In India, a superspreader found asymptomatic at Delhi airport after a trip on 17 March had ignored orders This article is protected by copyright. All rights reserved.

for self-quarantine, infecting around 100 people in Jaipur. 14 Worse still, a religious Sikh, who had returned from a trip to Europe's virus epicentre at the time -Italy -and Germany, and had ignored self-confinement orders, was suspected to have infected several hundreds of people, causing mass quarantining in India, as 40 000 persons from 20 villages in the Punjab state underwent strict home quarantine. 15 Despite knowing he had contracted COVID-19, a super-spreader teacher continued to come to work to a Jerusalem high school, infecting around 200 students and staff members, forcing more than 1400 individuals to enter quarantine. 16 Ms. "S" was identified as the COVID-19

super-spreader in Ningbo, China, in mid-January. 4 Despite having flu-like symptoms, she joined a blessing ceremony in a temple without mask. On February 12, a total of 77 confirmed infected cases were reported, and an accumulative total of 1257 contacts were isolated; a spread in Ningbo was stopped only due to the aggressive contact-tracing and testing adopted by the Chinese government. 4 In the Alpine ski resort of Ischgl, Austria, hundreds of tourists were believed to have contracted the coronavirus and taken it to their homeplace, mostly to Northern Europe and Germany. Thus, Ischgl, which attracts at least 500,000 tourist each winter, became one of the principal epicenters of the COVID-19 spread in Europe. A German bartender, believed to be Ischgl's "patient-zero", fell sick with flu-like symptoms on February 5. However, the novel coronavirus lingered around Ischgl undetected for more than a month, spreading from customer to customer, infecting 611 Austrians -and many more international guests. Indeed, the bartender was tested positive for coronavirus only on March 7 and the bar was finally closed on March 9. 17 Grey literature and social media have reported numerous such stories of infection and super-spreading events that we cannot detail here. It should be highlighted that if such behavioural manipulation by SARS-Cov-2 takes place, this still concerns only a small fraction of infected persons, as the majority of infected individuals appeared to wellrespect self-confinement orders, followed social distancing and employed other defensive behaviour such as hand washing. Interestingly, it was also estimated that 10% of the cases are super-spreaders, resulting in 80% of viral spread, meaning that the majority of SARS-CoV-2 carriers do not appear to unaccountably transmit the virus.

Indeed, most COVID-19 patients are believed not to transmit the disease. 1 It seems that the mode of the transmission of COVID-19 is highly heterogeneous, since the dispersion factor (k), which describes how much a disease clusters, is very low (k= 0. 1 Of course, it is possible or even likely that other aspects influencing personal behaviour of super-spreaders, including cultural and religious aspects, do also play important roles. Given that behaviour is being determined by several factors including biological, psychological, and social determinants, as well as situational factors including environmental challenges, it is likewise possible that this behaviour, reflecting the human complexity, is explainable by the stressful situation -perceived or real-in which persons find themselves". For instance, the behaviour of ignoring social distancing and public safety rules could also be explainable by anger and resentment triggered by fear for loss of rights, labour and income, among others. It could be interesting to study whether during the COVID-19 crisis, more such odd behaviour is truly found -and reportedcompared to other stressful, comparable incidences or diseases, or to compare the behaviour in diseased vs. non-diseased subjects or in the pre-vs. post-infection state, especially in super-spreaders -but such data has at present not been at our disposal and would require carefully controlled studies. However, similar virus-induced modified behaviour was observed in the deadly rabies virus, typically hosted in dogs and foxes, which can inhibit nicotinic acetylcholine receptors in the CNS, 18 the area required for rational behaviour and decision-making.

This causes structural changes of the CNS, induced by a snake-like glycoprotein, resulting in hyperactivity, increased bite-frequency (and elevated saliva-flow) and longer social contacts, a behavioural pattern fundamental to the persistence of rabies in dog populations for millennia. 19 As another viral example, irritability episodes were reported For instance, Toxoplasma gondii, a protozoa, manipulates rodent behaviour, converting host innate aversion to cat odours into rather an attraction, enhancing the chance of cat predating, thus ensuring its transmission efficiency to complete its life-cycle within the cat's intestine. Toxoplasma gondii is also influencing personality and behaviour of infected humans, e.g. by tampering with psychomotor performance. 20

In this perspective, we highlighted the possibility that COVID-19 is facilitated by altered human social behaviour that benefits SARS-CoV-2 transmission (Figure 1 ).

Regrettably, direct scientific evidence for behavioural changes from COVID-19 infected individuals are not (yet) available, and carefully controlled studies in this domain are warranted. However, a loss of chemosensory function has already been reported for COVID-19, influencing taste and smell, which may be related to CNS changes. Brain alteration and a myriad of neuropsychological symptoms including cerebrovascular complications and encephalopathies were reported as a consequence of SARS-CoV-2 infection. Evidence has shown that SARS-CoV-2 may affect directly CNS. CNS disturbances could also result from the immune response to SARS-CoV-2 or as the consequence of the virus' effects on the gastrointestinal tract (Figure 1) , thus both the brain-immune and the gut-brain axis could be involved. Therefore, while we surely should monitor our behaviour in handling the COVID-19 crisis, we must also consider that we may be somewhat handled by the virus, emphasizing that we should be doublecautious regarding our behaviour. behaviour. The scheme highlights the potential manipulative strategy of the novel coronavirus, resulting in viral spread, following an altered behavioural pattern in some COVID-19 patients, as a consequence of a direct impact on brain structure/function, owing to viral infiltration into the CNS, and/or via perturbation of the brain-immune axis or the gut-brain axis.

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