Differential symptoms among COVID-19 outpatients before and during periods of SARS-CoV-2 Omicron variant dominance in Blantyre, Malawi: a prospective observational study

Background It is widely reported that the SARS-CoV-2 Omicron variant has resulted in high number of cases, but relatively low incidence of severe disease and deaths, compared to the pre-Omicron variants of concern. We aim to assess the differences in symptom prevalence between Omicron and pre-Omicron infections in a sub-Saharan African population. Methods In this cross-sectional observational study, we collected data from children and adult outpatients presenting at two primary healthcare facilities in Blantyre, Malawi. Eligible participants were aged >1month old, with signs suggestive of COVID-19, and those not suspected of COVID-19. Nasopharyngeal swabs were collected for SARS-CoV-2 PCR testing and positive samples whole genome sequenced to identify the infecting variant. The primary outcome was the likelihood of presenting with a given symptom in individuals testing positive during the period in which Omicron-dominated (December 2021 to March 2022) with those infected during the pre-Omicron period (August 2021 to November 2021). Findings Among 5176 study participants, the median age was 28 years (IQR 21-38), of which 6.4% were under 5, 9.2% were 6 to 17 years, 77% were 18 to 50 years, and 7.1% were above 50 years old. Prevalence of SARS-CoV-2 infection was 23% (1187/5188), varying over time, with peaks in January 2021, July 2021 and December 2021, driven by the Beta (B.1.351), Delta (B.1.617.2) and Omicron (BA.1/2) variants, respectively. Headache (OR 0.47[CI 0.29 – 0.79]), cough (OR 0.37[CI 0.22 – 0.61]), fatigue (OR 0.20[CI 0.08 – 0.48]) and abdominal pain (OR 0.38[CI 0.18 – 0.78]) were less common in participants infected during the Omicron-dominant period than during pre-Omicron period. Fever was more common in participants infected during the Omicron-dominated period than during pre-Omicron period (OR 2.46[CI 1.29 – 4.97]). COVID-19 vaccination, accounting for number of doses and days since last dose, was not associated with a reduced risk of PCR-confirmed SARS-CoV-2 infection (1 dose, OR 1.10[CI 0.39 – 2.66]; 2 doses, OR 1.11[CI 0.40 – 2.57]; all p=0.8). Interpretation In this Malawian population, the prevalence of clinical symptoms associated with Omicron infection differ from those of pre-Omicron infections and may be harder to identify clinically with current symptom guidelines. To maintain robust surveillance for COVID-19 and emerging variants, case definitions and testing policies will need to be regularly reviewed to ensure case ascertainment. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The work is supported by funding from Wellcome [220757/Z/20/Z] and the National Institute for Health Research (NIHR) [16/136/46]. KCJ is supported by an MRC African Research Leader award [MR/T008822/1]. RSH is a NIHR senior investigator. The views expressed in this publication are those of the authors and not necessarily those of the NIHR or the UK government. A Wellcome Strategic award number 206545/Z/17/Z supports MLW. The funders were not involved in the design of the study; in the collection, analysis, and interpretation of the data; and in writing the manuscript. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the College of Medicine Research and Ethics Committee (COMREC P.08/20/3099) and Liverpool School of Tropical Medicine Research Ethics Committee (LSTMREC 21-058). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors