Longitudinal Clinical Phenotyping of Post COVID Condition in Mexican Patients Recovering from Severe COVID-19: A Prospective Cohort Study

Background: ‘Post COVID-19 condition’ (PCC) arising after SARS-CoV-2 infection may soon reach global epidemic proportions. While recent studies have provided important insight on the clinical determinants of PCC, few studies have focused on patients from Latin America, who have contributed disproportionately to the global COVID-19 burden. In this prospective study, we performed detailed and longitudinal clinical phenotyping, including the frequency, co-occurrence, and duration of over 20 PCC symptoms in a cohort of Mexican patients.Methods: Adult patients hospitalized for severe COVID-19 at a tertiary care center in Mexico City were prospectively enrolled and followed clinically for up to two years. The presence of 23 PCC symptoms was determined using structured questionnaires at 90-day intervals. Analyses included unsupervised clustering of PCC symptom co-occurrence, and Kaplan Meier analysis of symptom persistence. The effect of baseline clinical characteristics was evaluated using Cox regression models.Findings: Ninety six percent (n=194) of patients reported at least one PCC symptom 90 days after acute SARS-CoV-2 infection. Respiratory problems were the most prevalent (58% for O2 saturation < 94%) and commonly co-occur with functional activity impairment. Sixty-eight percent of patients had five or more persistent symptoms, with neurocognitive symptoms persisting for the longest (median 496 days for depression). Prior SARS-CoV-2 vaccination, infection during the Delta variant wave, male gender, and age less than 40 years were associated with decreased PCC symptom persistence, while hypertension and diabetes with increased PCC duration.Interpretation: While nearly all patients in this cohort suffered from PCC, substantial patient variability was observed in the frequency and persistence of individual PCC symptoms. These findings emphasize the need for future research in Latin American and other lower- and middle-income (LMIC) populations that is focused on risk prediction, as well as interventions to prevent or reduce the severity and duration of PCC.Funding Information: This work was supported in part by: the Bill and Melinda Gates foundation COVID-19 Pilot Award OPP1113682 (GPN, DRM, HC) and INV-002704 (GPN); Consejo Nacional de Ciencia y Tecnología, Gobierno de México, grant A1-S-18342 (SIVF); Fundación Gonzalo Río Arronte (SIVF); the Centre for Human Systems Immunology (BG); 17 a CEND Covid Catalyst Award (BG); the Doris Duke Charitable Foundation (BG); German Academic Exchange Service with funds from the German Federal Ministry of Education and Research (AB); the Centres for Disease Prevention and Control contract number 75D30120C08009 (JDK); The Sunshine Foundation (KCN), David A. Crown Foundation (KCN), and Sean N Parker Foundation (KCN). National Institutes of Health 5U19AI100627-09 Systems Approach to Immunity and Inflammation COVID supplement (GPN, DRM, HC); US Food and Drug Administration Medical Countermeasures Initiative contracts 75F40120C00176 and HHSF223201610018C (GPN, DRM, HC).Declaration of Interests: None declared.Ethics Approval Statement: All study participants gave written informed consent before their inclusion in the study. This study was approved by the Ethics Committee of Research in Humans of the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (ID: NER-3378-20-21-1) and performed in accordance with the Declaration of Helsinki.