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After the first pandemic wave, a nationwide survey assessed the seroprevalence of SARS-CoV-2 antibodies in Spain and found notable differences among provinces whose causes remained unclear. This ecological study aimed to analyze the association between environmental and demographic factors and SARS-CoV-2 infection by province. The seroprevalence of SARS-CoV-2 antibodies by province was obtained from a nationwide representative survey performed in June 2020, after the first pandemic wave in Spain. Linear regression was used in the analysis. The seroprevalence of SARS-CoV-2 antibodies of the 50 provinces ranged from 0.2% to 13.6%. The altitude, which ranged from 5 to 1131 m, explained nearly half of differences in seroprevalence ( R  2 = 0.47, p &lt; 0.001). The seroprevalence in people residing in provinces above the median altitude (215 m) was three-fold higher (6.5% vs. 2.1%, p &lt; 0.001). In the multivariate linear regression, the addition of population density significantly improved the predictive value of the altitude ( R  2 = 0.55, p &lt; 0.001). Every 100 m of altitude increase and 100 inhabitants/km 2 of increase in population density, the seroprevalence rose 0.84 and 0.63 percentage points, respectively. Environmental conditions related to higher altitude in winter-spring, such as lower temperatures and absolute humidity, may be relevant to SARS-CoV-2 transmission. Places with such adverse conditions may require additional efforts for pandemic control.

Altitude and SARS-CoV-2 Infection in the First Pandemic Wave in Spain