The Seasonality Issue: Wishful Thinking for SARS-CoV-2?

We are used to the seasonal nature of influenza virus infection. In the northern hemisphere, we expect to see cases emerge in October, surge in the winter months, and begin to tail off in April.¹ Many generalizations have been made comparing influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), so it has been tempting to think of SARS-CoV-2 as a seasonal infection too. However, we do not yet know if SARS-CoV-2 will behave in a seasonal way.

The seasonality of influenza virus is well established in temperate regions of the world, but in many tropical regions the number of cases is steadier throughout the year.^2,3 Infection from respiratory syncytial virus and common human coronaviruses (a category of coronaviruses, but not referring to SARS, Middle Eastern respiratory syndrome [MERS], or coronavirus disease 2019 [COVID-19]) also mostly occur in the winter; however, some respiratory viruses such as adenovirus and rhinovirus cause infection year-round, and others such as some parainfluenza viruses and some enteroviruses occur most commonly in summer and fall.⁴

The number of cases of a communicable disease in a population depends upon the reproductive number for the pathogen, or the R₀, which is the number of secondary cases caused by a given primary case in a susceptible population. ⁵ One way to look at seasonality of a virus is that it represents a change in the R₀ (ie, during the off-season, fewer people can be infected by another person).^{5, 6}The virus is not eliminated — it is still present in the environment — but its ability to cause disease has changed. Numerous factors may influence this, and they are not well understood; some may be related to host behavior, some may involve effects on host resistance by the environment, and some may involve effects on the virus by the environment.⁷

The most obvious host behavior during cold weather months that might influence the incidence of a communicable disease is the tendency to congregate indoors for longer periods of time. People are nearer to one another and logically can infect others by droplet, aerosol, or contact more easily than if they were farther apart.  A retrospective study of school children in Israel demonstrated a marked reduction in respiratory tract infection diagnoses, physician visits, and medication purchases during a winter labor dispute that caused school closure compared with the periods before and after the closure.⁸

Animal studies suggest that seasonal environmental changes may affect host response to infection. These studies have focused on the effects of lower temperatures and humidity, which is characteristic of winter months. In a mouse model of influenza A virus infection, tracheal mucociliary clearance, repair of lung epithelial cells, and interferon-stimulated gene expression in lung tissue were all impaired at 10% relative humidity compared with 50%.⁹ In guinea pigs, dry air had been linked to tracheal epithelial cell damage.¹⁰ A study of nasal cilia and tracheal cilia beat frequency in human cells demonstrated that the cilia became immobile at 50°C, with increasing motility to normal by 20°C.¹¹ Decreased serum vitamin D levels as a result of reduced sunlight during the winter months has been postulated to negatively impact host response to infection.¹² In a small randomized, double-blind, placebo-controlled trial from Japan, children who received vitamin D₃ supplementation had significantly fewer documented infections with influenza A but not influenza B compared with those who received placebo.¹³ A meta-analysis of randomized controlled trials showed significantly fewer participants with at least 1 respiratory tract infection if they received vitamin D₃ supplementation and if they started with vitamin D deficiency.¹⁴

