OPEN ACCESS EDITED BY Two-year follow-up of the COVID-pandemic in Mexico

The study addresses how COVID-19 evolved in Mexico over its first two years, focusing on incidence, severity, and outcomes across demographic groups, comorbidities, and successive variant waves. After SARS-CoV-2 was identified in late 2019 and COVID-19 was declared a pandemic in March 2020, early reports showed higher fatality among older adults and a constellation of respiratory and systemic symptoms. Over time, multiple variants emerged, prompting WHO surveillance and classification (VUM, VOI, VOC). This work aims to contextualize Mexico’s epidemiological trajectory, the impact of public health policies (e.g., distancing measures, testing expansion, vaccination), and the role of variants on disease severity and symptomatology, while quantifying major risk factors for hospitalization and death.

The paper references global findings that older age and male sex increase vulnerability to severe COVID-19 and that comorbidities (e.g., obesity, diabetes, hypertension) heighten risk. It notes early symptom profiles (fever, cough, dyspnea, headache, myalgia, fatigue) and later recognition of anosmia/dysgeusia. Variant evolution in Mexico mirrored global trends: initial lineage diversity; dominance of B.1.1.519 in wave 2; rapid spread of Alpha/Gamma in specific locales; Delta dominance by mid-2021; and Omicron BA.1 predominance by early 2022. Literature also indicates increased transmissibility across successive VOCs and changing symptom profiles (e.g., more upper respiratory features with Omicron), as well as treatment advances (e.g., steroids) that reduced mortality.

Design: Population-based longitudinal study using national surveillance data (SISVER). Setting/Period: Epidemiological week 14 of 2020 (starting March 29, 2020) to week 11 of 2022 (ending March 19, 2022). Population: All suspected COVID-19 cases in SISVER. Outcomes: Suspected cases (SCs); confirmed cases (CCs: RT-PCR+, antigen+, or epidemiologic association); deaths among CCs (with death certificate); hospital admissions among CCs; case fatality proportion (CFP = deaths/CCs); hospital admission proportion (HP = admissions/CCs). Independent variables: Sex; age (0–17, 18–29, 30–39, 40–49, 50–59, 60+); self-reported comorbidities (hypertension, obesity, diabetes, asthma, heart disease, renal insufficiency, COPD, immunosuppression, HIV/AIDS); symptoms; prevalent SARS-CoV-2 lineages (GISAID); monthly vaccination coverage (Our World in Data). Data sources: SISVER for cases, demographics, comorbidities, symptoms, testing results (last result per patient used); GISAID (n=47,572 Mexican genomes, <1% of CCs) for variant dynamics; Our World in Data for vaccination percentages. Statistical analysis: Cases grouped by symptom onset date. Epidemic dynamics assessed via the weekly growth factor Gn = ln(NI(tn)) − ln(NI(tn−1)) with a three-week moving average to delineate waves. Descriptive statistics by wave, sex, age. CFP and HP estimated as averages of 100 subsamples (n=15,000 each); normality (Shapiro–Wilk) assumed for 95% CIs. Symptom dynamics explored by clustering (pheatmap, complete linkage). Combined effects of frequent comorbidities (diabetes, hypertension, obesity) examined. Multivariable logistic regression modeled hospital admission and death as outcomes versus predictors: epidemic wave (1–4), sex, age group, any comorbidity (yes/no). Analyses conducted in R 4.1 (ggplot2 for variant pile density; pheatmap for symptoms). Health policy context (e.g., Safe Distance campaign, testing expansion to antigen tests, vaccination rollout) and variant timelines integrated with epidemiologic trends.

