**Background:** The COVID-19 pandemic has altered the epidemiology of common community respiratory tract infections (RTI), with some pathogens (e.g., influenza, RSV) declining while others (e.g., rhinovirus) have risen. In Central Asia, particularly Kazakhstan, data on regional RTI dynamics are limited. By spring–summer 2021, up to 60% of Kazakhstan's population had been exposed to SARS-CoV-2, and national surveillance reported a rise in non-COVID symptomatic RTI. This pilot study aimed to characterize viral pathogens associated with symptomatic upper RTI in adults during a low COVID-19 transmission period in Almaty, Kazakhstan.
**Methods:** Adults (aged 17–45) presenting with RTI symptoms (cough, sore throat, runny nose, fever) at two public outpatient clinics in Almaty were screened using SARS-CoV-2 PCR on nasopharyngeal swabs (Syntol kits, targeting orf1ab). A subset of 50 COVID-19-negative participants was then tested using a multiplex PCR panel (Amplisens ARVI-screen-FRT) for common RNA viruses (RSV, MPV, hPIV-1–4, coronaviruses OC43/HKU-1 and NL63/229E, rhinovirus) and DNA viruses (adenovirus B/C/E, bocavirus), plus a separate IAV PCR. Positivity threshold was Ct ≤ 32. Virome sequencing was performed on all PCR-positive samples using the Ion Torrent S5 platform, with bioinformatic analysis via EDGE, GOTTCHA2, Kraken2, BWA, MethaPhlAn2, and Diamond. Phylogenetic trees were constructed using MEGA 11 with maximum likelihood and 500 bootstrap replicates.
**Key Results:** Of 1,812 symptomatic adults screened, 21 (1.16%) tested SARS-CoV-2-positive. Among the 50 COVID-negative participants (median age 31 years, 76% female), 33/50 (66%) had a positive multiplex PCR result for a non-COVID respiratory virus. Specifically, 25/50 (50%) had hPIV mono-infection (24 hPIV-4, 1 hPIV-3), 2/50 (4%) had hRV mono-infection, 4/50 (8%) had hPIV4-hRV co-infection, and 2/50 (4%) had adenovirus or OC43/HKU-1 coronavirus mono-infection. No IAV, RSV, MPV, bocavirus, or NL63/229E coronavirus was detected. Virome sequencing successfully characterized viral sequences in 6/33 (18%) PCR-positive samples: 5 rhinoviruses (all species A: A56, A30, A100, and two A1B strains) and 1 hPIV-3 (respirovirus-3). One hRV-A1B sample achieved 100% linear coverage with 69,393 reads. Phylogenetic analysis showed the hRV-A strains were diverse with global origins, while the hPIV-3 clustered distinctly with other hPIV-3 sequences.
**Clinical Implications:** This study provides the first pilot data on RTI dynamics in a Central Asian population during a low COVID-19 transmission period. The finding that only 1.2% of symptomatic adults had COVID-19, while 66% of COVID-negative individuals had detectable non-COVID respiratory viruses (predominantly hPIV and hRV), suggests that clinical management and prevention strategies for adult RTI in the post-pandemic era should not focus exclusively on SARS-CoV-2. The high proportion of hPIV-4 (50% of tested subset) is notable and warrants further investigation. Limitations include the small sample size (n=50 for multiplex testing), cross-sectional design precluding seasonality analysis, limited PCR panel (not covering all viral/bacterial pathogens), and low sequencing success rate (18% of PCR-positive samples). Despite these limitations, the study highlights the need for more comprehensive, adequately powered RTI surveillance in Central Asia to inform healthcare resource allocation and outbreak preparedness.