The study of virus stability under different environmental conditions has also demonstrated a link to seasonal variation of infection. The animal coronaviruses known as transmissible gastroenteritis virus and the mouse hepatitis virus survived on stainless steel longer at 4°C compared with 40°C; they also survived longer at 20% relative humidity compared with 50% and 80%.¹⁵ The viability of the transmissible gastroenteritis virus in aerosol was greatest at 30% relative humidity compared with ≥50%.¹⁶ A study of SARS-CoV-1 viability on plastic showed that the virus became inactive faster at relative humidity >95% compared with 80% to 89% at a temperature of 38°C.¹⁷ In a study of MERS-CoV viability, the virus maintained viability on steel or plastic for up to 48 hours at 20°C with 40% relative humidity, for 8 hours at 30°C/80% relative humidity, and for 24 hours at 30°C/30% relative humidity; in aerosol, MERS-CoV was significantly less viable at 70% relative humidity compared with 40% at 20°C.¹⁸ Decades-old studies showed that influenza virus in aerosols survives best with lower relative humidity^{19, 20} and temperature.¹⁹ In an aerosol exposure simulation chamber with a coughing manikin, influenza A viability 60 minutes after coughing was much higher at 7% to 23% relative humidity compared with > 43% relative humidity.²¹ In an interventional study of classrooms at a Minnesota preschool, the presence of influenza A virus was significantly increased on fomites and in the air of intentionally humidified rooms compared with rooms that were not humidified over a 30-day period from January to February.²² Ultraviolet A (UVA) light has been shown to be ineffective at inactivating SARS-CoV-1.²³ Ultraviolet C (UVC) light is much more effective than UVA and ultraviolet B (UVB) at causing nucleic acid damage,²³ but UVC light is filtered by the earth’s atmosphere before reaching the surface^{24, 25}; its antiviral usefulness is in the decontamination of room air and surfaces.²⁶ However, in a simulated sunlight model, increasing light intensity or duration accelerated influenza A virus inactivation in aerosols.²⁵

Animal studies also support more efficient transmission of influenza virus in cold, dry conditions. In guinea pigs, transmission of influenza A virus between infected and uninfected animals grouped in separate cages was much greater at 5°C compared with 30°C and was greater in dry laboratory conditions compared with humid.²⁷ This study also showed that influenza A viral titers in nasal wash specimens were higher and more prolonged at 5°C compared with 20°C.  Similarly, airborne transmission of influenza B virus between 2 groups of guinea pigs was more efficient at 5°C compared with 20°C, and nasal wash viral titers were higher and prolonged at the lower temperature.²⁸ However, when infected and uninfected guinea pigs were caged together, allowing contact transmission to occur, the climate effects were eliminated.²⁸ This finding was corroborated in another study that showed that a decreased transmission efficiency of influenza A in guinea pigs at 30°C compared with 20°C was eliminated when contact between animals was allowed.²⁹ Although these observations imply that the experimental conditions influence influenza transmission through the air but not through direct contact, they do not distinguish whether the differences in viral transmission might have been due to effects on host response vs effects on virus stability. Human studies of the effects of climate on viral infection are epidemiologic, correlating environmental conditions to disease incidence, and similarly do not shed light on the possible mechanisms for the observations.

A recent preprint reviewed 17 observational studies of the effects of temperature and humidity on SARS-CoV-2 infection rates and showed that although 16 of 17 studies concluded that low temperature and/or low humidity encouraged infection spread, the overall quality of the evidence was low.³⁰ Most of the studies included have not yet been peer reviewed, and in many of the studies other factors may have played a significant role in determining infection rates.³⁰ Another non-peer-reviewed study showed that in an analysis of worldwide cases of coronavirus disease 2019 (COVID-19), travel restrictions most significantly correlated with decreased infection growth rate compared with any climate parameters.³¹

While experimental evidence suggests that environmental conditions may play a role in the seasonality of influenza infection, the mechanisms are unclear and their real-world contributions are unknown. After all, host crowding indoors may occur in very hot weather as well as in cold weather. The weather issues considered responsible for seasonality in temperate climates seem to imply that infection would not occur much in tropical climates, but this is not the case. Even for influenza infection, with well-known seasonality, there is still much to be learned. It is certainly too early to know if there will be any seasonal variation to SARS-CoV-2 infection. There is no reason to specifically compare this virus with the seasonal behavior of influenza virus or other seasonal respiratory viruses. Even if low temperature, low humidity, or even sunlight do have a negative effect on SARS-CoV-2 infectivity via mechanisms affecting the host and/or the virus, innate properties of the virus and the overwhelming susceptibility of the world’s population to SARS-CoV-2 might be far more important and override any climate effects.

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