Overall period (to March 19, 2022): • Suspected cases: 15,458,158; CCs: 5,702,143; non-CCs: 9,108,393; unreported/invalid: 647,622. • Hospitalized: 680,063 (11.9% of CCs); deaths: 324,436 (5.7% of CCs). • Sex: Similar infection susceptibility; males had higher severity: CFP 7.3% vs 4.2%, HP 14.4% vs 9.5%. • Age: Severity rose with age; 60+ had the highest CFP (26.8%) and HP (43.1%). HP by age showed a J-shape, with 0–17 having HP 4.0% (higher than 18–29 at 2.5%). • Comorbidities prevalence among CCs: hypertension 12.7%, obesity 10.5%, diabetes 9.5%; less prevalent: renal insufficiency 1.1%, COPD 0.7%, immunosuppression 0.6%. • Mortality by comorbidity: renal insufficiency 38.1%, COPD 32.8%, diabetes 21.9%, hypertension 19.8%, immunosuppression 21.6%, all exceeding global averages. • Symptom clusters: (a) >50%: cough, headache, fever, odynophagia, myalgias, arthralgias; (b) 30–50%: rhinorrhea, chills, sudden onset; (c) <30%: vomiting, cyanosis, polypnea, abdominal pain, conjunctivitis, shortness of breath, chest pain, anosmia, dysgeusia, irritability, diarrhea. Symptom prevalence shifted across waves, with less anosmia in Omicron. • Variant dynamics: Early mix (B.1, B.1.1, B.1.1.222); Wave 2 dominated by B.1.1.519; Wave 3 dominated by Delta (87% by Aug 2021); Wave 4 dominated by Omicron BA.1 (>90% by Mar 2022). • Vaccination: Began late 2020; within 1 year, 63.6% had at least one dose. Wave-specific (excluding inter-wave): • Wave 1 (Mar 29–Sep 26, 2020): Tested 1,670,308; CCs 809,387; admissions 203,992; deaths 100,228; CFP 12.3% (95% CI 10.8–13.7); HP 25.1% (23.0–27.1). • Wave 2 (Sep 27, 2020–Apr 17, 2021): Tested 4,302,882; CCs 1,538,110; admissions 251,245; deaths 132,638; CFP 8.7% (7.8–9.5); HP 16.4% (15.3–17.6). • Wave 3 (May 23–Nov 6, 2021): Tested 4,289,906; CCs 1,439,463; admissions 140,266; deaths 61,155; CFP 4.2% (3.6–4.9); HP 9.8% (9.1–10.6). • Wave 4 (Dec 19, 2021–Mar 19, 2022): Tested 3,035,537; CCs 1,722,625; admissions 60,021; deaths 20,659; CFP 1.2% (0.9–1.5); HP 3.4% (2.8–4.0). Growth factor Gn: Early high values shrank in W1; increased to ~20% in W1–W2 peaks, >30% in W3, and ~100% at W4 start; sharp decline after W4 peak (Gn < −50%). Multivariable logistic regression: • By wave (vs W1): Admissions ORs: W2 0.72 (0.64–0.81), W3 0.52 (0.45–0.60), W4 0.15 (0.12–0.18). Death ORs: W2 0.59 (0.52–0.66), W3 0.46 (0.40–0.53), W4 0.15 (0.13–0.18). • Sex: Men had higher odds—admission OR 1.59 (1.44–1.75); death OR 1.78 (1.60–1.97). • Age (vs 0–17): Risks rose steeply with age; highest in 60+ (adjusted ORs up to 9.63 and 53.05 for admission and death, respectively); intermediate increases across 30–59 groups; 18–29 showed reduced odds vs 0–17 for admission (OR 0.52, 0.37–0.73) and not significant for death. • Any comorbidity: Admission OR 2.40 (2.17–2.66); death OR 2.38 (2.14–2.66). Hypertension–diabetes combination showed particularly high risk. Health policies/testing/vaccination: Safe Distance National Campaign (Mar–May 2020) aligned with reduced growth; antigen testing (Nov 2020) expanded detection; vaccination roll-out aligned with declines in severity despite more transmissible variants.

The four waves in Mexico reflect interplay among variant transmissibility, public health measures, clinical management, and vaccination. Early mitigation (Safe Distance campaign) likely helped curb transmission growth but coincided with limited testing and the highest proportional risks of hospitalization and death. Wave 2’s larger burden stemmed from increased mobility and expanded testing; hospital saturation may have contributed to a high deaths-to-admissions ratio. Despite Delta’s virulence, Wave 3 saw reduced admissions and deaths—consistent with vaccine roll-out (including 18–59-year-olds) and improved clinical care (earlier presentation, dexamethasone, antivirals). Wave 4 (Omicron BA.1) produced the largest case surge yet the lowest severity, likely due to intrinsic variant characteristics, accumulated immunity, vaccination (including boosters), and better treatment protocols. Symptom shifts (e.g., more upper-respiratory features and less anosmia in Omicron) complicate diagnosis but align with altered tissue tropism. Consistent with global data, male sex, older age, and comorbidities were major severity determinants; the hypertension–diabetes combination notably increased risk. Declines in severity across waves (ORs ~0.15 in W4) underscore the combined benefit of vaccination, evolving care, and possibly reduced pathogenicity of later variants. The findings support targeted protection of older adults and those with cardiometabolic comorbidities, continued vaccination/booster strategies, and sustained surveillance of variants and symptoms to adapt clinical and public health responses.

This study provides a comprehensive, population-based account of Mexico’s first two years of COVID-19, documenting four epidemic waves with increasing case peaks but steadily decreasing hospitalization and death risks, particularly by the Omicron-dominated fourth wave. Male sex, advanced age, and comorbidities—especially hypertension and diabetes—were the strongest predictors of severe outcomes. Changes in variant prevalence, symptom profiles, testing availability, vaccination coverage, and patient management collectively shaped the observed trends. Future work should refine risk stratification (including combined comorbidity profiles), monitor variant-driven clinical shifts, and evaluate the long-term impact of booster strategies. Strengthening surveillance, early care access, and health system capacity (notably ICU thresholds and contact tracing) will be crucial for future epidemics.

Under-ascertainment, particularly during the first wave due to limited testing, introduces bias. Genomic sequencing represented <1% of CCs, limiting precise linkage between all cases and variants. Symptom and comorbidity data are self-reported/recorded at admission and may be incomplete. Changes in testing strategies (e.g., antigen test introduction) affect comparability over time. Despite these limitations, the national registry provides robust insights into policy impacts and epidemiological trends.